Methods of detecting and treatment of cancers using Scutellaria barbata extract

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Isaac Cohen

JUSTIA: 8512961

USPTO: 8512961

BioSeek: 8512961

Raktažodžiai

Patentų informacija

Patento numeris	8512961
Paduota	11/18/2008
Patento data	08/19/2013

Santrauka

An extract of Scutellaria Barbata D. Don is effective in the arrest of cancer cell growth. The extract of Scutellaria Barbata D. Don may be used as a therapeutic treatment for patients who have been identified as having cancer. In some situations, a patient is identified as having a type of cancer by detecting the presence of a biomarker for that cancer in the patient's system and by further determining the level of that biomarker in the patient's system. If the level of the biomarker is above a predetermined threshold level for that biomarker, the patient may be diagnosed with cancer. Subsquently, treatment using an extract of Scutellaria Barbata D. Don may begin. Biomarkers of interest in the detection of the presence of metastitic breast cancer include 8-oxoguanine and lactate dehydrogenase.

Pretenzijos

What is claimed is:

1. A method for the treatment of breast cancer, comprising: (a) contacting a portion of a biological sample comprising breast tumor cells obtained from a patient with a composition comprising an extract of Scutellaria barbata D. Don to produce a treated sample; (b) detecting a level of DNA oxidation in the treated sample and in an untreated sample comprising breast tumor cells obtained from the patient; (c) if the level of DNA oxidation in the treated sample meets or exceeds a predetermined threshold, which is three times the level of oxidation in the untreated sample, administering to the patient an effective amount of the composition comprising an extract of Scutellaria barbata D. Don; and, (d) if the level of marker of DNA oxidation in the sample is below said predetermined threshold, administering an alternative treatment to the patient.

2. The method of claim 1, comprising detecting the level of a marker of DNA oxidation.

3. The method of claim 1, wherein the marker of DNA oxidation is 8-oxoguanine or lactate.

4. A method of deciding whether to continue anti-breast cancer chemotherapeutic treatment with a composition comprising an extract of Scutellaria barbata D. Don, comprising: (a) obtaining a biological sample comprising breast tumor cells from a patient undergoing anti-breast cancer treatment with a composition comprising an extract of Scutellaria barbata D. Don; (b) contacting a portion of the biological sample with a composition comprising an extract of Scutellaria barbata D. Don to produce a treated sample; (c) detecting a level of a marker of DNA oxidation in the treated sample and in an untreated sample comprising breast tumor cells obtained from the patient; (d) if the level of marker of DNA oxidation in the treated sample exceeds a predetermined threshold, which is three times the level of DNA oxidation in the untreated sample, continuing to administer to the patient an effective amount of an extract of Scutellaria barbata D. Don; and (e) if the level of marker of DNA oxidation in the treated sample is below the predetermined threshold, discontinuing treatment with the composition comprising an extract of Scutellaria barbata D. Don and/or administering an alternative treatment to the patient.

5. The method of claim 4, wherein the marker of DNA oxidation is 8-oxoguanine or lactate.

apibūdinimas

BACKGROUND OF THE INVENTION

While advances in early detection and adjuvant therapy for breast cancer have had a favorable impact on patient survival in general, patients who develop advanced metastatic breast cancer are generally likely to face a less favorable prognosis. Commonly used hormonal and chemotherapeutic agents can lead to transient regression of tumors and can also palliate symptoms related to cancer. However, these treatments are often accompanied by toxicities and intolerable side effects and eventually become ineffective in controlling advanced stage breast cancer and its symptoms. Improvements in survival are modest, even with newer targeted biological agents. Moreover, in most metastatic cancers resistance to available conventional treatment ultimately develops or excessive side effects are seen with conventional therapies.

It is interesting to note that greater than 60% of all chemotherapeutic agents used in the treatment of breast cancer are derived from natural substances (Newman 2003). A fairly recent example is the development of taxanes from the Pacific yew tree, Taxus brevifolia. Throughout the world, it is estimated that approximately 80% of the world population still relies on botanical medicine as the primary source of therapy. In the West botanical medicine is considered a popular form of complementary and alternative medicine among patients diagnosed with cancer. However, few clinical trials have been conducted to firmly assess the safety and efficacy of botanical agents for the treatment of breast cancer, despite anecdotal case reports of cures and clinical efficacy in women who have relied solely on botanical medicine for treatment. It has previously been shown that the aqueous extract of Scutellaria Barbata can lead to growth inhibition of breast cancer cell lines in vitro ("Antiproliferative activity of Chinese medicinal herbs on breast cancer cells in vitro," Anticancer Res., 22(6C):3843-52 (2002)). BZL101, a concentrated aqueous extract of Scutellaria Barbata, was evaluated for antiproliferative activity on five breast cancer cell lines (SK-BR-3, MCF7, MDA-MB-231, BT-474, and MCNeuA). These cell lines represent important prognostic phenotypes of breast cancer expressing a range of estrogen and HER2 receptors. BZL101, tested at a 1:10 dilution (15 .mu.g/ml), demonstrated>50% growth inhibition on four of the five cell lines (Campbell, 2002). BZL101 showed>50% growth inhibition on a panel of lung, prostate and pancreatic cancer cell lines. BZL101 at the same dose did not cause>25% of growth inhibition on normal human mammary cells (HuMEC), demonstrating selectivity to cancer cells (Table 1). More so, BZL101 had a mild mitogenic effect on normal human lymphocytes. In cell cycle analysis, BZL101 caused an S phase burst and G1 arrest. BZL101 also attenuated mitochondrial membrane potential causing caspase-independent high molecular grade (HMG) apoptosis.

SUMMARY OF THE INVENTION

The inventor has recognized a need for improved methods of treating various types of cancer, especially ER.sup.- (e.g. ER.alpha..sup.- and/or ER.beta..sup.-) breast cancer. Various embodiments of the invention provided herein meet the foregoing need and provide related advantages as well.

Some embodiments described herein provide a method of treating cancer in a patient, comprising: obtaining a tumor sample from the patient; (a) contacting a portion of the tumor sample with a composition comprising an extract of Scutellaria barbata D. Don; (b) detecting a level of a marker of DNA oxidation in the sample from the patient; and (c) if the level of marker of DNA oxidation in the sample exceeds a predetermined threshold, administering to the patient an effective amount of an extract of Scutellaria Barbata D. Don. In some embodiments, the cancer is breast cancer. In some embodiments, the cancer is metastatic breast cancer. In some embodiments, the cancer is selected from the group consisting of sarcoma, carcinomas, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, Kaposi's sarcoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma and retinoblastoma. In some embodiments, the marker of DNA oxidation is 8-oxoguanine or lactate. In some embodiments, the level of the marker of DNA oxidation is determined by mass spectrometry.

A method of deciding whether to continue anticancer chemotherapeutic treatment with an extract of Scutellaria barbata D. Don, comprising: (a) obtaining a sample from a cancer patient treated with an extract of Scutellaria barbata D. Don; (b) determining a level of a marker of DNA oxidation in the sample; and (c) if the level of marker of DNA oxidation in the sample exceeds a predetermined level, continuing treatment with the extract of Scutellaria barbata D. Don. In some embodiments, the cancer is a breast cancer. In some embodiments, the cancer is metastatic breast cancer. In some embodiments, the cancer is selected from the group consisting of sarcoma, carcinomas, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, Kaposi's sarcoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma and retinoblastoma. In some embodiments, the marker of DNA oxidation is 8-oxoguanine or lactate. In some embodiments, the sample is a bodily fluid or a solid tissue. In some embodiments, the sample is a bodily fluid. In some embodiments, the bodily fluid is blood serum or urine. In some embodiments, the marker of DNA oxidation is 8-oxoguanine or lactate.

Some embodiments described herein provide a kit comprising a therapeutically effective amount of an extract of Scutellaria barbata D. Don and a means for determining a level of a marker of DNA oxidation in a sample from the patient. In some embodiments, the marker of DNA oxidation is 8-oxoguanine or lactate.

Some embodiments described herein provide a kit comprising a therapeutically effective amount of an extract of Scutellaria barbata D. Don and a means for detecting a level of a gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD, LTB4R, PBEF1, WDR3, NEK6, PLEKHF1, PLEK2, FKSG27, CORO1C, SNAI1, MOBKL1A, CYP27B1, PUS1, NFKBIB, UBE2E1, HA-1, PWP2H, TPST1, CDKN1A and ZNF529. In some embodiments, the gene participates in a xenobiotic response pathway, an oxidative response pathway, a NF.kappa.B pathway or an apoptosis/cell death pathway.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

FIG. 1 shows dose-response curves showing the response of several solid cancer tumor cells to aqueous extract of the herb of this invention.

FIG. 2 shows dose-response curves showing the response of several breast solid cancer tumor cells to aqueous extract of the herb of the invention.

FIG. 3 shows dose-response curves comparing the response of breast solid cancer tumor cells and normal breast epithelium to aqueous extract of the herb of this invention.

FIG. 4 shows gel electrophoresis plate, which demonstrates that nuclear DNA disintegration occurs during apoptosis of solid tumor cancer cells in contact with aqueous extracts of the herb of this invention.

FIG. 5 shows the effect of the herb extract of the invention administered intraperitoneally (IP) on the tumors of mice in a xenograft model.

FIG. 6 shoes the effect of the herb extract administered by oral gavages and in interaction with cyclophosphamide administered in low dose in the drinking water on the tumors of mice in a xenograft model.

FIG. 7 shows that the herb extract induces apoptosis without activating caspases.

FIG. 8 shows that the herb extract in cell cycle analysis arrests the cells at the G1 phase.

FIG. 9 shows that illustrates that BZL101 leads to oxidative DNA damage. Formation of 8-oxoguanine, the most ubiquitous marker of DNA oxidation, was quantified through flow cytometric analysis of fixed permeabilized cells incubated with avidin fluorescein, that was shown to bind relatively specifically to 8-oxoguanine. There is a clear increase in binding of avidin to BZL101 treated SKBr3 cells versus untreated cells.

FIG. 10 shows that the conversion of non-fluorescent CM-H.sub.2DCFDA into fluorescent compound is indeed due to ROS. Incubation of cells with ROS scavenger N-acetyl-cysteine (NAC) prior to addition of BZL101 prevented most of the increase in ROS generation.

DETAILED DESCRIPTION OF THE INVENTION

Some embodiments described herein provide a method of treating cancer in a patient, comprising: (a) obtaining a tumor sample from the patient; (b) contacting a portion of the tumor sample with a composition comprising an extract of Scutellaria barbata D. Don; (c) detecting a level of a gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don; and (d) if the level of the gene exceeds a predetermined threshold, administering to the patient an effective amount of an extract of Scutellaria Barbata D. Don. In some embodiments, the cancer is breast cancer. In some embodiments, the cancer is metastatic breast cancer. In some embodiments, the cancer is selected from the group consisting of sarcoma, carcinomas, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, Kaposi's sarcoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma and retinoblastoma. In some embodiments, the gene is functionally involved in a xenobiotic response pathway, an oxidative response pathway, a NF.kappa.B pathway or an apoptosis/cell death pathway. In some embodiments, the gene is up-regulated by at least about 1.7 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD, LTB4R, PBEF1, WDR3, NEK6, PLEKHF1, PLEK2, FKSG27, CORO1C, SNAI1, MOBKL1A, CYP27B1, PUS1, NFKBIB, UBE2E1, HA-1, PWP2H, TPST1, CDKN1A and ZNF529. In some embodiments, the gene is up-regulated by at least about 1.8 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD, LTB4R, PBEF1, WDR3, NEK6, PLEKHF1, PLEK2, FKSG27, CORO1C, SNAI1, MOBKL1A, CYP27B1, PUS1, NFKBIB, UBE2E1 and HA-1. In some embodiments, the gene is up-regulated by at least about 1.9 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD and LTB4R. In some embodiments, the gene is up-regulated by at least about 2.0 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2 and TUBB2. In some embodiments, the gene is up-regulated by at least about 2.1 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL and SLC2A6. In some embodiments, the gene is up-regulated by about 2.2 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1 and CXCL16. In some embodiments, the gene is up-regulated by at least about 2.7 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6 and BBC3. In some embodiments, the gene is a gene involved in a cellular xenobiotic response. In some embodiments, the gene is CYP1A1, CYP1B1, HSPA6, CYP27B1. In some embodiments, the gene is a gene involved in the oxidative response pathway. In some embodiments, the gene is selected from the group consisting of HMOX1, TNFAIP3, OKL38, GCLM, CBS, ATF3, and TXNRD1. In some embodiments, the gene is involved in the NF.kappa.B pathway. In some embodiments, the gene is selected from the group consisting of HMOX1, CXCL1, CYP1B1, TNFAIP3, IGFL1, TNF, CLC, BIRC3, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, BBC3, ATF3, GADD45A, CCL11, RASD1, NFKBIE, PANX1, IRF1, TRAF3, EDN1, PBEF1, NEK6, NFKBIB, TPST1 and CDKN1A. In some embodiments, the gene is involved in the apoptosis/cell death pathway. In some embodiments, the gene is selected from the group consisting of TNFAIP3, TNF, BIRC3, CCL2, SQSTM1, CLC, TNFRSF21, BBC3, GADD45A, SAT, CCL11, NFKBIE, TRAF3, MMD and CDKN1A. In some embodiments, the method further comprises detecting a level of a second gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don. In some embodiments, the method further comprises detecting a level of a third gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don.

Some embodiments provide method of deciding whether to continue anticancer chemotherapeutic treatment with an extract of Scutellaria barbata D. Don, comprising: (a) obtaining a sample from a cancer patient treated with an extract of Scutellaria barbata D. Don; (b) determining a level gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don in the sample; and (c) if the level of gene that is up-regulated exceeds a predetermined level, continuing treatment with the extract of Scutellaria barbata D. Don. In some embodiments, the cancer is breast cancer. In some embodiments, the cancer is metastatic breast cancer. In some embodiments, the cancer is selected from the group consisting of sarcoma, carcinomas, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, Kaposi's sarcoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma and retinoblastoma. In some embodiments, the gene is functionally involved in a xenobiotic response pathway, an oxidative response pathway, a NF.kappa.B pathway or an apoptosis/cell death pathway. In some embodiments, the gene is up-regulated by at least about 1.7 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD, LTB4R, PBEF1, WDR3, NEK6, PLEKHF1, PLEK2, FKSG27, CORO1C, SNAI1, MOBKL1A, CYP27B1, PUS1, NFKBIB, UBE2E1, HA-1, PWP2H, TPST1, CDKN1A and ZNF529. In some embodiments, the gene is up-regulated by at least about 1.8 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD, LTB4R, PBEF1, WDR3, NEK6, PLEKHF1, PLEK2, FKSG27, CORO1C, SNAI1, MOBKL1A, CYP27B1, PUS1, NFKBIB, UBE2E1 and HA-1. In some embodiments, the gene is up-regulated by at least about 1.9 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD and LTB4R. In some embodiments, the gene is up-regulated by at least about 2.0 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2 and TUBB2. In some embodiments, the gene is up-regulated by at least about 2.1 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL and SLC2A6. In some embodiments, the gene is up-regulated by about 2.2 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1 and CXCL16. In some embodiments, the gene is up-regulated by at least about 2.7 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6 and BBC3. In some embodiments, the gene is a gene involved in a cellular xenobiotic response. In some embodiments, the gene is CYP1A1, CYP1B1, HSPA6, CYP27B1. In some embodiments, the gene is a gene involved in the oxidative response pathway. In some embodiments, the gene is selected from the group consisting of HMOX1, TNFAIP3, OKL38, GCLM, CBS, ATF3, and TXNRD1. In some embodiments, the gene is involved in the NF.kappa.B pathway. In some embodiments, the gene is selected from the group consisting of HMOX1, CXCL1, CYP1B1, TNFAIP3, IGFL1, TNF, CLC, BIRC3, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, BBC3, ATF3, GADD45A, CCL11, RASD1, NFKBIE, PANX1, IRF1, TRAF3, EDN1, PBEF1, NEK6, NFKBIB, TPST1 and CDKN1A. In some embodiments, the gene is involved in the apoptosis/cell death pathway. In some embodiments, the gene is selected from the group consisting of TNFAIP3, TNF, BIRC3, CCL2, SQSTM1, CLC, TNFRSF21, BBC3, GADD45A, SAT, CCL11, NFKBIE, TRAF3, MMD and CDKN1A. In some embodiments, the method further comprises detecting a level of a second gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don. In some embodiments, the method further comprises detecting a level of a third gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don.

Some embodiments described herein provide a method of treating cancer in a patient, comprising: (a) treating the patient with a first dosage of extract of Scutellaria barbata D. Don; (b) obtaining a sample from the patient; (c) detecting in the sample a level of a gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don; (d) if the level of the gene that is up-regulated exceeds a predetermined level, continuing treatment with the first dosage of extract of Scutellaria barbata D. Don; and (e) if the level of the gene does not exceed the predetermined level, discontinuing treatment with Scutellaria barbata D. Don. In some embodiments, the cancer is breast cancer. In some embodiments, the cancer is metastatic breast cancer. In some embodiments, the cancer is selected from the group consisting of sarcoma, carcinomas, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, Kaposi's sarcoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma and retinoblastoma. In some embodiments, the gene is functionally involved in a xenobiotic response pathway, an oxidative response pathway, a NF.kappa.B pathway or an apoptosis/cell death pathway. In some embodiments, the gene is up-regulated by at least about 1.7 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD, LTB4R, PBEF1, WDR3, NEK6, PLEKHF1, PLEK2, FKSG27, CORO1C, SNAI1, MOBKL1A, CYP27B1, PUS1, NFKBIB, UBE2E1, HA-1, PWP2H, TPST1, CDKN1A and ZNF529. In some embodiments, the gene is up-regulated by at least about 1.8 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD, LTB4R, PBEF1, WDR3, NEK6, PLEKHF1, PLEK2, FKSG27, CORO1C, SNAI1, MOBKL1A, CYP27B1, PUS1, NFKBIB, UBE2E1 and HA-1. In some embodiments, the gene is up-regulated by at least about 1.9 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD and LTB4R. In some embodiments, the gene is up-regulated by at least about 2.0 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2 and TUBB2. In some embodiments, the gene is up-regulated by at least about 2.1 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL and SLC2A6. In some embodiments, the gene is up-regulated by about 2.2 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1 and CXCL16. In some embodiments, the gene is up-regulated by at least about 2.7 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6 and BBC3. In some embodiments, the gene is a gene involved in a cellular xenobiotic response. In some embodiments, the gene is CYP1A1, CYP1B1, HSPA6, CYP27B1. In some embodiments, the gene is a gene involved in the oxidative response pathway. In some embodiments, the gene is selected from the group consisting of HMOX1, TNFAIP3, OKL38, GCLM, CBS, ATF3, and TXNRD1. In some embodiments, the gene is involved in the NF.kappa.B pathway. In some embodiments, the gene is selected from the group consisting of HMOX1, CXCL1, CYP1B1, TNFAIP3, IGFL1, TNF, CLC, BIRC3, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, BBC3, ATF3, GADD45A, CCL11, RASD1, NFKBIE, PANX1, IRF1, TRAF3, EDN1, PBEF1, NEK6, NFKBIB, TPST1 and CDKN1A. In some embodiments, the gene is involved in the apoptosis/cell death pathway. In some embodiments, the gene is selected from the group consisting of TNFAIP3, TNF, BIRC3, CCL2, SQSTM1, CLC, TNFRSF21, BBC3, GADD45A, SAT, CCL11, NFKBIE, TRAF3, MMD and CDKN1A. In some embodiments, the method further comprises detecting a level of a second gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don. In some embodiments, the method further comprises detecting a level of a third gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don.

Some embodiments described herein provide a method of treating cancer in a patient, comprising: (a) treating the patient with a first dosage of extract of Scutellaria barbata D. Don; (b) obtaining a sample from the patient; (c) detecting in the sample a level of a gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don; (d) if the level of the a level of the gene that is up-regulated exceeds a predetermined level, continuing treatment with the first dosage of extract of Scutellaria barbata D. Don; and (e) if the level of the gene does not exceed the predetermined level, discontinuing treatment with Scutellaria barbata D. Don. In some embodiments, the cancer is breast cancer. In some embodiments, the cancer is metastatic breast cancer. In some embodiments, the cancer is selected from the group consisting of sarcoma, carcinomas, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, Kaposi's sarcoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma and retinoblastoma. In some embodiments, the gene is functionally involved in a xenobiotic response pathway, an oxidative response pathway, a NF.kappa.B pathway or an apoptosis/cell death pathway. In some embodiments, the gene is up-regulated by at least about 1.7 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD, LTB4R, PBEF1, WDR3, NEK6, PLEKHF1, PLEK2, FKSG27, CORO1C, SNAI1, MOBKL1A, CYP27B1, PUS1, NFKBIB, UBE2E1, HA-1, PWP2H, TPST1, CDKN1A and ZNF529. In some embodiments, the gene is unregulated by at least about 1.8 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD, LTB4R, PBEF1, WDR3, NEK6, PLEKHF1, PLEK2, FKSG27, CORO1C, SNAI1, MOBKL1A, CYP27B1, PUS1, NFKBIB, UBE2E1 and HA-1. In some embodiments, the gene is up-regulated by at least about 1.9 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2, TUBB2, CPEB2, FADS3, NCOA7, TRAF3, TRIM21, EGR1, MOBKL2C, PEO1, DDX31, TXNRD1, EDN1, TIGA1, TM4SF14, AXIN1, MMD, CEBPD and LTB4R. In some embodiments, the gene is up-regulated by at least about 2.0 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4AT, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL, SLC2A6, TUBB6, RCL1, ABCC2, LRFN1, MGC35521, IRF1, SAT, OPTN, SESN2 and TUBB2. In some embodiments, the gene is up-regulated by at least about 2.1 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1, CXCL16, KRT5, MYEOV, SNAPC4, ERBP, UBE2E2, ZFP36, PLK2, SQRDL and SLC2A6. In some embodiments, the gene is up-regulated by about 2.2 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6, BBC3, ELL2, ATF3, C20orf139, GADD45A, SAT, SLCO4A1, NKX3-1, CCL11, MGAM, RASD1, ZSWIM4, NFKBIE, P53AIP1, NICAL, CCRN4L, RAPGEFL1, CA8, ARRDC2, NELF, PHLDA2, CLDN1, IER5, PIK3CD, PANX1 and CXCL16. In some embodiments, the gene is up-regulated by at least about 2.7 fold over cellular expression in the absence of Scutellaria barbata D. Don. In some embodiments, the gene is selected from the group consisting of CYP1A1, HMOX1, LOC255324, CXCL1, CYP1B1, LOC440449, TNFAIP3, IGFL1, NPAS2, TNF, CLC, BIRC3, OKL38, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, CDH5, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, RNF24, AMSH-LP, ADM, HSPA6 and BBC3. In some embodiments, the gene is a gene involved in a cellular xenobiotic response. In some embodiments, the gene is CYP1A1, CYP1B1, HSPA6, CYP27B1. In some embodiments, the gene is a gene involved in the oxidative response pathway. In some embodiments, the gene is selected from the group consisting of HMOX1, TNFAIP3, OKL38, GCLM, CBS, ATF3, and TXNRD1. In some embodiments, the gene is involved in the NF.kappa.B pathway. In some embodiments, the gene is selected from the group consisting of HMOX1, CXCL1, CYP1B1, TNFAIP3, IGFL1, TNF, CLC, BIRC3, ICAM1, IL8, RELB, CCL2, SQSTM1, CLC, TIPARP, CCL2, PLAUR, TNFRSF21, GCLM, CBS, BBC3, ATF3, GADD45A, CCL11, RASD1, NFKBIE, PANX1, IRF1, TRAF3, EDN1, PBEF1, NEK6, NFKBIB, TPST1 and CDKN1A. In some embodiments, the gene is involved in the apoptosis/cell death pathway. In some embodiments, the gene is selected from the group consisting of TNFAIP3, TNF, BIRC3, CCL2, SQSTM1, CLC, TNFRSF21, BBC3, GADD45A, SAT, CCL11, NFKBIE, TRAF3, MMD and CDKN1A. In some embodiments, the method further comprises detecting a level of a second gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don. In some embodiments, the method further comprises detecting a level of a third gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don.

Pharmaceutical Compositions and Modes of Administrations

An extract of this invention can be administered to a patient either as a "tea," without combination with any other substances or further manipulation, or it can be administered as a pharmaceutical composition where the extract is mixed with suitable carriers or recipient(s). In treating a patient exhibiting a disorder of interest, a therapeutically effective amount of the extract is administered. A therapeutically effective amount refers to that amount of the extract that results in amelioration of symptoms or a prolongation of survival in a patient, and may include destruction of a malignant tumor of a microbial infection.

When administered without combination with any other substances, the composition comprising extract of Scutellaria Barbata (especially Scutellaria Barbata D. Don) may be encased in a suitable capsule, such as a gelatin capsule. When administered in admixture with other excipients, adjuvants, binders, diluents, disintegrants, etc., the dry extract of Scutellaria Barbata may be compressed into a capsule or caplet in a conventional manner that is well-known in the art.

Toxicity and therapeutic efficacy of the extracts, i.e., determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population) can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The dose ratio between toxic and therapeutic effects is therapeutic index and it can be expressed as the ratio LD50/ED50. Extracts that exhibit large therapeutic indices are preferred. The data obtained from these cell culture assays and animal studies can be used in formulating a range of dosages for use in humans, in particular for internal use, that include ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. In general, since the extracts used in the methods of this invention have been used in TCM, they are known to be relatively non-toxic to humans and therefore it is expected that they will exhibit large therapeutic indices.

For any extract used in the method of invention, therapeutically effective dose can be estimated initially from cell culture assays. For example, a dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by HPLC.

The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition and based on knowledge of TCM. (See e.g. Fingl et al., in The Pharmacological Basis of Therapeutics, 1975, Ch. 1, p. 1). It should be noted that the attending physician would know how and when to terminate, interrupt, or adjust administration due to toxicity, or organ dysfunction. Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response is not adequate. The severity of the condition may, for example, be evaluated, in part, by standard prognostic evaluation methods. Further, the dose and perhaps dose frequency will also vary according to the age, body weight, and response of the individual patient. A program comparable to that discussed above may be used in veterinary medicine.

If desired, standard western medicine techniques for formulation and administration may be used, such as those found in Remington's Pharmaceutical Sciences, 18.sup.th ed., Mack Publishing Co., Easton, Pa. (1990). Suitable routes may include: oral, rectal, transdermal, vaginal, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections; as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections, to name a just a few. In particular embodiments, the extract of the invention is administered orally.

For injection, an extract of this invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer, For such transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.

Use of pharmaceutically acceptable carriers to formulate an extract herein use in the methods disclosed for the practice of this invention in dosages suitable for systemic administration is within the scope of the invention. With proper choice of carrier and suitable manufacturing practice, an extract of the present invention, in particular those formulated as solutions, may be administered parenterally, such as by intravenous injection. Likewise, an extract can be formulated, using pharmaceutically acceptable carriers well known in the art, into dosages suitable for oral administration. Such carriers enable extracts to be formulated as tablets, pills, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated.

Pharmaceutical compositions suitable for use in the present invention are compositions wherein an extract is contained in an effective amount to achieve its intended purpose. Determination of the effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein. A pharmaceutical composition may contain suitable pharmaceutically acceptable carriers including excipients and auxiliaries that facilitate processing of the extracts into preparations that can be used pharmaceutically. The preparations formulated for oral administration may be in the form of tablets, dragees, capsules, or solutions. The pharmaceutical compositions of the present invention may be manufactured in a manner that is itself known, e.g., by means of convention mixing, dissolving, granulating, dragees, capsules, or solutions. The pharmaceutical compositions of the present invention may be manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levitating, emulsifying, encapsulating, entrapping or lyophilizing processes.

Pharmaceutically formulations for parenteral administration include aqueous solutions of an extract in water-soluble form. Additionally, suspensions of an extract may be prepared as appropriate oily injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents that increase the solubility of an extract to allow for the preparation of highly concentrated solutions.

Pharmaceutical preparations for oral use can be obtained by combining an extract with solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.

Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum Arabic, talc, polyvinyl pyrrolidone, carpool gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of extracts and/or doses.

Pharmaceutical preparations that can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules contain the extract in admixture with fillers such as lactose, binders such as starches, and/or lubricants such as talc or magnesium separate and, optionally, stabilizers. In soft capsules, the extract may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols.

The dosage of extract of Scutellaria barbata D. Don will vary depending upon the tumor type, the stage of disease, the species of patient and the individual patient. In some embodiments, the amount of extract of Scutellaria barbata D. Don (BZL) administered to a human patient will be the dry solid residue extracted from about 0.1 g to about 20,000 g of dried solid plant parts of BZL. In some embodiments, the effective dose is the dry solid residue extracted from about 1 to about 1000 g of BZL. In some embodiments, the effective dose will be the dry solid residue extracted from about 10 to about 800 g of BZL.

Treatment of Cancers

Extracts of Scutellaria barbata D. Don may be used to treat solid tumors. Such tumors may include so-called estrogen receptor negative (ER.sup.-) breast cancer, estrogen receptor positive (ER.sup.+) cancer, and other solid tumor cancers. As used herein, the terms "estrogen receptor negative breast cancer" and "estrogen receptor positive breast cancers," have meanings commonly ascribed to them in the art. The person skilled in the art will recognize that the terms "positive" and "negative" are relative terms describing levels of expression in a cell. In general, saying that a cell is "negative" for expression of a particular cell product means that the level of expression detected, if any, falls below a predetermined threshold. That threshold may be a detection limit, a background noise level or some arbitrary cutoff known and understood by one of skill in the art. As extracts of Scutellaria barbata D. Don do not necessarily require presence of ER.alpha. or ER.beta. in order to induce apoptosis in solid cancer cells, it is considered that doses of Scutellaria barbata D. Don may be used to treat, inter alia, either ER.sup.+ or ER.sup.- breast cancers as well as other solid tumors. The dose of Scutellaria barbata D. Don extract may vary, however it is considered that a dose comprising the dry soluble portion of a hot water or ethanolic extract of about 1 to about 20,000 g, especially about 50 to about 10,000 g of dry aerial portions of Scutellaria barbata D. Don, is a therapeutically effective dose. When used in combination with another chemotherapeutic agents, the dose may be lowered to take advantage of synergetic effects. C that extracts of Scutellaria barbata D. Don may be used to treat include sarcoma, carcinomas, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, Kaposi's sarcoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma and retinoblastoma. In some particular embodiments, the

Kits

Also provided herein are kits for treatment of cancer. In some embodiments, the kits comprise an extract of Scutellaria barbata D. Don. In some embodiments, a the extract of Scutellaria barbata D. Don is in an oral dosage form. In some embodiments, the kit will contain sufficient extract of Scutellaria barbata D. Don for administration over 1, 2, 3, 4 or more weeks. In some embodiments, the dosage of extract of Scutellaria barbata D. Don will be divided into daily or twice daily doses. The daily dose of extract of Scutellaria barbata D. Don may vary depending on the second chemotherapeutic agent, the disease to be treated, the condition of the patient, etc. In general, the daily dose of extract of Scutellaria barbata D. Don will be the dried soluble extract of about 1 to 20,000 g, 10 to 10,000 g or 50 to 5000 g of dried aerial portion of Scutellaria barbata D. Don. The daily dose may be divided into 2, 3, 4 or more doses per day. When administered as a tea, the doses may be combined with a flavor or flavor-masking agent in order to enhance palatability.

Some embodiments described herein provide a kit for treatment of cancer, comprising a therapeutically effective amount of a first chemotherapeutic agent comprising an extract of Scutellaria Barbata D. Don and a means for testing a level of expression of a gene that is up-regulated in a cell in which an extract of Scutellaria barbata D. Don is cytotoxic and which has been contacted with Scutellaria barbata D. Don. The means for testing may include reagents and/or instructions for work-up methods for preparing a sample for evaluation on a gene chip or by mass spectrometry or both. The means may include antibodies (including labeled antibodies) for ELISA or similar methods. The means may include PCR probes and/or mass spectrometry standards for mass spectrometry measurements.

EXAMPLES

The herb from which the extracts of this invention were obtained were purchased from Shen Nong Herbs, Berkeley, Calif. Their identity was confirmed by reference to traditional pharmaceutical literature.

Preparative Example 1

Preparation of BZL101 for in vitro and Mouse Experiments

Herbal extract was prepared as "boiled teas", which is how most are prepared for use in traditional treatment regimes. Aqueous extracts were prepared by adding 7.5 g of dry ground herb to 125 ml distilled water, bringing the mixture to a boil and then simmering for 45 minutes, The mixture was cooled, during which period most of the solids sank to the bottom of the vessel. The aqueous layer was carefully decanted off of the residual solids, centrifuged for 5 minutes at 1500 rpm, sterile filtered through a 0.45 .mu.m filter and stored at 4.degree. C. until used. Generally, the extracts were tested within 1-2 weeks of preparation although most of the active extracts were found to retain activity after storage at 4.degree. C. for several additional weeks. An aliquot of each extract was dried under vacuum and the dry weight of the water soluble substances extracted from each herb determined.

Preparative Example 2

Preparation of BZL101 for Human in vivo Experiments

BZL101 is an aqueous extract of the aerial part of Scutellaria Barbata D. Don of the Lamiaceae family. Herba Scutellaria Barbata D. Don (Chinese pin yin transliteration--Ban Zhi Lian (BZL)) is grown mainly in areas southeastern of the Yellow River (Huang Po) in the provinces of Sichuan, Jiangsu, Jiangxi, Fujian, Guangdong, Guangxi and Shaanxi. The plant is harvested in late summer and early autumn after it blooms. The aerial part (leaves and stems) is cut from the root and is used as starting material (BZL). The aerial part of the herb is dried in the sun, packed as a whole plant. The herb is identified and verified through botanical, morphological and chemical characteristics to ensure purity.

A single dose of BZL101 is made through the following procedure and is termed BZL101 (Bionovo, Inc., Emeryville, Calif.). 180 grams of the raw herb is ground to fine powder (25 mesh) The powder is mixed with 1800 ml of distilled water to form a slurry The slurry is than simmered at 70-72.degree. C. for 60 minutes The extract is decanted and filtered through 22 .mu.m filter The supernatant weight after extraction is 168 gm The volume of the solution is 1750 ml The extract is concentrated with a vacuum evaporator to reduce the volume of water to 350 ml which constitutes a 5:1 concentration of the original solution The dry weight of soluble material in the extract is 12 gm It is packaged in a sterile, vacuum sealed container Testing for bacteria, yeast and heavy metals are preformed by an accredited laboratory

Comparative Example 1

In vitro Inhibition of Cancer Cell Activity Cell Lines and Culture

The extract obtained in Preparative Example 1, above, was tested against four human breast cancer cell lines, SKBR3, MFC-7, MDA-MB231 and BT474, and one murine breast cancer cell line, MCNeuA. All lines were maintained in 90% DME supplement with 2.0 mom L-glutamine, 100 IU/ml penicillin, 100 .mu.g/ml streptomycin and 10% heat-inactivated fetal bovine serum. Cells at 70-80% confluence were used for plating for growth inhibition assays.

Cells were plated in 96-well flat bottom plates at 5,000 to 10,000 cells/well. The difference in number of cells plated adjusts for differences in the growth rates of these cell lines. Cells were allowed to adhere to the well walls overnight; then the extracts were added to triplicate wells at a 1:10 final dilution in culture medium for initial screening. For generating dose-response curves, serial 3-fold dilutions, starting at 1:10 dilution over 6 rows of wells were used. Water was added to the control wells at 1:10 dilution in culture medium. The plates were incubated at 37.degree. C., 5% CO.sub.2, for 3 days and then assayed for growth inhibition using a crystal violet assay (Bernhardt, G., et al., Standardized Kinetic Microassay to Quantify Differential Chemosensitivity on the Basis of Proliferative Activity, 1992, J. Cancer Res. Clin. Oncol., 118:35-43). Cells remaining adherent to the well walls were rinsed with PBS, the fixed cells were stained with 0.02% aqueous crystal violet (50 .mu.l/well) for 30 minutes after which the wells were washed thoroughly with distilled water. The crystal violet stain bound by the cells was solubilized in 79% ethanol (100 .mu.l/well) and the plates analyzed on a microplate reader (Molecular Devices) ay 595 nm. The percent inhibition was calculated as the average optical density of the control wells minus average optical density extract well divided by the average optical density of the control wells. Dose-response curves on SKBR3, MCF7 and MCNeuA cells for several of the extracts are shown in FIGS. 1-3. As can be seen, the concentration at which the extracts inhibited the activity of the cells by 50% (the IC50) ranged from over 1 mg/ml down to about 10 .mu.g/ml.

Induction of Apoptosis

To assay for DNA fragmentation as a marker of apoptosis, a procedure for the isolation of genomic DNA that allows for the analysis of both high and low molecular weight DNA fragmentation during apoptosis was used. MCNeuA cells were plated at 5.times.10.sup.5 cells/well in 6-plates and allowed to adhere overnight. Aqueous herbal extracts were added to each well at a 1:10 and a 1:50 dilution. Sterile water, diluted 1:10 in culture medium, was added to the control wells. After 24 hours, the cells were visually examined under a microscope and morphological changes noted. Attached and floating cells were harvested, washed with cold PBS and embedded in lysis buffer (50 mM NaCl, 20 mM Tris HCl, pH 8.0, 20 mM EDTA, 0.5% sodium sarkosyl, 50 .mu.g/ml Rnase A and 100 .mu.g/ml proteinase K) for 1 hour at 37.degree. C. The cells were then washed with PBS and distilled water and placed in the wells of a conventional 1% agarose gel and electrophoresed overnight at approximately 1 V/cm. The gels were then stained with ethidium bromide and photographed under UV transillumination to give intense images. The images obtained are shown in FIG. 4.

BZL101 was evaluated for antiproliferative activity on five breast cancer cell lines (SK-BR-3, MCF7, MDA-MB-231, BT-474, and MCNeuA). These cell lines represent important prognostic phenotypes of breast cancer expressing a range of estrogen and HER2 receptors. BZL101, tested at a 1:10 dilution (15 .mu.g/ml), demonstrated>50% growth inhibition on four of the five cell lines (Campbell, 2002). BZL101 showed>50% growth inhibition on a panel of lung, prostate and pancreatic cancer cell lines. BZL101 at the same dose did not cause>25% of growth inhibition on normal human mammary cells (HuMEC), demonstrating selectivity to cancer cells (Table 3). Moreso, BZL101 had a mild mitogenic effect on normal human lymphocytes. In cell cycle analysis, BZL101 caused an S phase burst and G1 arrest. (See FIG. 8). BZL101 also attenuated mitochondrial membrane potential causing caspase-independent high molecular grade (HMG) apoptosis. (See FIG. 7).

The results of this in vitro experiment are summarized in Table 3, below.

TABLE-US-00001 TABLE 3 In vitro growth inhibitory effect of BZL101 aqueous extract of Scutellaria Barbata 1:10 dilution- < 50% inhibition, + 51-75% inhibition, ++ > 75% inhibition. BZL is active on all cancer cell lines but is not active on HuMECs. Breast Pancreas MDA- Lung Panc Prostate MB- A549 LLC Panc-1 02 PC-3 LNCaP MCF7 BT474 SKBR3 231 MCNeuA HuMEC + + + ++ + + ++ + ++ + ++ -

Example 1

Methods of Detecting Urinary Analysis of 8-oxoguanine, 8-oxoguanosine, fapy-guanine and 8-oxo-2'-deoxyguanosine as a Biomarker of Efficacy in the Treatment of BZL101 in Patients with Adenocarcinoma

Rationale

Reactive oxygen species (ROS) have been strongly associated with cellular aging, cancer, and other degenerative diseases by virtue of their potential to damage several cellular constituents, such as nucleic acids, proteins, and lipids. It is now well established that free radical mediated oxidation of DNA leads to a broad spectrum of chemical modifications which translate into single or double DNA strand breaks, and base as well as sugar modifications. Among the DNA base modifications induced by oxidative damage, 8-oxoguanine (8-oxoGua) is of particular relevance and has been proposed as a biomarker of DNA oxidation. The DNA guanine base oxidation product 8-oxo-2'-deoxyguanosine (8-oxodG) is potentially mutagenic and commonly quantified as a steady-state estimate of oxidative stress in tissues and urine using chromatographic techniques.

The urinary excretion of products of damaged nucleotides in cellular pools or in DNA may be important biomarkers of exposure to relevant carcinogens and may predict cancer risk or response to treatment. It is important to recognize that in steady state the excretion reflects the rate of damage. Among the many oxidative DNA damage products 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is probably the most studied because of the relative ease of measurement and the mutagenic properties resulting in G.fwdarw.T transversion mutations upon replication of DNA.

Oxidized guanine in DNA is mainly repaired by oxoguanine glycosylase (OGG1) resulting in release of 8-oxoguanine. This enzyme shows a common genetic polymorphism with a variant Ser326Cys, which in complementation assays in vitro appears to increase susceptibility to mutagenic properties of ROS considerably, whereas 8-oxodG levels and incision activity in leukocytes and some target tissues generally show no difference between the genotypes. In addition, repair of 8-oxodG may to some extent occur by nucleotide excision repair and transcription coupled mechanisms. A specialized enzyme (MTH1 or NUDT1) sanitizes the nucleotide pool by cleaving phosphates of 8-oxodGTP which if incorporated during DNA synthesis is highly mutagenic and mice deficient in that enzyme develop tumors. 8-OxodG from this process as well as from putative nucleotide excision repair and possibly mitochondrial turn-over is excreted unchanged into the urine and may serve as a biomarker of oxidative stress and oxidative damage to nucleotides and possibly DNA. The urinary excretion of 8-oxodG has consistently been found to be increased among smokers and with a number of occupational exposures, including air pollution among bus drivers. Moreover, some case--control studies have suggested that the urinary excretion of 8-oxodG or 8-oxoguanine is increased among cancer patients, although this could very well be a consequence of the disease with ongoing oxidative stress, inflammation and tissue turn-over.

Furthermore, a great emphasis has being placed on the role of ROS-induced DNA damage in carcinogenesis and aging as a consequence of genomic degradation.

In recent years, there has been an increased interest in the use of mass spectrometry (MS) for the analysis of DNA oxidation products. MS typically provides structural information and selective detection in the picogram to femtogram range.

Therefore, given these characteristics, mass spectrometry is well positioned to play a significant role in the detection and characterization of DNA adducts. Besides the well-established role of DNA oxidative damage in many disease conditions, growing evidence points towards a significant involvement of RNA oxidative damage in the pathophysiology of several age-related degenerative disorders including cancer. Indeed, although little is still known about the consequences of RNA oxidation on the cellular homeostasis, it has been recently shown that oxidized RNA is associated with impaired protein synthesis as a consequence of translation errors. Moreover, RNA has been found to be significantly oxidized in age-related degenerative diseases.

BZL101 and 8-oxo-guanine

It is considered that differential induction of DNA damage by BZL101 in different cell types might be related to the extent of oxidative stress generated by BZL101 treatment. BZL101 induced a significant accumulation of ROS in SKBr3 cells as measured by staining with the ROS-sensitive probe CM-H.sub.2DCFDA. Incubation of cells with ROS scavenger N-acetyl-cysteine (NAC) prior to addition of BZL101 has prevented most of the increase in ROS generation, confirming that the conversion of non-fluorescent CM-H.sub.2DCFDA into fluorescent compound is indeed due to ROS. To confirm that BZL101 induces oxidative stress responses, the levels of transcriptional factor Nrf2 in BZL101 treated cells were examined. Nrf2 is a key regulator of phase II detoxifying and antioxidant enzymes that are upregulated in response to oxidative stress. Western blot analysis showed a significant and sustained increase in Nrf2 levels in BZL101 treated BT474 cells and SKBr3 cells. In MCF10A cells, there was also an increase in Nrf2 levels, though it was more transient in nature.

There is a different fold increase of ROS levels in different cells treated with BZL101 compared to control untreated cells. It is of particular interest that the increase in ROS correlates well with the degree of DNA damage induced in these cells. The lowest induction is seen in MCF10A cells which also have the lowest number of comets after treatment with BZL101, and the highest increase in ROS is observed in SKBr3 cells where the DNA damage is most extensive. In fibroblasts IMR90 and in BT474 cells the moderate increase in ROS paralleled the relatively lower extent of DNA damage compared to SKBr3.

To further implicate ROS in the induction of DNA damage, comet formation in cells pretreated with the antioxidants NAC and pyruvate prior to the addition of BZL101 were examined. Both compounds have significantly reduced the number of cells forming comets, in particular in normal cell lines. DNA damage repair in cancer cells in the presence of NAC or pyruvate was also greatly accelerated (not shown). At the same time, pretreatment of cells with the nitric oxide scavenger PTIO had no effect on the numbers of cells with comets (not shown), indicating that most of DNA lesions induced by BZL101 are oxidative in nature.

To verify that BZL101 leads to oxidative DNA damage, it was determined whether the DNA of BZL101-treated cells contains 8-oxoguanine, the most ubiquitous marker of DNA oxidation. Formation of 8-oxoguanine has been quantified through flow cytometric analysis of fixed permeabilized cells incubated with avidin fluorescein, that was shown to bind relatively specifically to 8-oxoguanine. There is a clear increase in binding of avidin to BZL101 treated SKBr3 cells versus untreated cells. (See FIG. 9). This increase was completely abolished if cells were pretreated with NAC prior to addition of BZL101, confirming the specificity of observed staining. (See FIG. 10).

Analysis of the 8-oxoguanidine and apurininc/apyrimidinic (AP) bases in DNA. The Calbiochem kit was used for staining of the fixed and permeabilized cells with avidin fluorescein. Quantification of apurinic/apyrimidininc nucleotides in genomic DNA was performed using the DNA damage quantification kit from BioVision Research Products.

Example 4

Micro Array Gene Expression Signature Profiling for Patient Selection for Treatment with BZL101

A micro array gene expression analysis was performed, using Phalanx human gene chip containing 45,000 gene probes of 36,000 unique human genes. SKBR3 and BT474 breast cancer cells were treated with BZL101 for 18 hours and compared with untreated control cells.

The mRNAs that are induced by BZL101 was grouped into functional groups. Only RNAs induced at higher that 2.5 fold were considered. Among these genes there is only one that is difficult to assign (AMSH-LP).

There are very few functions that are affected by BZL, and they are:

Apoptosis

Cytokines with proliferative effects

NF kappa B pathway

Oxidative stress

DNA damage response

Cell adhesion

There are obviously overlaps between these groups. Many of cytokines could go into NFkB pathway group. Virtually all oxidative stress responders could also go into NFkB pathway group because they are induced by transcription factor NRF2 with the involvement of NFkB. A number of genes in different groups are induced by TNF. DNA damage responders could go into oxidative stress group because they are induced by oxidative DNA damage.

The oxidative stress responders have links to the glycolytic pathway and DNA damage.

Apoptosis TNFAIP3=A20 (six fold) TNFRSF21=death receptor 6 (3 fold) TNF (4.7 fold) BBC3=PUMA (2.7 fold in SKbr3)

Cytokines with Proliferative Activities

Chemokine CXCL1(melanoma growth factor); seven-fold

Insulin growth factor like family IGFL1 (five fold)

Cardiotropin-like cytokine NNT-1 or CLC (4.6 fold) twice

Chemokine ligand 2 CCL2=macrophage chemoattractant protein MCP1 (3.3 fold)

Adrenomedullin ADM (2.8 fold in SKbr3 and 1.9 in BT474)

NFkappaB Pathway

a Interleukin 8(4.1 fold)

RelB (3.9 fold)

Sequestosome 1 (3.3 fold in SKbr3 and 2 fold in BT474)

Cell Adhesion ICAM1 (4.3 fold)

Cadherin 5=Vascular endothelim (VE) cadherin (3.3 fold)

PLAUR=uPAR (3 fold)

DNA Damage Response

TIPARP (3 fold)

ATF3 (induced in both cell lines, stronger in BT474)

GADD45A

Oxidative Stress Response Pregnancy-induced growth inhibitor OKL38 (4.3 fold in SKBr3 and 2.3 fold in BT474) Glutamate cysteine ligase modifier subunit GCLM (about threefold in both SKBr3 and BT474) Heme oxygenase (11 fold in SKBrs) Cystathionine-beta-synthase (2.9 fold in SKBr3)

Other Groups Associated molecule with the SH3 domain of STAM (AMSH) kike (2.8 fold in SKBr3)

A micro array gene expression chip containing 225 unique genes, 112 up regulated and 113 down-regulated for the diagnosis of patients with adenocarcinoma to test eligibility for treatment with BZL101, an extract of Scutellaria barbata.

Tumors Expressing Genes, Up or Down Regulated, within the Common Paths Affected by BZL101 will be Eligible for BZL101 Treatment. These Tumors should Show Dependency or Damage in their Apoptosis, Cytokines with Proliferative Effects, NF Kappa B Pathway, Oxidative Stress, DNA Damage Response and Cell Adhesion Associated Genes.

TABLE-US-00002 TABLE 1 Genes up-reguated in response to BZL101 treatment in SKBr3 cells. Functional Entrez Gene Average fold Entrez Entrez Gene Description annotation Name upregulation Gene ID cytochrome P450, family 1, Xenobiotic response CYP1A1 43.9 1543 subfamily A, polypeptide 1 heme oxygenase Oxidative HMOX1 10.9 3162 (decycling) 1 response/NFkB pathway similar to Epigen protein LOC255324 9.0 255324 chemokine (C-X-C motif) NFkB pathway CXCL1 7.3 2919 ligand 1 (melanoma growth stimulating activity, alpha) cytochrome P450, family 1, Xenobiotic response CYP1B1 6.8 1545 subfamily B, polypeptide 1 hypothetical gene LOC440449 6.2 440449 supported by AF086204 tumor necrosis factor, Oxidative/NFkB TNFAIP3 6.1 7128 alpha-induced protein 3 pathway/Cell death insulin growth factor-like NFkB pathway IGFL1 5.2 374918 family member 1 neuronal PAS domain NPAS2 5.2 4862 protein 2 tumor necrosis factor (TNF NFkB pathway/Cell TNF 4.7 7124 superfamily, member 2) death cardiotrophin-like cytokine NFkB pathway CLC 4.6 23529 baculoviral IAP repeat- NFkB pathway/Cell BIRC3 4.6 330 containing 3 death pregnancy-induced growth Oxidative response OKL38 4.3 29948 inhibitor intercellular adhesion NFkB pathway ICAM1 4.3 3383 molecule 1 (CD54), human rhinovirus receptor interleukin 8 NFkB pathway IL8 4.1 3576 v-rel reticuloendotheliosis NFkB pathway RELB 3.9 5971 viral oncogene homolog B, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3 (avian) chemokine (C-C motif) NFkB pathway/Cell CCL2 3.4 6347 ligand 2 death sequestosome 1 NFkB pathway/Cell SQSTM1 3.3 8878 death cardiotrophin-like cytokine NFkB pathway/Cell CLC 3.3 23529 death cadherin 5, type 2, VE- CDH5 3.3 1003 cadherin (vascular epithelium) TCDD-inducible Oxidative/DNA TIPARP 3.1 25976 poly(ADP-ribose) damage polymerase response/NFkB pathway chemokine (C-C motif) NFkB pathway CCL2 3.0 6347 ligand 2 plasminogen activator, NFkB pathway PLAUR 3.0 5329 urokinase receptor tumor necrosis factor receptor NFkB pathway/Cell TNFRSF21 3.0 27242 superfamily, member 21 death glutamate-cysteine ligase, Oxidative GCLM 2.9 2730 modifier subunit response/NFkB pathway cystathionine-beta-synthase Oxidative CBS 2.9 875 response/NFkB pathway ring finger protein 24 RNF24 2.8 11237 associated molecule with AMSH-LP 2.8 57559 the SH3 domain of STAM (AMSH) like protein adrenomedullin ADM 2.8 133 heat shock 70 kDa protein 6 Xenobiotic response HSPA6 2.8 3310 (HSP70B') BCL2 binding component 3 NFkB pathway/Cell BBC3 2.7 27113 death elongation factor, RNA ELL2 2.6 22936 polymerase II, 2 activating transcription Oxidative/DNA ATF3 2.6 467 factor 3 damage response/NFkB pathway chromosome 20 open C20orf139 2.5 140809 reading frame 139 growth arrest and DNA- DNA damage GADD45A 2.5 1647 damage-inducible, alpha response/Cell death/NFkB pathway spermidine/spermine N1- SAT 2.5 6303 acetyltransferase solute carrier organic anion SLCO4A1 2.4 28231 transporter family, member 4A1 NK3 transcription factor NKX3-1 2.4 4824 related, locus 1 (Drosophila) chemokine (C-C motif) NFkB pathway/Cell CCL11 2.4 6356 ligand 11 death maltase-glucoamylase MGAM 2.3 8972 (alpha-glucosidase) RAS, dexamethasone- NFkB pathway RASD1 2.3 51655 induced 1 zinc finger, SWIM domain ZSWIM4 2.3 65249 containing 4 nuclear factor of kappa light NFkB pathway/Cell NFKBIE 2.3 4794 polypeptide gene enhancer in death B-cells inhibitor, epsilon p53-regulated apoptosis- Cell death P53AIP1 2.3 63970 inducing protein 1 NEDD9 interacting protein NICAL 2.3 64780 with calponin homology and LIM domains CCR4 carbon catabolite CCRN4L 2.3 25819 repression 4-like (S. cerevisiae) Rap guanine nucleotide RAPGEFL1 2.2 51195 exchange factor (GEF)-like 1 carbonic anhydrase VIII CA8 2.2 767 arrestin domain containing 2 ARRDC2 2.2 27106 nasal embryonic LHRH factor NELF 2.2 26012 pleckstrin homology-like PHLDA2 2.2 7262 domain, family A, member 2 claudin 1 CLDN1 2.2 9076 immediate early response 5 IER5 2.2 51278 phosphoinositide-3-kinase, PIK3CD 2.2 5293 catalytic, delta polypeptide pannexin 1 PANX1 2.2 24145 chemokine (C-X-C motif) NFkB pathway/Cell CXCL16 2.2 58191 ligand 16 death keratin 5 (epidermolysis KRT5 2.1 3852 bullosa simplex, Dowling- Meara/Kobner/Weber- Cockayne types) myeloma overexpressed gene MYEOV 2.1 26579 (in a subset of t(11;14) positive multiple myelomas) small nuclear RNA SNAPC4 2.1 6621 activating complex, polypeptide 4, 190 kDa estrogen receptor binding ERBP 2.1 30836 protein ubiquitin-conjugating UBE2E2 2.1 7325 enzyme E2E 2 (UBC4/5 homolog, yeast) zinc finger protein 36, C3H ZFP36 2.1 7538 type, homolog (mouse) polo-like kinase 2 PLK2 2.1 10769 (Drosophila) sulfide quinone reductase- SQRDL 2.1 58472 like (yeast) solute carrier family 2 SLC2A6 2.1 11182 (facilitated glucose transporter), member 6 tubulin, beta 6 TUBB6 2.0 84617 RNA terminal phosphate RCL1 2.0 10171 cyclase-like 1 ATP-binding cassette, sub- ABCC2 2.0 1244 family C (CFTR/MRP), member 2 leucine rich repeat and LRFN1 2.0 57622 fibronectin type III domain containing 1 pellino 3 alpha MGC35521 2.0 246330 interferon regulatory factor 1 NFkB pathway IRF1 2.0 3659 spermidine/spermine N1- SAT 2.0 6303 acetyltransferase optineurin OPTN 2.0 10133 sestrin 2 Cell cycle regulation SESN2 2.0 83667 tubulin, beta 2 TUBB2 2.0 7280 cytoplasmic polyadenylation CPEB2 1.9 132864 element binding protein 2 fatty acid desaturase 3 FADS3 1.9 3995 nuclear receptor coactivator 7 NCOA7 1.9 135112 TNF receptor-associated NFkB pathway/Cell TRAF3 1.9 7187 factor 3 death tripartite motif-containing 21 TRIM21 1.9 6737 early growth response 1 EGR1 1.9 1958 MOB1, Mps One Binder MOBKL2C 1.9 148932 kinase activator-like 2C (yeast) progressive external PEO1 1.9 56652 ophthalmoplegia 1 DEAD (Asp-Glu-Ala-Asp) DDX31 1.9 64794 box polypeptide 31 thioredoxin reductase 1 Oxidative response TXNRD1 1.9 7296 endothelin 1 NFkB pathway EDN1 1.9 1906 TIGA1 TIGA1 1.9 114915 transmembrane 4 TM4SF14 1.9 81619 superfamily member 14 axin 1 AXIN1 1.9 8312 monocyte to macrophage Cell death MMD 1.9 23531 differentiation-associated CCAAT/enhancer binding CEBPD 1.9 1052 protein (C/EBP), delta leukotriene B4 receptor LTB4R 1.9 1241 pre-B-cell colony NFkB pathway PBEF1 1.8 10135 enhancing factor 1 WD repeat domain 3 WDR3 1.8 10885 NIMA (never in mitosis NFkB pathway NEK6 1.8 10783 gene a)-related kinase 6 pleckstrin homology domain PLEKHF1 1.8 79156 containing, family F (with FYVE domain) member 1 pleckstrin 2 PLEK2 1.8 26499 FKSG27 protein FKSG27 1.8 126298 coronin, actin binding CORO1C 1.8 23603 protein, 1C snail homolog 1 (Drosophila) SNAI1 1.8 6615 MOB1, Mps One Binder MOBKL1A 1.8 92597 kinase activator-like 1A (yeast) cytochrome P450, family Xenobiotic response CYP27B1 1.8 1594 27, subfamily B, polypeptide 1 pseudouridylate synthase 1 PUS1 1.8 80324 nuclear factor of kappa light NFkB pathway NFKBIB 1.8 4793 polypeptide gene enhancer in B-cells inhibitor, beta ubiquitin-conjugating UBE2E1 1.8 7324 enzyme E2E 1 (UBC4/5 homolog, yeast) minor histocompatibility HA-1 1.8 23526 antigen HA-1 PWP2 periodic tryptophan PWP2H 1.7 5822 protein homolog (yeast) tyrosylprotein TPST1 1.7 8460 sulfotransferase 1 cyclin-dependent kinase NFkB pathway/Cell CDKN1A 1.7 1026 inhibitor 1A (p21, Cip1) death zinc finger protein 529 ZNF529 1.7 57711

TABLE-US-00003 TABLE 2 Genes down-reguated in response to BZL101 treatment in SKBr3 cells. Functional Entrez Ave Fold Entrez Gene Description annotataion Gene Name downregulation Entrez_Gene_ID inhibitor of DNA binding 1, NF.beta.B ID1 5.0 3397 dominant negative helix-loop- pathway/Cell helix protein cycle regulation cyclin-dependent kinase Cell cycle CDKN2C 3.3 1031 inhibitor 2C (p18, inhibits regulation CDK4) zinc finger protein 339 ZNF339 2.9 58495 peroxiredoxin 3 Oxidative PRDX3 2.9 10935 damage/NF.beta.B pathway KIAA0644 gene product KIAA0644 2.8 9865 eyes absent homolog 2 EYA2 2.6 2139 (Drosophila) SMAD, mothers against DPP Cell cycle SMAD6 2.6 4091 homolog 6 (Drosophila) regulation ecotropic viral integration site 1 EV1l 2.6 2122 ras homolog gene family, RHOU 2.6 58480 member U gap junction protein, alpha 5, GJA5 2.6 2702 40 kDa (connexin 40) tensin TNS 2.5 7145 RAB26, member RAS RAB26 2.5 25837 oncogene family chromosome 15 open reading C15orf20 2.5 80119 frame 20 PTPRF interacting protein, PPFIBP2 2.5 8495 binding protein 2 (liprin beta 2) centrosomal protein 1 CEP1 2.5 11064 antigen identified by Cell cycle MKI67 2.4 4288 monoclonal antibody Ki-67 regulation kinetochore associated 2 Cell cycle KNTC2 2.4 10403 regulation hyaluronan-mediated motility Cell adhesion HMMR 2.4 3161 receptor (RHAMM) kinesin family member 20A KIF20A 2.4 10112 zinc finger protein 467 ZNF467 2.4 168544 topoisomerase (DNA) II alpha DNA damage TOP2A 2.3 7153 170 kDa response inhibitor of DNA binding 2, Cell cycle ID2 2.3 3398 dominant negative helix-loop- regulation helix protein MAX dimerization protein 3 Cell cycle MXD3 2.3 83463 regulation UDP-N-acetyl-alpha-D- GALNT12 2.3 79695 galactosamine:polypeptide N- acetylgalactosaminyltransferase 12 (GalNAc-T12) transcription factor AP-2 beta TFAP2B 2.3 7021 (activating enhancer binding protein 2 beta) centromere protein E, 312 kDa Cell cycle CENPE 2.3 1062 regulation cell division cycle associated 3 Cell cycle CDCA3 2.2 83461 regulation sema domain, immunoglobulin SEMA3F 2.2 6405 domain (Ig), short basic domain, secreted, (semaphorin) 3F myosin VIIA (Usher syndrome MYO7A 2.2 4647 1B (autosomal recessive, severe)) Rho-related BTB domain RHOBTB3 2.2 22836 containing 3 otoraplin OTOR 2.2 56914 centromere protein F, Cell cycle CENPF 2.2 1063 350/400ka (mitosin) regulation kinetochore protein Spc25 Cell cycle Spc25 2.2 57405 regulation CDC42 effector protein (Rho Cell cycle CDC42EP4 2.2 23580 GTPase binding) 4 regulation baculoviral IAP repeat- Cell cycle BIRC5 2.2 332 containing 5 (survivin) regulation/Cell death ankyrin 3, node of Ranvier ANK3 2.2 288 (ankyrin G) solute carrier family 40 (iron- SLC40A1 2.2 30061 regulated transporter), member 1 peroxisomal biogenesis factor PEX11A 2.2 8800 11A Nedd4 binding protein 3 N4BP3 2.1 23138 SLIT-ROBO Rho GTPase SRGAP2 2.1 23380 activating protein 2 cytochrome P450 4Z2 CYP4Z2P 2.1 163720 pseudogene X-box binding protein 1 ER stress XBP1 2.1 7494 ectodermal-neural cortex (with ENC1 2.1 8507 BTB-like domain) FGD1 family, member 3 FGD3 2.1 89846 centromere protein A, 17 kDa Cell cycle CENPA 2.1 1058 regulation high-mobility group box 2 DNA damage HMGB2 2.1 3148 response dedicator of cytokinesis 11 DOCK11 2.1 139818 transducer of ERBB2, 1 TOB1 2.1 10140 sortilin-related receptor, SORL1 2.1 6653 L(DLR class) A repeats- containing HRAS-like suppressor 3 Cell cycle HRASLS3 2.1 11145 regulation epithelial cell transforming NF.beta.B ECT2 2.1 1894 sequence 2 oncogene pathway single-stranded DNA binding SSBP2 2.1 23635 protein 2 nuclear factor I/A NFIA 2.1 4774 delta sleep inducing peptide, DSIPI 2.1 1831 immunoreactor phosphodiesterase 8B PDE8B 2.1 8622 BUB1 budding uninhibited by Cell cycle BUB1B 2.1 701 benzimidazoles 1 homolog beta regulation (yeast) SWI/SNF related, matrix SMARCA2 2.1 6595 associated, actin dependent regulator of chromatin, subfamily a, member 2 zinc finger protein 552 ZNF552 2.0 79818 polo-like kinase 1 (Drosophila) Cell cycle PLK1 2.0 5347 regulation phosphoglucomutase 1 PGM1 2.0 5236 erythrocyte membrane protein EPB41L1 2.0 2036 band 4.1-like 1 thioredoxin-related TMX2 2.0 51075 transmembrane protein 2 kinesin family member 14 KIF14 2.0 9928 LPS-responsive vesicle LRBA 2.0 987 trafficking, beach and anchor containing dehydrogenase/reductase (SDR DHRS3 2.0 9249 family) member 3 pleckstrin homology domain PLEKHK1 1.9 219790 containing, family K member 1 succinate-CoA ligase, GDP- SUCLG1 1.9 8802 forming, alpha subunit epithelial protein lost in EPLIN 1.9 51474 neoplasm beta histamine receptor H1 HRH1 1.9 3269 histone 1, H2ac HIST1H2AC 1.9 8334 cingulin CGN 1.9 57530 SAM and SH3 domain Cell cycle SASH1 1.9 23328 containing 1 regulation tight junction protein 3 (zona TJP3 1.9 27134 occludens 3) mucin 15 MUC15 1.9 143662 chromosome condensation- Cell cycle CNAP1 1.9 9918 related SMC-associated protein 1 regulation UDP-N-acetyl-alpha-D- GALNT10 1.9 55568 galactosamine:polypeptide N- acetylgalactosaminyltransferase 10 (GalNAc-T10) aurora kinase B Cell cycle AURKB 1.9 9212 regulation ATPase, H+ transporting, ATP6V0A4 1.9 50617 lysosomal V0 subunit a isoform 4 G-2 and S-phase expressed 1 DNA GTSE1 1.9 51512 damage/Cell cycle regulation spectrin repeat containing, SYNE2 1.9 23224 nuclear envelope 2 heat shock 60 kDa protein 1 HSPD1 1.9 3329 (chaperonin) nebulette NEBL 1.9 10529 protein kinase C, delta PRKCD 1.9 5580 neurexin 3 Cell adhesion NRXN3 1.9 9369 transglutaminase 3 (E TGM3 1.9 7053 polypeptide, protein-glutamine- gamma-glutamyltransferase) mesoderm posterior 1 MESP1 1.9 55897 hexosaminidase B (beta HEXB 1.9 3074 polypeptide) RWD domain containing 2 RWDD2 1.9 112611 fibroblast growth factor FGFR2 1.9 2263 receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) Down syndrome critical region DSCR1 1.9 1827 gene 1 cyclin A2 DNA CCNA2 1.8 890 damage/Cell cycle regulation calcyphosine CAPS 1.8 828 methylcrotonoyl-Coenzyme A MCCC1 1.8 56922 carboxylase 1 (alpha) keratin 15 KRT15 1.8 3866 GPAA1P anchor attachment GPAA1 1.8 8733 protein 1 homolog (yeast) actin related protein 2/3 Cell adhesion ARPC5 1.8 10092 complex, subunit 5, 16 kDa ATP-binding cassette, sub- ABCA1 1.8 19 family A (ABC1), member 1 epidermal growth factor EPS8 1.8 2059 receptor pathway substrate 8 HMBA-inducible Cell cycle HIS1 1.8 10614 regulation transcription elongation factor TCEAL1 1.8 9338 A (SII)-like 1 breast carcinoma amplified BCAS1 1.8 8537 sequence 1 distal-less homeobox 4 DLX4 1.8 1748 protein phosphatase 1H (PP2C PPM1H 1.8 57460 domain containing) heat shock 70 kDa protein 8 HSPA8 1.8 3312 Kruppel-like factor 13 KLF13 1.8 51621 15 kDa selenoprotein 15- 1.7 9403 eukaryotic translation initiation EIF4EBP2 1.7 1979 factor 4E binding protein 2 branched chain keto acid BCKDHA 1.7 593 dehydrogenase E1, alpha polypeptide (maple syrup urine disease) eukaryotic translation initiation EIF3S6IP 1.7 51386 factor 3, subunit 6 interacting protein zinc fingers and homeoboxes 2 ZHX2 1.7 22882 SUMO-1 activating enzyme SAE1 1.7 10055 subunit 1

Example 3

Methods of Diagnosing and Treating Humans with Breast Cancer Using 8-oxoguanine Biomarker

A group of up to thirty patients who have and who do not have breast cancer will be tested for the presence of 8-oxoguanine. All patients will be at least 18 years of age. Patients representing an individual having breast cancer will present both histological confirmation of breast cancer as well as clinical evidence of metastatic involvement. The testing will be done in a double blind fashion. Patients who enter into the test will have a blood sample drawn. The blood will be tested for presence of 8-oxoguanine biomarker by reacting the blood with a diagnostic tool that detects the presence of 8-oxoguanine. For each patient, a level of 8-oxoguanine will be output to a display indicating the level of 8-oxoguanine for that specific patient. The patient's level of 8-oxoguanine will then be compared to a predetermined level of 8-oxoguanine as determined from sampling a population of 50 individuals who have not been diagnosed with breast cancer, or normal individuals. The predetermined threshold level will include the average 8-oxoguanine level for the group of normal individuals plus and minus the standard deviation for the population. Patients in whom a level of 8-oxoguanine biomarker is detected to be above the threshold level will then be singled out as potentially having breast cancer. These patients will then be compared to any histological data present for that patient. Once it is confirmed that the patient does in fact have breast cancer, the patient will be administered 350 ml (equivalent to 12 grams dry soluble extract of 180 grams of BZL) BZL101 extract per day. These patients will then be monitored by having blood drawn at specified intervals, preferably once a month to detect levels of 8-oxoguanine in the blood. BZL101 will continue to be administered to the patient until an adverse event more severe than a grade I or grade II adverse event occurs, the patient self-elects to forego treatment or the disease progresses to a clinically significant degree. Throughout treatment, periodically (e.g. once per week), the level of 8-oxoguanine biomarker will be detected to track the progress of treatment.

Example 3

Methods of Diagnosing and Treating Humans with Breast Cancer Using Lactate Dehydrogenase and a 8-oxoguanine Biomarkers

A group of thirty patients who have and who do not have breast cancer will be tested for the presence of lactate dehydrogenase and 8-oxoguanine biomarkers. All patients were at least 18 years of age. Patients representing an individual having breast cancer will present both histological confirmation of breast cancer as well as clinical evidence of metastatic involvement. The testing will be done in a double blind fashion. Patients who enter into the test will submit a urine sample. The urine sample will be tested for presence of lactate dehydrogenase and 8-oxoguanine biomarkers by reacting the urine with a diagnostic tool that detects the presence of both the lactate dehydrogenase and the 8-oxoguanine biomarkers. For each patient, a level of lactate dehydrogenase and 8-oxoguanine will be output to a display indicating the levels of lactate dehydrogenase and 8-oxoguanine for that specific patient. The patient's level of lactate dehydrogenase and 8-oxoguanine will then be compared to a predetermined levels of lactate dehydrogenase and 8-oxoguanine as determined from sampling a population of 50 individuals who have not been diagnosed with breast cancer, or normal individuals. The predetermined threshold levels will include the average lactate dehydrogenase and 8-oxoguanine levels for the group of normal individuals plus and minus the standard deviation for the population. Patients in whom a level of lactate dehydrogenase and 8-oxoguanine biomarker is detected to be above the threshold level will then be singled out as potentially having breast cancer. These patients will then be compared to any histological data present for that patient Once it is confirmed that the patient does in fact have breast cancer, the patient will be administered a therapeutic amount of an extract of BZL101 in order to treat the cancer.

CONCLUSION

The herbal extract BZL101, its uses for the inhibition of solid tumor cancer cells and the treatment of such cancers in patients are described herein. Although certain embodiments and examples have been used to describe the present invention, it will be apparent to those skilled in the art that changes to the embodiments and examples may be made without departing from the scope and spirit of this invention.

While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

SEQUENCE LISTINGS

1761100DNAHomo sapiens 1gattattagt ataaaagggg agataggtag gagtagcgtg gtaagggcga tgagtgtggg 60gaggaatggg gtgggttttg tatgttcaaa ctgtcatttt 100287DNAHomo sapiens 2gagaaaatat ccttgactgg gtatgcattt tagcaaagca aagagtgatt ctcaggcaat 60caagttgaaa ccaactacac agtgttt 873122DNAHomo sapiens 3attccagctg tactggcctc tttgctgttg catcggctgt ttcctctgcc tcatactctt 60ccccaggcat ctgcatggct aagtccttca cctccttcaa gtgtttgctc aaatgtcacc 120tt 122491DNAHomo sapiens 4ggtaagggag ggatcgttga cctcgtctgt tatgtaaagg atgcgtaggg atgggagggc 60gatgaggact aggatgatgg cgggcaggat a 915131DNAHomo sapiens 5gaattcgttc ggaaatatcc cctgacctga agttctggtt tccctgcacc ccagaccgga 60cattttcttt tgtccttatc tcagtaagta ctgagtattg tgagaggaac aagtgagtct 120cttttgtttc t 131673DNAHomo sapiens 6attgtaaata gggattcttt gtctagggtt tggggtttaa gcctgttaat ttagtagaac 60ctcatttttc tct 737268DNAHomo sapiens 7cttagctgtg ctgtaggatg ggacctgggc ttctgtgttg aggtaacttc tattgtgagg 60aagaagaggg cgaaattgtg tggcatgatt tttttgtatg aaaagtgaag ggcctattct 120taattttgaa caactgcctg ctttctgatt tacttttgat ccggatttgt tggattcctc 180actgtactgt gtaggttgag cttacaaagg tgtggatttt gagcagtgcg attaccccct 240ttcagatttg gggttgctgt tgtttttg 2688314DNAHomo sapiens 8ccctgtgtgg ccggctctta ggtggttccg ataagacaca atgcagatgc aactgggggg 60ccctgcatcc ggctagctta cgtagccaaa cgggatttaa cgaggaagca aacgtgttgt 120ctaatgttcc ctgtgtcaaa tgattcactc cgcccaggaa agggatgggg tcctggagga 180agatctgcaa gtcacaagtt cccatcaatc actcgataat ataagagata ggagttttaa 240acataactag tatcaggcaa ctgctatcac atccacaccc tgcagctcat tatgttaaat 300agtcccttcg ggga 3149197DNAHomo sapiens 9gcagactgca gcgttctgag aaacatcttt gtgatgtttg tattcaggac acagagttga 60acattcccta tcatagagca ggttgggatc actccttttg tagtatctgg aagtggacat 120ttggagcgct ttcaggccta tgttgaaaaa agaaaaatct tcccataaca actagacaga 180agcattctca gaaactt 19710467DNAHomo sapiens 10cctgattagg tcaggctcac catgatactc tcccttttga tcaatgtgaa gtcagctgac 60tggggacgtt acttgtaaca tctgcaaaat cccttcactt ttgccatata caacataatc 120acaggagtga tatcccatta cctttgccat agcctattgg ttagaatcaa attacgagtt 180ccccctacca cttgaagact taccttttct tataagataa atcaatacat atgacaagag 240ttagagtcgg ttttgaagga taagggtgat tcttttcttt tttttttttt tttttttgag 300gtggaatctc gctctgtcgc ccaggctgga gtgcagtggc gggatctcag ctcactgcaa 360gctccgcctc ctgggttcac gccattttca tgcctcagcc tcccgagtag ctgggactac 420aggcacccgc caccacgcct ggctaatttt ttgtatttgg agtaggg 46711177DNAHomo sapiens 11ttccctaaat cctgagacag aaaaatggaa agaaatgatt tcacagtagg tagaaggaat 60tccattagca cagcgcaatt aaaaaattgt ttcacgctgt gtaggcacaa atctgtccat 120tagcacagcg gcaattaaaa aaattgtttt ccagctgtgt aggcacaaaa tctgttt 17712187DNAHomo sapiens 12tcctctttcc ctgttcggac tgcagtctca gtagttagga gcactaggta gggtccttcc 60aagctagtac gagtttccct tccttccacc ctttgatgag gacgtggtct ccaggctgat 120gctgatgtgc tgaaaactcc aggggcagcg cctgtgctag gagaccttct gtcttaaggg 180aagagaa 1871380DNAHomo sapiens 13ttgcatttac acaaagcagt tctagatgga agggaggaga tagaccccac ctctcaatgg 60agtgtccctc ttcggtggcc 8014369DNAHomo sapiens 14gttggactac gtggcttctg agacccttcc agagctaaca ttttatgatc tatgattaag 60actgagatga cattgttcag cccactgtcc agagggtgac ccaccaactt tcataaaaac 120aatcatcatt aacctatgtt aattggtcaa taaaacatca caattttata gcatgaaacc 180tgagacctgc tgagatcaac actactggta agccaagtgg aagttcagcc ttagaaacga 240aattgctgac tagtaacccc agtgtcatat tagtcaaagt gacatagact caaacttatt 300ctggttgaaa tgaaaacaac tgatggagaa actgagtggc acataaaaca agcttggggt 360tggaagaac 36915198DNAHomo sapiens 15tcgatggaaa ggaaatgaga ggttctgaga ggcgggctag tggcttgtac tatagcatag 60cctgcctttg ctggtgtgtg gcgattaggc ctggtggaac tgccatcaat aaatcaagag 120tgatcagggt gaggaatagg aaagaaggaa atacagggaa atggggtgaa tatcaggtgg 180atcagagaga tacagtcg 19816381DNAHomo sapiens 16agctccttct ctgtgcttct tattctatac actgtcaggg cacaagtcat gtatgaccag 60ttccttgtct tcaagaagct tatattcaga ttggaaaagt aaagttaaac tagatattaa 120attgttatgg tctaaactgt gcactccagc ctgggtgaca gagtgagact ctgtttattt 180ctttttattt ttttgggggg tacagagtct caggctggag tgcagtggca cgatcttggc 240tcactgcaac ctctgcctcc caggttcaag caattctcct gcctcagcct cccgagttgc 300taggattata agtggtagct aggattacag ctaccatgcc accacgcctc gctaattttt 360gtatttttgg tagagacggg g 38117352DNAHomo sapiens 17agtaactctt gcctaaattc taatgcaatt tcctaatgga tgtccttcct ataactttgt 60cccattataa ccctttcctc tacgactcac ccaaaagtat ctttttaata agaaaaatag 120atgatgttta ataccttcga gtggcttgcc atttaggtac ctaaaacacg acgaattctc 180tagatatcaa gcttgaattc gttatgtatc tttttggtgg acacaattca acaaacgtga 240accatgtgcc caacatgagt ggagaagcca ccttatgcca ggctccaaac aacaatctag 300gaagatgggc cccaggatat aagatgctat gaacacagaa aacaaatagg ac 35218224DNAHomo sapiens 18agatttgatc acagatgata catgtaagaa tgtcatagca caaaaaaatg cacagatatt 60tttaaaagga caaatttcag gacactttcc atctgagttc ataagaaagt cctcttgagt 120atccttcaaa gttaaaaccc tctccccttc agattaatga aaatattagg atgcatagaa 180cacaatgggc actggtgata tggcccatgg tagctgaatt agat 22419175DNAHomo sapiens 19tgtgcccttt caggtgctga aaggcctcga gacgagctcc caggaccact gagttctggc 60cttggtgttc gagggctaaa ggagaccaag agggacactc acaaacccca gtggcaaccc 120ctttcctcta ccatcccctg gcctcggttc cccagccttc gagcccaggt tcccc 17520342DNAHomo sapiens 20tttatctaat acagaagttt taaagtgtgg tttctgtacc agaagcattg gcatcacctg 60ggaacttgtt agaaatgcaa attctaggct gggcgcagtg gctcacgcct gtaatcccaa 120cactttggga ggccgaggca ggcagatcac gaggtcaaga gttcaagacc ggcctgacta 180acatggtgaa acctcatctc tactaaaaat acaaaaatag gccaggtgtg gtggtgcaca 240cctgtaatcc cagctactca ggaggctgag gcaggagaat tgcttgaacc ccggaggcag 300aggttgcagt gaactgagat agtgctactg cactccagcc ta 34221193DNAHomo sapiens 21ttatgcttga ccttagccta cttcacaatc ttttgactgg gtcttccaga tgagctggaa 60ggtcctacct gttcaatggt ctcacaccat tctggatgat tggatgttat atcacacact 120atacataaaa ctattacaac atgacagaat catgcattgc agacctgaca ttcttctaac 180aggacttgat aag 19322567DNAHomo sapiens 22tttagctctc tcttcattgc tattttatac acgaggaaac taaatctcag agaggttaaa 60tccaaggccc tttagctagc aaatgacaga gcttctattc aaactcaggt ctgcctcaag 120ccaaagcctc gtcctgatcc atttcattaa attactacca agtattacag atctttccta 180gggcaatcat tttcttctat ataggactcc tggagtcact ctgagtattt ctaatgaggc 240tgacaacaaa gggaagcttg gaagtttcta agcagtcact tccacagagt tgcttaattt 300gccctaattc ctggtttttg cagcccctgt cctaggctct tgctcacata tggacttgaa 360tttgtggaaa ggtcaaaaat gatattctag atggagagat agtcttggag tacaaagaac 420ataagcagaa atgagtaaat aaagctctag gagagcgtgt gatccagctc aattaaaggt 480tagataagcc atggtggcac ataagctttg aaggtagagt tcaaatcata ccattaggat 540tttgactgcc aggcagaaga gtttgat 56723330DNAHomo sapiens 23gtctctctat gtgttctctc ctcatggcag ctctgagttc tgagagtgag tgtgccagga 60gactggaagt agaggctgtc tgtttttaag gccagggttt ggaagctggc acagttgcat 120ttacacaaag cagttctaga tggaagggag gagatagacc ccacctctca atggagtgtc 180cctcttcggt ggccccttta atggccattt catagggtga agattaaata agacaatgag 240cacaacgggc ttagcatagc acctgaaaca tcttaagagc tcaatgaatg gtagccattg 300tcattatcag aggtagtatc agggtcattg 33024383DNAHomo sapiens 24taatgtattt aattccttta tcattagaaa ttagtttttc tcacttacta caattgtaca 60ttacaccaat cacctatcaa attctgctca gtttccaaga ataattcctg acctcagctg 120atccacctgc ctcggcctcc caaagtgccg ggattatagg catgagccac catgcctggc 180ccataataag attttttata aaactttggt ttttctattt gttagttttt ggagacagag 240tctcactgtg tcccccaggc tgaaagtgca gtggtgtgat catggctcac tgcagcctca 300accccaccag gggttctcct actttagcct ccccagtagc tgggaatata gacattcaac 360acgatgccca gctagtatct aaa 38325238DNAHomo sapiens 25gtggaaaagg aattatcttc aaatcaattc tacacagaag cattcagaca aacttctttg 60tgatgagtgc attggtcaca cagaattgaa ccttcccttt gattgagcaa ttctgaaaca 120ctcttttgga gggtctgcaa gtggatattt tagagctttg ggacaactgt ggaaaagtaa 180atatcttcac ataaaaacta cacggaagca ttctgagaaa cttctttgga ggtgtgca 23826282DNAHomo sapiens 26tcctccccca gccatgccat gcagccctcc tcctttgctg tcctaagaag aagggcctcc 60gcccacatgt gcacattgga gacagactgt atgtagctca tgtgttcaag aaaccagagc 120aggtggaggc ccaggcacga cactggggag cactcccagc gcgggaagta attttctcag 180tgaacgacaa agcctctttg tgtgcacatg ttcatgtgct gagcacacac ccagtacgca 240cacacctacc atatgtctta agagtttata gaaattgtgg tt 28227261DNAHomo sapiens 27aaaaatagtt tatcaaggca aatttgctgt ttggaaggga cacccagaat aatcagcaag 60ttttagagaa aaagggctca aaaaatagtt cattagctta atgacaaaat acaaaatgtt 120tgattagttg taatccaaca ttttttaagt attttatcac cctttccaaa aaaaaaacaa 180cctgttgctg ttgacttatg agatcccagg tgaatttcat tctgaatttt tgaggtactt 240gccggggtgg ggtgggggtg g 26128179DNAHomo sapiens 28tccctttccc agagcctcca aagtctgctt gcctgagggc catgactaaa gcgatggcct 60tttctttatc ccgtttgtcc cgttccgcct gctcctcctg atctctatta taaaaaacca 120aagttgccaa gttcaatagg gtttctaagt tttgcttcgg gcctaaggtg gacttttga 17929351DNAHomo sapiens 29gtgggtggag gaagatctta ttgtgggcca cattgaggat gttgactttg acttggagtg 60aattgggcac tcattagctt agaccagagg atttactttg aataatatga aacagtctca 120ataactgatc tattcagtat ggtagccgct agtcatgtgt ggctgttgaa tacttgtgat 180gtggctacct tgaattgaga tgtgctatat gtaaaacaca catggatttt gaagatgtcg 240tatgaaaact aagaaaagtg aaatcatctg atatataatt acagtaatag gatcactagc 300tgctgtactg agaaaagata taggggtgga agtgtcaaat ggtttggatc a 35130362DNAHomo sapiens 30atatccacta gcagatactc caaaagagtc tttcaaaact gctctgtgaa tagaaatgct 60caactctgtt agctgacgac atacgtcaca aagcagtttc tgagaatgct tctgtctagg 120ttttatggga cgatatttcc tttttcacca taagcgtcca agagctccaa gtggacgaat 180tctctagata tctagagaat tcgtcgtgcc catagttgtg agtaattata ctcgcctcac 240tgagatgcca tgagacatca ataatacatg tcggggaaat gtccagcaga ggttgatact 300cactaatcat gaagccccat ctccttctct tctggccagg gttgctgagc attggaggtg 360ac 36231189DNAHomo sapiens 31aaggtggggg gcagcttaac ttcaagggca cttcaaggat agccaggtgg ctgtcagccc 60agctttccag gatgggagca ggatcttgac agaagggttg actgggaggg gcagttgctg 120gtttgggctt cgttaggttg catttttgtt tgttgtcctt tcatttccct ggggcagcac 180cccttcctg 18932250DNAHomo sapiens 32agcttgcttc tcatctacct acaacttatt tgagcccacc cacatccttc cataaattct 60attttgctaa aaataggcag aggcgatgtc tgttgcttgc aaccaagtat cctaactgct 120actccaccat gtagacccta attcaagtcc caggcctgct attatactta gcagctgatc 180cttgtccagg aattgtaccc cgccattatc atgggcccag gttccttcta tcactgttct 240actattgtgg 25033204DNAHomo sapiens 33aacaatgtct caattctcaa accagcagag actaggaagg ggtcatatga tgcaataatg 60ctggaatgca gattaaacaa aggaggcttc tccttttaca aactgactaa acagggaggg 120ttctcatgaa agatttatag agcatccagg gcaaagtctg accacttaac ttttcatgaa 180ttggtcacca ctctaacaaa cctg 20434108DNAHomo sapiens 34taaattgtgg ctcatgcccc agttccttaa agggaaactg cagtttgtgg cagataagaa 60atgtaggatc ccatgttttc caaatttagt tctctttagt atttgctg 10835478DNAHomo sapiens 35agcttgtcac agtctcagtt ttttattttc acacagagtc tggttttatt tttaaaaaga 60gaaggaaaaa agtgataaat gctagtgagg tgccacttcc ctccttcttc caggctctaa 120ccgccagcta gctctctttc acaaaaccca cggatgcaga atcaggacat gttaaaatgg 180aacagtcttt agagagggtc tagtcttttt aaaataagta aggatttggg gactaacaga 240gaggaagccc ctgacttgct gaattgttag gagcaggcgg ttctcgagat tctgagccca 300ggatcctttt ctgtgaacca tgcacgtgct ggcactggcc tcaggagaca gtgccctgcc 360ttggctgtca ggtccacgga gaagtctcag gtttgcccca tcactacgga tgccctaaga 420agcaagggca taggaagctt taagggtcat cgagactggg acaagagaaa tgagtgca 47836216DNAHomo sapiens 36agcttgtgct ggtgtgaatg tgtatgggtt acagctgtgt tttcatattg tttaaaatga 60aataaaacca tgttttgatt ctattaaaaa tagagaagct ggctgggtgt ggtggctggt 120gcctgtaatc ctagcacttt gggaggctaa ggtgggcaga tcacctgagg tcaggagttc 180gagaccagcc tgcccaacat ggtgaaaccc ccatct 21637123DNAHomo sapiens 37ggtaggagtt caagaccatc ctggccaaca tggtgaaatc ccatctccgc taaaaataca 60aaaaattagc cagatgtggt ggcatatgct gtaaccccag ctacttggga ggctgcagga 120taa 12338233DNAHomo sapiens 38ggttctgcgc accaaaatgt ttggtggaca tctgtgtccc cccccacccc aaaatccacc 60ccagcacaca ctcaactctt ttaggccgag gggcacgtcc aactcatctg gtgaatacat 120cagctgaatg caatctgctc tcacaaacag atgtcccagg aggcggagct tgcagtgagc 180tgagattgtg cccctgcact ccagcccggg cgacagagca agactctgtc tca 23339529DNAHomo sapiens 39atcaccagca tggatcaaat ctctgctctc ccctcatctt gttgaccata aaaataattt 60ctaagaggca ctttaaaatg gacaaactaa atgacacact agccacccaa agtctcctat 120attctaaagt gtgtgatgag acaaactgat tcaaaatagc cctagggtga gaatttcctg 180ttcaaatctg cagtgacaca ttggtgagga atctactttc tccactcttg cctcactctg 240acccttcaaa gggcagtctg tgaagatcac agataacgtt tgtgtctttc agaggtaacc 300tgacctctcc actgaagggc gtgtggcttt ctgatgacag taggtaagtg ttgctcctct 360ccctgtttct ctactagctc atctcattta gtagaagatt gtaagtactg gctgtgatgc 420acctgaggta aagttgatat agacgaaaat caaggtagaa atttattcac gtgaataatt 480caaggtgaaa aacgagccaa aatataaact atgtttaagg atttcttag 52940177DNAHomo sapiens 40gtctcggcta ctgactgcaa ccccgcctcc tgggttaagc aattctcttg tctcagcctc 60ccgagtagct gggcctacag gtgtaccacg cctggctaat ttttgtattt ttagtagaga 120cagggtttca ccatattgat caggctggtc tgaaactcca aacctgagga aatccaa 17741293DNAHomo sapiens 41atttctggat gtcaatgagg tattaacaca taagagagga gacatttttt atgttctttt 60cttctgttcc tagataccag aagcatcatg ggagtggtgg cgtaaggata ctgagagtag 120atagagaagg cactaaactc agagagaggc tagaaaggtg gaagtggtat tagttattcc 180ctgtgttttc tcctctcaca ttcttttgca atatgtctgc ttttgagtgt gatggtgttg 240cacacttcct aggtactcaa acctccatgc ttagcattcc catggcactg atc 29342309DNAHomo sapiens 42ttatcctgct gggtactatg aattatcctg ctgggtcact gggtggatcc ctaggcaggc 60agtattgcct taatctgtat ctgagaggat ctggaactga gtttcagggc tattttaggg 120tctatagctg ggaccaatgt cagcaggcct gcccagagga ctcaggctgc atgtagtcct 180ctgtgtccct gtgctgctgg caggactgat cacagaccac tactgagagg ggctgagctg 240agactcagaa ccatttcagg atctgctgta ggcctggggt cagcaagcat gtcctggcaa 300atgtttctt 30943180DNAHomo sapiens 43accactcaca gattcactcc aaaggttact gcaaatgagc acccttcaaa tattcgcaca 60acaccatggg gaaatgttct ttgctaacat aagcagagga tcccagcgcg aggagagagg 120gaacctcagc tgcgaaggtt tccacattca aggtggggct gaccaccagg aaacaaaggc 18044308DNAHomo sapiens 44agcttctaac ttgcttgctg ctaccacctg ctgtgtggcc tggttcctat agcccacaga 60cccataccag tccatggcct ggggcttggg gaccgttgct ataagaagtc agaaatagtg 120gttccctagg aagggtctcc gtcagaacat ttttggcaca taactaatac cttgtatgac 180agctgctcag gagagggtga agcaggcatt cactgctagg tctgatctct taagagagcc 240ccttaaggcc caggaagctt ggccttgacc caggcaggaa gccacaaggg gaatattctg 300gatatgag 30845217DNAHomo sapiens 45ccacccttgt taccgggctg ctcaccagga cctgggtagt ttaccggggt gcacaaaggc 60acgaacatat gacagagtgg gcaagatgaa ggaaggagcg ctgcaagcca gagggaaagg 120gagacagaga agtcaggagc aggggctggg tgacggggct cactctctac ttaaagtggt 180ccatgagaca tctccacctc atgccaaaga acggaga 21746155DNAHomo sapiens 46tgtctcgatc tcctgacctc gtgatccgcg caccttggcc tcccaaagtg ctgagattac 60aagcatgagc caccgcgcct agcctgggtg ggggctgttt ttaaatctta tctcaagttc 120atgtcggctt tggagatttc attaaacacg acaag 15547567DNAHomo sapiens 47ttcctgcaaa actaggccat cggctcctcc atgccccagc ctcagggagt cattagattg 60tcagggctga gtcagtgccc aaggtcacac agcaattaac tagaggccca gactagaacc 120aatgtctgac tcggacaccc taaggctgac ttttgaatag gtggacccgg agcctcggag 180ctgaggggag gagtcaggca cagaggatga gagacctgag acagcaggct gtgcttcctg 240atttgacact cctctgattc catgttggct ctgggctcct taaaacaagg ccagtcctgc 300aggtgggcgg gatgtgtggt ggggaccaga gcctctccag ccggaagtca gaggcccagg 360gttttggaag gactccaggt ctttccttgc atctggaatt aaaaccttcc ccggctgagg 420cgcgtagatc acctgacgtc gggagttcga gaccagcctg accaacatga agaaaccccg 480tcactactaa aaatacaaac aattagctgg gtgtggtggc cgcgtgcctg taatccaaac 540tactcaagaa gctgatgcag gacaaat 56748290DNAHomo sapiens 48ccacggagcc gtccccagcc cagctgggga cacgtccccc ttctctccga cacaccctgc 60ctgccaccac gacacaccgg cctgttgggg gtctctttta agtgcttgcc actctgaggt 120gactgtccct ttccaaagag gtttctgggg cccaggtggg atgcgtcggc ctgagcagga 180ggatctgggc cgccaggggc tggggactgt ctcctgggga aggaagcgcc tgggagcgtg 240tgtgctgacc caggaccatc cagggaggcc cgtctgtggg gcaagcggga 29049276DNAHomo sapiens 49gtatttagga attagaggta aaactctatg ttattatctc tgaagataat gacaagcaat 60tcaagcaatg aaaaattcaa atatacattt gcttcgccac ataactacgt cactgctggt 120ggatacatga aagaggaacc catactattc tggctgatgc ccagcttccc aggaattagt 180gggatatagt gctggacatg acgttacctt gagtacatga cagtcagccc ctaaccaggc 240tctgattcac aagactagga ggtactcgct ttaagt 27650156DNAHomo sapiens 50catgtatcta gaatttgctt tactatttga cttctgtgaa aagtttctgt gaagactgct 60ttcagagtgg aggttatgat

ctcaattctg ttggccctgc caaacatcac attcacgtca 120tcatgcttgg actgtttgtc ttctcattga tattcg 15651345DNAHomo sapiens 51agtagggatt tctttgtaac tgccctgacc ctggattatg ccctactcct tattttgtct 60aaacattagc tgggcatggt ggcatgggcc tatagtccca gctacgcagg aggctgagtc 120aggagagtca cttgagtcca ggagcttaag gctacagtga gctatgatcc agccactaca 180ccccagcctg ggcgacagat cctgtctcta taaaagaaaa aaaaaatcct tgagagtagc 240ttggctttgc agaatgcagc tgtttcttgc ttttgagggt gtttgtttgc catttgaccc 300tcttttttta aaccttatgt ttataaggga aagcctctta cagta 34552150DNAHomo sapiens 52tgtgtacaat aacagaaaaa gttgcaattc cttgcctcca ctgtgagaca aaccccagcc 60acatctccag cacacaagaa cttccaaatg cctgaactgc agcagccagg tgtttctcca 120gaacctcctc ccccaggagc ttgctacacg 15053189DNAHomo sapiens 53atctgatgaa agagtagcat gaagatggag taagaattcg tcctgtggag gcaagggcaa 60taacattcca gcaaatagaa tcacataagg aaaggcatgc aggagggaaa ggacagggga 120caggacatac ttgggaaaga cgaggggatc aaatttggct ggattatgcc atatcttgtg 180caaaagagg 18954190DNAHomo sapiens 54cacttgcact gaggaatgga ggagcagggc gctgtctggc cagcggtgcc atagcaacca 60ctggctccga tgctgccacc acctccaggg ttgttcttcc tatctgaaag ggactaagca 120gaatgaggcc tctgctgccc cagggctgaa atgggtttct gcgaagtctg tttcttacag 180tttgatccac 19055643DNAHomo sapiensmodified_base(630)..(630)a, c, g, t, unknown or other 55cattaactca gtctctgccc ccactttact tgggccatga gctttcatgc ctcgaattta 60ataatgaatt ttataacaca taactcccta atgacactcc aaaggaagga attgtgtcat 120ttttgttgat ggttgccatt tgttcactta tttttatcac tttttcaaaa catgaggtca 180attttacctc caatgggttc tccaggacga attctctaga tatcaagctt gaattcgtcg 240tttccaacga aatcctcaaa gctatccaaa tatcctcttg cagattttac aaaaagagtg 300ttccaaaact gctctatcaa aagaaagctt caacactgtt agttgagggc gcacatcaca 360aataagattc tgagaatgct tctgtctagt tttcagggga agatatttcg tttttcacca 420taggcctgaa agcgctccaa atgtccacat ccagatacta caaaaagagt gtttcaaccc 480tgctctatga aagggaatgt tcaactctgt gacttgaatg caaacatcac aaagaagatt 540ctgggaatgc tgctgtctgc ttttcatatg taatcccgtt tccaacgaaa tcctcaaagc 600tagacaaata tccacttgca gattccacan aaagagtgtt tca 64356139DNAHomo sapiens 56atagtggagg ccatccaagg cttttatcct tgctaaggat cttcaacctc ctgcaacatg 60ggaatctgga tgaagaggcc aatgaactgg aacttacaat gtaaccacca acctaattaa 120cagtaagaca atgctatag 13957225DNAHomo sapiens 57gtggatcacc tgaagtcggg agtttgagac cagcctgacc acatggagaa acccatctct 60acaaaaaata caaaattagc caggcatggt ggcacatgcc tgtaatccca gctactacgg 120aggctgaagc aggagaatcg cttgaacctg ggaggcggaa gttgtggtga gccgagatca 180tgccattgca ctccagcctg ggcaacaaga gcgaaactcc atctc 22558327DNAHomo sapiens 58ccattagcct tctgatggca gggcaaataa taattctcat tgcaaagaaa taaatatggg 60tttaaattcc aactttttag attttagaga atagccgggc acagtggctc acgcctgtaa 120tcccagcaca ttggaaggcc gaggcagacg gataacgagg tcaggagatc gagaccatcc 180tggctaacac ggtgaaacct cgtctctact aaaaatacaa aaaaaattag ctgggcctgg 240tggcacacgc ctgtaatccc agctactcag gaggctgagg caggagaatc gcttgagccc 300aggaggcaaa ggttgcagtg agccgag 32759109DNAHomo sapiens 59gttaatcaac aacatttttt ggccatttat tctgtgccag gccttttgcc gggttctggg 60aattcagcag gaaagaagtc tgacacactg gctgcccttt agtgaagga 10960236DNAHomo sapiens 60aataacagtg gccgctaggt gatgcccgaa gacaccgatg cctgcctgca aatgtccgtc 60agcagggaaa agaattaatg aattaattaa tttccgtatt tatttagaga ccgagtctca 120ctcactctac agcctgggcc gtagtgcagt ggcgcgatct cggctccctg cagcctccgc 180ttccctggtt caagcgattc tcccgcctca gcctcccgag gagctggcat tacagg 23661445DNAHomo sapiens 61tggtgaaatc catctctacc agccggcata gtggcaggtg cctgtagtcc tagctacttg 60ggaggctgag acaggagaat cacttgaacc tgggaggcag aggttgcagt gagccaagat 120cgcgccactg tactccagcc tggcaacaga gagagactcc gtctcaaaaa caaaatacaa 180acaaaacagg aggacgagac agcgagagga acagcgtccg gggcgacccc cagtccaccg 240cgggggcctg gcgcgcttgg ggcaaaggcc ctaggagacc ccttctggcc acaaaatcga 300gtatgacaga aaagggccag cgggggcgct ttccttccag ggccacttgc cggaatgtaa 360gagggacgga gagacgtccg gaaaaggctg ccacgctcgg agcgctgcgc caggccaggc 420acctaggcca ggggagcgga gacct 44562535DNAHomo sapiens 62ggaagtactg cagatgtggt agaaatagaa agagaaccag aattagaaac agagcctgaa 60gatgtgactg aactgctgca atcttgtgat caaacttgaa cagatgagga gctgcttctt 120atgaatgagc aaagaaagtg atttcttgag atggaatgta ctcctggtga atatgctgtg 180actactgcag aaatgagaac aaaggattta ggatataatc tcagctgata aagcagcagc 240agggtttgag aggactgatt ccaattttga aagttctact atgggtaaaa tgctataatg 300cctggggtgc tggctactgt agtcccagct aatcaggagg cagaagtaag atgatcactt 360gagtctaaga gtttgagtcc tgcctggaca acacagtgag acacccatct ctattaaaaa 420ctaaaaacaa atataacgct atcaaacagc atctcatgca acagagaaat cttccgtgaa 480aggaagagtc aattaatcca gcaaacttca tggttgtctc cttttaaaca attgg 53563316DNAHomo sapiens 63aaatgacagc aagaggtgtt gggggcaccc agtgaggagc tggggagaag ggaagaaggt 60gctcccatgt tttctaagca cttccctggc cattggctct tttttccttt ctttcctttt 120tttttttttt tttttttttt tttttttttt taaaaagggg gtcttgcaat gttgcctaaa 180ctggtctaaa attcttggac aaaattggtc ctcccaccta acccacccaa ttagctggaa 240ttacaaccgt ttacaaccaa attgggttgc caagggcttt ttcttttaaa aaggagttta 300actcggttgc ccatgc 31664282DNAHomo sapiens 64atccgggcat ggtggctcac gcctgtaatt ctaacacttt gggaagccga ggcaggccga 60tcatctgagg tcaagagctc aagacaagcc tagccaacat ggcgaaacct catctctact 120aaaaatacaa aaattagctg ggtgtggagg cacacgcctg taatcccagc tacttgggag 180gctgaggcgg gagaatcgct tgaacctggg agttagaggt tgcagtgagc cgagatcatg 240ccattgcact ccagtctggg agacagagtg agatcccatc tc 28265279DNAHomo sapiens 65ccatcttggc caggctggtc ttgaactcct aaccttgtga tccatgcccc tcggcctccc 60aaagtgatga ctgtagtttt aagtcctagc atctgaaagt aaaagtcctc caattttgtt 120cttcaagatt gtgttgggta ttcttcagcc tttgcatttc cacattaaat ttagaatcag 180cttctcaatt gctgattctt tagtaaaaga aaaacaaccc tgctggaatt ttgattggaa 240gtttgttgta gcataaggct ttggaagctg caaaataaa 27966261DNAHomo sapiensmodified_base(21)..(21)a, c, g, t, unknown or other 66ttcctgtggg tctaaaaccg naacgctttc ttccccgacc cctgctcccg tatcacccca 60acctcaagtc ttttggcaca gccggctaca gactcgagtg tcagtttaat gcttgttccc 120taaggtctcc ccagggctct taggacggcg tcaggattag gattcgggtt cgggtgcgcc 180tcttcgcgcc tgcgccggcg ctggcagggg gagggcctct ctgcgcctgc cccggcgctg 240ggggcctttg caagggtgga g 26167521DNAHomo sapiens 67caagttgcta tacattgtac tttttaatgg aaaaatctct gtatttgagc tcttgttata 60ttttctgtgg tatctcaaaa attctcttgg atataagcca tctggatttt tctgcagtcc 120tctcaagttt caaaatagtg atacttagaa cgtattttgc agggtttcta tcggtcaagg 180gcatgcagtt ctgaaaatct tgtgctgtga ggtcagacag gaccgttggc catctgccaa 240ttgacttgca ttgtttacct ttttaactca caaccctgga aacgctgttg gtgtcccccc 300ggccttcact ggttttctga gtatctgccc ctttgcctgc ttgaagtgct tagtcctggc 360gagtgaagcc tttaggagtt cccaatttct tgcttcacag gttactaaaa atgaagacat 420atctgttaag tgttgctcaa gagaccaaaa cataatccta ggacaggatg tctggaaagg 480atgtcttgcc tgtcacgcag cataatacat ggtaacaagt a 52168253DNAHomo sapiens 68ggtaggactg ttcttccttg atgcaggtgg gaggttggcc ccagggatgt gatgtgctgc 60cctctctggc tccctctggc acagcgcttc ctcagatggt gcaattttcc cactcacata 120aatctgactc catttcctga gtccctaatt ttcccaagga gaaaagggca ggaagtagtg 180gagagggccg ttgactaaag agggcccacc agtgactaag ccatttacat tcacaaagga 240gacaggccct gca 25369251DNAHomo sapiens 69tggattagac aatggtttct taggtatgac accacaagca caaacaacaa aaggggaaag 60agataaatcg gactttatca aaattaaaaa ctgtggtgtt caaaaggata ctgtcaagaa 120agtgagccaa cataccacag aatgagagaa aatatttgca gtttatgcat ctcatatggg 180acttgtacag gttatatacg gaactcttat aggtcaatga aaggataaat aacccattta 240aagaatagac a 25170351DNAHomo sapiens 70ttgagtggac atcagaatga tctgaagagc ctatcaaagc atagagggct gagccccact 60ccaataggtt ctgatctatg gatttcgcat ggggtctaag aatatgcatt tctaaacaaa 120attcctagag gctactggtt ctgcttgtct aaagaccaca cacttgctga aaacaactgc 180tttaggccat ataattaagg ctcctactct ctctagttgg cctcatatcc ttagttcact 240caagctttga actacttatt aaaagtgact tctgcaatcc taaacatgta agacattata 300cagcatcaag cccaccaaat agtccctaaa gataaactct ataagctgga c 35171397DNAHomo sapiens 71ctaacctagc ttgggcccgc tgaaagtaac tgaacccaaa gcagcggccc agccagctcc 60atgcaggaca acttcccatg tgaacgtgga ggagctgtga aacagaaacc tactcactca 120cagatcttta acaaatagcc cccgaactga accaaaccaa actgaaataa agggaggaac 180ttaggccggg cacggtggtt cacacctgta atcccagcac tttggggggt caaggcaggt 240gggtcacctg agctctggag ttcaagacca gcctggccaa catggtgaaa cctcatctct 300atttaaaatg caaaaattag ccgggcatca tggcacatgc ctgtagtccc agctactcag 360gaggctaagg cagaagaatg gcttgaaccc aggagga 39772265DNAHomo sapiens 72gttggttggg cttaggaaat gtaaattata gtgagaacca tatcaggtcc ctcaagggca 60gaatttttct tcttgagtaa aattttgaaa tctagggaaa tcttgttttc cctagagtgt 120cacatgatgg ctagacttaa aaatttctct tcccttatga cagaaatgaa aactttattt 180ttttaaatgg tatatacttc ttgcagttgt ttcatttaat agacttttat gctgttattt 240tggtcagagt aaatattgtt gtggt 26573416DNAHomo sapiens 73tctaaaaaac tccctactat gcttagaccc tccttgagtg cattcctgcc cacaatccca 60agccatcttc tccatccttg agtctgtgga atatgagagt cctggcatat tgctttagga 120taggactgta tagttgactg ctgagatgag gagtcccaga aatcttcctt ccagctgtgg 180cccaggaaga ttacccaatg aaacctgtgt gtgggggtgt gtgtgggaca tatgctgggt 240gaggtggggt caggagtaag taaaattaat attgtgctga agaatgctca ctgaaaatag 300tcaccacccc tacagaagat ggaatcggga agagtttttg acccaaatcg tccactcatg 360ccccgtggag cttgtgctat gatgagaaca gacactaccc agggaaaata atccac 41674417DNAHomo sapiens 74ttagatcaaa agaaagtcag aatacaacaa gatatagaag tacggaaaga cagatctgat 60gcagtgagaa attctaacat acataataag attcatgaaa gagataaaaa acagttggat 120cccagcactt tgggtagccg aggcaggtgg atcacttgaa gttgggagtt tgagaccagc 180ctaggcatct ttcattcatt caaaggagag agggggtgtg acggctggga ctgacaatga 240aaacagagac agcctcacat gtggacaaac ctcctggtaa caacctaaat ccatgtactg 300ctgccatgag gccatggaaa ttcagtctct ggttcctgga cagtgtcctc aactgttccc 360cagcccaaga agagctgaag ctcaaagagg agggcaagtg actgcagatc agctcct 41775228DNAHomo sapiens 75cctgggaggc tgagacgaag atcacttgaa tccaggaggc ggaggttgta gtgagccgag 60atcgcgccac tgcactccag cttgggcaac aaagaggaaa actccatctc aaaaacaaaa 120acaaaacaaa caaacaaaaa accccacaaa cctgcatgtg tagccccgaa cctaaaagaa 180aaatttttta aaaacccagc atatcaaagt ccttcaatac atatgatg 22876220DNAHomo sapiens 76gggctcgcac gggtaggggg ctccggcgga gttgggtgac cgtgaggcgg ttggtttgga 60gaggttgtca ctaaggagga gtttactttt catttgtgga gatgatggga gcccaggaaa 120tgtggtcaga aaaaggcccc tggaggggtc ctggaagcgt ccttagctgg tcctggggga 180ctgggcgggg aagggagcgc agaaggaagc aggtgggctg 22077352DNAHomo sapiens 77ccccttcgcc aggcaacgcg cgagactgac aggcctcccc ctccctctgg ccttccgaag 60cgcgcggtgg cggctaagcc tcagcggcag tctcctccct ccttccctcc ctccccgact 120ccctccctcc cgccttccct ctccgctctc ctccctccac ccgctctcct tccccctccc 180ccctccgaac ccgggcgcaa ggggggaatt agaaactgct ctagaaggat tttaaacaac 240tggctgttct ctccgccgcc acccctcccc ccgcgccgcc cgcgctcagc tcctcactgg 300agagaaggcg ccgggaggag gagaaactgc ggcctggagt ctccggccgg ag 35278309DNAHomo sapiens 78tggacctcta gtgactgacc gacaggaaaa caggtaccag aaagaatgaa gacttttaca 60tcaggtgttt ttagaaggga ttcgtggtta tctgagtaga gttatgatac cagagtggtg 120tgttcatcca aggctgataa ggaaccttaa cttgacaaga taaacaagag tgaatcagct 180aaatgacatt tgtgattctg gcttatcctc tgaagatgaa aaataatcac tgtctcaggg 240tcaaagtaat gactcatctc ttagaaattg aggtggaaat gtccagattt gggaagaata 300atatttcac 30979228DNAHomo sapiens 79tgtatgttta ggattgtgat attttcctgt tggacaaggc tgttcatcat tatataatgt 60ccccctttgt cttttttaac tgctgttgct ttaaagtttg ttttgtctga tataagaata 120gctactccca ctcacttttg gtgtctattt gcatgaaata tctatttcca agtctttacc 180ttaagtttgt gtgagtcctt atgtgttagg tatatctctt gaaagcag 22880172DNAHomo sapiens 80ggtctcttct agtttctttt cctttttctt acctagcata accattaaat tgaattcaca 60acccacaaag aggtcacagc ctgaggactg gaaaacagtg aactagacaa cctcagcgct 120ctggcgcttc cagaaaaccg cgtgtcactg cagcatcctc cgcatcatcc ag 17281340DNAHomo sapiens 81cttaggagaa ataaaaacat atattcacaa aagacgtgta tagcaaatgt tcataacagc 60attatagata atagccaaaa agtgaaaaac acccaaatgt gattggataa acaaaatgtg 120gcatatccct acaacagact actactcagc aataaaaagg aacaggccgg gcgcagtggc 180tcatccctgt aatcccagca ctttgggagg ctgaggcagg cggatcacct gaggtcggga 240gttcaagacc agcctgacca acacggagaa accccgtctc tactaaaaat acaaaatttg 300ccaggcgtgg tggcgggtgc ctgtaatccc aggtactcga 3408284DNAHomo sapiensmodified_base(9)..(9)a, c, g, t, unknown or other 82gtatttcant ttcttgcagc cagtctctca gtttgctgat gtcttatttc aattctgtga 60gaccttatct tcttggttta tgca 8483209DNAHomo sapiens 83acaaattgca gactgcagcg ttctgagaaa catctttgtg atgtttgtat tcaggacaca 60gagttgaaca ttccctatca tagagcaggt tgggatcact ccttttgtag tatctggaag 120tggacatttg gagcgctttc aggcctatgt tgaaaaagga aaaatcttcc cataacaact 180agacagaagc attctcagaa acttgttgg 20984360DNAHomo sapiens 84gttctcagat tgagtggaca tcagaatgat ctgaagagcc tatcaaagca tagagggctg 60agccccactc caataggttc tgatctatgg atttcgcatg gggtctaaga atatgcattt 120ctaaacaaaa ttcctagagg ctactggttc tgcttgtcta aagaccacac acttgctgaa 180aacaactgct ttaggccata taattaaggc tcctactctc tctagttggc ctcatatcct 240tagttcactc aagctttgaa ctacttatta aaagtgactt ctgcaatcct aaacatgtaa 300gacattatac agcatcaagc ccaccaaata gtccctaaag ataaactcta taagctggac 36085191DNAHomo sapiens 85taggaggagt aggggcaggt tttggctcgt aagaaggcct agatagggga ttgtgcggtg 60tgcgatgcta gggtagaatc cgagtatgtt ggagaaataa aatgtgcata gtggggattt 120tattttaagt ttgttggtta ggtagttgag gtctagggct gttagaagtc ctaggaaagt 180gacagcgagg g 19186265DNAHomo sapiens 86tattattact tttctaagtc ctttggtaag caacttcctc ttttcctctg ttctccattg 60cttttaccta tttttaaaag tttttaagct gttaccgatc gggtgcagat taaactgtga 120ggtctggctc catccaatgg acacaggaca tagtaacaag gacaagctgt atacagaata 180aaaaatgctt cgctcctttg tacaaatgtg ctgtcaccaa tgtaccatgt gcaaggagaa 240acctttctgc aaaaaataga attgc 26587179DNAHomo sapiens 87gattgcttag tccagttgat tatgctcaga aagtatttcc taaagccttc aaatttactt 60taaatacctt tgagaccaac tcagtcctga agaataccta caaaggccca gatgaaaaca 120atttactgaa accctaactc taccattaaa ttttactatc aggttgatca gaggaggcc 17988172DNAHomo sapiens 88ttctactaat aatacagaat tagctgggcg tggtgttgca tgcctgtaat ctcagctact 60caggaggctg aggcaggaga atcgcttgaa cccgggaggc agaagttgta gagagccaac 120atcgtgccat tgcattccag cctgggtgac aagagcaaaa ctctgtcgcg aa 17289231DNAHomo sapiensmodified_base(180)..(180)a, c, g, t, unknown or other 89agcttgggca agctgatacc tacatttggt tccgtcactt tgaagtttag cacaaaagag 60caaatggtaa tgattggtca gaaatgtgtt taccaggcaa ataaagccca tacaccatcc 120tgatggtctg tactgagctt tgttgggtgg ggtgaagttt gggatgaggg ctggatggtn 180agntgggaac tgntggtggn tggaggggag gtgttggagt gggggaggtg g 23190180DNAHomo sapiens 90tatgagatat tgtcagggtt ggcttccctg ggctcaagct ggagaatggg actgcctacg 60aggctcttcc tgccactgct tctactttta tatttcattc agctccccaa atctgtttta 120gctgtaggta aggttaagtc cttctcccgt gatctggatt ttcagattcc ccagtgggga 18091437DNAHomo sapiens 91gccctcatgg tccctgtcct gctcatgttc aacactattt tctttagaat gagattctcc 60tgaaaatttg ttttgcattg gatcctagag ctgaggagct attttactag atcctcaaat 120ttcctttcca ctcacaaatg gagtagagtg tacaaaatcc ctcatcatat cagtggcaga 180tcttaaatta gtaaccacca ctttccagtg agtacctatt aggtcttatg gggttttccc 240acctgcaagt gtacaatttg cccatttact tcagtcttct ttcttctgca cagcttctga 300taccatgcag gtcttgcagc ttatgatgtc ggtgaacata tgcagttatt tgtcaatgag 360ttattttgtt tgtatgttta attaccttag ttactctgtt ttggggtgga ataaggggaa 420atcagggaga ttaaaag 43792235DNAHomo sapiens 92gccatctcct tcagctctca atcctggagc agccattcta tgctgggcct tgaagagtct 60catcctgagc atgtgctttt ctctctgtaa acccaggatc cacaggagat ctccgtacag 120tctcctgccc ctcattccat ccagcccttt ttcactggca ccttgctcca caaattcaag 180tcaccttagc aatctcgaac tacagtttct gcctcttcag cttcacaaaa ccaca 23593319DNAHomo sapiens 93ttttgttctt tcactccttc ccttctgctc tgtgaagaca tagcattact cccctttgga 60ggatgcagca ttcatagcaa catctcggaa gccaggacca gaccctcacc agacaccaaa 120tctgccagcc tctagaactg tgaggactgt ctattggtta taagttagtt tgcggtaatc 180tgttatagta gcacaaacac actaagacag aagttgatac cagagaagtg gcctgttgcc 240ttaacaaata cctaaatata tagaagtggt ttcggcacta ggtaatggat agaggctgga 300agagttttga tatgaatac 31994202DNAHomo sapiens 94agctttctgt ggtcctggtc acttcacttg ggctaagggg ccaattaact tactgagcca 60tcccatgcca atggggaagg gctggaggaa accccaccac catcccacac atagtctgga 120cagccctcac tcctacccca ggagcacaga tccacatcca gagcaaatgc catctcatcc 180tggacatctt ccttgatttt gc 20295426DNAHomo sapiensmodified_base(409)..(409)a, c, g, t, unknown or other 95ccattaaaca ctaactccat tccctcctcc catcttacct ctggcaacca ccactgtact 60ttctgtttct atggttttga ttattctaag tacctcatat aagtggaatc atgcactatt 120tgtctttttt tgttgttggc agatttcact tagcatactg tcctcaagtt tcatccatgt 180gtcagaattt ccttcctttt tgcagctgaa taatatttta ttatatgtgt gtaccacatt 240ttgtttatcc attcattcat cagtggacac ttgggttgct cctacttgtt agctattatg 300aatgatagag

tttgggtgtg tgtccccacc caaatctcat atggaaatgt aatcttcaat 360attggaagtg gggcttggtg ggaggtgatt ggatcatggg ggtggattnt tcagggccga 420tttatc 42696185DNAHomo sapiens 96agcttcgagc tctaaaatgt tcatctgttt agcaactgct ggataaacat ctggtatgag 60gtcaattctc tgtaagtatg tcactcctgt gccacatgat gtgttgatga tttaatgcaa 120gcttgtttca cccgcggccc aacacagatt cataagcttt cttaaaacag tatgagttcc 180tttgc 18597311DNAHomo sapiens 97ataatatgac atctattttt aaaacatcac cctgtaatgg actacagagg gaaagagcaa 60aaacagggag acatctgcaa taatctaggt tagagatgag acggtggcta aggaattttg 120gccatacttg gaaggtaaag ctgacaagat ttgctgaaag atttgatttg ggctattctc 180caagagagta gtcaaggatg accctgagaa tgggtcatcc atccatggag ttgctgttca 240ttggtgcagg gaagaaaata gaagaaactt gtgagaaggt ggtagaaggt aggagtttca 300tgttggacat g 31198267DNAHomo sapiens 98gtctcatctg aaggcttgac taggggagga ttcatttcca ggctcactta tgtagttgtt 60ggaaggattt agtttcttgc agcctgttgg aatgaaggcc ttagttaatt tctggctgtt 120ggttggaggc ttgtctcaat tctttgctat gtggacgtca tagggcagga tgaaacatgg 180cagctgactt cccctgggca agtaagagag tgaaagaggt tgggctggca cagtggctca 240tgcctgtaat cccagcactt tgggatg 26799230DNAHomo sapiens 99cagtgaccgt gcaagggaaa tgttataagg tcggtcctga cagtagttag cttccttggg 60aattcatgtt gttgttcatt atgcgagaca attactgtgt agaagagcca aacacgctca 120gagcaaaaat aaaacttaga tcaggaaagc aaacgaaaat agcacattct gtgttgatag 180tgtcattcgc atatacccca aagagtacca tcagaaagga tgaagggatg 230100144DNAHomo sapiens 100ctgagagcct gtgtttgagc ttttccacca gggtaaggag cagtagatgt taggagcctc 60gtgcttagag ccaagtgaac cagctttttc tgggaaggag agaccaaatc atccctggga 120ggatagagcc tgtcttctgc agtg 144101396DNAHomo sapiens 101tttccctgac tttgaacctt ggctctgatg tcatgtagtt agttgaggcc aaaggaaaac 60tgatggggac tgttcatgtc tgtgtgtgag ctggagtgaa ggaaggtgtg cctaggcagg 120gccttcggtt cctggcagtc ccctccccag cattcttgta ttttcctgcc gtgaatctac 180tggagataga gatctggctc tgttctgctc ttcctcttct ctctgagtgg ctttgggcat 240atccatccct tgcactggaa ctccgttacc tcctctctac agcgaggggc taactgatct 300tgcaggcccc ttgctcctag aatagcctgt gactctgact cccagcctcc tgtttatttc 360tgaggcttct tcccagagtg ggtaaacacc tcctct 396102546DNAHomo sapiens 102tatctatgac ttcctcttct gccatcagcc agtaaacaaa aactctcttc ttttaagaca 60ttcctgagat gaggtaaggc ccaccaaaat aattttccca ccttaaggtc aactaattag 120taagcctaat ttcatctgca gtatcccttt gctatttaat catgggtggg acatcaggtg 180gctgagatca tgggatcacc ttaaaattct gcgtgtcaca ttgtccttcc tatgtgtgat 240ccatgagtgc cagcccaggg gaggtagaag ggcatgttgc tgtggccagc atagctggtg 300acttctgaga agcccgagaa ccagaaggct agaaagcgag gcatttaatg gggtccccct 360aacggcggaa tctgtgaacc aaaaagggat gtatggtcac tatgagttcc agatagaatc 420ccatttgggg cctgtttttt ttgttgttgt tgaaccttag aaataataag gattatttgt 480caaagggaac taagatatta ttaagcaagg aagggcctat agaatcagaa gatatttgag 540ttacat 546103464DNAHomo sapiens 103atctttttct ttgcagtggt ttgcaaagca ccttgcaatt tcctctcttc ttaattcctg 60gaattctgtt tgaacttgaa ttgcttaaag ctctctgtta agcaaactat ctcttgtgtt 120ttttcctctg atgtccacag gctttgaaac agtagctttt ccataatctt tgacaaaagt 180ttgcactaac tccctgaagg actggtttta gtacagcctt ctcgtccatc tggctcgttc 240tgtttttttt tttttttttt cctttcctca agatcttttc tctttgttta gttttttaaa 300ggggaatctc ttgaaagtct cctctaacat attcttactc cccttttcaa gattaagctg 360ttatcttggt gacaggtact gacaaatacc acatagactc acaaatggtc atgtggtttg 420gctcacagat tagtgccttt ttcaggtgat aattatcccc tggg 4641041243DNAHomo sapiensmodified_base(1)..(1)a, c, g, t, unknown or other 104naagtaacga ctgccagctg aatcttttga gtgaatnctg cccgggttca ctggtctttg 60gggtttaaac actcccttcc ctggctccat gtactccatt ctctctagga ccggtggata 120agttcttatc acacgacagg ggcgagcaag attgcaaccg gatggcacat aggggaatga 180ctaggataag cgcgaccaaa aaggagaaaa accatagctg tagacattct gaccgaaccc 240gctaaagagc cgcataacgc ccccgaacct cggccccatc ccgcgcagaa agccacaagg 300ggactattcc cgtttttttt ttttgggaaa ccggatcatc cggcccgcag acagaagcga 360cgcgaacgca ccagaacgca gagggaccca ggagcaaccc gacagacaac ggccatagcg 420acccccacac gagaccacgg aagcgcaacc agccgcacca gaacagaggg aaacaagcag 480cacaccagga acacaacgga caggcccggc gccccgcaaa acgacaggaa caaggaagcc 540accgacaaca accgcacaag gacaggaacg aggaacaccc ggacacccgg agcaaggcca 600caaaacgacg cacgcaacca aagagaacac caaaaaccca gacaaaggac cgaaagccag 660cgaagagagg gacagagcca cggcccaaac cacgccacac gaacgaccaa cagaaaggaa 720cgcaagcagc gaccacccac cgcgcaacca caaaagcccg gggccggagc aagaaaaaca 780caaccgaaga cacccagaac gaccgacagg ccagcaacaa cgaaaggaag gcggacaaga 840gcccccccga aggagcagac acaaacccaa acgccaagga gaaaccccac caaaaaggcg 900accaacgaaa caacacgaaa agccccacaa aaaaacaacc cccacggggc aacaaaacag 960aaaaaaaccg cgaaaaaaaa aaacggaaac aaccccacaa cacccaagac aaaaagaaca 1020ccaaagggac caccaaaccc cgaacaaaca cgaaggagaa aaagaaaaac acaggccaaa 1080caccaaagaa acacagggaa gacggaaaca aaaacccaac gaccaaacac aagaaaaaca 1140ggccgaagaa caacagaaga gaaaacgcac agaggggaac aaacacagca ccgcccaaag 1200agaaacagca cacacgccaa acaaaacaag ggcaggcaac gaa 1243105179DNAHomo sapiens 105cacatgtatt caaggctctg taaaggatgg aagacttgtc aatcatctct gtgtttgcat 60tcacagtgtg tgacaaacaa ctggaactga gtaaatattt gttggatgaa taagtgaaca 120catgaatgtg tggtttacag tatgctcagt atcctactgg caccaaatat aaccttttg 179106237DNAHomo sapiens 106gtcaccaggt gttcctcact ctcagcactg cctgctgagt gcacgagaac ccactggcct 60gtccatcacc ctgtttctcc cagtcctcct tccctcctca aaagaaggtt tttttctgtt 120cagtaccatt ctttttaatt tttctaacgc gattttgtca aggagctttg gttctagaat 180ttagatttca ttacaaaaac aggcttaagt gaaaccacgg aaagctcaat gtcccag 237107327DNAHomo sapiens 107atgcttaaca gtctggaagc aagcattggt tacaattgtt tagtggctca ttgatttcag 60cagggtatgg actgcttctg tcctttctct cttctaccct tatgggaaca agatggtggc 120cacagttcca agcaccaact cgtcacatga gacaccatga gcagaagtag gcaggggtca 180aaggtcactt cccttcacat ctctctttga tcagaaggaa tatctttccc aagcagaatt 240ccttcatgtt tcattggcca gaatgggacc agacgccaac cttagaccaa tcactggcaa 300aagcaattgc tttgttgatg tagatca 327108599DNAHomo sapiens 108actttttaat ctgacatgtt ggtaagttcc taagtgcttt tatcaaaaga actacttttt 60aatcgttcta ctctagtgtc aatgttttaa aacaggaacc acatctcact cagagtcgca 120cctcctgctt agatgctcca cagagtaggt atccacagga gacatttgtt cagttaattg 180tatgccaagt acagcctata aaattgagag tataggccag gcatggtggc tcacgcctgt 240aatcctagct ctttgggagg ctgaggcagg tggatcacct gagcttagga gttcaagacc 300agcctggcca acatggcgaa accctgtctc tactaaaaat aaaaaattag ccaggcgtgg 360tggcaagtgg ctaatcctag ctctttggga ggccgaggtg ggtggatcac ccgagcttag 420gagttcaaga ccagcctggc caacatggca aaatcccgtc tctactaaaa ataaaaaatt 480agccagtcat cgtggcaggc gcctgtaatc ccagctactc gggaggctga ggcaggagaa 540ttgcttgaac ccaggaggca ggcattgaag tgagctgaga tcgtgccact gcactgcag 599109594DNAHomo sapiens 109ataaatcgtg ctacaatcag atgtgctgtc atccaggctt tgctgttcca tttatagagc 60acaggcagag tcgatttacc caaatactta agggccctag aattttcaga atggtaagtg 120agcgctggct tcaacattaa gtcaccagca gcattaaccc ctaacaagag agtcagcctt 180tcccttgaag ttttgaaaca ttgacttctc cactatagct atgaaaatct tagatggtat 240cttcttccaa caggaggcta tttcgtctac attgaaaatc ttgtttagtg tagccacctt 300catcaatgat cttaattaaa tcttctggat aacctgctgc agcttcttca ttagcacttg 360ctgtttctcc ttgcatcttt atgttataaa gacatcttgg cgtgattgag tgaaaatggc 420agataggaag caagactagt ttgtagcttc cacttagaca gacagagcag catgtggaga 480ctcacattgt gaactttggc tcccagaact actgcaggaa catatcagga aagtcaagag 540aatccacaga ccctttgaaa gaactaggtc actgtgcagc atccctgaga tgcc 594110348DNAHomo sapiens 110tacctttctc tctggctgcc cttaacgttt tttccttcat ttcaactttg gtgaatctga 60gaatgatgtg tcttggagtt gctcttctcg aggagtatct ttgtggcgtt ctgtgtattt 120cctgaatctg aacgttggcc tgccttgtta gattggggaa gttctcctgg gtaatatcct 180gcagagtgtt ttccaacttg attccattct ccccgtcact ttcaggtaca ccaatccgac 240gtagatttgg tcttttcaca tagtcccata tttcttggag gctttgccca tttcttttta 300ttcttttttt ctctaaactt cccttctctc ttcatttcat tcatttcc 348111170DNAHomo sapiens 111aatgtttatc tgtttagcaa ctgctggata aacatctgga ttgaggtcaa ttctctgtaa 60gtatgtcact cctgtgccac atgatgtgtt gatgatttaa tgcaagcttg tttcacccgc 120ggcccaacac agattcataa gctttcttaa aacagtatga gttcctttgc 170112274DNAHomo sapiens 112agtaagcaac agagatccaa tggaaaaata tcttatgagt acacagaaag agattggttt 60gatcaggaac acagaaaatc ccaaagagcc tatgtaaaaa caagaaagaa tgcagttggc 120taccactaga tggagcccgt atttaatgcc ttaatccaca tgtattatgg gtgagccaaa 180taaaaaagat ggcaatccct ttgttatcac aggatacagc cacatgtcag gatgaacagg 240caggtactat tgcaattatg aaagcagaaa aaag 274113327DNAHomo sapiensmodified_base(172)..(172)a, c, g, t, unknown or other 113tacccttcta taagaggtta tataatatga gacttgagaa agggcaggat ttatataggc 60agaaagaggg cactgcaagg gatcatgggt aggaatttga atgcaagtga tagcttcaga 120gttgtgacgt gtgtggatgt gggtgtgtgg gttatgagga tgaggaaagg cngacnaggc 180cntctgccng agcatcagag tagcagccaa tggcatttct agggtctctt ggaggaagga 240gctggcatct gagctacctc gggctccagc tcagctaagg caggaagctg caattctgag 300gggggtcatt gaaaggagcc cgcgcga 327114206DNAHomo sapiens 114atgctttatc cagttgcagt gccttcaata agatttttat tccttttaga cacacatatc 60actaaagggc agttgtactt cccatattct ctagcctttg ttattatttt ttcttaaaat 120ttgcacctgg gaattaaagg ctaggagtcc ttggcttaag tctgctgcac agaaggaatc 180ttttaaaaat gtaagtgatc tattag 206115139DNAHomo sapiens 115cccaaccaag acatgccatt cccagataac ctcctctcca ccagagagat gtcagcccca 60agataacctt ccttctgacc agagacattc caaccctgca ataaacttct cctccacaca 120gaaactttcc aagcctgtg 139116236DNAHomo sapiens 116actcttggct gctctgcaag actgagcccc atgaaggagc cacgtgcggc gtggaaagag 60tgctgagttc aaattgtagc cctgccacta atttgctggg ccagtcactt aatcatctga 120agtcacaagt acctcatcag aaaagtggtc ccagctcttc ctgctgtgga aggatcagaa 180gagaggaggc acgacagaga cctagtgaac tccgaagccc gagtgctaaa tatttg 236117441DNAHomo sapiens 117atcagataaa atgcaggtta agtatgagca catcatcccc caattttttc atctataggc 60taacatccca atttatatta aggattccat tttctttctc ttcctgcccc agttgggtct 120ttctgtggct ccagccttgc cagattgagc cgggactgtc ctgctctgct gctcctgtgc 180tcacaggagc tgtgaactac gaaatgttca ctgttttaag ccactgagct ccgtagtaat 240ttgttctaca ccaacagtca acacacacac actaccagac tctatctgtc gactgtttgt 300gtcctctggg atgcaggcat tcttcctgtt ttattacaca ctgctgcagg cctaggactc 360tacaggtctg taatggggcc tggcccaaac tagctgttga gtgacgatgg gggctaaaat 420tatacttgcg tgtattgaaa c 441118256DNAHomo sapiens 118aatgcatggg acacaccaag ggtagtggta ggcacatggt cagtgttcgg tgaaagtggc 60tttttaccac cacgatgatt gctgctcttg ttaggcagca cacattcacc tggtggcggg 120agcctgtagt gtcacaagga aagcaacact cagcgttcac ataaggtctc tactgcttct 180tagctaaggg acttgggaaa tcactccttc tctctggcca cagtttaccc tcctataaag 240tggggataat gctact 256119110DNAHomo sapiens 119aaaattctga atgtggacct gcaccttgct attttttccc ccacttggat cttctttggt 60gtgtatgtga ctgtgtttat atgtgtctcc tatgtgtcca tcttgttttt 110120124DNAHomo sapiens 120cccgatctct gggaaatagg gctctagcgg gagctgtgag gctctgtccc cagtcaaggt 60cctggctaac atttttcctg gcaacttagg gatacagttg ggattttgtg gactatagca 120gtgg 124121103DNAHomo sapiens 121cctattttcc tacattggac tgtgctcctc catcaagaaa ctgtttctta tacttggttc 60ataggatcta gcacaaaact aaacatgtgg ttggggctca gtt 10312288DNAHomo sapiens 122ctttatttta acaacccaac aacagtgaat tggaaaggat ctaataacag aacagaattt 60gtagtcagac aactttgttt tgaaacta 88123231DNAHomo sapiens 123acgttgacag ttttacatgt tctaataact cggaacagat gggacaagac ctgatgtgga 60gaagtggggg tgatataatt accctgtatt acccccctta aatccattca cttgcactca 120tcttaatgag caatcattaa aggagacagc actaaatatt cttgaggtaa ctgacaggcg 180gaaagagttg cttatttata ttcaaatcat ttagctcctc aaaagaaagt g 231124706DNAHomo sapiens 124cttggtagtt cctcgcaaat tgaacacaga gttaccacat gacccaacaa ttccactcct 60agccgtatat ccaagagaaa tgaaaacata tgtccacgca gaaactggta cacaaatgtt 120cacagcagct ttatttgtca tggccaaaac ctggtaacaa cccaaatgtc catcaacagg 180tattcaacag gtattgtggt ccacccatac aatgggatcc taccaacaat aaaaaaaaat 240ggagtactga tatgcacaaa aacacctgat gaaaaaagaa ttgtgctgag tgaaagaggc 300cagacataca ctgtatgagt ccatttctat ggaattctag aaaatgggaa ttaatctata 360gtgacagcaa gccaagcagt ggcggtgggg atgggggaca gtgaggacga attctctaga 420tatcaagctt gaattcgttc aaagtactat aagtcctagc aagagaaatt agaaaagaaa 480aggacataaa aggcatccaa attggaaagg aagaattttt ccagttctgt gaagaaagtc 540attggtagct tgatggggat ggcactgaat ctataaatta ccttgggcag tatggccatt 600ttcacaatat tgattcttcc tacccatgag catggaatgt ttttccattt gtttgtatcc 660tcttttattt cattgagcag tggtttgtag ttctccttga agaaga 706125198DNAHomo sapiens 125aatgattctg tctagtttct atttgaagat atttcctttt ctactgttgg catcaaatcg 60cttgaaatct ccacttgcaa attccacaaa aagagtgttt caaatctgct ctgtgcaaag 120ggacgttcca ctctgtgagt tgaatacaca cagcacaaag aagttactga gaattcttct 180gtctagcatg aaatgaag 198126265DNAHomo sapiens 126agctttatag tcactatatt agtggattgc cctctgtgga tctgatagca attttttaaa 60tgattcacgt ttcaacttgt taaacctttc ccattcctca ggccaggttt accccacgat 120ggacttaaaa ataagcttgt cttgctacca ggaagatttt ccaccaggag cctgcataat 180tggcccttcc cattccaaga tgcagaaggt agaataggaa acaaaagtgc tggtcctttc 240tctcaagtac cagccaggac tataa 265127345DNAHomo sapiens 127agcctctgtc tgctctgaag gacccccaga gtgaatagct ttttccaagt gtctcagtac 60acacagggtc attcataaaa aaccaaggtc aacaaacact atccgagcat gtggaaccct 120gtggtttcat gctctaagca cctcacatta tatacaggag aaaacggagg cttcatctcc 180tgtaggccct gtctacacta gggcaggtgg gatggtcata gttccaggtg cccacagagg 240tgggctgcag gaccccagtt ctgtcctttc aaggctgtgc tgggcaaggc cctggcccag 300gcagaaccct gggaagcttg cggattctcc tgcccatcct ctagg 345128307DNAHomo sapiens 128caatgatgaa atcacctgat aatgcatttc tcagaacata gccccatcct tgagtgacgc 60atgactgtat aaaaatacac aggtttcctt gtttctttgg gtcttcattt ctgaaggctc 120ccatgccatg taaaatttac attaagtaaa tctgtatggt tttctcttgt tagtctgtgt 180tttttttata gaagcctcag tcataaacct agcgatgggt gaaaagatat atttttttta 240atcccctaca gaacccacaa aggcttctga gaaagggcag gtgtaccagg gcagaaaaac 300aggagtg 307129509DNAHomo sapiens 129acaggtattt gttatccaga gtttatacat tatgcatggt tcattttcaa agaaatgtgg 60aagagaaggg aacatgtgtg tcctccttag ataagtgaga atattcattc aaaatgagag 120aattaaaata tgtgataatc tctcagcata tggggcagac aggtgtatat ggaccctgga 180tgtgcattac ccaggcaagt aagttgtact tttgtaccca ggcaagtcaa gagtttaggc 240atctcttcct tgccatcagt aataaggccc actggaccca tgggttgacg agggaaatgt 300cagcagttgc aatacacgag ttcagttttt aaccctatga tgatagtaag atagtttttt 360ccccctcatc tctgtctaat aattccacta tctggagtat ctgtgagcct ctttctgttt 420tctatttttc ctgcttactt tcgctcttat tttatttctt gttatgcctg gttatctttg 480attggttgtg agaaactgtc ctcgaaaaa 509130207DNAHomo sapiens 130cccaattgtg gccgggcgca gtggctcatg cctgtaatcc cagcactttc agaggccgag 60gctggcagat cacaaggtca agagatcaag accatcccgc caacatggtg aaaccccatc 120tctactaaaa atacaaaaaa tttagccggg tgtgatggcg ggcgcctgta gtcctagcta 180ctcaggaggc tgaggccaga gaatgga 207131404DNAHomo sapiens 131cggagttgaa cttttctttt gaaagagaag ttttgaaaca ccctttttgt agaatctgca 60aatgggtatg tagcctgctt tgaggccttc attggaaacg ggaatatctt cacataaaac 120tagacagaag cattctcaga aacttcgttg tgatgtgtgc attcaactcc cagagttgaa 180cctctctttt gatagagcag ttctgaaaca atctttttgt ggtatccgga agtggacgtt 240tggagcgatt cgaggcctat ggtgaaaaag gcaatatctt cacctaaaaa ctagacagaa 300gcatcctcag aaactgcttt gtgatatgtg tagtcaactc acggagttga aactttgttt 360tgatgcagca gttttgagac actcttttgt tagaatcttc aaga 404132440DNAHomo sapiens 132gctgaggaca ggaggtcccc ggggaggcag gagggaagcc tgggaaacct gggcagggta 60gaggtcgcag cagagcagga gtgccgcaga tatggccagg ctgggccctg caaggcggga 120aagaggctgg gctggtctgt ggggacacca gccatcagac tcggccagtg agcaccctct 180gtcttccctc caggcgtcct tctggacatc cagcagcact ttggggacga attctctaga 240tatcaagctt gaattcgttc ctcccaccat gattctgagg cctccccagc catgtggaac 300tataagtcca attaaacctc tttttctctc cagtctcagt atgtcttcat cagccagcat 360gaaaacagac taatacaagt agtaaacctg aacagaacaa caccaagtaa caagactgaa 420tcaattttaa taaaaagtct 440133500DNAHomo sapiens 133aacaataatt tcctgttaca ataaccagcc tgtgacccat tgtccatgat tatctcaaaa 60atgtctttaa tggcccggcg tggtggctca cgtctgtaat cccagccctt tgggaggctg 120aggcgagctg attgcttcag gacaggagtt tgagaccagc ctgggcaaca taccaagacc 180tcatctctac aaaaaataca aaaaaattag ctgggcatgg tggcacgtac gacgaattct 240ctagatatca agcttgaatt cgttcctttc ctttgaagga gtagtttgaa aacaatgtat 300ttgtagaatc tgcgaagcca tatttgggag tgctttcagg cctctggtga aaagggaaat 360atcttcagat aaaaactagg cagaagatac ctgtgaaacg gctttttgat gtgtactttc 420atctcagagt taaacctttc ctttgatgga gtagtttgta aacactgttt ttgtataatt 480ggtgaagaga aattttggag 500134538DNAHomo sapiens 134tgctagtttt aagaatggat gtccgaggag ttcctgggct gttgctctct gagagggctc 60cctcaccaac atcaagtcta ggaatccccg gagcactgaa gaaacctgtg aaaacacaca 120gataccaatc tgaggactaa cacagacacc taacccagtc cccaaaatgt tttccccatt 180catcctatca acaacttcaa

attccagaaa gttaccttaa ggagaaagat gttgtgaaag 240caaaagcatg tcttgtcttt gttaacattt cgtgttttcc ttaccttttt caagtgtgaa 300ataataggtg taaatgacag ctcaactaag aatgaaaact tatttactac ataaaataac 360agtggcaatc acagtgataa gagcagctat tacaaaatat ttagtatgtg caggtgctgg 420tcacacgtgc ttgatgaagc atagtataaa cagggagccg ttttattttt ctaacaactg 480caaccacaca ggctctgtgg aacccctttc tttaagagaa acaagcttct gtaaggat 538135234DNAHomo sapiens 135cacggaagag ctggcaggaa ggctggctca gaagtgattg gaatggtctg gagagagagg 60atgagaacag gaggatgtcc cactctccat gggacagaga ggcgctgggg ctctgagagc 120tatgtaggtg gtgaacttga tgccaggccc cagcttggag agtgtacgtg cagccagctg 180cctcctgttg agatttcttg tgcctccttt gcaagctctg gagtctttgg gttc 234136191DNAHomo sapiens 136caatttagtt tctgacaatg cttccatcta gtttttatgt gaagattttc cttttcccca 60caggcctcaa agccctccaa atgtccactt gcagattcta gaaaaagagg gtttcagagc 120tgctctgtca agaggaaagt tcaattcttg aagtggaaca aaaacatcac aaagcagttt 180ctgagaatgc t 191137161DNAHomo sapiens 137tggatgggga ggagctgacg aaggcatttc ggaggaggtg acgtcttacg gggaaatttg 60tgtgttggaa tcaaagtgag ggaagggctt tggggtggag tggccaacag gagctaaggc 120ttggaagcca tagagaatct tatcggcact ctggctgggg a 161138235DNAHomo sapiens 138ggaactctgc ctcccgggtt cacaccatcc tcctgcttca gcctcctgag tagctaggac 60tacaggcgcc caccaccgtg cccggctaat tttttgtatt tttagtagag atggggtttc 120tctgtgttag ccaggatggt ctccatctcc tgaccttgtg atccgcccac ctcagcctcc 180caaagtgctg ggatgacagg cgtgagccac tgcacctggc cagcctgact cattc 235139232DNAHomo sapiens 139atctctgcct cccgggttcc accatcctcc tgcttcagcc tcctgagtag ctaggactac 60aggcgcccac caccgtgccc ggctaatttt ttgtattttt agtagagatg gggtttctct 120gtgttagcca ggatggtctc catctcctga ccttgtgatc cgcccacctc agcctcccaa 180agtgctggga tgacaggcgt gagccactgc acctggccag cctgactcat tc 232140441DNAHomo sapiens 140tacttcatta gaaccccggc aaaaccgatt atacttagag ataggttctg gccaaaaacc 60atctttctgt atgttggtgt ggtgtaacag tcattattac tgtcgagtca ggtgtctgtg 120caaatagtga gcaagcaagg tgctggcttt cctgactgct cctgagctct caagcctttg 180tctttttgtt gttgttgtgg agacggagtc tcattctgtc acccaggctg gagtgcactg 240gcacgatctt gacttactgc aatctctgcc tcctgggttc aagtgatttt cctgcctcag 300cctcccaagt agctgcgatt acaggtgtgc accaccatgc ctggctaatt tttgtatttt 360tagtagagat gggggtttca ccatgttggc caggctggtc ttgaactcct gacctcaagt 420gatccacctg cctcagcctc g 441141393DNAHomo sapiens 141atttgttagc atccacagta cataagaaaa tgttggggca tcaaacatga aacttcatca 60gttaccactg tgtttgccta caagtaaaag aaaaacctca ttatagtggc ttaagcaaag 120agaggttgat ttgttctcat atgaagaagt ctggaagtaa gcagttgtct gcttaggttt 180agtaactcaa agttatcatg acctttctct gtggtttcca gatagctgct tgggctctgt 240attcacagga agaagaagaa aagggaagag attatattat aaatttcaac atgtatctcg 300ttggcaagag ctatgtcaaa gggcacccct aattgcaagg gagaccagga aatcaagact 360tcagctctta cagtcttgac agtagacaca aac 393142234DNAHomo sapiens 142tgggcatgaa caaccacccc acgcccccag gtgttcacgc tgcccaaggt gagtgccaag 60ctgaagttga agctgacggc cctggagggc tcaagagtgc ggcgggtcag cgtggcccac 120ttcggcagtc gtcgagccga ggactacggg gagcaccacc tggcagtcct taccaacctg 180ggcgacatcc aggtggtctc gctgcccctg ctcaagcccc aggtgcgcta cagc 234143169DNAHomo sapiens 143ctgcagtggc atgatctctg ctcactacaa cctccgcctc ccgggctcaa gcaattctcc 60tacctcagcc tcccgagtgg ctgggattat aggcatgcgc cactatgcct ggctaatctt 120tgtatgctta gtagagatgg ggtttcatca tgtcggccag gctggtcta 169144186DNAHomo sapiens 144tgcttgctct atgggcagac tataacacag gaagcccttt tctatgcctt gtgtctcgta 60acctctccag caaccttata agatactcac ctgaggctta cagaggtgaa ggggtttttc 120accttactca tcttgtaagt ggcagactga gaatttaaac tcatttttga gtccaaagtc 180tgtgct 186145317DNAHomo sapiens 145tctgctgcct tctttgaaag gttatatgtg ttgttatttt gagatatgac tataaataca 60ttgacaattt tcctatcaag tagtatcccc tccctttgaa gtttggcaaa ctttgtaact 120gtctcaacta aaagaaggta gtgaaaataa tgcagctaag ttttcaaagc tctgctggaa 180acagagcatg ttctcgctct gtttctcctt ctctctttct gtctcttctt ttcatgtctt 240tttttctgtc actattaccc aacacctcaa caactcagtc agtagtcccc ataacaaatg 300acaatttggt agagaga 317146315DNAHomo sapiens 146agctttttat ttctctgccc gtggctaggc tacaaattta tcaagctttt gcactctgct 60tcctatttga atatgtgttg caactttaag tcatttcttt gcttatgtgt ttgagtgcag 120gttgttagaa gcagccaggc cacttcttga acactttgct gcttagaggt ttcctctacc 180agattcccta aatcatcatt ctttaggtca gacttccata gatccctagg gtgtgaacca 240aatgcagcca agctctctgc taagacgtaa catacttgac ctttgctcta gttcccgata 300agttcctcat ttcca 315147182DNAHomo sapiens 147agcactatag ttgtagcagg aatcttctta ctcatccgct tccaccccct agcagaaaat 60agcccactaa tccaaactct aacactatgc ttaggcgcta tcaccactct gttcgcagca 120gtctgcgccc ttacacaaaa tgacatcaaa aaaatcgtag ccttctccac ttcaagtcaa 180ct 182148507DNAHomo sapiens 148cagctacatc ctaaagacat tcattcctag attatttcaa acagcacaaa atggaagcaa 60caagaagttc caagaagaga aggatttgta ataaaactaa agcacattgg aaatgatatt 120gtaaccatcc aataagttca tttttgccca cggcccggat agagccaatt tgtcaagaca 180ggggaactgc aatagagaaa gagtttaatt catgcagagc catctgaatg ggaaaccagg 240gttttattat tattcaaatc agtctcccca aaaattcaga gactagggtt tttcaaggac 300agtttggcag gtagggggcc agggagtgct aattggttgg atcagagatg agatcataga 360gagtctgagg gtacatagct aggaagaggc ggctctggga tttgaactcc tcttctctga 420gaggatgcgt catctgcctt gctcgtgcag cctcccctgc aggcttcagc agagcgggtg 480gggccgatga ctgctgtact ggaaggg 507149466DNAHomo sapiens 149aggattgtag gagttgtatg ccaggaaatg gggatgaaga ctgtgaaagg aaaataaatc 60ttggggcccc caaattacta aactaaaggg aaaagtcaag ctgggaactg cttaaggcct 120atctgcctcc cattctattc aaagtcaccc ctctgctcac tgagagaaat gcatatctga 180ttgcttcctt tgcagaggct aatcagaaac tcaaaagaat gcagccattt gtctcttatc 240tacctatggc ttagaagccc ctcccctccc tacttcacat cttcccacct ttgcttctag 300ttgtcccgcc tttccagacc aaaccaatat tcatcttaca tatatttgat tgatgtctca 360tatctcccta aaatgtatga aaccaaactg tgttctaacc accttgggca catgtcatca 420gaacctcctg aggctgtatc atgggcgcac atcttcaaca ctggga 466150333DNAHomo sapiens 150cagcctgggt gacagagtga gactctgtct cacttaagag tgtgcccacc tttatcctaa 60gtgatgtgag ctaagctgct ccatgcccca gtctttctgg gataaactca gatttcactt 120taaaaaagag acagaatggc tttttggtga gtaacgcacc aatttgctga ggaactcacc 180tctattacag acttttgtat ccgaacagtg agatttccat aaagataaaa gactggcttt 240tctttttcca cccccacaat gccacaggaa aggagctctt aaagcctaat gtgaaattat 300ccagggaatc acctttcctg caggaaggaa gac 333151433DNAHomo sapiens 151tcttccctcc caggcttaat catattttgg aacgggtgag gtcttttgtt gggtgggcac 60cccctgattg cttgtctgtt tattttttaa tgtgcaacta atttgatttg aatttccttc 120agtttccagg ccttcctagg gaaagctaag ggagagggaa tatgcttttt aaaaatcgtt 180ttctttcttt ctttctttct ttctttcttt ctttcttttt ctttctttct ataattcctt 240acagttctgc tatataggtt ataagaactg ttctcatttg gccctcacaa agtccctgag 300gtaggccagt gttgttttcc ccacaaggtg gcagactcgg tttggcatac aaaatacaca 360gtacactcat ctctgtcctc ccacagttta caatcatggt aagttacact acacaagaca 420atatggccaa gtg 433152417DNAHomo sapiens 152tgccgggccc cagccaggcc tgtcccctcc cgctggcccc gggctcgcgg gtgacctctg 60agcctcagct ccccgccacg cttggcggtg tgccccccgg aaaaatcaca cacacatttc 120cttccaccca ggaacatgag gagccatctc cctagaacct ccagggcctc tctttgagcc 180tcagtttacc cagatgcaca gtgagattgc tggacaaaac tttcatgaaa cccatactcc 240gtgctgttct gcctgggagc agccagggct gaccttggtg gaaactcaag gaggggctcc 300caagtttggg aggaggggga gacagcccag ctctctcaga acccctgtgg tcggggttgg 360ggttagggag gatcagagct gggggtggga gtgggggcag gctcagccag gatttag 417153563DNAHomo sapiens 153aagaaacaaa aagattcctg tatagctgta taatgagttt gtgttttaag ctaagtttta 60ttacataaga gtcaaaattt ttttaaatta aagtttatga agttaaaaag ctaccatagg 120ctgtttatta tcggagaaag aaaaaacaat tttaataaat gtagtatagc ctaagtgtac 180agtgtttaca aagttgacag tagggtacag taacttcctg agccatcact ttcactgcca 240aatcactcac tgactcaccc agagcagcct ccagtcctgt gagcaccatt cattcaacaa 300tggtacacct gtacaccact gtacaccact acaggccagg tacggtggct cacgcctgta 360atcccagcaa tgggaggctg aggtgggtgg atcacaaggt caggagatcg agaccatctt 420ggctaacatg gtgaaacacc gtctctacta aaaatttttt taaaaaatta gccgggtgtg 480gtgacatgcg cctgtagtcc cagctactcg ggagtctgag acaggagaat cactaaaacc 540tgaaaggcag aggttgcagt gag 563154179DNAHomo sapiens 154tcaatttaga gtcctcctgc tcttttcttt ataatgttcc attgtcgcat gctacagtat 60ttataataat ttgaaattat atctgtatgt tcatgtgttt gatgtctgtt ttctcaacct 120gactgacaat tctatttgtt ttgttcacca acttacacct aatatttgga catggtctg 179155130DNAHomo sapiens 155ggtgactgta atcctagcta cttgggaggc tgaggcagga gaatcacttg aactcgggag 60acagagattg cagtgagcca agatcacgcc actgcactcc agcctgggca acagagcgag 120actcggtctc 130156227DNAHomo sapiens 156cgttgggata caagtgtgag ccactgtgcc cagccttccc ctctcttttc actttattta 60gtcctaaagg agagaggatg tcactgttgt catgagctgt atgtagacca cgcccctttc 120taggacaagg cttgagggat aaacccccag tggggagtgt gttccctgag gccctggtct 180gtgtctttaa tcatattggg tttttactgg cagatccacg tggtaac 227157238DNAHomo sapiens 157ccacatcttc tgactccggt ttcatagatt tcctgtagaa tatatcataa attttagttg 60aacaaacaca gtcttctgcc tggaattttg tctgttgtcc tggtgctcct ggcgtgctga 120aggacttgtt agatcattgt cctatgtgtc attctgtaca acgccaagaa attattatca 180taggaagcta aatcaaaaga aatcgtagca gtgcttcatg gtggggctgc tctggaag 238158236DNAHomo sapiens 158atcccttaat tctttccgcc tgggattcaa ttgcgccaag aggactaatt gtgctaaagc 60tataaaagtg tgctttgctc tcagtaacga cacaagctgg atgttgttag tgtgtcccgg 120aaggaggtta ctcaggtgta atctgggtta ggctttaggt ggaattcatc ctcagagttg 180gtcactccct ggtcgagcac gaggtaatat aaaatgcttc gcgtttttaa catgac 236159136DNAHomo sapiens 159agtagccatg tcctacttct ctcccaccta cagtgtcctg cagatgacag tgggagtgcc 60acaaggatgg gtgaatggag cagcatacag ggctgataat tacaaatggc ccaacaagga 120ggtggccacg tgtgct 136160248DNAHomo sapiens 160aagtagcttg ttatacagca gtaatgacta aaacacttat tatcactacc accaccacac 60tggtattacc tgttaaacat aaacacagct gcacagtagt taaagtggtg aaaacagatt 120ttactggcca agggccttgg ctcatgcctg taatcctggc actttgggag gctgagacag 180gaggattgct tgaggccagg agtttgagac caacctgggc aacacagtga gacccttgtc 240tctacaag 248161186DNAHomo sapiens 161cccacgcgcc cccgcaagct caggtctcca gcgaaagctg agtaactgag ccgggggaac 60accaggagag agaacggggt gcgggaatgg agtcatactg aggacccaga gtacaagaaa 120agagatccag agtgacagga gagagtgtga gtggtgagca gagtcacagt gaaggtctca 180gggggc 186162232DNAHomo sapiens 162atctctgcct cccgggttcc accatcctcc tgcttcagcc tcctgagtag ctaggactac 60aggcgcccac caccgtgccc ggctaatttt ttgtattttt agtagagatg gggtttctct 120gtgttagcca ggatggtctc catctcctga ccttgtgatc cgcccacctc agcctcccaa 180agtgctggga tgacaggcgt gagccactgc acctggccag cctgactcat tc 232163457DNAHomo sapiens 163tctatgaaaa gaaagttaaa ctctgtgagt tgaacgcaca catcacaaag gagtttctga 60gaatcattct gtctagtctt tatacgaaga tatttccttt ctaccattga cctcaaagcg 120gctgaaatct ccacttgcaa attccacaaa aagagtgttt caagtctgct ctgtgtaaag 180gatcgttcaa ctctgtgagt tgaatacaca caacacaagg aagttactga gaattcttct 240gtctagcaga gatcacctga ggtcaggagt tcgagaccag cctggccaat atggtgaaac 300cccgtctcta ctaaaaatac aaaaaagtag ccaggcatgg tggcacgcgc ctgtagtatt 360ggctaactcg ggaggctgaa gcaggagaat cgcttgaacc cgagaagcag aggttgcagt 420gagccgagat agtgccactg tactccagcc tggggac 457164588DNAHomo sapiens 164agcacagtta gcactagatt tccttccttt tctcctcctt tgatttctta aagaaaagaa 60aatgtttatc atcattagat aattactctg tggacatatt agttttatta gcaacaatga 120agtcttctct atattttatt gccatattga cttcttttca gaagcaaaaa tatgcttctt 180ggatttggtt aaaatccagt catagatccc acacacgctc aaagggaagg gcccacaaaa 240ggccagggat gccagaagat gggatcatgg ggacgcccat gagcctagag tctgtctgcc 300acaacttgag aaagctttcc tccattgaag agaataaaac tgttagccac tggttcaagt 360agcttgctat ttcatgtata tattcttagt ccattggagt cttagtctga gctactataa 420cagaataccc gagactgggt aatttataaa caatagacat ttcttttctc atggttctgg 480aggctgggaa gtccaagagc aaggcgccag caggttccat tgtctggcaa gggctgatct 540ttgcatctaa cacagtgcct tgagcactgc atcctccaga ggaaagga 588165128DNAHomo sapiens 165ggcagtggta tagattcttt tctgtttaat ttgtacagca ggtgcttgcg ctggtaggta 60ccagtgcagg ttgtaccctt ttctatggga acctggataa gtttccaggc aaggcttcat 120agacagct 128166316DNAHomo sapiens 166taacttttat atgcaccaaa aagttgtgtg actcacttta tagcgatatt caccttattg 60taatggtctg gaaccaaacc cacaatatct ctgagttgct cctttatttt agaggcattt 120aatcagcata tattgtatgc ttacagggtc agctatagcc acataattta tgaaaaacca 180atatgcaggg ctgtgtattc agaaattatt aagaatttca agacaatgac agcagaacat 240taaaccattt tgaggccctg tgtgaatgca taggtttcaa gaccatgaaa ccagctttgt 300gtccttagaa ctgtgg 316167402DNAHomo sapiens 167atgcttcatc cttttcagtc agctgctaac aagaatgcat taaatccaca ctggaggatg 60ggggattttc aagatctctt attaagtggt aagagcaaac tgcagagaaa tgtgcataat 120aaaacagtga ctgaacttct ctctgtctct gtgtatttgt atatgattat atgagcataa 180aggaagtatg gaatgatacg taccaggctg tcaccactgt gttcttggga tgggatggcc 240atgagcagat aaacaatgga aaaaaaaaat cttcactgca aaatgactca tgcgaacggt 300aacatgtata acattttaat ctcatttatt taattacagg ttaagatgta tatctctgta 360tagctatgtg tgtgcataca tagacacaca gacacatata ct 402168430DNAHomo sapiens 168aaaagaggtt cctaggatga gctgcatcag aatcacctat ggtaattatt taaaaagcaa 60actgatggcc tctatcccag atcaactaaa tccaaatttc tagtagatgg gacccaggaa 120tctgtatgtt agtggtccat gacctagttg attcctttta gaaacaaagt taggagaatt 180cacatccgtt ggcccctatg gagacaacaa aactgactcc ttgcccaacc accattatga 240ctaagcatat aaagtcgcac cattggagag gaaaaacaaa aatctttaca accctgagat 300aagctaaaaa tgaggaagaa gattctacct agtcttccaa atcaatgaag ccttgagccc 360tttcctataa attgctaact ctctaatgta aacaacttca tccctgactt ttgcaacact 420gacacctaca 430169227DNAHomo sapiens 169ctttcttggc agtggccatg ggcccagcaa aacagacctc tgaaaggcga gcagattaat 60cattttgaag gcatgctcgc ctcaacagtt cccctgcagg atgtcggaga accggagaga 120ggggactgct gtagttcaca aggggcacag ggaaatgcct gaagactcac aaaaacaagg 180gggtgaacaa cagaaaaaga atgagtgctt ttaaattgta catgctg 22717093DNAHomo sapiens 170gagactcgct tgaaccgggg aggcggaggt tgcagtgagc cgagatcatg ccaccgcgct 60ccagtctggc gacagagtga gactccgtct tgg 93171472DNAHomo sapiens 171taattattgt tgttattaat ctctctatgc ctgatagcaa aagtgtttta tgaggaaagt 60gtataccata ttaaaaatgt aggaggaaag cgaaggatcc gagttcagga caaactctta 120gagtgttttt ttcttcttct tcaattatgc ctccttatgt tttcatcaga tgagaatgac 180taggacaatt taagtaaaat tgataaggaa tatcagggaa aaatgtgtgt aggagcaagt 240cacagatgta tctgttggtg agttaaaaat caacacgaac aatgagaact tcgtgacaaa 300atctaccaat ctattatctt gcacaactgt tgatagtgaa ctttataata agaggtcatt 360ccagtggtta taaagcccag tctcctcatt ctacaggaaa aacagaggta tggagaagat 420caatgactga atttacatgt cttgtgacag gattggaact tgtagccagg ac 472172196DNAHomo sapiens 172atgtgggggc ctcatgttcc cagagagaca ctaaagcttt gctgactggt ctcctcatcc 60tgggtcagga cgagtgtttt cttctctgtg gatagggcag gagaagttca cctttatgct 120gccatatgtg aattctgggt taacaaggtc acctcctcct caggctgtgg ttttcaggct 180gtttcaacag gttgga 196173444DNAHomo sapiens 173tttgcaaaca tgcattcgac aaaagtctaa tatccagaat ccaaaaagaa cttagaaaaa 60tcaacaagca aaaacctaac aaccccatta aatgggcaaa ggagaggacc agacacttct 120caaaagaaga caaacacgta gtcaacaagt atatggaaaa atattcaaca tcaccccagc 180agcagagcgg gtgctcacgt caaccacgtt cttcctacaa atggcctagg tgcagggacc 240gacctgacca ctagagaaag tgtcactgtg gcaagggaac ttcaccagcc aagggccaac 300cttgccagcc ggtggcctca ggcctgctgg ttactctctt ttgcaaaggg gtcttggttc 360ttgtgagtgg gaccattggg tcaaagggca gggaggtttc tgtggttctc attcggtcct 420gcttctgccc tccagacaga tgga 444174175DNAHomo sapiens 174aacagaatct tcaaggttga gatgaaactc catcatactt actagcaata acctctagca 60aagttgaggt ggtctgtttt ggctaaataa aatggacata gcattgctgg gcccctgtga 120agggctggaa gcagggaaat gtcagcagtg gcaagcgtgc cctctgggga gtagg 175175186DNAHomo sapiens 175cccacgcgcc cccgcaagct caggtctcca gcgaaagctg agtaactgag ccgggggaac 60accaggagag agaacggggt gcgggaatgg agtcatactg aggacccaga gtacaagaaa 120agagatccag agtgacagga gagagtgtga gtggtgagca gagtcacagt gaaggtctca 180gggggc 186176405DNAHomo sapiens 176caggagccct tcaggtcaca aaggaaaaat cccgctctat gaccaccatc tcatttacct 60taaactagct actctttggg agaatgattc aactgatttt gactgttctc aggggtagac 120ttgtgaagtt gtccagtgat gttgagaaca tatacttttc atcctatcaa aagctatttt 180cttaagtcaa ttcaggcttc tataacaaag taccatacac tgggtggctt ataaacaaca 240gaaacttact tctcacagtt ttggaggctg gaagtcaaag atcagggaac cagcttggtt 300gggttctgtg agggccctct tcagggttgt aaactgtctt ctcattgtat tcacatgata 360gaaagagggt gaggagagct ctctgggatc ccttttataa gggca 405

Methods of detecting and treatment of cancers using Scutellaria barbata extract

Raktažodžiai

lactate dehydrogenase

krūties vėžys

vėžys

kalpokė

scutellaria barbata

priešgrybeliniai

Patentų informacija

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Pretenzijos

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