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While N-phosphonacetyl-L-aspartic acid (PALA), an inhibitor of de novo pyrimidine biosynthesis, demonstrated a unique spectrum of activity during preclinical drug evaluation, multiple clinical trials have shown it to possess minimal clinical activity. One explanation for the disappointing results is
The interaction of analogs of L-aspartic acid with adenylosuccinic acid synthetase, L-asparagine synthetase, and L-aspartic acid transcarbamylase is discussed. Each of these enzymes is of critical importance in the economy of certain types of tumor cells. L-Alanosine, a new antitumor antibiotic, is
Daunorubicin was bound to poly-L-aspartic acid via the methylketone side chain of the drug to avoid reaction of the sugar amino group believed to be essential for optimal drug activity. Attachment of the drug to the polyamino acid by an ester linkage was achieved by nucleophylic substitution
We conducted a multicenter phase II trial in patients with advanced colorectal cancer to investigate the antitumor efficacy of double alternate modulation of high-dose infusional 5-fluorouracil (5FU) (60 mg/kg/48 h = 2400 mg/m(2)/48 h) by interferon alpha-2b (IFN alpha) (10 MU/dose s.c. prior to and
The use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. Polyaspartic acid and polylactic acid are the most intensively studied biodegradable polymers. In the present study, novel amphiphilic biodegradable co-polymer NPs,
OBJECTIVE
To investigate mechanism-directed regimens in maximizing the efficacy of fluorouracil (5-FU) in advanced colorected cancer.
METHODS
Based on promising phase II data, a randomized comparison of various methods for the biochemical modulation of 5-FU was undertaken in patients with advanced
Fifty-two patients with advanced gastrointestinal (GI) malignancies who had not received previous chemotherapy or radiation therapy were randomized to be treated either with 24-hour infusion of weekly fluorouracil (5-FU) or the same plus N-(phosphonacetyl)-L-aspartic acid (PALA). Forty-seven
OBJECTIVE
Several agents have been evaluated for their effect as biochemical modulators of fluorouracil (5-FU) in the treatment of metastatic colorectal carcinoma. In this study, we used folinic acid (FA), N-phosphonacetyl-L-aspartic acid (PALA), and recombinant interferon alfa-2a (IFNalpha-2a) in a
Folate-functionalized copolymers of poly(ethylene glycol) and 2-(diisopropylamino) ethylamine grafted poly(L-aspartic acid) are synthesized. The copolymers can self-assemble into nanoscaled micelles encapsulated with hydrophobic model drug Fluorescein Diacetate (FDA) and MRI diagnostic agents
L-Alanosine, an analog of L-aspartic acid, was investigated as one of a series of chemical compounds that may have inhibitory effects on the repair of potentially lethal damage caused by radiation using an in vivo murine fibrosarcoma (Meth-A tumor) in BALB/cBy male mice. The combined treatment of
Advanced materials that have controllable pH-responsive properties when submerged in the lysosome have a great potential in intracellular drug delivery. We developed novel poly(L-amino acid) nanogels that were prepared by a facile cross-linking of poly[L-aspartic
N-Phosphonacetyl-L-aspartic acid (PALA) resistance may be due to the ability of tumor cells to utilize preformed circulating pyrimidine nucleosides, thereby overcoming the block of de novo pyrimidine biosynthesis which PALA causes. To test this hypothesis we examined the effects of PALA and
The effects of amino acids on the enhanced agglutinability of bladder cells with concanavalin A induced by subcarcinogenic treatment with N-butyl-N-(4-hydroxybutyl)nitrosamine were examined. The amino acids examined were L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-cysteine, L-glutamic
A novel cyclic tetrapeptide containing L-arginine-glycine-L-aspartic acid-L-phenylglycine (cyclo-RGDPhg) was synthesized and found to be a potent inhibitor of platelet aggregation induced by highly metastatic murine squamous cell carcinoma (SCCVII) cells (IC50 = 3.3 microM) as well as ADP (1.5
This study was performed to characterize the transport of the endogenous photosensitizer delta-aminolevulinic acid in tumor cells of the extrahepatic biliary duct. Uptake of [(3)H]delta-aminolevulinic acid into human cholangiocarcinoma SK-ChA-1 cells was linear for up to 10 min, independent of a