Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antineoplaston AS2-1 is a mixture of two products of hydrolysis of Antineoplaston A10 and consists of sodium salts of phenylacetylglutamine and phenylacetic acid in the ratio of 1:4. Antineoplaston AS2-1 injections were administered to 20 patients diagnosed with 21 types of neoplastic diseases. The patients' diagnoses included: lung cancer, stage III, 4 cases; colorectal, stage IV, 3; breast, stage IV, 2; breast in remission, 1; glioblastoma, 3; head and neck, stage IV, 3; uterine cervix, stage IA, 1; chronic myelocytic leukaemia, 2; lymphocytic lymphoma, stage IV, 1; and leiomyosarcoma of the uterus, stage IVB, 1. Antineoplaston AS2-1 was administered every 6 h i.v. through subclavian vein catheter. The treatment was administered from 38 to 872 days. The highest dosage taken was 160 mg/kg/24 h. The treatment was associated with minimal side-effects, including slight nausea and vomiting in one patient, mild allergic reaction in the form of maculopapular rash in another patient and moderate elevation of blood pressure in an additional patient. One patient developed febrile reaction and three patients had mild electrolyte imbalance. Only one patient showed slight decrease of WBC. Desirable side-effects included improved healing of chronic atrophic ulceration. The response to the treatment included 6 complete remissions, 2 partial remissions, 7 cases of stabilization and 6 cases of increasing disease. Three patients are alive, well and free from cancer 5 years after the beginning of the study. The hypothetical mechanism of action of Antineoplaston AS2-1 as an anticancer agent is described.
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PMID:Toxicology studies on antineoplaston AS2-1 injections in cancer patients. 374 78

Phenylacetate, a deaminated metabolite of phenylalanine, has been implicated in damage to immature brain in phenylketonuria. Because primary brain tumors are highly reminiscent of the immature central nervous system, these neoplasms should be equally vulnerable. We show here that sodium phenylacetate can induce cytostasis and reversal of malignant properties of cultured human glioblastoma cells, when used at pharmacological concentrations that are well tolerated by children and adults. Treated tumor cells exhibited biochemical alterations similar to those observed in phenylketonuria-like conditions, including selective decline in de novo cholesterol synthesis from mevalonate. Because gliomas, but not mature normal brain cells, are highly dependent on mevalonate for production of sterols and isoprenoids vital for cell growth, sodium phenylacetate would be expected to affect tumor growth in vivo while sparing normal tissues. Systemic treatment of rats bearing intracranial gliomas resulted in significant tumor suppression with no apparent toxicity to the host. The data indicate that phenylacetate, acting through inhibition of protein prenylation and other mechanisms, may offer a safe and effective novel approach to treatment of malignant gliomas and perhaps other neoplasms as well.
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PMID:Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria. 831 77

Malignant gliomas, the most common form of primary brain tumors, are highly dependent on the mevalonate (MVA) pathway for the synthesis of lipid moieties critical to cell replication. Human glioblastoma cells were found to be uniquely vulnerable to growth arrest by lovastatin, a competitive inhibitor of the enzyme regulating MVA synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase. The sodium salt of phenylacetic acid (NaPA), an inhibitor of MVA-pyrophosphate decarboxylase, the enzyme that controls MVA use, acted synergistically with lovastatin to suppress malignant growth. When used at pharmacologically attainable concentrations, the two compounds induced profound cytostasis and loss of malignant properties such as invasiveness and expression of the transforming growth factor-beta 2 gene, coding for a potent immunosuppressive cytokine. Supplementation with exogenous ubiquinone, an end product of the MVA pathway, failed to rescue the cells, suggesting that decreased synthesis of intermediary products are responsible for the antitumor effects observed. In addition to blocking the MVA pathway, lovastatin alone and in combination with NaPA increased the expression of the peroxisome proliferator-activated receptor, a transcription factor implicated in the control of lipid metabolism, cell growth, and differentiation. Our results indicate that targeting lipid metabolism with lovastatin, used alone or in combination with the aromatic fatty acid NaPA, may offer a novel approach to the treatment of malignant gliomas.
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PMID:Lipid metabolism as a target for brain cancer therapy: synergistic activity of lovastatin and sodium phenylacetate against human glioma cells. 859 43

Phenylacetate (PA) inhibits the growth of tumor cells in vitro and in vivo and shows promise as a relatively nontoxic agent for cancer treatment. A recent report shows that prolonged exposure of cells to low concentrations of PA can enhance the radiation response of brain tumor cells in vitro, opening up the possibility of using this drug to improve the radiation therapy of brain tumor patients. We investigated the cytotoxicity produced by sodium phenylacetate (NaPA) alone and in combination with X-rays in SF-767 human glioblastoma cells and in two medulloblastoma cell lines, Masden and Daoy. Exposure of all three cell lines to relatively low concentrations of NaPA for up to 5 days did not enhance the subsequent cell killing produced by X-irradiation. However, enhanced cell killing was achieved by exposing either oxic or hypoxic cells to relatively high drug concentrations ( > 50-70 mM) for 1 h immediately before X-irradiation. Because central nervous system toxicity can occur in humans at serum concentrations of approximately 6 mM PA, translation of these results into clinical trials will likely require local drug-delivery strategies to achieve drug concentrations that can enhance the radiation response. The safety of such an approach with this drug has not been demonstrated.
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PMID:Radiopotentiation of human brain tumor cells by sodium phenylacetate. 1046 69