Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandins of the A series have been reported to inhibit tumor cell growth and induce tumor cell differentiation by a yet unknown mechanism. We propose that these effects are due to the presence of a reactive alpha, beta-unsaturated carbonyl group (delta 10,11) in the cyclopentane ring of the PGA molecule. PGA was effective whereas PGB (sterically hindered alpha, beta-unsaturated carbonyl at delta 8, 12) and PGA conjugated to glutathione were ineffective. 15-Epi-PGA2 was as effective as PGA2 suggesting that the S absolute configuration of the 15-hydroxyl group is not essential. There was no correlation between generation of cAMP and inhibition of cell proliferation or induction of differentiation by various prostaglandins. The data suggest that PGA's and PGA-like compounds inhibit tumor cell growth and induce differentation because of the chemical reactivity of the alpha, beta-unsaturated carbonyl rather than hormonal activity of the prostanoid nucleus.
 ...
PMID:Requirement of a reactive alpha, beta-unsaturated carbonyl for inhibition of tumor growth and induction of differentiation by "A" series prostaglandins. 403 34

Vitamins, either as coenzymes or hormone-like substances play an important role in the expression of genetic information and in the regulation of cellular metabolism, differentiation, and maturation. Recent epidemiologic evidence suggests that certain forms of cancer are more prevalent among populations with a limited intake of certain nutrients. Other evidence indicates that localized deficiency of a nutrient can occur in hormone-sensitive cells without overt systemic manifestations of deficiency disease. Folic acid, because of its key role in nucleic acid biosynthesis, and vitamin A, because of its role in epithelial maintenance are of particular interest. The recognition of folate-dependent fragile sites on chromosomes suggests that folate and related compounds may play a role in preventing tumor-specific chromosome translocations and the insertion of viral oncogenes. Improved understanding of the role of nutrients in cellular maturation could provide clues for primary cancer prevention and better methods of treatment.
Med Oncol Tumor Pharmacother 1985
PMID:Vitamin deficiency and cancer. 406 3

Folate transport in phenylhydrazine-induced rabbit reticulocytes was studied with the non-metabolized folate-analog, methotrexate. The time-course of methotrexate uptake into a mixed population of reticulocytes and mature erythrocytes is a two-component process consisting of a small, but rapid, initial uptake phase followed by a much slower uptake component which remains essentially constant over the period of observation. The velocity of the latter uptake component is directly proportional to the per cent reticulocytes and appears to represent a unidirectional influx of methotrexate into these cells. Uptake of methotrexate into reticulocytes was found to have the following characteristics: (a) temperature sensitivity, Q(10) of 4; (b) uptake velocity as a function of the extracellular methotrexate concentration approximated Michaelis-Menten kinetics with a maximum transport velocity of 48 pmoles/min per g dry wt; the extracellular methotrexate level at which the uptake velocity was one-half maximum was 1.4 muM; (c) 5-formyltetrahydrofolate markedly inhibited methotrexate uptake but pteroylglutamic acid inhibition was weak; (d) uptake was stimulated in cells preincubated with 5-formyltetrahydrofolate, indicative of hetero-exchange diffusion; (e) uptake was independent of extracellular sodium but was inhibited by anions including nitrate, phosphate, and glucose-6-phosphate; (f) uptake was enhanced by azide plus iodoacetate. These data indicate that folate transport in rabbit reticulocytes is mediated by a carrier mechanism which disappears with reticulocyte maturation. The mechanism of folate transport in rabbit reticulocytes is qualitatively similar to tumor cells previously studied; both appear to have an energy-dependent mechanism limiting folate uptake, and influx in both is inhibited by structurally unrelated inorganic and organic anions. These studies suggest that circulating pteroylglutamic acid is of little importance in meeting the folate requirements of folate-dependent tissues and raise the possibility that clinical conditions associated with alterations in the anionic composition of the blood may be accompanied by impaired utilization of the folates.
 ...
PMID:The mechanism of folate transport in rabbit reticulocytes. 503 20

Polymer polyglycolic acid is biocompatible in the body. A needle-shaped long-acting anti-cancer preparation (F-PGA needle) was prepared by compounding polyglycolic acid and the anti-cancer drug 5-Fluorouracil (5-FU). The release of 5-FU from the needle was maintained for about 10 days, and the needle disappeared after one year. A clinical study with the F-PGA needle was made on patients with terminal carcinomas. Shrinkage of tumors and tumor necrosis were observed in two patients with metastatic liver carcinomas. The F-PGA needle supplies high-dose 5-FU locally for a long time with fewer side effects by embedding it into the tumor tissue. Therefore the F-PGA needle can be said to be promising in the treatment of unresectable cancer as a topical application of chemotherapy.
 ...
PMID:[Studies on the new long-acting anti-cancer preparation, 5-fluorouracil-polyglycolic acid composite]. 608 66

The purpose of these studies was to characterize the effect of the new anticancer preparation, 5-fluorouracil-polyglycolic acid-composite (F-PGA needle), on experimental tumors and in patients with solid tumors. The formative composite in a F-PGA needle was found to easily dissociate in physiologic saline resulting in the release of 5-fluorouracil (5-FU). The aspect of 5-FU release was observed to be relative to 5-FU content in the needle, but not to the length of the needle. When a F-PGA needle of 10mm in length and 30% in 5-FU content was subcutaneously or intrahepatically implanted in healthy rats, the release of 5-FU was maintained for 9 days in each case. Pathophysiologic examination of the liver following the implantation of a F-PGA needle revealed an increase in severe necrosis and/or degeneration and infiltration of small-round cells with the increase in release of 5-FU. Implantation of F-PGA needles into tumor mass of AH 130-bearing rats resulted in an increased 5-FU level in tumor tissue reaching the maximum level of 16.00 +/- 1.98 micrograms/g after 24 hours, and in a marked inhibition of the tumor growth indicating 2.4% of T/C (tested/controlled) at 10 days after implantation of the needle. A study of the F-PGA needle was made for 10 patients with terminal carcinomas and in 5 of these were verifiable. Of these 5 patients, shrinkage of tumors or improvement of symptoms was observed in 3 cases. From these results, the F-PGA needle is promising in the treatment of unresectable cancer as a long-acting chemotherapy.
 ...
PMID:[Studies on the new anticancer preparation, 5-fluorouracil-polyglycolic acid-composite and its therapeutic evaluation]. 609 6

Prostaglandins (PGs) are bioregulatory substances and are widely distributed in a variety of tissues. Numerous facts have been described in relation to cancer biology with PGs. The purpose of our study lies in the creation of anti-tumor PGs. We have described that PGD2 has strong cell growth inhibitory activity; furthermore, we discovered that PGJ2, 9-deoxy-delta 9-PGD2, has 3 times stronger activity than the mother compound, PGD2. In vivo experiments showed that only PGA2 and PGJ2 exert antitumor activity. Thus, cyclopentenone ring structure in PG seems to be an essential moiety for cytotoxicity of PG. On the basis of the above facts, we propose tha name of antineoplastic PGs for PGA and PGJ derivatives which have cyclopentenone ring. Recently, we developed several antineoplastic PGs which showed IC50 value less than 0.3 microgram/ml against L1210 leukemia cells, and these compounds also showed antitumor activity against Ehrlich ascites tumor in vivo comparable to that of cyclophosphamide. The action mechanism seems to be in its alkylation activity of the cyclopentenone structure and not in receptor-cAMP route. Spectrum of anti-tumor activity and its toxicity in vivo are now under investigation. In this brief review, mainly our recent approaches in this field are discussed.
 ...
PMID:[Development of antineoplastic prostaglandins]. 657 12

Thiazolidine-4-carboxylic acid (TC) is a cyclic sulfur amino acid, a condensation product of cysteine and formaldehyde. The chemistry, biological effects and clinical use of TC are reviewed. Extensive animal experiments and studies on human subjects carried out in Europe indicate that a combination of TC and folic acid, 'Folcysteine', has revitalizing effects on age-related biochemical variables of blood and tissues. Further animal studies confirmed the anti-toxic effects of TC, particularly on the liver. The evidence accumulated so far suggests that addition of TC to the diet slows the aging process in mammals and prolongs their life span. On the other hand, findings suggesting that TC caused reverse transformation of tumor cells into normal cells and was effective against human cancers could not be confirmed in additional studies. TC has been clinically used for about 20 yr, mainly in the treatment of liver diseases and related gastrointestinal disturbances. Derivatives of TC with similar applications have been developed. Djenkolic acid is a naturally occurring relative of TC which is abundant in djenkol beans. The toxic effects of djenkolic acid and its possible conversion into TC are discussed.
 ...
PMID:Thiazolidine-4-carboxylic acid, a physiologic sulfhydryl antioxidant with potential value in geriatric medicine. 676 6

The effect of aminohexyl-2-hydroxyethylmethacrylate polymer (HEMA-Hex) with sorbed methotrexate (MTX) or 3',5'-dibromoaminopterin (BrAP) on the survival of C3H mice with Gardner lymphosarcoma was studied. The measured bits of HEMA-Hex-MTX or HEMA-Hex-BrAP were implanted into the solid tumor growing 4 to 8 8 days. The doses of sorbed antimetabolites amounting in MTX 4.3 to 13.5 mg.kg-1 and in BrAP 5.1 and 12.6 mg.kg-1 were calculated from the area of the carrier and mean weight of animals. Following implantation i. p. injections of leucovorin or anhydroleucovorin were applied. The treatment of early tumors showed better results than that of advanced ones if evaluated either as prolonged survival or as a number of mice surviving the observation period. The 18-hr. interval between implantation of HEMA-Hex-MTX and anhydroleucovorin injection was optimum if considered both the protection of mice from lethal MTX toxicity and therapeutic effect measured as prolonged survival. Doses of leucovorin or anhydroleucovorin close to MTX doses in term mg.kg-1 resulted in best results. In case leucovorin was applied to tumor-bearing mice pretreated with HEMA-Hex with nonlethal dose of MTX, the survival of mice was shortened. Folic acid did not show this effect. Intra-tumorous implantation of HEMA-Hex-BrAP toxicity even if applied into an advanced tumor. The therapeutic effect of the sorbed BrAP seemed to decrease with tumor progression at a lower rate than of that the sorbed MTX. The application of anhydroleucovorin after implantation of HEMA-Hex-BrAP shortened the survival of tumor-bearing mice.
 ...
PMID:Localized chemotherapy of Gardner's lymphosarcoma of C3H mice using combinations of carrier-sorbed antifolics and detoxicating tetrahydrofolates. 697 53

Suramin is an experimental anti-neoplastic agent which has shown promising activity against prostatic carcinoma and lymphoma in clinical trials. To elucidate its mechanism of action, suramin was examined for an effect on the transport of folate compounds by tumor cells. Influx of the anti-folate methotrexate via the reduced-folate carrier system of CCRF-CEM cells was found to be highly sensitive to inhibition by suramin but not to various other arylsulfonic acids. Inhibition by suramin was competitive, and the inhibition constant Ki was 1.3 microM, a value 3-fold lower than the Kt for half-maximal influx of methotrexate. Folate binding to the membrane-associated folate-binding protein of KB cells was not affected by suramin. Growth studies revealed that the response of human CCRF-CEM, KB, PC-3 and MCF-7 cells to methotrexate was antagonized from 6- to 17-fold by pharmacological levels (10-200 microM) of suramin. Conversely, growth inhibition was additive or synergistic when suramin was combined with metoprine, a lipophilic anti-folate which enters cells by diffusion. Synergism was observed between metoprine and suramin in CCRF-CEM cells, which take up folate exclusively through the reduced-folate carrier (inhibitable by suramin), whereas additivity was observed for KB cells, which rely largely on the folate-binding protein (unaffected by suramin) for folate import. Our results indicate that inhibition of cellular transport of folate compounds may explain part of the anti-neoplastic effects of suramin on tumor cells.
 ...
PMID:Suramin sodium: pronounced effects on methotrexate transport and anti-folate activity in cultured tumor cells. 779 Jan 20

Both leucovorin (LV) and cisplatin (cis-dichlorodiammine platinum II, CDDP) act as modulators of 5-fluorouracil (5-FUra) by increasing the intracellular concentration of reduced folate. We measured intracellular folate levels following the administration of LV or cisplatin in tumor-bearing rats to determine the optimal schedules for their use as 5-FUra modulators. Donryu rats were inoculated with Yoshida sarcoma cells on the right flank. Seven days after tumor inoculation, the animals were injected with LV or CDDP. The kinetic and dose-related changes in intracellular folate concentration were analyzed by means of a binding assay. Folate levels in the tumor tissues were significantly higher than baseline 1 and 2 h after administration of LV and remained significantly high until 8 h after administration. Folate levels in the tumor tissues were significantly higher than baseline 1 and 2 h after cisplatin administration, then decreased to a rather low level 8 h after, and to a significantly lower level than baseline 24 h after administration. The folate levels in the tumor tissue increased in proportion to the dose of LV, but did not increase when the dose of cisplatin was increased from 1 mg/kg to 8 mg/kg. Repeat high-dose administration of LV and repeat low-dose administration of cisplatin are advocated when they are used as modulators of 5-FUra.
 ...
PMID:Changes in folate concentration in Yoshida sarcoma after administration of leucovorin or cisplatin. 780 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>