Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) on antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil (ftorafur, FT) and a mixture of FT and uracil (UFT) were determined in nude mice bearing human ovarian carcinoma (KF cells). All nude mice developed palpable tumor 17 days after KF cell inoculation unless treated. A combination of UFT and calmodulin antagonists (W-5 and W-7) resulted in a delay in tumor formation in nude mice. One of 10 nude mice treated with a combination of UFT and W-5 and 3 of 10 nude mice treated with UFT and W-7 did not develop tumors during the experimental period. Tumor volumes in groups treated with the combinations of UFT and calmodulin antagonists were significantly smaller than those in the untreated group after 31 days of tumor inoculation. In addition, tumor volumes in a group treated with UFT plus W-7 were significantly smaller than not only those in the untreated group but also those in groups treated with UFT alone, FT alone, W-5 alone, or W-7 alone. The longest median survival time was also observed in the group treated with UFT plus W-7. 5-Fluorouracil (5-FU) content of the tumors of groups treated with FT plus W-5 or W-7 was similar to that of the group treated with FT alone. On the other hand, 5-FU content of a group treated with UFT plus W-7 was about twofold higher than that of a group treated with UFT alone. These results suggest that a synergistic effect of W-7 and UFT on inhibition of tumor growth and prolongation of survival time may result from accumulation of 5-FU in the tumor.
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PMID:Adjuvant effects of calmodulin antagonists on antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil (ftorafur) and a mixture of ftorafur and uracil (UFT) in nude mice bearing human ovarian carcinomas. 250 1

The effect of calmodulin antagonists (W-5 and W-7) on antitumor activity of 1-(2-Tetrahydrofuryl)-5-fluorouracil (Tegafur; FT) and FT plus uracil (UFT) was examined by using nude mice bearing human ovarian carcinoma (KF cells). All nude mice developed a palpable tumor 17 days after KF cell inoculation unless treatment was done. A combination of UFT and calmodulin antagonists (W-5 or W-7) resulted in a delay in tumor formation in nude mice. One of 10 nude mice treated with a combination of UFT and W-5 and 3 of 10 nude mice treated with UFT and W-7 did not develop tumors during the experimental period. Tumor volume in the treatment groups combined with calmodulin antagonists was significantly less than in those in the untreated group after 31 days of tumor inoculation. In addition, tumor volume in a UFT plus W-7 treated group was significantly less than those not only in the untreated group but also in the UFT alone, FT alone, W-5 alone and W-7 alone treated groups, suggesting a synergistic inhibitory effect on tumor growth. The longest median survival time was also observed in a UFT plus W-7 treated group. 5-Fluorouracil (5-FU) content in the tumor of groups treated with FT plus W-5 or W-7 was similar to that in a group treated with FT alone. On the other hand, that of a group treated with UFT plus W-7 was about 2-fold higher than that of a UFT -only treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of calmodulin antagonists (W-5 and W-7) on antitumor activity of Tegafur and UFT (Tegafur plus uracil)]. 313 62

The present study was designed to potentiate antineoplastic effects of cisplatin by combination with a calmodulin antagonist (W-7) using nude mice bearing human ovarian carcinoma. Tumor growth in nude mice treated with W-7 after (but not before) administration of cisplatin was significantly inhibited. Although treatment with cisplatin alone markedly inhibited lytic activity of the spleen cells in tumor-bearing nude mice against the tumor cells, the inhibitory effect was eliminated by subsequent treatment with W-7. There was no significant difference in the survival time between untreated and cisplatin-treated groups. Only when cisplatin was followed by W-7 was a significant enhancement by W-7 of the antitumor effect of cisplatin observed with respect to inhibition of the tumor growth as well as prolongation of the survival time.
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PMID:Enhancement of antineoplastic effects of cisplatin by a calmodulin antagonist (W-7) in nude mice bearing human ovarian carcinoma. 318 Jan 42

The present study was designed to potentiate the antitumor effects of cisplatin by combination with calmodulin antagonists (W-7 and W-5) by using nude mice bearing human ovarian carcinoma. Tumor growth in nude mice treated with W-7 or W-5 combined with cisplatin was significantly inhibited, compared to that in nude mice treated with W-7 alone, W-5 alone or cisplatin alone. Although treatment with cisplatin alone markedly inhibited lytic activity of the spleen cells from tumor bearing nude mice against the tumor cells, the inhibitory effect was eliminated by combination with W-7 or W-5. There was no significant difference in the survival time among untreated, cisplatin-treated, W-7-treated and W-5-treated groups. Only when cisplatin was followed by W-7 or W-5, a significant enhancement by W-7 or W-5 of the antitumor effect of cisplatin was observed with respect to inhibition of the tumor growth as well as prolongation of the survival time.
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PMID:[Potentiation of the antitumor effect of cisplatin by calmodulin antagonists (W-7 and W-5) in nude mice bearing human ovarian carcinoma]. 335 66

Oncogenes, onc-gene products and the concept of autonomous self-stimulation of tumor growth by autocrine production of growth factors are discussed with regard to the development of new antitumor agents. The significance of the plasma membrane as an attractive target in tumor chemotherapy is emphasized. Membrane bound enzymes and related reactions which are involved in growth factor dependent regulation of cell proliferation offer new targets for antitumor chemotherapy. Examples demonstrating the antiproliferative effects of phospholipase-C and calmodulin inhibitors are presented. A synergistic effect of these drugs with alkylating agents is observed. Studies devoted to the improvement of alkylating antitumor agents have also led to the plasma-membrane as a particularly suited target. The same may be true for other antitumor agents like anthracyclines and platinum complexes for which evidence exists implicating the involvement of cellular membranes in the mechanism of cytotoxic action.
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PMID:[Tumor biochemistry as basis for advances in tumor chemotherapy]. 348 47

The present study was designed to potentiate the antineoplastic effects of cisplatin by combination with calmodulin antagonists [N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5)] in nude mice bearing human ovarian carcinoma. Tumor growth of nude mice treated with W-7 or W-5 combined with cisplatin was significantly inhibited, compared to that of nude mice treated with W-7 alone, W-5 alone, or cisplatin alone. Although treatment with cisplatin alone markedly inhibited lytic activity of spleen cells from tumor-bearing nude mice against the tumor cells, the inhibitory effect was eliminated by combination with W-7 or W-5. There was no significant difference in survival time among untreated, cisplatin-treated, W-7-treated, and W-5-treated groups. Only when cisplatin was followed by W-7 or W-5 was a significant enhancement by W-7 or W-5 of the antitumor effect of cisplatin observed with respect to inhibition of tumor growth as well as prolongation of survival time.
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PMID:Enhancement of antineoplastic effects of cisplatin by calmodulin antagonists in nude mice bearing human ovarian carcinoma. 367 86

Based on our in vivo observation that growth of VX2 carcinoma transplanted in rabbits paralleled development of hypercalcemia, we studied the regulation of VX2 tumor growth using a clonal cell line isolated from VX2 tumor (VX2-L). VX2-L cell growth was dependent on prostaglandins released by the cultured cells into the medium, since indomethacin suppressed VX2-L growth, and prostaglandins A2, E1, E2, F1 alpha, and F2 alpha stimulated VX2-L proliferation. In contrast, prostaglandins D2 and I2 inhibited VX2-L proliferation. In contrast to previous reports, increases in extracellular calcium concentration promoted VX2-L growth not only directly but indirectly through augmentation of prostaglandin E synthesis. Antagonists of the intracellular calcium binding protein calmodulin inhibited cell replication. Increases in extracellular calcium also stimulated production of a nonprostaglandin macromolecular bone-resorbing factor. This factor may account for the hypercalcemia which we were unable to block by indomethacin. These results suggest a close relationship between VX2-L growth, prostaglandin production, and hypercalcemia. It is proposed that calcium blockers and anticalmodulin drugs might be powerful anticancer and/or antihypercalcemic agents for malignant cells such as VX2-L.
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PMID:Control of VX2 carcinoma cell growth in culture by calcium, calmodulin, and prostaglandins. 391 74

Nodules of tumor cells have been isolated from 7, 12-dimethylbenz (alpha)anthracene-induced rat mammary tumors. These nodules consist of at least two cell populations which can be subfractionated by selective attachment in calcium-free medium. One cell population which attaches in the absence of calcium (basal cells) stains intensively with antibodies against type IV collagen and also with antibodies against keratin. The nonattaching population, the epithelial cells, stains much more weakly with either antibody. Biochemical analyses indicate that 27% of the protein labeled in basal cell culture is type IV collagen, while 8% is keratin. With epithelial cells, only 0.35% of the protein made is collagen, and only 2.4% is keratin. Basal cells contain about 2 times as much calmodulin as epithelial cells but only about one-tenth as many estrogen receptors. In culture, the basal cells stimulate the attachment and/or division of the epithelial cell population. The epithelial cells have little effect on the division or attachment of the basal cells. Interaction between the two cell populations may be important for tumor growth in vivo.
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PMID:Characterization of rat mammary tumor cell populations. 620 5

Calmodulin is a ubiquitous intracellular calcium binding protein which has been shown to be associated with cell cycling. Previous studies using animal tumor models have suggested a positive correlation between tumor calmodulin content and rate of tumor growth. We studied the role of calmodulin in renal cell carcinoma (RCC) cell lines and compared this with short term normal fetal kidney cell lines. The effects of calmodulin inhibition was determined using the calmodulin inhibitor W13 (Naphthalene-sulfonamide) and its less active partner W12. Cell size, calmodulin content and inhibition studies using W13 did not reveal any simple correlations for the RCC cell lines, although the RCC lines did have a higher content than the fetal kidney cell lines. Calmodulin content determination of RCC and normal adult kidney tissue failed to show any difference. We conclude that, contrary to previous reports using animal models, there is no simple relationship between tumor growth rates and calmodulin content for human RCC.
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PMID:The role of calmodulin in human renal cell carcinoma. 688 57

The endogenous estrogen metabolite 2-methoxyestradiol (2-MeOE2) suppresses experimental tumor growth in vivo and inhibits angiogenesis activity in vitro. Moreover, 2-MeOE2 has been observed to block mitosis in cell cultures. As high concentrations of 2-MeOE2 prevent microtubule assembly in vitro, the mitotic arrest has been attributed to inhibition of tubulin polymerization. Here we report that concentrations of 2-MeOE2 that cause complete metaphasal arrest do not inhibit the assembly of mitotic spindles. In contrast to the chromosomal dispersal seen in cells arrested by the tubulin depolymerizing drug colcemid, the chromosomes of cells treated with 2-MeOE2 remained in the metaphasal plate indicating a functional defect of the mitotic spindle. The 2-MeOE2 arrest resembles those induced by compounds affecting microtubule dynamics such as taxol and vinblastine. The 2-MeOE2 block is also similar to that induced by several anti-calmodulin agents. Given that metaphase to anaphase transition is a calmodulin-dependent step and our observation that 2-MeOE2 inhibits calmodulin activity in vitro, we suggest that the 2-MeOE2 metaphasal arrest may occur via inhibition of calmodulin.
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PMID:2-Methoxyestradiol arrests cells in mitosis without depolymerizing tubulin. 892 Sep 36


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