Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-fluoro-3,4-dihydro-2,4-dioxo-N-[2-2- (dimethylphenylsilyl)ethylthioethyl]-1(2H)-pyrimidinocarb oxamide (SDK-12B-5), a novel antitumor agent, is covalently linked with 5-fluorouracil (5-FU) and 2-[(2-dimethylphenylsilyl)ethylthio] ethylamine(SDK-103) which possesses itself antitumor activity against murine solid tumors. It has a broad antitumor spectrum in experimental tumor systems including murine leukemias. Furthermore, SDK-12B-5 administered p.o. with various treatment schedules inhibited significantly the tumor growth of human breast cancer (MX-1), colon cancer (Co-4) and lung cancer (LX-1 and OAT) cells in BALB/c nu/nu mice and the chemotherapeutic index was about 10 for 4 different human cancer xenografts. In the Lewis lung carcinoma (LLC) metastasis model, SDK-12B-5 in combination with amputation of tumors inhibited significantly both the lymph node metastases and lung metastases of LLC and prolonged the life span (%ILS:91%) of BDF1 mice. We also found that the cell killing effect of SDK-12B-5 was affected by both concentration and exposure time in cultured human lung cancer (OAT) cells using soft-agar colony assay. A significant augmentation of delayed type hypersensitivity (DTH) response induced by SDK-12B-5 in comparison with the mixture of SDK-103 and 5-FU was seen when it was administered p.o. simultaneously with the immunization of sheep red blood cell (SRBC) in retired CD1 mice. From the studies on tissue distribution and pharmaco-kinetics of SDK-12B-5 by HPLC and ICP analysis. the persistence of SDK-12B-5 levels in serum and tumors was correlated with the findings that a maximum chemotherapeutic effect was obtained when SDK-12B-5 was administered p.o. repeatedly with every other day to avoid the cumulative toxicity.
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PMID:[Antitumor effects of 5-fluorouracil-bound organic silicon compound]. 278 16

The brain uptake of xenobiotics is restricted by the blood-brain brain barrier formed by brain capillary endothelial cells. Active efflux transport systems in the blood-brain barrier work as a detoxification system in the brain by facilitating removal of xenobiotic compounds from the brain. Drugs, acting in the brain, have to overcome such efflux mechanisms to achieve clinically significant concentration in the brain. Multiple transporters are involved in this efflux transport in the brain capillaries. In the past few years, considerable progress has been made in the cloning of these transporters and their functional characterization after heterologous expression. Members of the solute carrier family (SLC) play an important role in the efflux transport, especially for organic anions, which include organic anion transporting polypeptides (OATP/SLCO) and organic anion transporters (OAT/SLC22A). It is believed that coordination of the members of SLC family, and ABC transporters, such as P-glycoprotein, multidrug resistance protein, and breast cancer-resistant protein (BCRP/ABCG2), allows an efficient vectorial transport across the endothelial cells to remove xenobiotics from the brain. In this review, we shall summarize our current knowledge about their localization, molecular and functional characteristics, and substrate and inhibitor specificity.
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PMID:Active efflux across the blood-brain barrier: role of the solute carrier family. 1571 59

Polyoxometalates are negatively charged inorganic compounds which contain metal ions such as tungsten, molybdenum, vanadium etc. and which make clusters with the surrounding oxygen atoms. [NH3Pri]6[Mo7O24].3H2O (PM-8) was found to be a significant antitumor polyoxomolybdates. It had already been reported that the PM-8 suppressed the growth of Co-4 human colon cancer, MX-1 human breast cancer and OAT human lung cancer xenografted in nude mice. However, the mechanism of the antitumor activity has not been clarified. In this study, the antitumor activity of one of the metal oxide clusters (polyoxometalates), hexabis(isopropylammonium) heptamolybdate trihydrate, [NH3Pri]6[Mo7O24].3H2O (PM-8) were shown in an MTS assay. DNA ladder formation and detection of apoptotic bodies in nuclei were revealed that antitumor activity of PM-8 in MKN45 cells was due to apoptosis. It is concluded that the observation of significant tumor growth suppression of PM-8 in MKN45-bearing mice results from the induction of apoptosis. PM-8 shows promise as a novel anti-cancer agent.
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PMID:Antitumor activity of polyoxomolybdate, [NH3Pri]6[Mo7O24].3H2O, against, human gastric cancer model. 1686 May 28

Anticancer polyoxomolybdates have been investigated for medical application of polyoxometalates as discrete cluster anions of metal oxides. [NH3Pri]6[Mo7O24].3H2O (PM-8) has been recognized as one of significant antitumoral polyoxomolybdates. PM-8 had shown the growth suppression against several tumors, for examples, Co-4, human colon cancer, MX-1, human breast cancer, and OAT, human lung cancer. PM-8 showed the tumor growth suppression for MKN-45 human gastric cancer in tumor bearing mice. PM-8 inhibited the cell growth of AsPC-1 which depended on the dose with showing DNA ladder formation and DNA fragmentation, and positive Hoechst staining indicating apoptosis. The ratio of apoptotic cells on flow cytometry analysis were 35%, and 57% with treatment of PM-8 after 48, and 72 h, respectively. One of the anti-tumor activity of PM-8 result from the activation of apoptotic pathway. It is thought that polyoxomolybdates will be applied as a novel anti-tumor agent especially against cancers which are difficult to be treated clinically.
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PMID:Anticancer activity of polyoxomolybdate. 1686 May 29

Mammary tumors are a major health threat to women and female dogs. In both, metastasis of the primary tumor to distant organs is the most common cause of tumor-related death. Nevertheless, the molecular mechanisms of tumor metastasis are far from being understood, and it is still unknown why some human and canine carcinomas metastasize and others do not. Using 2D-DIGE and MALDI-TOF-MS we identified 21 proteins with significant changes (fold change >1.5; p < 0.05) in protein expression between metastasizing (n = 6) and nonmetastasizing (n = 6) canine mammary carcinomas. Quantitative RT-PCR was used to identify transcriptional or post-transcriptional regulation of protein expression. Up-regulated proteins in metastatic carcinomas included proliferating cell nuclear antigen, ferritin light chain, bomapin, tropomyosin 3, thioredoxin-containing domain C5, adenosin, ornithine aminotransferase, coronin 1A, RAN-binding protein 1,3-phosphoglycerate dehydrogenase, and eukaryotic translation elongation factor 1. Down-regulated proteins in metastatic carcinomas included calretinin, myosin, light chain 2, peroxiredoxin 6, maspin, ibrinogen beta chain, vinculin, isocitrate dehydrogenase 1, tropomyosin 1, annexin A5, and Rho GTPase activating protein 1. Interestingly, 19 of these 21 proteins have been described with a malignancy-associated expression in human breast cancer and other human cancer types before. Further investigations are now necessary to test whether these markers are of prognostic value for canine mammary carcinomas and whether their expression is directly involved in canine mammary carcinogenesis or represent solely a secondary reactive phenotype.
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PMID:Proteome of metastatic canine mammary carcinomas: similarities to and differences from human breast cancer. 2093 60