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)

The methods of mobilization and collection of stem cells in peripheral blood stem cells transplantation (PBSCT) and the association between the number of stem cells transplanted and hematopoietic recovery were studied. The investigation was carried in 22 patients (11 acute leukemia, 6 multiple myeloma, 4 non-Hodgkin's lymphoma, 1 breast cancer). Three regimens for mobilization were carried out as follows: 1) chemotherapy + tetrahydrofolic acid + dexamethasone, 2) chemotherapy + rhGM-CSF + dexamethasone, 3) chemotherapy + rhG-CSF + dexamethasone. Besides, CD34/CD33 dual-color direct immunofluorescence flow cytometry assay was performed in 7 cases in the rhG-CSF group. The results showed: 1) The mean number of collected cells (MNC) in the rhG-CSF group was MNC (8.29 +/- 6.14) x 10(8)/kg and CFU-GM (21.35 +/- 17.24) x 10(4)/kg, being highest among the 3 groups. 2) The number of CD34+ cells correlated with MNC and CFU-GM. CD34+ cells in the peripheral blood were 0 or < 0.5% before mobilization and increased markedly 6-8 days after rhG-CSF administration. Harvesting should be started at that time and carried out every day until CD34+ cells reached 5 x 10(6)/kg. 3) The number of PBSC transplanted was the key to hematopoietic recovery.
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PMID:[A study on the peripheral blood stem cells mobilization, collection and their effects on engraftment]. 873 24

A novel mono-THF containing synthetic anticancer drug, COBRA-1, was designed for targeting a previously unrecognized unique narrow binding cavity on the surface of alpha-tubulin. COBRA-1 inhibited GTP-induced tubulin polymerization in cell-free tubulin turbidity assays. Treatment of human breast cancer and brain tumor (glioblastoma) cells with COBRA-1 caused destruction of microtubule organization and apoptosis. Like other microtubule-interfering agents, COBRA-1 activated the proapoptotic c-Jun N-terminal kinase (JNK) signal transduction pathway, as evidenced by rapid induction of c-jun expression.
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PMID:COBRA-1, a rationally-designed epoxy-THF containing compound with potent tubulin depolymerizing activity as a novel anticancer agent. 1086 79

A mitogenic agent in corncob bedding and fresh corn products disrupts sexual behavior and estrous cyclicity in rats. The mitogenic activity resides in an isomeric mixture of linoleic acid derivatives with a tetrahydrofuran ring and two hydroxyl groups (THF-diols) that include 9, (12)-oxy-10,13-dihydroxystearic acid and 10, (13)-oxy-9,12-dihydroxystearic acid. Synthetic THF-diols stimulated breast cancer cell proliferation in vitro and disrupted the estrous cycle in female rats at oral doses of approximately 0.30 mg/kg body weight/day. Exposure to THF-diols may disrupt endocrine function in experimental animals at doses approximately 200 times lower than classical phytoestrogens, promote proliferation of breast or prostate cancer, and adversely affect human health.
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PMID:Identification of an endocrine disrupting agent from corn with mitogenic activity. 1452 57

(4R,5S)/(4S,5R)-4,5-Bis(4-hydroxyphenyl)-2-imidazolines bearing 2,2'-H (3a), 2,2'-Cl (3b), 2,2',6-Cl (3c), and 2,2'-F (3d) substituents in the aromatic rings were C2-alkylated (5a-i), N-alkylated (7, 7a-c), and N,N'-dialkylated (9a-c). The synthesis started from the diastereomerically pure (1R,2S)/(1S,2R)-1,2-diamino-1,2-bis(4-methoxyphenyl)ethanes 1a-d, which were cyclized to the imidazolines 2a-d and 4a-i with triethylorthoesters or iminoethers. Ether cleavage with BBr(3) yielded the (4R,5S)/(4S,5R)-4,5-bis(4-hydroxyphenyl)-2-imidazolines 3a-d and 5a-i. The N-alkylation and N,N'-dialkylation of 2b, employed for obtaining 7a-c and 9a-c, were performed prior to the ether cleavage with alkyl iodine in dry THF. By use of HPLC, the influence of the substitution patterns in the aromatic rings and alkyl chains at the C2- or N-atoms on the hydrolysis rate of the imidazolines was studied under in vitro conditions. It appeared that only imidazolines with C2- or N-alkyl substituents show sufficient stability to interact as heterocycles with the estrogen receptor (ER). The resulting gene activation was monitored in a luciferase assay using ERalpha-positive MCF-7-2a breast cancer cells stably transfected with the plasmid ERE(wtc)luc. It is interesting to note that C2-alkylation led to a strong reduction or even a complete loss of activity whereas N-alkylation improved the estrogenic profile. The (4R,5S)/(4S,5R)-N-ethyl-4,5-bis(2-chloro-4-hydroxyphenyl)-2-imidazoline 7b has proven to be the most active compound in this structure-activity relationship study (EC(50) = 0.015 microM).
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PMID:Effects of C2-alkylation, N-alkylation, and N,N'-dialkylation on the stability and estrogen receptor interaction of (4R,5S)/(4S,5R)-4,5-bis(4-hydroxyphenyl)-2-imidazolines. 1476 Nov 93

Aberrant CpG island hypermethylation in gene promoter regions may be an important epigenetic event in human neoplasias, including breast cancer. Dietary and genetic factors that alter DNA methylation levels in normal and tumour tissues could therefore influence both the susceptibility to this disease and tumour phenotype, respectively. In the present study of 227 breast cancers, we investigated whether common polymorphisms in 6 key genes involved in methyl group metabolism (thymidylate synthase, methylene tetrahydrofolate reductase, cystathione beta-synthase, DNA methyltransferase 3B, methylene tetrahydrofolate dehydrogenase, and methionine synthase) were associated with major pathological features of this disease or the frequency of CpG island hypermethylation. No associations were observed between any of the polymorphisms and patient age, tumour size, histological grade or patient outcome. However, tumours from patients who were homozygous for the methionine synthase A2756G polymorphism showed strikingly lower estrogen and progesterone hormone receptor concentrations compared to wild-type homozygotes. Moreover, patients who were homozygous for the methylene tetrahydrofolate dehydrogenase G1958A polymorphism showed a significantly higher frequency of tumour CpG island hypermethylation compared to wild-type homozygotes. Our results show that polymorphisms in two genes involved in methyl group metabolism are associated with hormone receptor content and DNA methylation frequency in breast cancer, however these observations are unlikely to be linked.
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PMID:Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in human breast cancer. 1632 59

Therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) is a malignancy occurring after exposure to chemotherapy and/or radiotherapy. Polymorphisms involved in chemotherapy/radiotherapy response genes could be related to an increased risk of developing this neoplasia. We have studied 11 polymorphisms in genes of drug detoxification pathways (NQO1, glutathione S-transferase pi) and DNA repair xeroderma pigmentosum, complementation group (3) (XPC(3), X-ray repair cross complementing protein (1)), Nijmegen breakage syndrome (1), excision repair cross-complementing rodent repair deficiency, complementation group (5) and X-ray repair cross complementing protein (3) and in the methylene tetrahydrofolate reductase gene (MTHFR(2), 677C>T, 1298A>C), involved in DNA synthesis. The analyzed groups were a t-MDS/AML patients group (n=81) and a matched control group (n=64) treated similarly, and they did not develop t-MDS/AML. We found no significant differences when the groups were compared globally. However, when analysis was carried out according to the primary neoplasia involved, a significant association was observed between the MTHFR haplotype (single nucleotide polymorphisms 677 and 1298) and the risk of developing t-MDS/AML in the breast cancer patients group (P=0.016) and cyclophosphamide-treated hematological disease group (P=0.005). Risk haplotype was different for each case, corresponding to the 677T1298A haplotype after breast cancer treatment and the 677C1298C haplotype after hematological malignancy treatment. We postulate that such differences are related to variations in chemotherapy schemes between hematological and breast cancers and their differential interaction with the MTHFR route.
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PMID:Role of MTHFR (677, 1298) haplotype in the risk of developing secondary leukemia after treatment of breast cancer and hematological malignancies. 1747 81

Reactions of 5-alkynyl-2'-deoxyuridines with dicobalt octacarbonyl Co2(CO)8 in THF at room temperature gave hexacarbonyl dicobalt nucleoside complexes (77-93%). The metallo-nucleosides were characterized, including an X-ray structure of a 1-cyclohexanol derivative. In crystalline form, the Co-Co bond is perpendicular to the plane of the uracil base, which is found in the anti position. The level of growth inhibition of MCF-7 and MDA-MB-231 human breast cancer cell lines was examined and compared to results obtained with the alkynyl nucleoside precursors. The cobalt compounds displayed good antiproliferative activities with IC50 values in the range of 5-50 microM. Interestingly, the coordination of the dicobalt carbonyl moiety to 5-alkynyl-2'-deoxyuridines led to a significant increase in the cytotoxic potency for alkyl/aryl substituents at the non-nucleoside side of the alkyne, but in the case of hydrogen (terminal alkyne) or a silyl group, a decrease of the cytotoxic effect was observed. As demonstrated using examples for an active and a low active target compound, the cytotoxicity was significantly influenced by the uptake into the tumor cells and the biodistribution into the nuclei.
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PMID:Metallo-nucleosides: synthesis and biological evaluation of hexacarbonyl dicobalt 5-alkynyl-2'-deoxyuridines. 1807 51

THF-diols (9,12-oxy-10,13-dihydroxyoctadecanoic and 10,13-oxy-9,12-dihydroxyoctadecanoic acids) are endocrine disrupters in rats and mitogens in breast cancer cells. Microarray analyses and real-time PCR analyses on RNA from THF-treated MCF-7 cells revealed a number of genes (caveolin 1, heat shock protein 90 alpha and 90 beta, vascular endothelial growth factor, ATPase, Ca++ transporting, ubiquitous) in the nitric oxide pathway (NOP) were targets for THF-diols. Chromatin immunoprecipitation studies suggest THF-diols modify of histone H4 acetylation at the caveolin 1 promoter via an epigenetic mechanism. These findings are consistent with the well-known involvement of NOP genes in cell proliferation and sexual behavior.
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PMID:Regulation of the nitric oxide pathway genes by tetrahydrofurandiols: microarray analysis of MCF-7 human breast cancer cells. 1834 45

This study evaluated the influence of genetic polymorphism influencing drug metabolism on survival in taxane- and cisplatin-treated advanced gastric cancer (AGC). Peripheral blood samples from 207 AGC patients treated with first-line chemotherapy of taxane and cisplatin were used. We investigated polymorphisms that influenced the metabolism of taxane (ATP-binding cassette transporter B1 (ABCB1)), cisplatin (glutathione S-transferase M1 (GSTM1), glutathione S-transferase P1 (GSTP1), glutathione S-transferase T1 (GSTT1), excision repair cross complementing 1 (ERCC1), X-ray Cross Complementing group 3 (XRCC3), X-ray Cross Complementing group 4 (XRCC4), X-ray Cross Complementing group 1 (XRCC1), breast cancer (BRCA1)), and 5-fluorouracil (methylene tetrahydrofolate reductase (MTHFR), thymidylate synthase (TYMS)). A total of 207 patients were enrolled between May 2004 and Dec 2008, and 200 patients were analyzed. The overall response rate was 38.5%. Time to progression and overall survival time were 4.3 +/- 0.19 months and 11.9 +/- 1.05 months, respectively. There was no significant association between genetic polymorphism and response rate. However, the BRCA1 mutant TT homozygote was associated with significant prolongation of overall survival (hazard ratio [HR] = 0.43; 95% confidence interval [CI], 0.20-0.92; P = 0.03) and progression-free survival (HR = 0.51; 95% CI, 0.26-1.00; P = 0.05). Also, the XRCC1 194 CT genotype was associated with inferior overall survival, relative to the XRCC1 194 CC homozygotes (HR = 1.49; 95% CI, 0.11-2.07; P = 0.018).These findings suggest that BRCA1 TT and XRCC1 194 CT genotypes could be modest prognostic markers of AGC response in taxane- and cisplatin-treated patients.
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PMID:BRCA1 and XRCC1 polymorphisms associated with survival in advanced gastric cancer treated with taxane and cisplatin. 2033 23

The purpose of the present study is to test the validity of the steroid carcinogenesis hypothesis in humans by investigating the problem whether or not a cancer-specific change of the hormonal milieu emerges at a specified stage of life where the growth rate of cancer risk is at its zenith. A case-control study of 14 urinary steroid excretions was conducted for each of 3 human neoplasias. The identification and the size (in parenthesis) of the population units used in this study were,given as follows: a) the male gastric cancer group (421); b) the male control group (104); c) the female breast cancer group (245); d) the cervical cancer group (345); e) the female control group (127). Two kinds of steroid parameters were employed for the statistical analysis of hormonal data: a) the logarithm of a steroid excretion figure (mu g/day), as expressed by log x; b) the logarithm of a relative weight of a given steroid to tetrahydrocortisol, as expressed by log x/THF. The case-control difference for each parameter was expressed in terms of a t-value of Student's t-test. The steroid deviation profile was prepared for each neoplasia and for each of the log x data set and the log x/THF data set. The results obtained are as follows: a) the 2 steroid parameters (log x and log x/THF) for each of 14 urinary steroids were both subject to change with the progress of host age. The rate of age-dependent change was different for each steroid parameter and for each population unit. b) The above differential age dependency of the steroid parameters gave rise to a continual transition of the steroid deviation profile in the course of aging. c) The hormonal traits of male gastric cancer, female breast cancer and cervical cancer were described each as a complex of androgen depression and glucocorticoid stimulation (male gastric cancer), a sequential emergence of premenopausal progestin depression and postmenopausal predominance of glucocorticoid over androgen (female breast cancer), and a complex of androgen-glucocorticoid depression over progestin (cervical cancer). d) The emergence of the above cancer-specific steroid disorders chronologically coincided with the quasiexponential growth phase of cancer risk (and slow growth phase of cancer risk in postmenopausal breast cancer). e) The usefulness of the log x/THF type deviation profile for the assessment of the hormonal milieu of the host was verified by both theoretical approach to the problem and its application to the real data of a case-control study. f) The age dependent decline of androgens was generally much faster in their progressions than that of glucocorticoids - a finding to suggest the possibility that the production of a cancer-specific steroid deviation profile might have taken the form of the stress shift of Hans Selye, since both phenomena share depletion of gonadal steroids relative to glucocorticoid in common. The etiological relevancy of the 3 cancer-specific steroid changes to the geneses of 3 cancers:was discussed in the light of the experimental pathology studies in our laboratory as well as in other laboratories.
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PMID:The relation between the aging of the steroid generating system and the geneses of cancers of the stomach, the breast and the uterine cervix. 2159 38


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