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To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk, we conducted a case–control study with 669 cases and 682 population-based controls in the Jiangsu Province of China. MTHFR C677T and A1298C genotypes were identified using PCR–RFLP (restrictrion fragment length polymorphism) methods. Dietary folate intake was assessed using an 83-item food frequency questionnaire. Odds ratios (ORs) were estimated with an unconditional logistic model. The frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32.37, 48.88 and 18.75% in cases and 37.66, 48.24 and 14.10% in controls, respectively. The difference in distribution was significant (χ2=6.616, P=0.037), the T/T genotype being associated with an elevated OR (adjusted for age, menopausal status, body mass index (BMI), income, work intensity and status of smoking and drinking) for breast cancer (1.62, 95% confidence interval (95% CI): 1.14–2.30). The frequencies of MTHFR A1298C A/A, A/C and C/C were 71.47, 27.08 and 1.44% in cases and 68.11, 30.13 and 1.76% in controls, respectively, with no significant differences being found (χ2=1.716, P=0.424). A significant inverse relationship was observed between folate intake and breast cancer risk. Compared with the lowest tertile of folate intake, the adjusted OR for breast cancer in the top tertile was 0.70 (95% CI: 0.53–0.92). However, no significant interaction was observed between folate intake and the MTHFR C677T polymorphism. Among individuals with the MTHFR A1298C A/A genotype, adjusted ORs for breast cancer were 0.89 (0.62–1.27) and 1.69 (1.20–2.36) for the second to the third tertile of folate intake compared with the highest folate intake group (tread test, P=0.0008). The findings of this study suggest that MTHFR genetic polymorphisms and dietary intake of folate may modify susceptibility to breast cancer.Journal of Human Genetics (2009) 54, 414–418; doi:10.1038/jhg.2009.57; published online 26 June 2009 [ABSTRACT FROM AUTHOR]

Purpose: To investigate the mechanism through which hyperthermia promotes exosome secretion and drug sensitivity in adriamycin-resistant breast cancer. Materials and Methods: We first evaluated the effect of hyperthermia on adriamycin-resistant breast cancer viability and used transmission electron microscopy, nanoparticle tracking analysis, and a bicinchoninic acid kit to validate the effect of hyperthermia on exosome secretion. The effective targeting molecules and pathways changed by hyperthermia were explored by RNA microarray and verified in vitro. The adriamycin-resistant MCF-7/ADR cells co-incubated with the exosomes produced by MCF7/ADR cells after hyperthermia were assessed. The uptake of exosomes by MCF-7/ADR cells after hyperthermia treatment was evaluated by confocal microscopy. Finally, the mechanism through which hyperthermia promotes exosome secretion by hyperthermia was determined. Results: Hyperthermia significantly suppressed the growth of adriamycin-resistant breast cancer cells and increased drug sensitivity by upregulating FOS and CREB5, genes related to longer overall survival in breast cancer patients. Moreover, hyperthermia promoted exosome secretion through Rab7b, a small GTPase that controls endosome transport. The upregulated FOS and CREB5 antioncogenes can be transferred to MCF-7/ADR cells by hyperthermia-treated MCF-7/ADR cell-secreted exosomes. Conclusions: Our results demonstrated a novel function of hyperthermia in promoting exosome secretion in adriamycin-resistant breast cancer cells and revealed the effects of hyperthermia on tumor cell biology. These hyperthermia-triggered exosomes can carry antitumor genes to the residual tumor and tumor microenvironment, which may be more beneficial to the effects of hyperthermia. These results represent an exploration of the relationship between therapeutic strategies and exosome biology. [ABSTRACT FROM AUTHOR]

Breast cancer (BCa) is one of the most frequently diagnosed cancers and leading cause of cancer deaths among females worldwide. Circular RNAs (circRNAs) are a new class of endogenous regulatory RNAs characterized by circular shape resulting from covalently closed continuous loops that are capable of regulating gene expression at transcription or post-transcription levels. With the unique structures, circRNAs are resistant to exonuclease RNase R and maintain stabilitymore easily than linear RNAs. Recently, an increasing number of circRNAs are discovered and reported to show different expression in BCa and these dysregulated circRNAs were correlated with patients’ clinical characteristics and grade in the progression of BCa. CircRNAs participate in the bioprocesses of carcinogenesis of BCa, including cell proliferation, apoptosis, cell cycle, tumorigenesis, vascularization, cell invasion, migration as well as metastasis. Here we concentrated on biogenesis and function of circRNAs, summarized their implications in BCa and discussed their potential as diagnostic and therapeutic targets for BCa. [ABSTRACT FROM AUTHOR]

Homo sapiens ceramide synthase 2 (CerS-2) plays an important role in inhibiting invasion and metastasis of tumor cells and has been reported as a tumormetastasis suppressor gene in diverse cancers. Thus, low level of CerS-2 protein might suggest a bad prognosis and up-regulation of CerS-2 protein might act as a promising therapeutic strategy for malignant tumors. In this review, we discussed the expression, as well as the clinical and pathological significance of CerS-2 in diverse human cancers. The pathological processes and molecular pathways regulated by CerS-2 were also summarized. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are recently regarded as a naturally forming family of widespread and diverse endogenous noncoding RNAs (ncRNAs) that may regulate gene expression in mammals. At present, above 30000 circRNAs have already been found, with their unique structures to maintain stability more easily than linear RNAs. Several previous literatures stressed on the important role of circRNAs, whose expression was relatively correlated with patients’ clinical characteristics and grade, in the carcinogenesis of cancer. CircRNAs are involved in many regulatory bioprocesses of malignance, including cell cycle, tumorigenesis, invasion, metastasis, apoptosis, vascularization, through adsorbing RNA as a sponge, binding to RNA-binding protein (RBP), modulating transcription, or influencing translation. Therefore, it is inevitable to further study the interactions between circRNAs and tumors and to develop novel circRNAs as molecular markers or potential targets, which will provide promising applications in early diagnosis, therapeutic evaluation, prognosis prediction of tumors and even gene therapy for tumors. [ABSTRACT FROM AUTHOR]

Paclitaxel has been widely used in the treatment of breast cancer. However, the development of drug resistance often increases the failure of chemotherapy. Growing evidence has reported the significant role of microRNAs (miRs) in drug resistance. The present study identified that miR-24 was significantly downregulated in paclitaxel-resistant (PR) breast cancer patients and in MCF-7/PR human breast carcinoma cells, and that overexpression of miR-24 could increase the effect of paclitaxel on drug-resistant breast carcinoma cells. Furthermore, miR-24 could directly bind to the 3'-untranslated region of ATP binding cassette B9 to downregulate its expression, thereby reducing drug transportation and improving the anti-tumor effect of paclitaxel on breast cancer cells. In vivo experiments also demonstrated that overexpression of miR-24 could increase the sensitivity of drug-resistant MCF-7 cells to paclitaxel. In conclusion, the present results suggested a novel function for miR-24 in reducing paclitaxel resistance in breast cancer, which may be of important clinical significance. [ABSTRACT FROM AUTHOR]

Objectives: MiRNA-139 is located at 11q13.4 and it has anti-oncogenic and antimetastatic activity in humans. However, its role in controlling apoptosis, invasion and metastasis and the development of chemosensitivity to docetaxel in breast cancer cells are not fully understood. The aim of this study was to research the biological function of miR-139-5p and the efficacy of chemosensitivity to docetaxel. Methods: MiR-139-5p expression in MCF-7, MCF-7/Doc cells and in selected breast cancer tissue samples was confirmed by real-time PCR; cell viability was analyzed by Cell Counting Kit-8 assay; apoptosis and cell cycle were analyzed by flow cytometry; control of metastasis and invasion of breast cancer cells was measured by transwell assay; expression of Notch1 was measured by western blot; a luciferase reporter vector was constructed to identify the miR-139-5p target gene. Results: MiR-139-5p was significantly down-regulated in breast cancer cells. MiR-139-5p inhibits the viability of breast cancer cells. MiR-139-5p induces apoptosis, causes cell cycle arrest in S phase, inhibits migration and invasion in breast cancer cells, however, MiR-139-5p play the opposite role in docetaxelinduced breast cancer cells. Conclusions: MiR-139-5p not only attenuated the development of breast cancer cells but also mediated drug-resistance by regulating the expression of the downstream target gene Notch1. [ABSTRACT FROM AUTHOR]

Sodium hydrosulfide (NaHS) is an exogenous hydrogen sulfide (H2S)-releasing molecule and has antitumor potential against a wide variety of human cancer types. The effect of exogenous H2S on the invasion of breast cancer and the possible underlying mechanisms remain unknown. The present study aimed to investigate the in vitro effects of H2S on transforming growth factor-β1 (TGF-β1)-induced human breast cancer cells and the associated mechanisms. MCF-7 cells were incubated with TGF-β1 to induce epithelial-mesenchymal transition (EMT) and an MTT assay was performed to detect cell viability. Flow cytometry, using propidium iodide (PI) staining, was used to determine the stages of the cell cycle. Apoptosis was detected with Annexin V-fluorescein isothiocyanate and PI double staining. Western blotting was performed to detect the protein expression of cystathionine γ-lyase (CSE, an endogenous H2S producer), phospho-p38 (a signaling protein associated with apoptosis), and SNAI1 (Snail, associated with the induction of EMT). A Boyden chamber invasion assay was performed to detect tumor invasion. The results demonstrated that when NaHS was administered to TGF-β1-treated MCF-7 cells, the cells exhibited decreased proliferation, G0/G1 phase cell cycle arrest and increased apoptosis. NaHS treatment following TGF-β1 administration also resulted in decreased cell invasion and decreased EMT, which was indicated by decreased Snail protein expression. In addition, incubation with NaHS increased endogenous CSE protein expression and decreased p38 mitogen-activated protein kinase phosphorylation in MCF-7 cells stimulated by TGF-β1. Furthermore, the inhibition of endogenous CSE by DL-propargylglycine increased EMT in the MCF-7 cells treated with NaHS and TGF-β1. In conclusion, the present study provides insights into a novel anticancer effect of H2S on breast cancer cells through activation of the CSE/H2S pathway and decreased expression of phospho-p38. [ABSTRACT FROM AUTHOR]

Objectives: This updated meta-analysis was conducted to assess the association between coffee consumption and breast cancer risk. Methods: We conducted a systematic search updated July 2012 to identify observational studies providing quantitative estimates for breast cancer risk in relation to coffee consumption. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least square trend estimation was used to assess dose-response relationships. Results: A total of 26 studies (16 cohort and 10 case-control studies) on coffee intake with 49497 breast cancer cases were included in the meta-analysis. The pooled RR showed a borderline significant influence of highest coffee consumption (RR = 0.96; 95% CI 0.93-1.00), low-to moderate coffee consumption (RR = 0.99; 95% CI 0.95-1.04), or an increment of 2 cups/day of coffee consumption (RR = 0.98; 95% CI 0.97-1.00) on the risk of breast cancer. In stratified analysis, a significant inverse association was observed in ER-negative subgroup. However, no significant association was noted in the others. Conclusions: Our findings suggest that increased coffee intake is not associated with a significantly reduced risk of breast cancer, but we observe an inverse association in ER-negative subgroup analysis. More large studies are needed to determine subgroups to obtain more valuable data on coffee drinking and breast cancer risk. [ABSTRACT FROM AUTHOR]

The purpose was to investigate the prevalence rate, characteristics and related factors of breast cancer among women in Eastern China. A total of 122,058 female subjects completed the study, with 320 confirmed cases of breast cancer (crude prevalence: 262.5/100,000; standardized prevalence: 207.7/100,000). Among all of the identified breast cancer cases, 91.6% were diagnosed after the age of 35 and 60.0% were diagnosed before menopause. The odds ratios (95% confidence interval) of those breast cancer risk factors as selected through multivariate logistic regression were as follows: 5.438 (1.553- 19.004) for family history of breast cancer, 3.556 (1.880-6.728) for high behavior intervention score, 3.556 (0.904-13.994) for history of diabetes, 3.357 (1.131-9.969) for history of benign breast tumors, 2.196 (1.355-3.556) for poor overall life satisfaction, 1.826 (0.995-3.350) for premenopause of breast cancer, 1.528 (1.083-2.155) for high BMI index, 1.500 (0.920- 2.446) for poor financial status, 1.497 (1.014-2.211) for multiple miscarriages/abortions, and 1.231 (0.972-1.559) for infrequent consumption of garlic (frequent garlic consumption is a protective factor). There were significantly more cases of breast cancer diagnosed prior to menopause than after menopause, and most of the patients were diagnosed after the age of 35. These findings suggest that attention should be focused on the incidence of breast cancer among premenopausal women older than 35. [ABSTRACT FROM AUTHOR]