METHODS: The cytotoxicity activity was measured using MTS assay. The mode of cell death was analysed by early (phosphatidylserine externalization) and late apoptosis (DNA fragmentation). The caspases 8, 9, 3/7 and apoptotic proteins bax, bcl-2 study were done by western blot and ELISA method.
RESULTS: The methanol extract was found to inhibit 50% growth of T-47D cells at the concentration of 79.43µg/ml respectively after 72hr. From seven fractions, fraction F1, F2 and F3 produced cytotoxicity effects in T-47D cell line with IC50 (72hr) < 30µg/ml. The results obtained by Annexin V/PI apoptosis detection assay and TUNEL assay suggest that active fractions of Vitex rotundifolia induced early and late apoptosis (DNA fragmentation) in T-47D cell line. Moreover, western blot analysis and Caspase GloTM luminescent assay demonstrated that fractions F2 and F3 triggered apoptotic cell death via activation of caspases -8, -9 and -3/7 and up-regulation of Bax and down-regulation of Bcl-2 protein. Furthermore, chemical profiling confirms the presence of potential metabolites (vitexicarpin) in fractions of Vitex rotundifolia.
CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in fractions of Vitex rotundifolia as future cancer therapeutic agent for the treatment of breast cancer.
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MATERIALS AND METHODS: The EGFR intron 1 polymorphism was analysed in three distinct healthy Asian subjects, namely, Chinese (N = 96), Malays (N = 98) and Indians (N = 100). Comparative genomic hybridisation was performed to investigate for changes in DNA copy number in relation to the polymorphic CA dinucleotide repeats in breast tumor tissues (N = 22).
RESULTS: The frequency of short alleles with 14 and 15 CA repeats were most common in the Asian populations and significantly higher than those reported for Caucasians. The frequency of 20 CA repeats was 5%, almost 13-fold lower than previous reports. EGFR amplifications were detected in 23% and 11% of breast tumor tissues harboring short and long CA repeats, respectively.
CONCLUSION: Our results show that the frequency of alleles encoding for short CA dinucleotide repeats is common in Asian populations. EGFR expression and amplification levels were also higher in Asian breast tumor tissues with short CA dinucleotide repeats. These findings suggest that the EGFR intron 1 polymorphism may influence response to treatment with tyrosine kinase inhibitors in breast cancer patients and further studies are warranted.
SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.
MATERIALS AND METHODS: A cross-sectional study was designed to assess surgeons' and patients' perceptions toward breast reconstruction. Questionnaires were distributed to general and breast surgeons in East Coast Malaysian hospitals and Hospital Kuala Lumpur and to postmastectomy patients with and without breast reconstruction at the Hospital Universiti Sains Malaysia and Hospital Raja Perempuan Zainab II. The response rates were 82.5% for the surgeons (n = 33), 95.4% for the patients with reconstruction (n = 63), and 95.5% for the patients without reconstruction (n = 278).
RESULTS: The median surgeon age and experience was 42 and 6 years, respectively. Each surgeon saw an average of 20 new breast cancer cases annually. Most surgeons (86.7%) discussed reconstruction options with their patients but had only referred an average of 4 patients for reconstruction during a 3-year period. Surgeons' concerns regarding the qualitative outcome increased the likelihood of a breast reconstruction discussion (β = 4.833; P = .044). The women who underwent breast reconstruction were younger (mean age, 42 vs. 50 years), were more often working (69.4% vs. 42.2%), and more often had previous awareness of the option (90.3% vs. 44.3%). The most common reasons for undergoing breast reconstruction were "to feel more balanced" (92.1%) and "surgeon's strong recommendation" (92.1%). Previous knowledge of breast reconstruction increased the likelihood of reconstruction (odds ratio, 5.805; P = .026). Although 70% of surgeons thought that patients would not be interested in reconstruction, only 37.9% of patients with previous awareness reported having no interest.
CONCLUSION: The low reconstruction rate (20.6%) can be attributed to the low referral rate. Patients' likelihood to undergo reconstruction with their surgeon's recommendation and with previous awareness were reflective of the surgeons' strong influence on their patients. Thus, clarification of surgeons' hypothetical criticisms could conceivably increase the reconstructive surgery rate.
METHODS: A total of 90 mice were used and divided into 15 groups, each group comprising of 6 mice. Tumour, body weight and mortality of the mice were determined throughout the experiment, to observe the effect of NDV and NDV + tamoxifen treatments on the mice. In addition, the toxic effect of the treatments was determined through liver function test. In order to elucidate the involvement of cytokine production induced by NDV, a total of six cytokines, i.e. IL-6, IFN-γ, MCP-1, IL-10, IL12p70 and TNF-α were measured using cytometric bead array assay (plasma) and enzyme-linked immunosorbent spot (isolated splenocytes).
RESULTS: The results demonstrated that 4 T1 breast cancer cells in allotransplanted mice treated with AF2240 showed a noticeable inhibition of tumour growth and induce apoptotic-related cytokines.
CONCLUSIONS: NDV AF2240 suppression of breast tumour growth is associated with induction of apoptotic-related cytokines. It would be important to further investigate the molecular mechanism underlaying cytokines production by Newcastle disease virus.