ABSTRACT
INTRODUCTION: Bangladesh has 22 million adult users of smokeless tobacco (ST). The prevalence among women is higher (24.8%). Health-related quality of life outcome (HRQoL) for ST use is little known. We investigated the association between HRQoL and daily ST use among adult women in Bangladesh. METHODS: Using multi-stage design, a cross-sectional survey was conducted. Adult women (randomly selected) were surveyed from 4 purposively selected divisions (Dhaka, Chittagong, Khulna and Rangpur). Female ST users and non-users were compared using HRQoL scores. Self-perceived Visual Analogue Scale (EQ-VAS) values and HRQoL scores were modelled to examine their association with ST use. RESULTS: A total of 2610 women (1149 users and 1461 non-users) were surveyed. The proportion reported any type of problem in all health dimensions was significantly higher among female ST users than non-users (mobility: 43.3% vs 19.5%, self-care: 29.6% vs 11.9%, usual activities: 48.7% vs 21.8%, pain or discomfort: 69.8% vs 40.6%, and anxiety or depression: 61.3% vs 37.5%). The average HRQoL scores were 0.79 (95% CI: 0.78-0.81) and 0.90 (95% CI: 0.89-0.90) for users and non-users, respectively. Moreover, EQ-VAS average values were significantly higher for non-users [80.7 (95% CI: 79.9-81.6) vs 70.27 (95% CI: 69.2-71.2)]. Controlling the sociodemographics, ST use significantly reduced the HRQoL score by an average of 0.15 points. The EQ-VAS values on average decreased by 0.04 points for ST use. CONCLUSIONS: ST use is significantly associated with the HRQoL of females in Bangladesh. Considering the higher prevalence of ST, especially among women, HRQoL hazards need to be communicated for awareness building.
ABSTRACT
PURPOSE: Selective estrogen receptor modulators (SERM) are used for the treatment and prevention of breast cancer (tamoxifen) and osteoporosis (raloxifene). Mechanisms of tamoxifen-resistance in breast cancer are incompletely understood but current research is focused on crosstalk between growth factor receptors and the estrogen receptor alpha (ERalpha) pathway. There is increasing clinical use of raloxifene for the treatment of osteoporosis, but the widespread use of this SERM will have consequences for the treatment of breast cancer in raloxifene-exposed women. EXPERIMENTAL DESIGN: We took the strategic step of developing a raloxifene-resistant tumor (MCF-7RALT) model in vivo and investigating the mechanisms responsible for resistance. RESULTS: MCF-7RALT tumors exhibited phase I SERM resistance, growing in response to SERMs and 17beta-estradiol. Epidermal growth factor receptor/HER1 and HER2/neu mRNAs were increased in MCF-7RALT tumors. The HER2/neu blocker, trastuzumab, but not the epidermal growth factor receptor blocker, gefitinib, decreased the growth of MCF-7RALT tumors in vivo. Consequently, trastuzumab decreased prosurvival/proliferative proteins: phospho-HER2/neu, total HER2/neu, phospho-Akt (protein kinase B), glycogen synthetase kinase-3, cyclin D1, and the antiapoptotic protein X chromosome-linked inhibitor of apoptosis, whereas increasing the proapoptotic protein, caspase-7, in raloxifene-treated MCF-7RALT tumors. Interestingly, ERalpha protein was overexpressed in untreated MCF-7RALT tumors and hyperactivated in cells derived from these tumors. Only fulvestrant completely inhibited the growth and ERalpha activity of MCF-7RALT tumors. The coactivator of ERalpha, amplified in breast cancer-1 protein was modestly increased in the raloxifene-treated MCF-7RALT tumors and increased both basal and estradiol-induced activity of ERalpha in cells derived from the MCF-7RALT tumors. CONCLUSIONS: These results suggest that overexpression and increased activity of HER2/neu might be responsible for the development of raloxifene-resistant breast cancer. The results also suggest that increased expression of basal activity of ERalpha could contribute to the hypersensitivity of MCF-7RALT tumors in response to estradiol because only fulvestrant blocked growth and ERalpha activity.
