We investigated the effects of individual fatty acids on breast cancer in a prospective study of 35 298 Singapore Chinese women aged 45 -74 years, who were enrolled during April 1993 to December 1998 (The Singapore Chinese Health Study). At recruitment, each study subject was administered, in-person, a validated, semiquantitative food frequency questionnaire consisting of 165 food and beverage items. As of December 31, 2000, 314 incident cases of breast cancer had occurred. We used the Cox regression methods to examine individual fatty acids in relation to breast cancer risk, with adjustment for age at baseline interview, year of interview, dialect group, level of education, daily alcohol drinking, number of live births, age when menstrual periods became regular, and family history of breast cancer. Consumption of saturated, monounsaturated or polyunsaturated fat overall was unrelated to risk. On the other hand, high levels of dietary n-3 fatty acids from fish/shellfish (marine n-3 fatty acids) were significantly associated with reduced risk. Relative to the lowest quartile of intake, individuals in the higher three quartiles exhibited a 26% reduction in risk (relative risk (RR) ¼ 0.74, 95% confidence interval (CI) ¼ 0.58, 0.94)); RRs were similar across the top three quartiles of intake (0.75, 0.75, 0.72, respectively). Overall, there was no association between n-6 fatty acids and breast cancer risk. However, among subjects who consumed low levels of marine n-3 fatty acids (lowest quartile of intake), a statistically significant increase in risk was observed in individuals belonging to the highest vs the lowest quartile of n-6 fatty acid consumption (RR ¼ 1.87, 95% CI ¼ 1.06 -3.27); the corresponding RR for advanced breast cancer was 2.45 (95% CI ¼ 1.20 -4.97, P for trend ¼ 0.01). To our knowledge, these are the first prospective findings linking the intake of marine n-3 fatty acids to breast cancer protection.
We investigated the effects of soy isoflavone intake on breast cancer in a prospective study of 35 303 Singapore Chinese women enrolled during April 1993 to December 1998 in the Singapore Chinese Health Study. At recruitment, each subject was personally administered a validated semiquantitative food frequency questionnaire covering 165 food and beverage items. As of December 31 2005, 629 had developed breast cancer following an accumulation of 338 242 person-years. Using Cox regression and adjusting for age at interview, year of interview, dialect group, education, family history of breast cancer, age when periods became regular, parity, menopausal status, body mass index (BMI), n-3 fatty acid, and other covariates, we found breast cancer risk was reduced significantly in association with high soy intake. Relative to women with lower (below median) soy intake (o10.6 mg isoflavone per 1000 Kcal), women with higher (above median) intake showed a significant 18% risk reduction (relative risk (RR) ¼ 0.82, 95% confidence interval (CI) ¼ 0.70 -0.97). This inverse association was apparent mainly in postmenopausal women (RR ¼ 0.74, 95% CI ¼ 0.61 -0.90), and was not observed in premenopausal women (RR ¼ 1.04, 95% CI ¼ 0.77 -1. 40). Among postmenopausal women, the soy -breast cancer association was stronger in those above median BMI (RR ¼ 0.67, 95% CI ¼ 0.51 -0.88) than in leaner women (RR ¼ 0.83, 95% CI ¼ 0.62 -1.11). Duration of follow-up modified the soy -breast cancer association, the effect being twice as large among women with 10 þ vs fewer years of follow-up. Neither oestrogen nor progesterone receptor status of the tumours materially influenced the association. These prospective findings suggest that approximately 10 mg of isoflavones per day, obtained in a standard serving of tofu, may have lasting beneficial effects against breast cancer development. Of at least 28 detailed studies of soy and breast cancer risk published in English since 1990, 14 were in western populations with very low intake of soy (o1 mg of isoflavone per day) and in these, intake was unrelated to breast cancer risk (Wu et al, 2008). Of the other 14 studies in Asia or in Asian -Americans with substantially higher soy intake, eight (Lee et al, 1991;Dai et al, 2001;Yamamoto et al, 2003;Hirose et al, 2005;Lee et al, 2005;Shannon et al, 2005;Do et al, 2007) covered the main sources of soy intake and carefully adjusted for relevant potential confounders. In a meta-analysis of these eight studies, we found a stepwise reduction in breast cancer risk with increasing soy intake. Compared to the lowest soy intake (o5 mg isoflavones per day), risk of breast cancer reduced significantly by 12% in association with moderate intake (B10 mg isoflavones per day) and 29% in association with high intake (20 isoflavones or more per day; Wu et al, 2008). However, only one Asian study was of cohort type (Yamamoto et al, 2003). Assessment of soy intake was incomplete in two other cohort studies (Key et al, 1999;Nishio et al, 2007) and they were not included in our...
Although oligomeric β-amyloid (Aβ) has been suggested to have an important role in Alzheimer disease (AD), the mechanism(s) of how Aβ induces neuronal cell death has not been fully identified. The balance of pro- and anti-apoptotic Bcl-2 family proteins (e.g., Bcl-2 and Bcl-w versus Bad, Bim and Bax) has been known to have a role in neuronal cell death and, importantly, expression levels of these proteins are reportedly altered in the vulnerable neurons in AD. However, the roles of apoptotic proteins in oligomeric Aβ-induced cell death remain unclear in vivo or in more physiologically relevant models. In addition, no study to date has examined whether Bax is required for the toxicity of oligomeric Aβ. Here, we found that treatment with oligomeric Aβ increased Bim levels but decreased Bcl-2 levels, leading to the activation of Bax and neuronal cell death in hippocampal slice culture and in vivo. Furthermore, the inhibition of Bax activity either by Bax-inhibiting peptide or bax gene knockout significantly prevented oligomeric Aβ-induced neuronal cell death. These findings are first to demonstrate that Bax has an essential role in oligomeric Aβ-induced neuronal cell death, and that the targeting of Bax may be a therapeutic approach for AD.
This case -control study of 310 colorectal cancer cases and 1177 controls in a nested prospective, population-based cohort of Singapore Chinese subjects found a statistically significant association between the cyclooxygenase (COX)-2 À765G4C gene polymorphism and colon cancer risk among high consumers of dietary n-6 polyunsaturated fatty acids (odds ratio ¼ 2.38, 95% confidence interval ¼ 1. 23 -4.59 Keywords: cyclooxygenase-2; n-6 polyunsaturated fatty acids; colon cancer; Chinese Diet is believed to be the single most important contributor to colonic carcinogenesis (Tomatis et al, 1990). Experimental data have shown that saturated fatty acids (SFAs) and n-6 polyunsaturated fatty acids (PUFAs) have tumour-enhancing properties in the colon (Reddy and Maeura, 1984;Zhao et al, 1991, Woutersen et al, 1999. Epidemiological data suggest that increased consumption of all meat or red meat, which contains high levels of SFAs, is strongly associated with colorectal cancer (Giovannucci and Goldin, 1997;Sandhu et al, 2001), but there is only limited evidence on the role of dietary n-6 PUFAs (Zock and Katan, 1998;Flood et al, 2003).The putative mechanism through which dietary n-6 PUFAs may enhance colonic carcinogenesis is the increased formation of prostaglandins, with the rate-limiting and committal step being mediated by the cyclooxygenase (COX)-2 enzyme (Dubois et al, 1998). Prostaglandins possess a wide spectrum of procarcinogenic properties (Handler et al, 1990;Cowlen and Eling, 1993;Coffey et al, 1997;Dermott et al, 1999). We therefore hypothesised that functional COX-2 gene polymorphisms may impact on the conversion of n-6 PUFAs into prostaglandins, with consequent change in level of cancer risk. A single nucleotide polymorphism (À765G4C) in the promoter region of the COX-2 gene was recently described (Papafili et al, 2002). We therefore investigated whether this COX-2 gene polymorphism was related to colorectal cancer risk within a population-based, prospective cohort of middle-aged and older Chinese men and women in Singapore. MATERIALS AND METHODS Study subjectsThe study design and subject recruitment of the Singapore Chinese Health Study have been described (Hankin et al, 2001). Briefly, 63 257 Chinese women and men aged 45 -74 years belonging to the Hokkien or Cantonese dialect group were enrolled in the study between April 1993 and December 1998. At recruitment, information on lifestyle factors and usual diet over the last year was obtained through in-person interviews. The dietary component of the questionnaire was validated through a series of 24-h food recalls (Hankin et al, 2001). Respondents were asked to choose from predefined frequency and portion size categories for each of the 165 listed food/beverage items that he/she consumed during the past 12 months. We used the Singapore Food Composition Table to estimate average daily intake of 96 nutrient and nonnutrient compounds for each study subject (Hankin et al, 2001). The Institutional Review Boards at the University of Southern California and the Nation...
We have previously demonstrated that baculovirus can efficiently transduce human mesenchymal stem cells (MSCs). In this study, we further demonstrated, for the first time, that baculovirus can transduce adipogenic, chondrogenic and osteogenic progenitors originating from MSCs. The transduction efficiency (21-90%), transgene expression level and duration (7-41 days) varied widely with the differentiation lineages and stages of the progenitors, as determined by flow cytometry. The variation stemmed from differential transgene transcription (as revealed by real-time reverse transcription-polymerase chain reaction), rather than from variability in virus entry or cell cycle (as determined by quantitative real-time PCR and flow cytometry). Nonetheless, the baculovirus-transduced cells remained capable of differentiating into adipogenic, osteogenic and chondrogenic pathways. The susceptibility to baculovirus transduction was higher for adipogenic and osteogenic progenitors, but was lower for chondrogenic progenitors. In particular, the duration of transgene expression was prolonged in the transduced adipogenic and osteogenic progenitors (as opposed to the MSCs), implicating the possibility of extending transgene expression via a proper transduction strategy design. Taken together, baculovirus may be an attractive alternative to genetically modify adipogenic and osteogenic progenitors in the ex vivo setting for cell therapy or tissue engineering.
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