Relation of Anthropometric Measurements to Ovarian Cancer Risk in a Population-based Case–control Study (United States)

Objective To examine the relationship between anthropometric measures and ovarian cancer by menopausal status. Methods We analyzed data from a population-based case–control study comprised of 700 incident cases of epithelial ovarian cancer and 5,943 population controls from Massachusetts and Wisconsin enrolled between 1993 and 2001. In a telephone interview, information was gathered on established ovarian cancer risk factors, as well as adult height and age-specific body weight. Logistic regression was used to estimate multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for body mass index (BMI) throughout life. Results Recent BMI had no significant association with ovarian cancer risk (P-trend 0.14 for continuous BMI), after adjustment for age and other ovarian cancer risk factors. However, a non-significant positive association (overall P-trend 0.08) was observed for BMI at age 20; the risk estimate comparing a body mass of >25 kg/m2 to the lowest quintile (≤18.88 kg/m2) was moderately but non-significantly elevated (OR 1.46; 95% CI 0.92, 2.31). Conclusion Results of this study suggest that maintenance of a lean body mass, particularly in early adult life, may decrease ovarian cancer risk.     

1-取代吡唑烷酮类抗惊构效关系的研究

1-正癸基吡唑烷-3-酮(Ⅱ结构式见表1)是欧洲专利报道的一种新型减肥剂。White等报道该化合物可通过血脑屏障,并对γ-氨基丁酸氨基转移酶(GABA-T)有强烈的抑制活性,但对谷氨酸脱羧酶的抑制作用较弱,因此可引起脑内γ-氨基丁酸(GABA)水平的升高,故我们相信应有抗惊活性。经我们合成后,发现Ⅱ确有良好的抗癲痫活性,抗小鼠最大电     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Vitamin and micronutrient intake and the risk of community-acquired pneumonia in US women

Background

There are limited data regarding the role of dietary and supplemental vitamin intake and the risk of community-acquired pneumonia.

Methods

We prospectively examined, during a 10-year period, the association between dietary and supplemental vitamin intake and the risk of community-acquired pneumonia among 83,165 women in Nurses’ Health Study II who were between the ages of 27 and 44 years in 1991. We excluded women who had pneumonia before 1991, those who did not provide complete dietary information, or those with a history of cancer, cardiovascular disease, or asthma. Self-administered food frequency questionnaires were used to assess dietary and supplemental vitamin intake. Cases of pneumonia required a diagnosis by a physician and confirmation with a chest radiograph. The independent associations between specific vitamins and pneumonia risk were evaluated.

Results

There were 925 new cases of community-acquired pneumonia during 650,377 person-years of follow up. After adjusting for age, cigarette smoking, body mass index, physical activity, total energy intake, and alcohol consumption, there were no associations between dietary or total intake of any individual vitamin and risk of community-acquired pneumonia. Specifically, women in the highest quintile of vitamin A intake did not have a significantly lower risk of pneumonia than women in the lowest quintile (multivariate relative risk [RR] = 0.88; 95% confidence interval [CI], 0.70-1.09, P for trend = .16). Similarly, vitamin C (RR = 0.94; 95% CI, 0.76-1.16, P for trend = .81) and E (RR = 0.95; 95% CI, 0.76-1.17, P for trend = .74) intake did not alter risk of pneumonia.

Conclusions

Higher vitamin intake from diet and supplements is unlikely to reduce pneumonia risk in well nourished women.     

Unopposed estrogen therapy and the risk of invasive breast cancer

BACKGROUND: Although short-term unopposed estrogen use does not seem to increase breast cancer risk, the effect of longer-term estrogen use remains unclear. We sought to assess the relationship between longer-term use of unopposed estrogen and the risk of invasive breast cancer over an extended follow-up period. METHODS: Within the Nurses' Health Study, a prospective cohort study, we observed 11 508 postmenopausal women who had a hysterectomy and reported information on estrogen use at baseline (1980). The study population was expanded every 2 years to include women who subsequently became postmenopausal and had a hysterectomy, so that 28 835 women were included in the final follow-up period (2000-2002). Estrogen use was assessed from self-reported data on biennial questionnaires. The main outcome was invasive breast cancer. RESULTS: A total of 934 invasive breast cancers were included in the analysis. Breast cancer risk increased with duration of unopposed estrogen use among longer-term users with the highest risk seen in cancers positive for estrogen receptor (ER+) and progesterone receptor (PR+). The multivariate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer with current use of unopposed estrogen for less than 5 years, 5 to 9.9 years, 10 to 14.9 years, 15 to 19.9 years, and 20 years or longer were, respectively, 0.96 (95% CI, 0.75-1.22), 0.90 (95% CI, 0.73-1.12), 1.06 (95% CI, 0.87-1.30), 1.18 (95% CI, 0.95-1.48), and 1.42 (95% CI, 1.13-1.77) (P for trend <.001). The risk of ER+/PR+ breast cancers was noted to be statistically significant after 15 years of current use (RR, 1.48; 95% CI, 1.05-2.07). CONCLUSION: Users of unopposed estrogen were at increased risk of breast cancer but only after longer-term use.     

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors

The molecular mechanisms involved in luteolysis are still unclear in the primate. This study aimed to investigate the effect of induced luteolysis on the ovarian luteinizing hormone (LH) receptor and the steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset monkey. Luteolysis was induced in the mid-luteal phase either directly by systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal using systemic gonadotrophin releasing hormone antagonist (GnRHant) treatment. The LH receptor was studied by isotopic mRNA in-situ hybridization and in-situ ligand binding and 3beta-HSD expression was studied using isotopic mRNA in-situ hybridization and immunohistochemistry. Induced luteolysis was associated with a reduction in the expression of LH receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a reduction in the LH receptor (P < 0.05) and 3beta-HSD protein concentrations within 24 h. There were no differences in the findings whether luteolysis was induced with PGF2alpha or GnRHant. This study shows that disparate mechanisms to induce luteolysis in the primate result in an identical rapid loss of the LH receptor and 3beta-HSD. In conclusion, induced luteolysis leads to rapid loss of the steroidogenic pathway in luteal cells.      

FTO Genotype,Vitamin D Status,and Weight Gain During Childhood

Previous evidence suggests that variants in the fat mass and obesity-associated gene (FTO) affect adiposity in an age-dependent fashion in children, and nutritional factors may modify genotype effects. We assessed the effect of FTO rs9939609 on BMI and BMI-for-age Z score changes during childhood in a population-based longitudinal study in the Brazilian Amazon and investigated whether these effects were modified by vitamin D status, an important nutritional factor related to adiposity. At baseline, 1,088 children aged <10 years had complete genotypic and anthropometric data; 796 were followed up over a median 4.6 years. Baseline vitamin D insufficiency was defined as <75 nmol/L. We observed a 0.07 kg/m²/year increase in BMI and a 0.03 Z/year increase in BMI-for-age Z score per rs9939609 risk allele over follow-up (P = 0.01). Vitamin D status significantly modified FTO effects (P for interaction = 0.02). The rs9939609 risk allele was associated with a 0.05 Z/year increase in BMI-for-age Z score among vitamin D–insufficient children (P = 0.003), while no significant genetic effects were observed among vitamin D–sufficient children. Our data suggest that FTO rs9939609 affects child weight gain, and genotype effects are more pronounced among children with insufficient vitamin D levels.     

Trastuzumab-induced cardiotoxicity in elderly women with HER-2-positive breast cancer: a meta-analysis of real-world data

Background: We conducted a meta-analysis to assess the overall risk of cardiac toxicity associated with trastuzumab treatment in elderly breast cancer patients.

Methods: We searched databases from PubMed, EMBASE and Cochrane Central Registry of Controlled Trials to identify relevant studies. Statistical analyses were conducted to calculate the incidence rate, overall hazard ratio (HR) and 95% CIs using a fixed effects model.

Results: A total of 116,342 and 360 elderly patients from five cohort studies and two randomized clinical trials (RCTs) were included for analysis. The pooled incidences of symptomatic congestive heart failure (CHF) and CHF/HF/CM were 6.4% (95% CI 4.1% – 9.4) and 16.4% (95% CI 16.19% – 16.61) in patients with median age of 67.5 years from two RCTs and in patients with median age of 67.5 (60 – 75), 71 (66 – 80+), 74.5 (65 – 89), 75 (66 – 81+) and 79.5 (60 – 99) from five cohort studies, respectively. Trastuzumab was significantly correlated with an increased risk of defined cardiac toxicities in five cohort studies (HR = 1.89, 95% CI 1.72 – 2.07, p < 0.00001) and two RCTs (HR = 3.00, 95% CI 1.71, 5.26, p < 0.00001). Sub-group analysis showed that the anthracycline-based chemotherapy increased the risk of CHF/HF and CM in patients among five cohort studies (HR = 2.16, 95% CI: 1.8 – 1.87, p < 0.00001).

Conclusion: Trastuzumab is likely associated with an increased risk of cardiac toxicity in elderly patients with HER-2-positive breast cancer. Carefully monitoring cardiac function in elderly patients receiving trastuzumab, particularly with concurrent use of anthracycline, is warranted.