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MicroRNA-155 (miR-155) is frequently upregulated in various types of human cancer; however, its role in cancer angiogenesis remains unknown. Here, we demonstrate the role of miR-155 in angiogenesis through targeting von Hippel-Lindau (VHL) tumour suppressor in breast cancer. Ectopic expression of miR-155 induced whereas knockdown of miR-155 inhibited human umbilical vein endothelial cell network formation, proliferation, invasion and migration. Furthermore, mammary fat pad xenotransplantation of ectopically expressed miR-155 resulted in extensive angiogenesis, proliferation, tumour necrosis and recruitment of pro-inflammatory cells such as tumour-associated macrophages. Expression of VHL abrogated these miR-155 effects. Moreover, miR-155 expression inversely correlates with VHL expression level and is associated with late-stage, lymph node metastasis and poor prognosis, as well as triple-negative tumour in breast cancer. These findings indicate that miR-155 has a pivotal role in tumour angiogenesis by downregulation of VHL, and provide a basis for miR-155-expressing tumours to embody an aggressive malignant phenotype, and therefore miR-155 is an important therapeutic target in breast cancer. [ABSTRACT FROM AUTHOR]

Background:Mutations in genes for hereditary non-polyposis colorectal cancer (HNPCC) in ovarian cancer patients remains poorly defined. We sought to estimate the frequency and characteristics of HNPCC gene mutations in a population-based sample of women with epithelial ovarian cancer.Methods:The analysis included 1893 women with epithelial ovarian cancer ascertained from three population-based studies. Full-germline DNA sequencing of the coding regions was performed on three HNPCC genes, MLH1, MSH2 and MSH6. Collection of demographic, clinical and family history information was attempted in all women.Results:Nine clearly pathogenic mutations were identified, including five in MSH6, two each in MLH1 and MSH2. In addition, 28 unique predicted pathogenic missense variants were identified in 55 patients. Pathogenic mutation carriers had an earlier mean age at diagnosis of ovarian cancer, overrepresentation of cancers with non-serous histologies and a higher number of relatives with HNPCC-related cancers.Conclusions:Our findings suggest that fewer than 1% of women with ovarian cancer harbour a germline mutation in the HNPCC genes, with overrepresentation of MSH6 mutations. This represents a lower-range estimate due to the large number of predicted pathogenic variants in which pathogenicity could not definitively be determined. Identification of mismatch repair gene mutations has the potential to impact screening and treatment decisions in these women. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide.Methods: We examined single nucleotide polymorphisms (SNPs) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) were genotyped using an Illumina assay.Results: Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population [odds ratio, OR(BB vs AA) 2.81 (1.29-6.09), P=0.01] was also observed in a replication population, and the association remained suggestive in the combined analysis [OR(BB vs AA) 1.59 (1.08-2.34), P=0.02]. No other SNP associations remained suggestive in the replication populations.Conclusion: ABL1 has been implicated in multiple processes including cell division, cell adhesion and cellular stress response. These results suggest that characterization of the function of genetic variation in this gene in other ovarian cancer populations is warranted. [ABSTRACT FROM AUTHOR]

Spatial variability in material fluxes within large river basins may arise from point source inputs, variable contributions from sub-basins and longitudinal variation in material transformation and retention. By measuring instantaneous fluxes throughout the Ohio River basin, we were able to draw inferences about the importance of these factors in determining the overall export of C, N and P from the basin. Our study spanned the lower 645 km of the Ohio River and included all tributaries that contributed at least 1% of the volume of the Ohio River at its confluence with the Mississippi. The intensively cultivated northern sub-basin (Wabash River) contributed a large fraction of N and P entering the Ohio River. In the southern sub-basins (Tennessee and Cumberland Rivers), impoundments and less intense cultivation appear to diminish and delay material delivery particularly with respect to N. The southern rivers account for a proportionately larger fraction of the water entering the Mississippi River during low discharge conditions and this fraction has increased during the past 50 years. The upper portion of the study reach was found to be a net source of CHLa and DOC and a net sink for inorganic N suggesting that this portion of the river provided a generally favorable environment for autotrophic production. Point source loadings of NH4 were significant inputs to the upper sub-reach but a relatively small component of the overall budget for dissolved inorganic N. [ABSTRACT FROM AUTHOR]

Objective: The present study examined whether levels of testosterone, sex hormone binding globulin (SHBG), or insulin levels might underlie an increased risk of postmenopausal breast cancer in women with both high waist-to-hip ratio and a family history of breast cancer disease that was noted earlier in the Iowa Women's Health Study.Methods: Participants for the current study were selected from 1922 sister groups (3978 women) in the Iowa Women's Health Study cohort. Two groups were included: (1) those with no family history of breast cancer and at least one sister with a high waist-to-hip ratio; or (2) those with a positive family history of breast cancer and at least one sister with a high waist-to-hip ratio. Testosterone, SHBG and insulin were measured by radioimmunoassay from 245 fasting blood samples.Results: Familial correlations among members of 66 families were estimated at 0.32, 0.28 and 0.25 for serum insulin, free testosterone and SHBG; respectively. Fasting serum insulin was significantly higher in breast cancer family history negative women than in family history positive women, in direct opposition to our a priori hypothesis. No significant differences were observed in serum SHBG or free testosterone across family history categories.Conclusion: This study corroborates a genetic component to fasting serum insulin, free testosterone and SHBG levels. It seems unlikely that insulin, SHBG, or testosterone explain the interaction between waist-to-hip ratio and family history of breast cancer among participants in the Iowa Women's Health Study. [ABSTRACT FROM AUTHOR]

We investigated the relation of alcohol consumption to risk of non-Hodgkin's lymphoma (NHL) in a cohort of 35 156 Iowa women aged 55-69 years who participated in the Iowa Women's Health Study in 1986. Alcohol consumption at baseline was obtained using a mailed questionnaire. During the 9-year follow-up period, 143 incident cases of NHL were identified. Higher alcohol consumption was significantly associated with a decreased risk of NHL (P-trend = 0.03). Compared to non-drinkers, multivariate-adjusted relative risks (RRs) were decreased for women with intake of < or = 3.4 g day(-1) (RR = 0.78; 95% confidence interval (CI) 0.51-1.21) and > 3.4 g day(-1) (RR = 0.59; 0.36-0.97). The inverse association could not be attributed to one particular type of alcoholic beverage, although red wine (RR = 0.21 for > 2 glasses per month vs non-drinker; 0.05-0.86; P-trend = 0.02) has the most distinct effect. The apparent protective effect was universal regardless of specific NHL grade or Working Formulation subtype, but was most pronounced for nodal NHL (RR = 0.48; 0.26-0.90; P-trend = 0.01) and low-grade NHL (RR = 0.52; 0.21-1.26; P-trend = 0.05). These data suggest that moderate alcohol consumption is inversely associated with the risk of NHL in older women and the amount of alcohol consumed, rather than the type of alcoholic beverages, appears to be the main effect determinant. [ABSTRACT FROM AUTHOR]

A population of Haliotis rubra Leach at Blubber Head in south-eastern Tasmania, Australia (43°19′S; 147°04′E) was sampled between February 1984 and October 1985. Relatively large numbers of 30 to 45 d-old new recruits were observed entering the population between October and February of each year. The annual instantaneous rate of natural mortality, Z, was 0.70 during the second year of life. The rate of natural mortality declined with age. The onset of sexual maturity began at 4 to 5 yr of age or an approximate maximum length of 90 mm, and most abalone in the population were mature at 6 to 7 yr of age or at lengths>110 mm. The onset of sexual maturity coincided with a decline in growth rates and the emergence of abalone from the subboulder habitat. These observations are discussed in the light of previous observations of population structure in haliotid populations. [ABSTRACT FROM AUTHOR]

Objective: The purpose was to investigate whether dietary associations with risk of colon cancer in women differ by family history of the disease.Methods: Data were analyzed from a prospective cohort study of 35,216 Iowa (United States) women aged 55 to 69 years at baseline. Through 31 December 1995, 241 colon cancers were identified through record linkage with the State Health Registry. The cohort was stratified on family history of colon cancer in first-degree relatives; nutrient intakes were divided into tertiles.Results: Analyses using Cox regression revealed that the association of most dietary components with colon cancer incidence were similar for individuals with and without a family history. However, total calcium intake was associated inversely with colon cancer among women with a negative family history (relative risk [RR] = 0.50 for upper cf lower tertile, P < 0.001), but was unrelated to incidence for women with a positive family history (RR = 1.1 for upper cf lower tertile, P = 0.69). Similarly, total vitamin E intake was associated with lower risk among women with a negative family history (RR = 0.67 for upper cf lower tertile, P = 0.04), but not among women with a positive family history (RR = 0.87 for upper cf lower tertile, P = 0.67). High intakes of fiber, fruits, and vegetables were each weakly inversely associated with risk among family-history negative women, but not among family-history positive women.Conclusions: These data, if corroborated, suggest that dietary factors typically associated with lower risk may be less effective risk-reduction interventions against colon cancer for individuals with a family history of colon cancer. [ABSTRACT FROM AUTHOR]

Objectives: As there are some suggestions that a family history of cancer or autoimmune disease might be associated with an increased risk of leukemia in children, we explored this possibility using data from a matched case-control study conducted by the Children's Cancer Group.Methods: We compared the family history of cancer and autoimmune diseases of 302 infant leukemia cases (diagnosed within the first 18 months of life) with that of 668 individually matched controls in the United States and Canada.Results: Although not significant, cancer history in parents was found to be associated with an elevated risk of infant leukemia (odds ratio [OR] = 1.4, 95 percent confidence interval [CI] = 0.6-3.6), predominantly acute myeloid leukemia (AML) (OR = 2.2, CI = 0.6-9.0). Cancer history among second-degree relatives was also related to a nonsignificantly elevated risk of AML. Family history of autoimmune diseases, on the other hand, was generally not found to be related to the risk of infant leukemia.Conclusion: This study provided no strong evidence that family history of cancer or autoimmune disease is a major risk factor for infant leukemia. [ABSTRACT FROM AUTHOR]

Extraction of chronically implanted pacing and defibrillator leads is facilitated by using specialized locking stylets placed in the lead to allow application of traction and to stabilize the lead during sheath dissection of fibrotic tissue. We report the initial multicenter series of cases using a novel lead locking device (LLD). In 57 consecutive patients presenting at 6 institutions for lead extraction, 99 leads were treated using the LLD. After removing the pulse generator, leads were severed, the inner coil dilated and an LLD was successfully inserted and locked in the inner lumen of 95/99 (96±%) leads. With traction applied to the LLD, a variety of sheaths were advanced over the lead body to separate it from adhesions. In 97/99 (98±%) leads, all or most of the lead was removed via the implant vein; 2 leads were removed via the femoral vein. No major complications were observed. The LLD deploys safely and reliably, and provides stable support for advancement of dissecting sheaths. [ABSTRACT FROM AUTHOR]