520 research outputs found

    Flow Around an Object Projected from a Cavity into a Supersonic Freestream

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    The pressure and flow field of a supersonic flow over a cavity, with and without a store, was the focus of this experiment. One cavity geometry (length to depth ratio 3.6) was studied; the freestream Mach number and the placement of the store relative to the cavity floor were varied. The pressure spectra on the cavity floor were markedly different between Mach numbers of 1.8 and 2.9. The Mach 1.8 case exhibited clear spectral peaks consistent with predictions by Rossiter, whereas the Mach 2.9 flow did not. With the store placed within the free shear layer, the pressure fluctuations on the cavity floor decreased for Mach 1.8 and increased for Mach 2.9. High-speed Schlieren photography was used to visualize the interaction of the free shear layer and the modeled store. Images revealed that flow structures in the free shear layer of the Mach 2.9 flow exhibited less spanwise coherence then their Mach 1.8 flow counterparts. Images also revealed vertical displacement of the free shear layer as the store traversed through it. Pressure-sensitive paint (PSP) was utilized to quantify the full-field mean pressure on the cavity floor and store. A pressure rise near the trailing edge was noted for both freestream Mach numbers. The mean pressure contour of the floor for the Mach 1.8 exhibited considerable three-dimensionality, despite the generally spanwise coherent structures in the free shear layer

    Prognosis of ovarian cancer subsequent to venous thromboembolism: a nationwide Danish cohort study

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    BACKGROUND: Venous thromboembolism (VTE) is associated with ovarian cancer and may impact the prognosis of ovarian cancer. Our aims were to examine the extent of disease at the time of the diagnosis of ovarian cancer and to estimate the impact of VTE on survival of ovarian cancer. METHODS: We identified 12,835 ovarian cancer patients diagnosed from 1980 to 2003 in the Danish Cancer Registry and obtained information on previous primary VTE diagnosis from the Danish National Hospital Discharge Registry. Ovarian cancer patients with previous VTE related to other cancers, surgery, or pregnancy were excluded. The vital status was determined by linking data to the Civil Registration System. RESULTS: We identified 50 ovarian cancer patients diagnosed less than 4 months after the VTE and 78 ovarian cancer patients diagnosed more than 4 months after the VTE diagnosis. Advanced stages tended to be more common among patients with VTE. One-year survivals were 44% and 54% among the two VTE groups, compared with 63% among patients without VTE. Adjusted (for age, calendar time, comorbidity, and FIGO-stage) mortality ratios were 1.7 (95% CI = 1.2–2.5) and 1.2 (95% CI = 0.8–1.7), respectively. CONCLUSION: Ovarian cancer diagnosed less than four months before VTE is associated with an advanced stage and a poorer prognosis

    Cooperation of decay-accelerating factor and membrane cofactor protein in regulating survival of human cervical cancer cells

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    <p>Abstract</p> <p>Background</p> <p>Decay-accelerating factor (DAF) and membrane cofactor protein (MCP) are the key molecules involved in cell protection against autologus complement, which restricts the action of complement at critical stages of the cascade reaction. The cooperative effect of DAF and MCP on the survival of human cervical cancer cell (ME180) has not been demonstrated.</p> <p>Methods</p> <p>In this study we applied, for the first time, short hairpin RNA (shRNA) to knock down the expression of the DAF and MCP with the aim of exploiting complement more effectively for tumor cell damage. Meanwhile, we investigated the cooperative effects of DAF and MCP on the viability and migration, moreover the proliferation of ME180 cell.</p> <p>Results</p> <p>The results showed that shRNA inhibition of DAF and MCP expression enhanced complement-dependent cytolysis (CDC) up to 39% for MCP and up to 36% for DAF, and the combined inhibition of both regulators yielded further additive effects in ME180 cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two protein individually.</p> <p>Conclusion</p> <p>These data indicated that combined DAF and MCP shRNA described in this study may offer an additional alternative to improve the efficacy of antibody-and complement-based cancer immunotherapy.</p

    Differential trends in the rising incidence of endometrial cancer by type: data from a UK population-based registry from 1994 to 2006

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    BACKGROUND: Endometrial cancer is the most common gynaecological cancer in the western world, the incidence increasing in the United Kingdom by over 40 % since 1993. Two types of endometrial cancer exist – oestrogen-dependent type 1 with good prognosis and non-oestrogen-dependent type 2 with poor prognosis. The histopathological distribution of the increase in endometrial cancer is unknown. This study investigates the observed incidence trends of the two types, the age, stage, and socioeconomic distribution of this increase and survival outcome. METHODS: Data were analysed from 6867 women with endometrial cancer registered between 1994 and 2006, at a UK population-based cancer registry. RESULTS: Increased endometrial cancer incidence is confined to type 1 cancers with a significant increase in age standardised incidenc

    Simultaneous siRNA Targeting of Src and Downstream Signaling Molecules Inhibit Tumor Formation and Metastasis of a Human Model Breast Cancer Cell Line

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    Src and signaling molecules downstream of Src, including signal transducer and activator of transcription 3 (Stat3) and cMyc, have been implicated in the development, maintenance and/or progression of several types of human cancers, including breast cancer. Here we report the ability of siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc to inhibit the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S, a widely used model for breast cancer research.Src and its downstream signaling partners were specifically targeted and knocked-down using siRNA. Changes in the growth properties of the cultured cancer cells/tumors were documented using assays that included anchorage-dependent and -independent (in soft agar) cell growth, apoptosis, and both primary and metastatic tumor growth in the mouse tumor model. siRNA-mediated Src knock-down alone, and simultaneous knock-down of Src and Stat3 and/or cMyc inhibited the neoplastic phenotype of a highly metastatic human model breast cancer cell line, MDA-MB-435S. This knock-down resulted in reduced growth in monolayer and soft agar cultures, and a reduced ability to form primary tumors in NOD/SCID mice. In addition, direct intra-tumoral injection of siRNAs targeting these signaling molecules resulted in a substantial inhibition of tumor metastases as well as of primary tumor growth. Simultaneous knock-down of Src and Stat3, and/or Myc exhibited the greatest effects resulting in substantial inhibition of primary tumor growth and metastasis.These findings demonstrate the effectiveness of simultaneous targeting of Src and the downstream signaling partners Stat3 and/or cMyc to inhibit the growth and oncogenic properties of a human cancer cell line. This knowledge may be very useful in the development of future therapeutic approaches involving targeting of specific genes products involved in tumor growth and metastasis

    Morbidity, Including Fatal Morbidity, throughout Life in Men Entering Adult Life as Obese

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    Background: The association between obesity in adults and excess morbidity and mortality is well established, but the health impact throughout adult life of being obese in early adulthood needs elucidation. We investigated somatic morbidity, including fatal morbidity, throughout adulthood in men starting adult life as obese. Methods: Among 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (defined as BMI$31.0 kg/m 2), and, as controls, a random 1 % sample of the others was identified. In the age range of 18–25 years, there were 1,862 obese, which encompass the men above the 99.5 percentile, and 3,476 controls. Information on morbidity was obtained via national registers. Cox regression models were used to estimate the relative morbidity assessed as first incidence of disease, occurrence of disease in the year preceding death and prevalent disease at time of death. Results: From age 18 through 80 years the obese had an increased risk of becoming diseased by or die from a broad range of diseases. Generally, the incidence of first event, occurrence in the year prior to death, and prevalence at time of death showed the same pattern. As an example, the relative hazard of type 2 diabetes was constant throughout life at 4.9 (95% confidence intervals [CI]: 4.1–5.9), 5.2 (95 % CI: 3.6–7.5), and 6.8 (95 % CI: 4.6–10.1), respectively. Conclusions: Our findings strongly support the continued need to avoid beginning adult life as obese, as obese young me

    High BMI is significantly associated with positive progesterone receptor status and clinico-pathological markers for non-aggressive disease in endometrial cancer

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    Background: Endometrial cancer incidence is increasing in industrialised countries. High body mass index (BMI, kg m−2) is associated with higher risk for disease. We wanted to investigate if BMI is related to clinico-pathological characteristics, hormone receptor status in primary tumour, and disease outcome in endometrial cancer. Patients and methods: In total, 1129 women primarily treated for endometrial carcinoma at Haukeland University Hospital during 1981–2009 were studied. Body mass index was available for 949 patients and related to comprehensive clinical and histopathological data, hormone receptor status in tumour, treatment, and follow-up. Results: High BMI was significantly associated with low International Federation of Gynaecology and Obstetrics (FIGO) stage, endometrioid histology, low/intermediate grade, and high level of progesterone receptor (PR) mRNA by qPCR (n=150; P=0.02) and protein expression by immunohistochemistry (n=433; P=0.003). In contrast, oestrogen receptor (ERα) status was not associated with BMI. Overweight/obese women had significantly better disease-specific survival (DSS) than normal/underweight women in univariate analysis (P=0.035). In multivariate analysis of DSS adjusting for age, FIGO stage, histological subtype, and grade, BMI showed no independent prognostic impact. Conclusion: High BMI was significantly associated with markers of non-aggressive disease and positive PR status in a large population-based study of endometrial carcinoma. Women with high BMI had significantly better prognosis in univariate analysis of DSS, an effect that disappeared in multivariate analysis adjusting for established prognostic markers. The role of PR in endometrial carcinogenesis needs to be further studied

    Tobacco smoking, body mass index, hypertension, and kidney cancer risk in central and eastern Europe

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    In a case–control study of kidney cancer in four central European countries, with 1097 incident cases and 1476 controls, we found an increased risk for self-reported hypertension and for obesity. Additional unknown risk factors are likely to be responsible for the high rates of kidney cancer in this region
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