The free β-subunit of human chorionic gonadotropin as a prognostic factor in renal cell carcinoma

The free β-subunit of human chorionic gonadotropin β is expressed in several nontrophoblastic tumours and this is usually associated with aggressive disease. Little is known about human chorionic gonadotropin β expression in renal cancer. We determined the pretreatment levels of human chorionic gonadotropin β in serum of patients with renal cell carcinoma, and studied whether elevated levels predicted the clinical outcome. Serum samples were collected before surgery from 177 patients with renal cell carcinoma and from 84 apparently healthy controls. Human chorionic gonadotropin β in serum was measured by a highly sensitive time-resolved immunofluorometric assay. The prognostic value of human chorionic gonadotropin β, and of usual clinical and pathological variables was analyzed by the Kaplan-Meier method, the log rank test and Cox multiple hazard regression. The serum concentrations of human chorionic gonadotropin β were increased in 23% of the renal cell carcinoma patients and they were significantly higher in patients with renal cell carcinoma than in controls (P<0.0001). The concentrations did not correlate with clinical stage and histopathological grade, but patients with increased human chorionic gonadotropin β levels had significantly shorter survival time than those with levels below the median (cut-off 1.2 pmol l−1, P=0.0029). In multivariate analysis human chorionic gonadotropin β, tumour stage and grade were independent prognostic variables. The serum concentration of human chorionic gonadotropin β is an independent prognostic variable in renal cell carcinoma. The preoperative value of human chorionic gonadotropin β in serum may be used to identify patents with increased risk of progressive disease

Association between depressive symptoms and serum concentrations of homocysteine in men: a population study

http://deepblue.lib.umich.edu/bitstream/2027.42/51506/1/Tolmunen T, Association Between Depressive Symptoms, 2004.pd

Water

Meta-analysis can be a powerful tool for demonstrating the applicability of a concept beyond the context of individual clinical trials and observational studies, including exploration of effects across different subgroups. Meta-analysis avoids Simpson's paradox, in which a consistent effect in constituent trials is reversed when results are simply pooled. Meta-analysis in critical care medicine is made more complicated, however, by the heterogeneous nature of critically ill patients and the contexts within which they are treated. Failure to properly adjust for this heterogeneity risks missing important subgroup effects in, for example, the interaction of treatment with varying levels of baseline risk. When subgroups are defined by characteristics that vary within constituent trials (such as age) rather than features constant within each trial (such as drug dose), there is the additional risk of incorrect conclusions due to the ecological fallacy. The present review explains these problems and the strategies by which they are overcome

Development of a novel small antibody that retains specificity for tumor targeting

<p>Abstract</p> <p>Background</p> <p>For the targeted therapy of solid tumor mediated by monoclonal antibody (mAb), there have different models of rebuilding small antibodies originated from native ones. Almost all natural antibody molecules have the similar structure and conformation, but those rebuilt small antibodies cannot completely keep the original traits of parental antibodies, especially the reduced specificity, which gravely influences the efficacy of small antibodies.</p> <p>Methods</p> <p>In this study, authors developed a novel mimetic in the form of V_HFR1_C-10-V_HCDR1-V_HFR2-V_LCDR3-V_LFR4_N-10for a parental mAb induced with human breast cancer, and the mimetic moiety was conjugated to the C-terminal of toxicin colicin Ia. The novel fusion peptide, named protomimecin (PMN), was administered to MCF-7 breast cancer cells to demonstrate its killing competency <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>Compared with original antibody-colicin Ia (Fab-Ia) and single-chain antibody-colicin Ia (Sc-Ia) fusion proteins, PMN retained the targeting specificity of parental antibody and could specifically kill MCF-7 cells <it>in vitro</it>. By injecting intraperitoneally into BALB/c athymic mice bearing MCF-7 tumors, with reduced affinity, PMN significantly suppressed the growth of tumors compared with control mice treated by toxicin protein, Fab-Ia protein, Sc-Ia protein or by PBS (<it>p </it>< 0.05).</p> <p>Conclusion</p> <p>This novel mimetic antibody retained original specificity of parental antibody, and could effectively guide killer moiety to suppress the growth of breast cancer by targeted cell death.</p

Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study

http://deepblue.lib.umich.edu/bitstream/2027.42/51490/1/Virtanen JK, Serum Homocysteine, Folate and Risk of Stroke, 2005.pd

Homocysteine as a risk factor for CVD mortality in men with other CVD risk factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study

http://deepblue.lib.umich.edu/bitstream/2027.42/51491/1/Virtanen JK, Homocysteine as a Risk Factor for CVD, 2005.pd

The use of fasting vs. non-fasting triglyceride concentration for estimating the prevalence of high LDL-cholesterol and metabolic syndrome in population surveys

<p>Abstract</p> <p>Background</p> <p>For practical reasons it is not easy to obtain fasting samples in large population health surveys. Non-fasting triglyceride (Tg) values are difficult to interpret. The authors compared the accuracy of statistically corrected non-fasting Tg values with true fasting values and estimated the misclassification of subjects with high low-density lipoprotein cholesterol (LDL-C) and the metabolic syndrome.</p> <p>Methods</p> <p>Non-fasting blood was obtained from a population-based sample of 4282 individuals aged 24-75 years in the National FINRISK 2007 Study. Fasting blood samples were drawn from the same persons 3 months later. Non-fasting serum Tg values were converted into fasting values using previously published formula. LDL-C was calculated and classification of the metabolic syndrome was carried out according to three different latest guidelines.</p> <p>Results</p> <p>The median (25^th, 75th percentile) non-fasting serum Tg concentration was 1.18 (0.87, 1.72) mmol/L and after postprandial correction 1.06 (0.78, 1.52) mmol/L. The true-fasting serum Tg concentration was 1.00 (0.75, 1.38) mmol/L (<it>P </it>< 0.001) vs. non-fasting and corrected value. Bias of the corrected value was +5.9% compared with the true-fasting Tg. Of the true fasting subjects, 56.4% had LDL-C ≥3.00 mmol/L. When calculated using non-fasting serum Tg, the prevalence of high LDL-C was 51.3% and using statistically corrected Tg it was 54.8%. The prevalence of metabolic syndrome was 35.5% among fully fasted persons and among non-fasting subjects 39.7%, which after statistical correction of Tg decreased to 37.6% (P < 0.001 for all comparisons).</p> <p>Conclusions</p> <p>Correction of non-fasting serum Tg to fasting values plays a minor role in population studies but nevertheless reduces misclassification of calculated high LDL-C from 5.1 to 1.6% and the metabolic syndrome from 4.2 to 2.1%.</p

Human chorionic gonadotropin and its relation to grade, stage and patient survival in ovarian cancer

Background: An influence of gonadotropins (hCG) on the development of ovarian cancer has been discussed. Therefore, we quantified serum hCG levels in patients with benign and malignant ovarian tumors and the hCG expression in ovarian cancer tissue in order to analyze its relation to grade, stage, gonadotropin receptor (LH-R, FSH-R) expression and survival in ovarian cancer patients. Methods: Patients diagnosed and treated for ovarian tumors from 1990 to 2002 were included. Patient characteristics, histology including histological subtype, tumor stage, grading and follow-up data were available. Serum hCG concentration measurement was performed with ELISA technology, hCG tissue expression determined by immunohistochemistry. Results: HCG-positive sera were found in 26.7% of patients with benign and 67% of patients with malignant ovarian tumors. In addition, significantly higher hCG serum concentrations were observed in patients with malignant compared to benign ovarian tumors (p = 0.000). Ovarian cancer tissue was positive for hCG expression in 68%. We identified significant differences in hCG tissue expression related to tumor grade (p = 0.022) but no differences with regard to the histological subtype. In addition, mucinous ovarian carcinomas showed a significantly increased hCG expression at FIGO stage III compared to stage I (p = 0.018). We also found a positive correlation of hCG expression to LH-R expression, but not to FSH-R expression. There was no significant correlation between tissue hCG expression and overall ovarian cancer patient survival, but subgroup analysis revealed an increased 5-year survival in LH-R positive/FSH-R negative and hCG positive tumors (hCG positive 75.0% vs. hCG negative 50.5%). Conclusions: Serum human gonadotropin levels differ in patients with benign and malignant ovarian tumors. HCG is often expressed in ovarian cancer tissue with a certain variable relation to grade and stage. HCG expression correlates with LH-R expression in ovarian cancer tissue, which has previously been shown to be of prognostic value. Both, the hormone and its receptor, may therefore serve as targets for new cancer therapies

Dietary and other lifestyle correlates of serum folate concentrations in a healthy adult population in Crete, Greece: a cross-sectional study

BACKGROUND: Folate has emerged as a key nutrient for optimising health. Impaired folate status has been identified as a risk factor for cardiovascular disease, various types of cancers, and neurocognitive disorders. The study aimed at examining the distribution and determinants of serum folate concentrations in a healthy adult population in Crete, Greece. METHODS: A cross-sectional sample of 486 healthy adults (250 men, 236 women) aged 39 ± 14 years, personnel of the Medical School and the University Hospital of Crete in Greece, was examined. Serum folate and vitamin B(12 )concentrations were measured by microbiological assay, and total homocysteine was determined fluorometrically and by high-pressure liquid chromatography. Lifestyle questionnaires were completed, and nutrient intakes and food consumption were assessed by 24-h dietary recalls. Multivariate analyses were performed using SPSS v10.1. RESULTS: The geometric mean (95% confidence interval) concentrations of serum folate were 15.6 μmol/l (14.6–16.8) in men and 19.2 μmol/l (17.9–20.7) in women (p < 0.001). Inadequate folate levels (≤7 nmol/l) were present in 6.8% of men and 2.1% of women (p < 0.001). Approximately 76% of men and 87% of women did not meet the reference dietary intake for folate (400 μg/day). Serum folate was inversely related to total homocysteine levels (p < 0.001). Increased tobacco and coffee consumption were associated with lower folate concentrations (p < 0.05 for both) but these associations disappeared after controlling for nutrient intakes. In multivariate analysis, intakes of MUFA, fibre, calcium, magnesium, folate, and vitamins A, E, C, B(1), and B(6 )were positively associated with serum folate. Consumption of potatoes, legumes, fruits, and vegetables were favourably related to the serum folate status. CONCLUSION: Serum folate concentrations were associated with various demographic, lifestyle and dietary factors in healthy Cretan adults. Large-scale epidemiological studies should be conducted within the general Greek adult population to assess the prevalence of impaired folate status and further examine associations with dietary patterns and chronic disease risk. Considering the importance of folate in health maintenance, it is important to increase the public's awareness of modifiable lifestyle patterns and diet and tobacco use in particular, which may be associated with improved folate status