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Examines the possibility of ret/papillary thyroid carcinoma (PTC)-1 activation in Hashimoto thyroiditis. Documentation of chromosomal translocations and inversions in PTC; Varieties of c-ret activation; Presence of chimeric transcripts of ret/PTC-1/3 in cases of Hashimoto thyroiditis.

Abstract: Objective. : The aim of this study was to assess whether microvessel density (measured by CD31), vascular endothelial growth factor (VEGF) or multidrug resistance (MDR1) could determine the response to chemotherapy or act as prognostic factors in ovarian cancer. Methods.: Seventy-nine ovarian specimens were immunostained. Pearson correlation, 1-way ANOVA and chi-square were used for univariate analysis. Kaplan Meier survival curves were used, log-rank was used for univariate analysis and a Cox proportional hazards regression model was used for multivariate evaluation. Response to chemotherapy was assessed after 6 months and again after 1 year. Result.: Quantifying VEGF proved to be a valuable independent prognostic indicator in progression-free survival (PFS) (p <0.05) and overall survival (OS) (p <0.0001). VEGF correlated with response to chemotherapy at the 6-month interval (r =0.446, p <0.001) but failed to correlate at the 1-year interval. Increased staining with CD31 was associated with decreased PFS (p <0.01) and OS (p <0.01) in univariate but not multivariate analysis. MDR1 failed to act as a prognostic marker or as a predictor of response to chemotherapy. Conclusion.: VEGF correlates with response to chemotherapy at the 6-month but not the 12-month interval. What should our criteria be for determining sensitivity to chemotherapy? CD31, VEGF and MDR1 do play a role in some ovarian malignancies but other factors are likely to be involved and perhaps molecular profiling will determine which factors will be important for determining the response to chemotherapy. [Copyright &y& Elsevier]

Introduction The close relationship between coagulation, thrombosis and cancer has long been established. Gynaecological cancers, in particular ovarian cancers, carry a high risk of thrombosis but coagulation activation is also thought to play a role in tumorigenesis and metastasis. In experimental animal models of metastasis, mice with a genetic procoagulant phenotype are prone to develop metastasis and anticoagulant therapy dramatically reduces pulmonary metastasis in these models. The aPC pathway is a key natural anticoagulant pathway, in addition to its role in venous thrombosis, dysregulation of this pathway is also thought to play a role in the pathogenesis of some cancers. No data exists in ovarian and endometrial cancers. Aim The aim of this study is to determine the expression of key proteins of the activated protein C pathway in endometrial and ovarian malignant tumours compared to benign tumours and to assess their role in patient survival. Materials and Methods RNA was extracted from 78 (54 malignant and 24 benign) fresh frozen ovarian and endometrial tumours samples. Tumour biopsies were mRNA expression of endothelial protein C receptor (EPCR), protein S (PS), protein C (PC), thrombomodulin (TM), Factor V (FV) and VIII (FVIII) and PAR-1 and PAR-2 was measured using TaqMan Low Density Arrays. mRNA fold change relative to benign expression was determined using the 2 -delta delta Ct method with 18s as internal standard. All patients gave full and informed consent and the study had the approval of the hospital ethics committee. Total cell protein was extracted from ovarian tumour tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure protein plasma expression Results EPCR (P < 0.001), protein S (P < 0.0001) and Factor VIII (P < 0.003) mRNA expression was significantly downregulated in malignant tumours compared with benign. Factor V and PAR-2 were significantly upregulated (P < 0.001; P < 0.004). Protein C was not consistently expressed. Reduced EPCR and TM protein expression was also observed in malignant tumours with increased plasma levels of Factor V. Reduced protein S and increased FV were associated with decreased survival. Plasma levels of Factor V were related to grade in the endometrial cancer group. PAR-2 mRNA expression was increased in ovarian tumours (P < 0.001) however PAR-1 expression remained unchanged. Conclusions Our results show reduced expression of key proteins associated with activation of protein C combined with increased expression in FV in gynaecological malignancies. These changes may contribute to local thrombin production and tumour progression and metastasis. Further work is required to determine the precise mechanisms involved. [ABSTRACT FROM AUTHOR]

Reports that a novel form of inflammatory bowel disease has been found in a cohort of children with developmental disorder, manifesting predominantly as regressive autism. Intestinal pathology included in the diagnosis; Possible association between measles virus and chronic enterocolitis among the children.