Utility of Anterior Zone Biopsy in Men Enrolled in Active Surveillance for Prostate Cancer

Background

Anterior zone (AZ) disease is present in one-fifth of men with newly diagnosed prostate cancer and has been associated with poor pathologic features. However, anterior targeted biopsies are not a routine part of active surveillance (AS) protocols. Our purpose is to assess the utility of AZ sampling for prostate biopsy in patients undergoing surveillance for low-risk prostate cancer.

Adrenomedullin expression in epithelial ovarian cancers and promotes HO8910 cell migration associated with upregulating integrin α5β1 and phosphorylating FAK and paxillin

Background

Epithelial ovarian cancer (EOC) is one of the leading causes of cancer deaths in women worldwide. Adrenomedullin (AM) is a multifunctional peptide which presents in various kinds of tumors.

Methods

In this study, we characterized the expression and function of AM in epithelial ovarian cancer using immunohistochemistry staining. Exogenous AM and small interfering RNA (siRNA) specific for AM receptor CRLR were treated to EOC cell line HO8910. Wound healing assay and flow cytometry were used to measure the migration ability and expression of integrin α5 of HO8910 cells after above treatments. Western blot was used to examine the phosphorylation of FAK and paxillin.

Results

We found that patients with high AM expression showed a higher incidence of metastasis, larger residual size of tumors after cytoreduction and shorter disease-free and overall survival time. Exogenous AM induced ovarian cancer cell migration in time- and dose- dependent manners. AM upregulated the expression of integrin α5 and phosphorylation of FAK, paxillin as well.

Conclusions

Our results suggested that AM contributed to the progression of EOC and had additional roles in EOC cell migration by activating the integrin α5β1 signaling pathway. Therefore, we presumed that AM could be a potential molecular therapeutic target for ovarian carcinoma.     

Overcoming resistance to antiangiogenic therapies

The concept of targeting new blood vessel formation, or angiogenesis, in tumors is an important advancement in cancer therapy, resulting, in part, from the development of such biologic agents as bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor (VEGF)-A. The rationale for antiangiogenic therapy is based on the hypothesis that if tumors are limited in their capacity to obtain a new blood supply, so too is their capacity for growth and metastasis. Additional evidence suggests that pruning and/or "normalization" of irregular tumor vasculature and reduction of hypoxia may facilitate greater access of cytotoxic chemotherapy (CT) to the tumor. Indeed, for metastatic colorectal cancer, bevacizumab in combination with established CT regimens has efficacy superior to that of CT alone. Despite ～2-month longer progression-free and overall survival times than with CT alone, patients still progress, possibly because of alternative angiogenic "escape" pathways that emerge independent of VEGF-A, or are driven by hypoxic stress on the tumor. Other VEGF family members may contribute to resistance, and many factors that contribute to the regulation of tumor angiogenesis function as part of a complex network, existing in different concentrations and spatiotemporal gradients and producing a wide range of biologic responses. Integrating these concepts into the design and evaluation of new antiangiogenic therapies may help overcome resistance mechanisms and allow for greater efficacy over longer treatment periods.     

Cutaneous melanoma susceptibility and progression genes

This review aims to provide an up-to-date view on our understanding of the molecular genetics of melanoma development. It gives an overview of genes (and loci) currently known to be substantially involved in melanoma predisposition and progression. Broadly, the review falls into 3 sections: genes/loci involved in melanoma susceptibility through germline mutation, tumor suppressor genes somatically mutated or deleted in melanoma, and oncogenes mutated somatically in melanoma. The main cellular pathways in which these genes are involved are summarized and discussed. From this it is evident that abberations of cell cycle regulation, DNA repair and receptor-mediated signal transduction are important for melanocytic neoplasia.     

Progression of vascular calcifications is associated with greater bone loss and increased bone fractures

SUMMARY: In this prospective study, we found a positive relationship between the prevalence of aortic calcifications and age. Aortic calcifications at baseline were positively associated with osteoporotic fractures. In addition, progression of aortic calcifications was also positively associated with the rate of decline in BMD at lumbar spine. INTRODUCTION: The aim of this study was to analyze the relationship between the progression of abdominal aortic calcification and osteoporosis in a Spanish cohort of men and women older than 50. METHODS: Men and women (n=624) aged 50 and over underwent two lateral X-rays of thoracic and lumbar spine and a dual X-ray absorptiometry (DXA) study at lumbar spine and hip, and were followed during 4 years. Abdominal aortic calcifications were classified as absent, mild-moderate and severe. RESULTS: There was a positive relationship between the prevalence of aortic calcifications and age. In both sexes, prevalent severe aortic calcifications were positively associated with prevalent osteoporotic fractures [odds ratio (OR)=1.93 (1.02-3.65)]. The association was stronger when only vertebral fracture was considered [OR=2.45 (1.23-4.87)]. In addition, progression of aortic calcifications showed a positive association with the rate of decline in bone mineral density (BMD) at lumbar spine. CONCLUSIONS: Aortic calcifications at baseline were positively associated with osteoporotic fractures. The progression of aortic calcifications was also positively associated with the rate of decline in BMD at lumbar spine.     

回纹型风湿症临床分析

目的 回纹型风湿症转归和预后。方法 对１５例诊断为回纹型风湿症病人的临床表现及实验室检查进行回顾性分析。结果 病人平均发病年龄为３９．２岁，病程为１．５～３０年，发作间期为半个月至４个月，８０％（１２／１５）的病人关节发作持续时间为数小时至３ｄ，多次发作期间，检查ＣＲＰ、血沉、血尿酸、血常规、尿常规结果均示正常。１５例回纹型风湿症病人关节受累表现不尽相同，８例病人关节炎作表现为同时多关节受累，其中     

Pathological review of late cerebral radionecrosis

Late cerebral radionecrosis may be considered to be a specific chronic inflammatory response, although it is unknown whether the initial damage by brain irradiation is to an endothelial cell or a glial cell. I discuss the pathological specificity of late cerebral radionecrosis by studying the published literature and a case that I experienced. In late cerebral radionecrosis, there are typical coagulation necrosis areas containing fibrinoid necrosis with occlusion of the lumina and poorly active inflammatory areas with many inflammatory ghost cells, focal perivascular lymphocytes, hyalinized vessels, and telangiectatic vascularization near and in the necrotic tissue, and more active inflammatory areas formed as a partial rim of the reactive zone by perivascular lymphocytes, much vascularization, and GFAP-positive astrocytes at the corticomedullary border adjacent to necrotic tissue in the white matter. It is difficult to believe that coagulation necrosis occurs without first disordering the vascular endothelial cells because fibrinoid necrosis is a main feature and a diffusely multiple lesion in late cerebral radionecrosis. Because various histological findings do develop, progress, and extend sporadically at different areas and times in the irradiated field of the brain for a long time after radiation, uncontrolled chronic inflammation containing various cytokine secretions may also play a key role in progression of this radionecrosis. Evaluation of the mechanism of the development/aggravation of late cerebral radionecrosis requires a further study for abnormal cytokine secretions and aberrant inflammatory reactions.     

Progression from normal cognition to mild cognitive impairment in a diverse clinic-based and community-based elderly cohort

Introduction

Investigation of the conversion rates from normal cognition (NC) to mild cognitive impairment (MCI) is important, as effective early intervention could potentially prevent or substantially delay the onset of dementia. However, reported conversion rates differ across studies and recruitment source. Our study examined predictors of conversion from NC to MCI in a racially and ethnically diverse sample drawn both from community and clinic recruitment sources.