Immunochemical and molecular-Genetic markers in diagnostics of gastric cancer

Intensive studies of molecular mechanisms responsible for tumor transformation results in identification of new proteins and their genes involved into tumor development. These proteins may be used as markers of tumor transformation of cells and the level of their expression may be evaluated by means of modern highly sensitive and technological methods of analysis. This review summarized literature data on currently used immunohistochemical and molecular genetic markers of gastric cancer. It highlights genetic and epigenetic changes detected in nucleic acids of tumor tissue cells in malignant and benign gastric diseases as well as in the level of DNA circulating in blood of patients with gastric cancer.     

The Notch pathway in prostate development and cancer

Abstract The Notch family of transmembrane receptors are important mediators of cell fate determination. Accordingly, Notch signaling is intimately involved in the development of numerous tissues. Recent findings have highlighted a critical role for Notch signaling in normal prostate development. Notch signaling is required for embryonic and postnatal prostatic growth and development, for proper cell lineage specification within the prostate, as well as for adult prostate maintenance and regeneration following castration and hormone replacement. Evidence for Notch as a regulator of prostate cancer development, progression, and metastasis has also emerged. This review summarizes our current understanding of the role of Notch pathway elements, including members of the Jagged, Delta-like, hairy/enhancer-of-split, and hairy/enhancer-of-split related with YRPW motif families, in prostate development and tumorigenesis. Data supporting Notch pathway elements as oncogenes and tumor suppressors in prostate tumors, as well as data implicating Notch receptors and ligands as potential markers of normal prostate stem/progenitor cells and prostate cancer stem/initiating cells, are also presented.     

The proteomics of prostate cancer exosomes

Exosomes and other microvesicles are emerging as rich reservoirs of tumor-specific proteins and biomarkers for cancer detection and progression. For prostate cancer, exosomes secreted by the prostate can be isolated from prostatic secretions, seminal fluid, tissue, urine or blood for further proteomic analysis. Structurally, prostate-derived exosomes are distinct in size, membrane composition and specific prostate protein content, potentially providing a novel and easily isolatable source of biomarkers from clinical biofluids. The key to these isolation strategies will be the targeting of specific prostatic proteins expressed in these exosomes, thus requiring detailed proteomic characterizations. A summary of ongoing efforts to characterize the proteome of these unique prostate cancer-associated exosomes and their potential applications for use in biomarker assays is presented.     

Sialyl-lewis-X, Gleason grade and stage in non-metastatic human prostate cancer

Early stage prostate cancers are now commonly encountered because of widespread use of screening tools. Increased cancer cell proliferation, and expression of sialyl Lewis could be important as predictors of clinical behaviour and survival in addition to histologic grade. In this study, the expression of sialyl-Lewisx (sLex) was determined by immunohistochemical methods in 38 routinely processed prostate biopsies and transurethral resections preceeding radical prostatectomies for organ confined prostate cancers. Histologic grades were determined from pathologic reports and divided into two (2) groups; low grade (Gleason score 2–4) and medium grade (Gleason score 5–7). Tumour stages were based on radical prostatectomy reports and 29 were T2 and 9 were T3. SLex was positive in 10 of 14 (71.4%) low grade and 14 of 24 (62.5%) medium grade cancers; 22/29 (75.9%) T2 and 8/9 (88.9%) T3 were sLex positive; 1 of 15 (7.2%) low grade and 5 of 24 (20.8%) medium grade were strongly positive (3+) or overexpressing sLex. Overexpression of sLex was a feature of medium grade cancer, suggesting that localized prostate cancers with increased potential for progression and metastasis exist in the clinically non-metastatic group. This revised version was published online in November 2006 with corrections to the Cover Date.     

MicroRNAs that affect prostate cancer: emphasis on prostate cancer in African Americans

Abstract

Although concerted efforts have been directed toward eradicating health disparities in the United States, the disease and mortality rates for African American men still are among the highest in the world. We focus here on the role of microRNAs (miRNAs) in the signaling pathways of androgen receptors and growth factors that promote the progression of prostate cancer to more aggressive disease. We explore also how differential expression of miRNAs contributes to aggressive prostate cancer including that of African Americans.     

Modulation of liver X receptor signaling as novel therapy for prostate cancer

Liver X receptors (LXRs) are important regulators of cholesterol, fatty acid, and glucose homeostasis. LXR agonists are effective for treatment of murine models of atherosclerosis, diabetes, and Alzheimer’s disease. Recently we observed that LXR agonists suppressed proliferation of prostate and breast cancer cells in vitro and treatment of mice with the LXR agonist T0901317 suppressed the growth of prostate tumor xenografts. LXR agonists appear to cause G1 cell cycle arrest in cells by reducing expression of Skp2 and inducing the accumulation of p27^Kip. T0901317 induced expression of ATP-binding cassette transporter A1 (ABCA1) and delayed the progression of androgen-dependent human prostate tumor xenografts towards androgen-independency in mice. Phytosterols, the plant equivalent of mammalian cholesterol, have recently been shown to be agonists for LXRs. β-Sitosterol and campesterol, the two most common phytosterols, suppressed proliferation of prostate and breast cancer cells. The anticancer activity of phytosterols may be due to LXR signaling. This review examines the potential use of LXR signaling as a therapeutic target in prostate and other cancers.     

人体激肽释放酶2与前列腺癌

人体激肽释放酶2(human kallikrein 2,hK2)是一种主要在前列腺中表达的丝氨酸蛋白酶,近年作为前列腺癌的血清标记物受到广泛关注.随着对hK2结构特征、组织表达、生物学活性和调节,及其与前列腺癌病理过程的关系的研究更一步深入,hK2在前列腺癌诊断、病理分期及治疗中的潜在应用价值将越加瞩目.     

前列腺癌内分泌治疗现状

前列腺癌（prostatecancerPC）是欧美国家男性发病率最高的恶性肿瘤,近年来其在我国的发病率也逐年升高。雄激素在PC的发生、发展过程中扮演着重要的角色,所以内分泌治疗一直是前列腺癌研究领域的重点,但是其可能诱发激素非依赖型PC这也是临床医学面临的一大问题。本文就前列腺癌内分泌治疗的分类、作用机制、用药策略及临床效果等作一综述。     

A mouse prostate cancer model induced by Hedgehog overexpression

Summary Hedgehog is a regulatory protein during embryonic development and its abnormal activation in adult tissues has been implicated in tumorigenesis within sites where epithelial–mesenchymal interactions take place. In the prostate, Hedgehog signaling activation was observed during advanced cancer progression and metastasis, but whether Hedgehog overexpression can initiate prostate tumorigenesis remains unknown. We introduced a Hedgehog-expressing vector by intra-prostate injection and electroporation to address the effects of Hedgehog overexpression. The manipulation caused lesions with characteristic prostatic intraepithelial neoplasia or even prostatic cancer (CaP) phenotypes within 30 days, with Hedgehog overexpression demonstrated by immunohistochemistry and Western blot detections. The tumorigenic phenotypes were confirmed by discontinuity of basal cell marker p63, mix-up of CK-8/CK-18 positive epithelial cells in the stoma as well as absence of α-SMA positive fibro-muscular sheath. Comparable Hedgehog overexpression was found in human CaP specimen. Thus, Hedgehog overexpression induced prostate tumorigenesis starting from the normal status. Furthermore, a mouse prostate cancer model induced by Hedgehog overexpression was established and may be used for testing novel therapeutical approaches targeting at Hedgehog signaling pathway.These authors have contributed equally to this work.     

EphrinA I-targeted nanoshells for photothermal ablation of prostate cancer cells

Gold-coated silica nanoshells are a class of nanoparticles that can be designed to possess strong absorption of light in the near infrared (NIR) wavelength region. When injected intravenously, these nanoshells have been shown to accumulate in tumors and subsequently mediate photothermal treatment, leading to tumor regression. In this work, we sought to improve their specificity by targeting them to prostate tumor cells. We report selective targeting of PC-3 cells with nanoshells conjugated to ephrinA I, a ligand for EphA2 receptor that is overexpressed on PC-3 cells. We demonstrate selective photo-thermal destruction of these cells upon application of the NIR laser.     

The androgen receptor: a potential target for therapy of prostate cancer

The androgen receptor plays a pivotal role in the prostate. Its primary function is to provide responsive gene products for differentiation and growth, but under abnormal conditions it contributes to the development of prostate cancer. The goal of this review is to elucidate the molecular functions of the androgen receptor and its role in prostate cancer. Initially the function of the androgen receptor will be described. Next, the clinical diagnosis, epidemiological impact, and treatments of androgen-dependent and -independent prostate cancer will be discussed. Finally we will examine how the mechanism of androgen action has played a role in the translation of new therapies and how this may influence future treatment modalities of prostate cancer.     

Modern methods of laboratory diagnostics of Chlamydia infections

Need for further improvement of methods for verification of etiological agent of urogenital and respiratory chlamydiosis on the basis of increased biotechnological requirements to antigens for serological reactions, primers for PCR assay (refinement of connection of primers with microorganism's zones of genome most significant for its life activity or formation of most diagnostically significant complexes of primers), and selection of cultivating conditions considering the predicted features of clinical strains of the agent was substantiated.     

Advances in mass spectrometry-based cancer research and analysis: from cancer proteomics to clinical diagnostics

Introduction: The last 20 years have seen significant improvements in the analytical capabilities of biological mass spectrometry (MS). Studies using advanced MS have resulted in new insights into cell biology and the etiology of diseases as well as its use in clinical applications.

Areas covered: This review discusses recent developments in MS-based technologies and their cancer-related applications with a focus on proteomics. It also discusses the issues around translating the research findings to the clinic and provides an outline of where the field is moving.

Expert commentary: Proteomics has been problematic to adapt for the clinical setting. However, MS-based techniques continue to demonstrate potential in novel clinical uses beyond classical cancer proteomics.     

Cancer-associated antigens and antigen arrays in serological diagnostics of malignant tumors

The appearance of antibodies to cancer-associated antigens in biological fluids (particularly, in blood sera) of cancer patients is now a well-established fact, and their detection by immunochemical methods is a promising approach to diagnostics of malignant neoplasms. In this review, we consider some immunobiological aspects of the most extensively studied cancer-associated B-cell antigens, various applications of autoantibodies as cancer biomarkers, and prospects for the use of antigen arrays for improving diagnostic sensitivity.     

DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation

Prostate cancer (CaP) is mostly composed of luminal-like differentiated cells, but contains a small subpopulation of basal cells (including stem-like cells), which can proliferate and differentiate into luminal-like cells. In cancers, CpG island hypermethylation has been associated with gene downregulation, but the causal relationship between the two phenomena is still debated. Here we clarify the origin and function of CpG island hypermethylation in CaP, in the context of a cancer cell hierarchy and epithelial differentiation, by analysis of separated basal and luminal cells from cancers. For a set of genes (including GSTP1) that are hypermethylated in CaP, gene downregulation is the result of cell differentiation and is not cancer specific. Hypermethylation is however seen in more differentiated cancer cells and is promoted by hyperproliferation. These genes are maintained as actively expressed and methylation-free in undifferentiated CaP cells, and their hypermethylation is not essential for either tumour development or expansion. We present evidence for the causes and the dynamics of CpG island hypermethylation in CaP, showing that, for a specific set of genes, promoter methylation is downstream of gene downregulation and is not a driver of gene repression, while gene repression is a result of tissue-specific differentiation.     

Polyphenols from green tea and pomegranate for prevention of prostate cancer

Prostate cancer (PCa) is the most common non-cutaneous cancer diagnosed in North America with similar trends in many Western countries. Geographic, epidemiological and laboratory studies suggest a role for dietary constituents in the etiology as well as prevention of PCa. The rising incidence of PCa in several countries appears to be coincidental with adoption of western lifestyle. Increase in the incidence of PCa has also been found in Asian populations migrating to the west. These facts give numerous leads to explore testable PCa prevention strategies. There is growing evidence in support of use of dietary ingredients in prevention and treatment of PCa. While substantial data exists in favor of use of polyphenols from tea as PCa chemopreventive agent, interest in anti-cancer properties of polyphenols from pomegranate has recently emerged. This review summarizes current literature on the effects of polyphenols from green tea and pomegranate against PCa.     

Quinazoline-urea,new protein kinase inhibitors in treatment of prostate cancer

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2), two protein tyrosine kinases, are involved in pathological disorders and the progression of different types of carcinomas. Concomitant inhibition of both tyrosine kinase activities appears to be an attractive target for cancer chemotherapy. A series of new quinazoline derivatives substituted by amide, urea, or carbamic acid ester groups have been synthesized. The biological activities of these new compounds have been evaluated for their enzyme inhibition and antiproliferative activities.