The emerging role of diffusion-weighted MRI in prostate cancer management

A significant amount of research has focused on the role of diffusion-weighted MRI (DW-MRI) in the management of patients with prostate cancer. Although uncertainties remain, a clearer picture of where this technique fits into clinical practice is now available. A combination of DW-MRI and T2-weighted MRI (T2W-MRI) demonstrates improved accuracy for lesion detection and localization compared with T2W-MRI alone, and has been suggested as a tool to guide tissue biopsy. DW-MRI could also have roles in active surveillance, evaluating treatment efficacy, and predicting disease recurrence. Furthermore, DW-MRI offers the exciting possibility of gathering information about tumor characteristics and aggressiveness in a noninvasive manner. Validation in large prospective multicenter trials is critical if this technique is to be integrated into current management algorithms for prostate cancer.     

The emergence of DNA methylation as a key modulator of aberrant cell death in prostate cancer

It is now well established that cancer cells exhibit a number of genetic defects in the machinery that governs programmed cell death and that sabotage of apoptosis is one of the principal factors aiding in the evolution of the carcinogenic phenotype. A number of studies have implicated aberrant DNA methylation as a key survival mechanism in cancer, whereby promoter hypermethylation silences genes essential for many processes including apoptosis. To date, studies on the methylation profile of apoptotic genes have largely focused on cancers of the breast, colon and stomach, with only limited data available on prostate cancer. Here we discuss the major developments in the field of DNA methylation and its role in the regulation of aberrant apoptosis in prostate cancer. The most significant advances have involved the discovery of apoptotic gene targets of methylation, including XAF1, (fragile histidine triad (FHIT ), cellular retinol binding protein 1 (CRBP1), decoy receptor 1(DCR1), decoy receptor 2 (DCR2 ), target of methylation-induced silenceing 1 (TMS1), TNF receptor superfamily, member 6 (FAS), Reprimo (RPRM) and GLI pathogenesis-related 1 (GLIPR1). These genes are reported to be hypermethylated in prostate cancer and some offer potential as diagnostic and prognostic markers. We also introduce the concept of an 'apoptotic methylation signature' for prostate cancer and evaluate its potential in a diagnostic, prognostic and therapeutic setting.     

DNA甲基化与结肠癌

DNA异常甲基化是肿瘤常见的表观遗传学改变.广泛的低甲基化和区域性高甲基化是基因异常表达的常见机制.某些基因异常甲基化与结肠癌发生密切相关,且常见于结肠癌发病早期.     

DNA甲基化与肿瘤

肿瘤发生、发展的分子生物学本质是细胞内遗传调控和表观遗传调控(epigenetic regulation)的紊乱。国内外对基因组所携带的遗传信息与疾病的关系已有深入的研究。相对而言,染色质所携带的表观遗传信息在疾病发生、发展中的重要作用才刚刚开始被认识。影响基因转录活性而不涉及DNA序列改变的基因表达调控方式称为表观遗传调控,其分子基础是DNA甲基化以及染色质的化学修饰和物理重塑。大量的临床和基础研究结果表明环境因素在肿瘤发生、发展中有巨大的影响,而表观遗传调控在遗传因素和环境因素的互动关系中起着桥梁的作用。     

DNA methylation and microRNAs in cancer

DNA methylation is a type of epigenetic modification in the human genome, which means that gene expression is regulated without altering the DNA sequence. Methylation and the relationship between methylation and cancer have been the focus of molecular biology researches. Methylation represses gene expression and can influence embryogenesis and tumorigenesis. In different tissues and at different stages of life, the level of methylation of DNA varies, implying a fundamental but distinct role for methylation. When genes are repressed by abnormal methylation, the resulting effects can include instability of that gene and inactivation of a tumor suppressor gene. MicroRNAs have some aspects in common with this regulation of gene expression. Here we reviewed the influence of gene methylation on cancer and analyzed the methods used to profile methylation. We also assessed the correlation between methylation and other epigenetic modifications and microRNAs. About 55,845 research papers have been published about methylation, and one-fifth of these are about the appearance of methylation in cancer. We conclude that methylation does play a role in some cancer types.     

DNA methylation in aging and cancer

DNA methylation processes appear to be disturbed in senescing mice and also in some tumor cells. Although it is possible that age-related demethylation of DNA could predispose cells to carcinogenic transformation, present evidence does not favor this hypothesis.     

DNA甲基化与胃癌的研究进展

表观遗传学主要涉及DNA甲基化作用的改变和染色质组蛋白的修饰作用、基因印记等,表现遗传调控机制维持着细胞的特性,以保证其发展、分化.表观遗传学调控机制在肿瘤发生、发展过程中扮演着重要的角色,其中DNA甲基化的研究对于胃癌早期诊断、靶向治疗以及明确胃癌的发病机制等方面具有十分重要的意义.现将DNA甲基化与胃癌的研究进展作...     

The role of prostate specific antigen measurement in the detection and management of prostate cancer

The introduction of prostate specific antigen (PSA) testing has revolutionised the early detection, management and follow-up of patients with prostate cancer and it is considered to be one of the best biomedical markers currently available in the field of oncology. Its use with annual digital rectal examination in prostate cancer screening programmes has led to a marked change in the distribution of stage at presentation towards earlier disease and led to a significant increase in the detection of potentially curable disease. In order to improve the specificity of PSA testing and thereby reduce the number of unnecessary prostatic biopsies, a number of refinements of PSA evaluation have been proposed. These include free to total PSA ratio, PSA density, PSA density, PSA density of the transition zone, PSA velocity and age-specific PSA reference ranges. The utility of these approaches is considered in this review. The role of PSA monitoring in the detection of recurrence following radical prostatectomy and radiotherapy is discussed, as well as its role in monitoring patients treated with endocrine therapy is discussed, as well as its role in monitoring patients treated with endocrine therapy in terms of correlating PSA response with outcome, in detecting disease progression and in guiding the use of subsequent therapies. Large continuing multicentre screening and outcome studies will provide important information enabling greater refinement of the use of this important diagnostic and monitoring tool in the future detection and management of prostate cancer.     

Prostate specific antigen: clinical use in the diagnosis and management of prostate cancer.

Prostate specific antigen (PSA) has replaced prostatic acid phosphatase as the preeminent clinical tumor marker in the management of patients with prostate cancer. Serum PSA levels have been shown to be proportional to clinical and pathologic stage of prostate cancer and in particular to correlate closely with prostate cancer volume. Serum levels of PSA thus serve as a useful adjunct in the initial clinical staging of men with prostate cancer. Serum PSA values provide a unique and valuable tool in monitoring prostate cancer progression over time and its response to surgical, radiation, and/or hormonal therapies. Unfortunately, its lack of specificity for prostate cancer leaves many questions unanswered as to the efficacy and advisability of using PSA as a screening test for this cancer.     

Hormonal management of prostate cancer

In advanced disease, androgen deprivation remains the usual treatment. The completion of current trials is awaited to confirm whether total androgen blockade will prolong survival. To make further advances in treatment the fundamental biology of the prostate cell, benign or malignant, and its relationship to endocrine manipulation, must be understood. This may then lead to an understanding of clonal escape mechanisms in transformed cells and the clinical correlate of escape, relapse.     

SIBLINGs and SPARC families: Their emerging roles in pancreatic cancer

Pancreatic cancer has a considerably poor prognosis with a 5-year survival probability of less than 5% when all stages are combined. Pancreatic cancer is characterized by its dense stroma, which is involved in the critical interplay with the tumor cells throughout tumor progression and furthermore, creates a barrier restricting efficient penetration of therapeutics. Alterations in a large number of genes are reflected by a limited number of signaling pathways, which are potential targets. Understanding more about the molecular basis of this devastating cancer type regarding tumor microenvironment, distinct subpopulations of cells, epithelial-to-mesenchymal transition and inflammation will lead to the development of various targeted therapies for controlling tumor growth and metastasis. In this complex scenario of pancreatic cancer, especially members of the “small integrin binding ligand N-linked glycoproteins” (SIBLINGs) and “secreted protein acidic and rich in cysteine” (SPARC) families have emerged due to their prominent roles in properties including proliferation, differentiation, apoptosis, adhesion, migration, angiogenesis, wound repair and regulation of extracellular matrix remodeling. SIBLINGs consist of five members, which include osteopontin (OPN), bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein. The SPARC family of modular extracellular proteins is comprised of SPARC/osteonectin (ON) and SPARC-like 1 (hevin); secreted modular calcium binding proteins; testicans and follistatin-like protein. In this review, we especially focus on OPN and ON, elaborating on their special and growing importance in pancreatic cancer diagnosis and prognosis.     

Systemic management of prostate cancer

The objective of this review is to explore different therapeutic options for metastatic adenocarcinoma of the prostate. Orchiectomy, estrogen therapy, synthetic LHRH analogs and possibly antiandrogens are equally effective frontline treatment modalities. Ketoconazole is indicated in emergency situations, but chronic use is prevented by serious idiosyncratic toxicity and by long term complications. Combined androgen blockade (CAB), with leuprolide (or tryptorelin) and flutamide is more effective than single modality treatment in patients capable of strict treatment compliance. Estramustine phosphate may be as effective as CAB and may be the frontline treatment of choice in sexually active patients. Institution of single modality treatment may be delayed until cancer becomes symptomatic. Controversy lingers over whether the institution of CAB at an earlier time may improve progression free survival (PFS) and survival. Research projects of immediate clinical relevance include: comparison of CAB and estramustine; determination of the optimal time for CAB; study of other forms of CAB; and phase II trials of new cytotoxic agents.     

DNA methylation and folate metabolism in gastric cancer

AIM To investigate DNA methylation status in gastric cancer and its relationship with folate metabolism.METHODS Serum before operation, the gastric mucosa from the lesion, and the surrounding area inpatients with gastric cancer and the remote normal-appearing mucosa of the resected stomach were collectedrespectively. The serum folate, mucosal tissue folate, S-adenosylmethionine ( SAM ), S-adenosylhomocysteine (SAH), and the DNA methylation levels were determined.RESULTS The tissue folate was significantly lower than that in ulcers, especially in the surrounding andnormal mucosa (0.38±0.13, 0.50±0.17 vs 0.53±0.50, 0.79±0.82ng/mg protein, P < 0.01), and itdecreased gradually in the lesion areas. The DNA methylation status showed similar decreasing trend incancers compared with the methylation increasing trend in ulcers. The SAM level ascended in the lesion areaswith a higher. concentration in cancer mueosa (63.5±43.0 vs 25.9±11.9nmol/g tissue, P < 0.01 ). Theaccumulation of SAH in the surrounding and normal mucosa of cancers was observed (17.3±24.6, 15.5±8.6vs 14.6±4.2, 10.0±1.9nmol/g tissue, P < 0.05 - 0.01). There were significantly negative correlationsbetween tissue folate and the SAM and SAH levels in the three areas.CONCLUSION Patients with gastric cancer have the regional folate deficiency in the stomach mucosa,although the serum folate level remains normal. This disturbs the local SAM and SAH metabolism withaccumulation of SAH and DNA hypomethylation which has been known as an important molecularmechanism for carcinogenesis. Folic acid can modulate DNA methylation status by its effect in one-carbongroup metabolism and thus affect the process of the carcinogenesis. Therefore, this may be an access for theprevention of gastric cancer.     

Stool DNA methylation assays in colorectal cancer screening

Colorectal cancer(CRC) is fourth most common cancer in men and third in women worldwide. Developing a diagnostic panel of sensitive and specific biomarkers for the early detection of CRC is recognised as to be crucial for early initial diagnosis, which in turn leads to better long term survival. Most of the research on novel potential CRC biomarkers in the last 2 decades has been focussed on stool DNA analysis. In this paper, we describe the recent advances in non-invasive CRC screening and more specifically in molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions. In several research papers these markers showed superior rates for sensitivity and specificity in comparison to previously described assays. These tests detected the majority of adenomas ≥ 1 cm in size and the detection rates progressively increased with larger adenomas. The methylation status of the BMP3 and NDRG4 promoters demonstrated effective detection of neoplasms at all sites throughout the colon and was not affected by common clinical variables. Recently, a multitarget stool DNA test consisting of molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions, mutant KRAS and immunochemical assay for human haemoglobin has been made commercially available and is currently reimbursed in the United States. Although this is the most sensitive noninvasive CRC screening test, there is the need for further research in several areas- establishment of the best timeframe for repeated DNA stool testing; validation of the results in populations outside of North America; usefulness for surveillance and prognosis of patients; cost-effectiveness of DNA stool testing in real-life populations.