Jun 2013, Volume 7 Issue 2

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    Miao Xu, Jianyong Shao, Yixin Zeng
    Chuanbao Zhang, Zhaoshi Bao, Wei Zhang, Tao Jiang

    Gliomas are the most common primary intracranial tumors in adults. Anaplastic gliomas (WHO grade III) and glioblastomas (WHO grade IV) represent the major groups of malignant gliomas in the brain. Several diagnostic, predictive, and prognostic biomarkers for malignant gliomas have been reported over the last few decades, and these markers have made great contributions to the accuracy of diagnosis, therapeutic decision making, and prognosis of patients. However, heterogeneity in patient outcomes may still be observed, which highlights the insufficiency of a classification system based purely on histopathology. Great efforts have been made to incorporate new information about the molecular landscape of gliomas into novel classifications that may potentially guide treatment. In this review, we summarize three distinctive biomarkers, three most commonly altered pathways, and three classifications based on microarray data in malignant gliomas.

    Yue Yu, Jie He

    Non-small-cell lung cancer (NSCLC) is the most common cause of premature death among the malignant diseases worldwide. The current staging criteria do not fully capture the complexity of this disease. Molecular biology techniques, particularly gene expression microarrays, proteomics, and next-generation sequencing, have recently been developed to facilitate effectively its molecular classification. The underlying etiology, pathogenesis, therapeutics, and prognosis of NSCLC based on an improved molecular classification scheme may promote individualized treatment and improve clinical outcomes. This review focuses on the molecular classification of NSCLC based on gene expression microarray technology reported during the past decade, as well as their applications for improving the diagnosis, staging and treatment of NSCLC, including the discovery of prognostic markers or potential therapeutic targets. We highlight some of the recent studies that may refine the identification of NSCLC subtypes using novel techniques such as epigenetics, proteomics, or deep sequencing.

    Jing Liu, Jinbo Yue, Ligang Xing, Jinming Yu

    Trimodality based on neoadjuvant chemoradiotherapy (nCRT) followed by surgery is gaining popularity as a treatment strategy for locally advanced esophageal cancer. In this review, we summarize the role of nCRT and the recommended nCRT regimens based on clinical trials and meta-analyses. We analyze the relationship of nCRT with pathologic complete response (pCR) and then identify potential predictive markers of response. Compared with surgery alone and neoadjuvant chemotherapy followed by surgery, trimodality provides longer survival and has the advantage of local control compared with definitive chemoradiotherapy. The standard regimen is a platinum-based regimen with a radiation dose range of 41.4–50.4βGy by conventional fractionation. Evidence shows that patients with pCR tend to live longer than non-responders, indicating that pCR is a significant prognostic factor for patients with esophageal cancer. Individualized medicine requires predictive markers of individual patients based on their own genes. Currently, no definite marker is proved to be sufficiently sensitive and specific for use in clinical practice, although 18-fluorodeoxyglucose positron emission tomography shows promise in predicting response to nCRT.

    Qingqing Xu, Xi Wu, Yuyu Xiong, Qinghe Xing, Lin He, Shengying Qin

    Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population, and heritability of up to 80%. Drug therapy is an important approach to treating the disease. However, the curative effect of antipsychotic is far from satisfactory in terms of tolerability and side effects. Many studies have indicated that about 30% of the patients exhibit little or no improvements associated with antipsychotics. The response of individual patients who are given the same dose of the same drug varies considerably. In addition, antipsychotic drugs are often accompanied by adverse drug reactions (ADRs), which can cause considerable financial loss in addition to the obvious societal harm. So, it is strongly recommended that personalized medicine should be implemented both to improve drug efficacy and to minimize adverse events and toxicity. There is therefore a need for pharmacogenomic studies into the factors affecting response of schizophrenia patients to antipsychotic drugs to provide informed guidance for clinicians. Individual differences in drug response is due to a combination of many complex factors including ADEM (absorption, distribution, metabolism, excretion) process, transporting, binding with receptor and intracellular signal transduction. Pharmacogenetic and pharmacogenomic studies have successfully identified genetic variants that contribute to this interindividual variability in antipsychotics response. In addition, epigenetic factors such as methylation of DNA and regulation by miRNA have also been reported to play an important role in the complex interactions between the multiple genes and environmental factors which influence individual drug response phenotypes in patients. In this review, we will focus on the latest research on polymorphisms of candidate genes that code for drug metabolic enzymes (CYP2D6, CYP1A2, CYP3A4, etc.), drug transporters (mainly ABCB1) and neurotransmitter receptors (dopamine receptors and serotonin receptors, etc.). We also discuss the genome-wide pharmacogenomic study of schizophrenia and review the current state of knowledge on epigenetics and potential clinical applications.

    Bing Li, Xinrong Zhou, Jiarui Wu, Huarong Zhou

    Increasing evidence suggests that the gut may influence the host’s metabolism and ultimately change the outcomes of type 2 diabetes mellitus (T2DM). We review the evidence on the relationship between the gut and T2DM remission after gastric bypass surgery, and discuss the potential mechanisms underlying the above relationship: gut anatomical rearrangement, microbial composition changes, altered gut cells, and gut hormone modulation. However, the exact changes and their relative importance in the metabolic improvements after gastric bypass surgery remain to be further clarified. Elucidating the precise metabolic mechanisms of T2DM resolution after bypass surgery will help to reveal the molecular mechanisms of pathogenesis, and facilitate the development of novel diagnoses and preventative interventions for this common disease.

    Zhiming Zhu, Peijian Wang, Shuangtao Ma

    Hypertension is a serious public health problem worldwide. More than 60% of the risk factors for hypertension are associated with metabolic disturbances. Metabolic abnormalities increase the risk for hypertension and cause high blood pressure. Improving metabolic disturbances is beneficial for hypertension treatment. Due to the importance of metabolic abnormalities in the pathogenesis of hypertension, we propose a concept of metabolic hypertension. In this review, we discuss and review the clinical types, pathogenesis, risk evaluation and management of metabolic hypertension. Elucidation of the mechanism of metabolic hypertension should facilitate the design of novel pharmacotherapeutics and dedicated antihypertensive manipulations.

    Yingjiang Zhou, Liangyou Rui

    Leptin is secreted into the bloodstream by adipocytes and is required for the maintenance of energy homeostasis and body weight. Leptin deficiency or genetic defects in the components of the leptin signaling pathways cause obesity. Leptin controls energy balance and body weight mainly through leptin receptor b (LEPRb)-expressing neurons in the brain, particularly in the hypothalamus. These LEPRb-expressing neurons function as the first-order neurons that project to the second-order neurons located within and outside the hypothalamus, forming a neural network that controls the energy homeostasis and body weight. Multiple factors, including inflammation and endoplasmic reticulum (ER) stress, contribute to leptin resistance. Leptin resistance is the key risk factor for obesity. This review is focused on recent advance about leptin action, leptin signaling, and leptin resistance.

    Rong Zhang, Di Wang, Zhuying Xia, Chao Chen, Peng Cheng, Hui Xie, Xianghang Luo

    Adipocytes differentiate from mesenchymal stem cells (MSCs) in a process known as adipogenesis. The programme of adipogenesis is regulated by the sequential activation of transcription factors and several signaling pathways. There is growing evidence indicating that a class of small non-coding single-stranded RNAs known as “microRNAs (miRNAs)” also are involved in this process. In this review, we summarize the biology and functional mechanisms of miRNAs in adipocyte differentiation. In addition, we further discuss the miRNAs profiling, the miRNAs function and miRNAs target prediction in the adipogenesis.

    Sandy Leung-Kuen Au, Irene Oi-Lin Ng, Chun-Ming Wong

    Hepatocellular carcinoma (HCC) development is characterized by the presence of epigenetic alterations, including promoter DNA hypermethylation and post-translational modifications of histone, which profoundly affect expression of a wide repertoire of genes critical for cancer development. Emerging data suggest that deregulation of polycomb group (PcG) proteins, which are key chromatin modifiers repressing gene transcription during developmental stage, plays a causative role in oncogenesis. PcG proteins assemble into polycomb repressive complex 1 (PRC1) and polycomb repressive complex 2 (PRC2) to impose the histone H3 lysine 27 trimethylation (H3K27me3) modification for repression. In this review, we will first recapitulate the mechanisms of two key epigenetic pathways: DNA methylation and histone modifications. Specifically, we will focus our discussion on the molecular roles of PcG proteins. Next, we will highlight recent findings on PcG proteins, their clinicopathological implication and their downstream molecular consequence in hepatocarcinogenesis. Last but not least, we will consider the therapeutic potential of targeting enhancer of zeste homolog 2 (EZH2) as a possible treatment for HCC. Improving our understanding on the roles of PcG proteins in hepatocarcinogenesis can benefit the development of epigenetic-based therapy.

    Beicheng Sun, Michael Karin

    Inflammation has been considered as one of the hallmarks of cancer, and chronic hepatitis is a major cause of liver cancer. This review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will discuss recent advances in understanding the chronic hepatitis-liver cancer link based on hot spots in liver cancer research, including cellular interaction, cytokines, microRNA and stem cells. All of these mechanisms should be taken into consideration because they are crucial for the development of more efficacious therapeutic strategies for preventing and treating human chronic hepatitis and hepatocellular carcinoma.

    Jiangyi Zhu, Yongquan Shi, Xinmin Zhou, Zengshan Li, Xiaofeng Huang, Zheyi Han, Jianhong Wang, Ruian Wang, Jie Ding, Kaichun Wu, Ying Han, Daiming Fan

    The efficacy of ursodeoxycholic acid (UDCA) on long-term outcome of primary biliary cirrhosis (PBC) has been less documented in Chinese cohort. We aimed to assess the therapeutic effect of UDCA on Chinese patients with PBC. In the present study, 67 patients with PBC were treated with UDCA (13–15 mg?kg-1?day-1) and followed up for 2 years to evaluate the changes of symptoms, laboratory values and histological features. As the results indicated, fatigue and pruritus were obviously improved by UDCA, particularly in patients with mild or moderate symptoms. The alkaline phosphatase and γ-glutamyl transpetidase levels significantly declined at year 2 comparing to baseline values, with the most profound effects achieved in patients at stage 2. The levels of alanine aminotransferase and aspartate aminotransferase significantly decreased whereas serum bilirubin and immunoglobulin M levels exhibited no significant change. Histological feature was stable in patients at stages 1–2 but still progressed in patients at stages 3–4. The biochemical response of patients at stage 2 was much better than that of patients at stages 3–4. These data suggest that, when treated in earlier stage, patients in long-term administration of UDCA can gain favorable results not only on symptoms and biochemical responses but also on histology. It is also indicated that later histological stage, bad biochemical response and severe symptom may be indicators of poor prognosis for UDCA therapy.

    Khurram Siddique, Shirin Mirza, Gandra Harinath

    The effect of the severity of appendiceal inflammation on post-operative stay in children following appendicectomy has shown conflicting results. This study was conducted to determine the association between the severity of appendiceal inflammation and post-operative stay amongst children undergoing open appendicectomy. A retrospective cohort study was conducted at a District General Hospital for two years. A total of 204 patients were included in the study with an age range between 3 and 16 years. Females were 54.9% while the rest were male. Mean age was 12.5±3 years. The association of the severity of appendiceal inflammation and post-operative stay was assessed by multivariable Cox Proportional hazards model. Mean post-operative stay was 2.32 days (95% CI 2.14–2.51). Macroscopically perforated appendix, histological inflammation and post-operative complications were significantly associated with post-operative stay on univariable analysis (P<0.05). Whereas, the multivariable analysis showed that the post-operative stay was significantly prolonged only in case of either perforated appendix or post-operative complications while it remained unaffected by the histological inflammation.

    Fei Liu, Ming-chon Hsiung, Haibo Song, Ke Dian, Hong Tang, Jin Liu

    In the presence of a large patent ductus arteriosus (PDA), aortic co-arctation (CoA) cannot be diagnosed clinically because PDA masks the clinical features. This condition impedes the identification of CoA by transthoracic echcocardiography. However, the closure of PDA can result in a severe clinical condition that causes a patient with undiagnosed CoA to suffer from shock and multi-organ failure. In this article, a case of PDA was presented, in which transesophageal echocardiography provided full information that could be used as reference to identify and define CoA during PDA ligation surgery.