Poor differentiation is an important hallmark of cancer cells, and differentiation therapy holds great promise for cancer treatment. The restoration of IkB kinase α (IKKα) leads to the differentiation of nasopharyngeal carcinoma cells with reduced tumorigenicity. The ifndings by Yan etal. validate the polycomb protein enhancer of zeste homologue 2 (EZH2) as a target for intervention.

作者： 刊期： 2016年第01期

The impact of maintenance therapy on progression?free survival and overall survival as well as quality of life of Chi?nese patients with metastatic colorectal cancer has long been under discussion. Recently, some phase III clinical trials have revealed that maintenance therapy can signiifcantly prolong the progression?free survival while maintain an acceptable safety proifle. Based on this evidence and common treatment practice in China, we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the neces?sity of maintenance therapy, suitable candidates for such treatment, and appropriate regimens.

作者： 刊期： 2016年第01期

Colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs were classiifed into three major groups according to frequently altered/mutated genes. These genes have been identiifed by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data. In the ifrst half of this review, we describe the genetic pathways of sporadic CRCs and their clinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a lim-ited number of pathways. Gene-oriented models of CRC progression are being replaced by pathway-oriented models. In the second half of this review, we summarize the present knowledge of this research ifeld and discuss its prospects.

作者： 刊期： 2016年第01期

Lower?grade gliomas (including low? and intermediate?grade gliomas, World Health Organization grades II and III) are diffusely inifltrative neoplasms that arise most often in the cerebral hemispheres of adults and have traditionally been classiifed based on their presumed histogenesis as astrocytomas, oligodendrogliomas, or oligoastrocytomas. Although the histopathologic classiifcation of lower?grade glioma has been the accepted standard for nearly a century, it suffers from high intra? and inter?observer variability and does not adequately predict clinical outcomes. Based on integrated analysis of multiplatform genomic data from The Cancer Genome Atlas, lower?grade gliomas have been found to segregate into three cohesive, clinically relevant molecular classes. Molecular classes were closely aligned with the status of isocitrate dehydrogenase (IDH) mutations, tumor protein 53 mutations and the co?deletion of chromosome arms 1p and 19q, but were not closely aligned with histologic classes. These ifndings emphasize the potential for improved deifnition of clinically relevant disease subsets using integrated molecular approaches and highlight the importance of biomarkers for brain tumor classiifcation.

作者： 刊期： 2016年第01期

Background:In the era of intensity?modulated radiotherapy (IMRT), the role of neoadjuvant chemotherapy (NAC) for locoregionally advanced nasopharyngeal carcinoma (NPC) is under?evaluated. The aim of this study was to com?pare the effcacy of NAC plus IMRT and concurrent chemoradiotherapy (CCRT) plus adjuvant chemotherapy (AC) on locoregionally advanced NPC.Methods:Between January 2004 and December 2008, 240 cases of locoregionally advanced NPC conifrmed by pathologic assessment in Sun Yat?sen University Cancer Center were reviewed. Of the 240 patients, 117 received NAC followed by IMRT, and 123 were treated with CCRT plus AC. The NAC+IMRT group received a regimen that included cisplatin and 5?lfuorouracil (5?FU). The CCRT+AC group received cisplatin concurrently with radiotherapy, and subsequently received adjuvant cisplatin and 5?FU. The survival rates were assessed by Kaplan–Meier analysis, and the survival curves were compared using a log?rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results:The 5?year overall survival (OS), locoregional relapse?free survival (LRRFS), distant metastasis?free survival (DMFS), and disease?free survival (DFS) were 78.0, 87.9, 79.0, and 69.8%, respectively, for the NAC+IMRT group and 78.7, 84.8, 76.2, and 65.6%, respectively, for the CCRT+AC group. There were no signiifcant differences in survival between the two groups. In multivariate analysis, age (<50years vs.≥50years) and overall stage (III vs. IV) were found to be independent predictors for OS and DFS; furthermore, the overall stage was a signiifcant prognostic factor for DMFS. Compared with the CCRT+AC protocol, the NAC+IMRT protocol signiifcantly reduced the occurrence rates of grade 3–4 nausea–vomiting (6.5 vs. 1.5%,P=0.023) and leukopenia (9.7 vs. 0.8%,P=0.006).Conclusions:The treatment outcomes of the NAC+IMRT and CCRT+AC groups were similar. Distant metastasis remained the predominant mode of treatment failure.

作者： 刊期： 2016年第01期

Current proposed mechanisms implicate both early and latent Epstein–Barr virus (EBV) infection in the carcinogenic cascade, whereas epidemiological studies have always associated nasopharyngeal carcinoma (NPC) with early child-hood EBV infection and with chronic ear, nose, and sinus conditions. Moreover, most patients with NPC present with IgA antibody titers to EBV capsid antigen (VCA-IgA), which can precede actual tumor presentation by several years. If early childhood EBV infection indeed constitutes a key event in NPC carcinogenesis, one would have to explain the inability to detect the virus in normal nasopharyngeal epithelium of patients at a high risk for EBV infection. It is perhaps possible that EBV resides within the salivary glands, instead of the epithelium, during latency. This claim is indirectly supported by observations that the East Asian phenotype shares the characteristics of an increased sus-ceptibility to NPC and immature salivary gland morphogenesis, the latter of which is inlfuenced by the association of salivary gland morphogenesis with an evolutionary variant of the human ectodysplasin receptor gene (EDAR), EDARV370A. Whether the immature salivary gland represents a more favorable nidus for EBV is uncertain, but in patients with infectious mononucleosis, EBV has been isolated in this anatomical organ. The presence of EBV-induced lymphoepitheliomas in the salivary glands and lungs further addresses the possibility of submucosal spread of the virus. Adding to the fact that the fossa of Rosen Müller contains a transformative zone active only in the ifrst decade of life, one might be tempted to speculate the possibility of an alternative carcinogenic cascade for NPC that is perhaps not dissimilar to the model of human papillomavirus and cervical cancer.

作者： 刊期： 2016年第01期

Background:Despite numerous previous studies, the consideration of tumor location as a prognostic factor in resectable non–small cell lung cancer (NSCLC) remains controversial. The present study analyzed the association between tumor location and clinical outcome in patients with resectable NSCLC who had undergone lobectomy with systematic lymphadenectomy and who had presented with varying nodal statuses.Methods:The data from a cohort of 627 eligible patients treated in Sun Yat?sen University Cancer Center between January 2000 and December 2008 were retrospectively collected, and the nodal statuses of patients with different tumor locations were compared. Cox proportional hazards regression model was used to determine the independent factors related to cancer?speciifc survival (CSS).Results:Multivariate analysis demonstrated that left lower lobe (LLL) tumors [hazard ratio (HR): 1.465, 95% conif?dence interval (CI) 1.090–1.969,P= 0.011], lymph node metastasis (HR: 2.742, 95% CI 2.145–3.507,P < 0.001), and a tumor size of >4cm (HR: 1.474, 95% CI 1.151–1.888,P= 0.002) were three independent prognosticators in patients with resectable NSCLC. However, LLL tumors were associated only with CSS in node?positive patients (HR: 1.528, 95%CI 1.015–2.301,P= 0.042), and a tumor size of >4cm was the only independent risk predictor in the node?negative subgroup (HR: 1.889, 95% CI 1.324–2.696,P < 0.001).Conclusions:Tumor location is related to the long?term CSS of NSCLC patients with lymph node metastasis. LLL tumors may be upstaged in node?positive patients to facilitate an optimal treatment strategy.

作者： 刊期： 2016年第01期

Low-density lipoprotein receptor-related protein 1 (LRP1, also known as CD91), a multifunctional endocytic and cell signaling receptor, is widely expressed on the surface of multiple cell types such as hepatocytes, ifbroblasts, neu-rons, astrocytes, macrophages, smooth muscle cells, and malignant cells. Emerging invitro and invivo evidence demonstrates that LRP1 is critically involved in many processes that drive tumorigenesis and tumor progression. For example, LRP1 not only promotes tumor cell migration and invasion by regulating matrix metalloproteinase (MMP)-2 and MMP-9 expression and functions but also inhibits cell apoptosis by regulating the insulin receptor, the serine/threonine protein kinase signaling pathway, and the expression of Caspase-3. LRP1-mediated phosphorylation of the extracellular signal-regulated kinase pathway and c-jun N-terminal kinase are also involved in tumor cell proliferation and invasion. In addition, LRP1 has been shown to be down-regulated by microRNA-205 and methylation ofLRP1 CpG islands. Furthermore, a novel fusion gene,LRP1-SNRNP25, promotes osteosarcoma cell invasion and migration. Only by understanding the mechanisms of these effects can we develop novel diagnostic and therapeutic strategies for cancers mediated by LRP1.

作者： 刊期： 2016年第01期