Poor differentiation is an important hallmark of cancer cells, and differentiation therapy holds great promise for cancertreatment. The restoration of IkB kinase α （IKKα） leads to the differentiation of nasopharyngeal carcinoma cells withreduced tumorigenicity. The findings by Yan et al. validate the polycomb protein enhancer of zeste homologue 2（EZH2） as a target for intervention.
Low-density lipoprotein receptor-related protein 1 （LRP1, also known as CD91）, a multifunctional endocytic and cellsignaling receptor, is widely expressed on the surface of multiple cell types such as hepatocytes, fibroblasts, neurons,astrocytes, macrophages, smooth muscle cells, and malignant cells. Emerging in vitro and in vivo evidencedemonstrates that LRP1 is critically involved in many processes that drive tumorigenesis and tumor progression. Forexample, LRP1 not only promotes tumor cell migration and invasion by regulating matrix metalloproteinase （MMP）-2and 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 theextracellular signal-regulated kinase pathway and c-jun N-terminal kinase are also involved in tumor cell proliferationand invasion. In addition, LRP1 has been shown to be down-regulated by microRNA-205 and methylation of LRP1CpG 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 strategiesfor cancers mediated by LRP1.
Colorectal cancer （CRC） results from the progressive accumulation of genetic and epigenetic alterations that lead tothe transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occurin people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs wereclassified into three major groups according to frequently altered/mutated genes. These genes have been identifiedby linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on thebasis of functional data. In the first half of this review, we describe the genetic pathways of sporadic CRCs and theirclinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes aswell as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a limitednumber 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 field and discuss its prospects.
The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinesepatients with metastatic colorectal cancer has long been under discussion. Recently, some phase III clinical trialshave revealed that maintenance therapy can significantly prolong the progression-free survival while maintain anacceptable safety profile. Based on this evidence and common treatment practice in China, we now generated oneExpert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the necessityof maintenance therapy, suitable candidates for such treatment, and appropriate regimens.
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 influenced 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 Muller contains a transformative zone active only in the first 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.
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 Iobectomy 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-specific survival （CSS）. Results： Multivariate analysis demonstrated that left lower lobe （LLL） tumors [hazard ratio （HR）： 1.465, 95% confi- 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 〉4 cm （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 〉4 cm 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.
Lower-grade gliomas （including low- and intermediate-grade gliomas, World Health Organization grades Ⅱ and Ⅲ） are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have traditionally been classified based on their presumed histogenesis as astrocytomas, oligodendrogliomas, or oligoastrocytomas. Although the histopathologic classification 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 1 p and 19q, but were not closely aligned with histologic classes. These findings emphasize the potential for improved definition of clinically relevant disease subsets using integrated molecular approaches and highlight the importance of biomarkers for brain tumor classification.
Background： In the era of intensity-modulated radiotherapy （IMRT）, the role of neoadjuvant chemotherapy （NAC） for Iocoregionally advanced nasopharyngeal carcinoma （NPC） is under-evaluated. The aim of this study was to com- pare the efficacy of NAC plus IMRT and concurrent chemoradiotherapy （CCRT） plus adjuvant chemotherapy （AC） on Iocoregionally advanced NPC. Methods： Between January 2004 and December 2008, 240 cases of Iocoregionally advanced NPC confirmed by pathologic assessment in Sun Yat-sen University Cancer Center were reviewed. Of the 240 patients, 11 7 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-fluorouracil （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 S-year overall survival （OS）, Iocoregional 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 significant differences in survival between the two groups. In multivariate analysis, age （〈50 years vs. ≥50 years） and overall stage （111 vs. IV） were found to be independent predictors for OS and DFS; furthermore, the overall stage was a significant prognostic factor for DMFS. Compared with the CCRT ＋ AC protocol, the NAC ＋IMRT protocol significantly 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 meta