恶性脑膜瘤的分子遗传学特征与诊疗进展

恶性脑膜瘤仅占全部脑膜瘤的1.0%~2.8%,但治疗上比较棘手。为此,我们在复习近年来研究进展的基础上,对恶性脑膜瘤定义的演变、与脑膜瘤恶性转化相关的基因和信号通路等分子机制、恶性脑膜瘤的病理学（组织学、免疫组织化学和核分裂像）和影像学特征、恶性脑膜瘤的治疗（手术、放疗、质子治疗和化疗）策略进行总结,以指导恶性脑膜的诊断与治疗。

论原生家庭对芥川龙之介作品的影响

芥川龙之介是日本大正时期著名文学家,以他名字命名的“芥川龙之介奖”至今影响着日本文学界,推动了日本近现代文学的发展。剖析芥川龙之介的作品,可发现其作品透彻地展现了人物心理,采用新技巧派的叙事方法,文笔精炼流畅,其中无不渗透着原生家庭对他带来的影响。养父母家浓厚的传统文化氛围,培养了芥川的兴趣爱好、审美情趣以及深厚的文化功底,使他能借古喻今,针砭时弊,赋予古典作品新的内涵与生命力。长期地寄人篱下又使芥川感悟到人性的利己主义,对人生的不安与苦恼渗透在芥川的多部作品中。一生受恶性遗传的困扰,使芥川龙之介产生厌世思想,遗作中多以此为题材,充满了对生死的哲性思考。

Mouse models of pancreatic cancer

Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are lacking.Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed.In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes.In the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed.These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer.Genetic alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice.These mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system.These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer treatments.Here,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

Early Age of Onset, Multiple Primary Malignancies and Poor Prognosis Are Indicative of an Inherited Predisposition to Esophageal Squamous Cell Carcinoma in Familial Rather Than Sporadic Disease- An Update Based on 14- to 23-year Follow-up

OBJECTIVE To demonstrate the effects of an inherited predisposition to familial esophageal squamous cell carcinoma （ESCC） through the comparison and analysis of the clinicopathologic differences between familial and sporadic ESCC cases. METHODS Differences in age of onset, prevalence rates of double primary ESCC, and survival rates between familial ESCC （n = 476） and sporadic ESCC cases （n = 1226） were analyzed. RESULTS Overall, familial ESCC cases showed a significantly younger age of onset （51.9±8.2 vs. 53.4 ±8.0, Pt.test = 0.00）, a significantly higher prevalence rate for double ESCC （2.73 % vs. 1.22%, adjusted with TNM：χMH2 = 4.029, P = 0.045）, and a lower survival rate than in sporadic cases （Pwald = 0.04）. The familial cases showed both a younger age of onset and poorer survival in most subgroups, and the differences were more marked in early-stage rather than in the .late-stage disease groups. CONCLUSION Theses findings confirm the existence of familial as opposed to sporadic ESCC. By the theory of the ＂two-hit＂ origin of cancer, these findings also suggest that the ＂first hit＂, a genetic predisposition, can affect the age of onset, number of primary carcinomas, and the prognosis for familial ESCC patients.

Anti-tumor immunity,autophagy and chemotherapy

Autophagy or self-digestion of cells is activated upon various stressful stimuli and has been found to be a survival and drug resistance pathway in cancer.However,genetic studies support that autophagy can act as a tumor suppressor.Furthermore,defective autophagy is implicated in tumorigenesis,as well.The precise impact of autophagy on malignant transformation has not yet been clarified,but recent data suggest that this complex process is mainly directed by cell types,phases,genetic background and microenvironment.Relation of autophagy to anticancer immune responses may indicate a novel aspect in cancer chemotherapy.

The role of circulating miRNAs in multiple myeloma

Multiple myeloma(MM) is a common malignant hematological disease. Dysregulation of micro RNAs(mi RNAs) in MM cells and bone marrow microenviroment has important impacts on the initiation and progression of MM and drug resistance in MM cells. Recently, it was reported that MM patient serum and plasma contained sufficiently stable mi RNA signatures, and circulating mi RNAs could be identified and measured accurately from body fluid. Compared to conventional diagnostic parameters, the circulating mi RNA profile is appropriate for the diagnosis of MM and estimates patient progression and therapeutic outcome with higher specificity and sensitivity. In this review, we mainly focus on the potential of circulating mi RNAs as diagnostic, prognostic, and predictive biomarkers for MM and summarize the general strategies and methodologies for identification and measurement of circulating mi RNAs in various cancers. Furthermore, we discuss the correlation between circulating mi RNAs and the cytogenetic abnormalities and biochemical parameters assessed in multiple myeloma.