An Ultrastructural,Immunohistochemical, and Cytogenetical Study of a Monophasic Pulmonary Synovial Sarcoma: Implications of the Frequent Ultrastructure of Oligocilia and Concentric Membranous Bodies with Positive Immunostaining for VS38c and MEF2

A rare case of a monophasic pulmonary synovial sarcoma is reported. A 44-year-old Japanese man underwent lower lobectomy for a nodular mass in his right lung. Immunohistochemical study of the excised primitive spindle cell sarcoma revealed occasional positive stains by hitherto reported antigens of S-100, cytokeratin 7, high molecular weight cytokeratin (34betaE12), pankeratin (AE1/AE3), and EMA, which were helpful for the differential diagnosis of other spindle cell sarcomas. Furthermore, positive immunostains for MEF2, VS38c (plasma cell antigen), and bcl-2 were rather significant findings in the present case. The definitive evidence that molecular genetic analysis showed a clonal single electrophoretic band of SYT-SSX mutated chimera gene was conclusive for the pathological diagnosis. The implications of the frequently seen ultrastructure of oligocilia and concentric membranous bodies with positive stains for VS38c and MEF2 are discussed. In the difficult pathological diagnosis of a rare and undifferentiated type of sarcoma with unusual clinicopathological features generated at an unusual site, comprehensive ultrastructural, immunohistochemical, and cytogenetic studies will lead to the correct pathological diagnosis and elucidate the detailed characteristics of the tumor.     

同种异体大鼠嵌合体动物模型的建立及意义

目的:探讨建立同种异体大鼠嵌合体动物模型的方法,初步研究嵌合体与耐受的关系。方法:采用两种诱导方法处理受体Wistar大鼠(♀) :Ⅰ组大鼠亚致死TBI(11Gy) ;Ⅱ组大鼠TBI(7Gy) ,两组均在4小时内输入SD大鼠(♂)BMC(8×10 7) ,Ⅱ组于2天后腹腔注射CTX(5 0mg kg)。分别于BMT后2 0、4 0天通过PCR方法检测SD大鼠源性BMC在Wistar大鼠体内植活情况,并通过皮肤移植、DTH和MLR检查,判断其耐受情况。结果:经上述处理两组大鼠外周血均可测出SD大鼠源性嵌合体,皮肤移植、DTH和MLR检查显示对SD大鼠产生特异性耐受,但Ⅰ组大鼠生存情况明显不如Ⅱ组。结论:应用7GyTBI +腹腔注射CTX(5 0mg kg) +供体BMT可成功建立同种异体大鼠嵌合体模型,诱导特异性免疫耐受。     

PROTAC technology: A new drug design for chemical biology with many challenges in drug discovery

Target Protein Degradation TPD is a new avenue and revolutionary for therapeutics because redefining the principles of classical drug discovery and guided by event-based target activity rather than the occupancy-driven activity. Since the discovery of the first PROTAC in 2001, TPD represents a rapidly growing technology, with applications in both drug discovery and chemical biology. Over the last decade, many questions have been raised and today the knowledge gained by each team has elucidated a number of them, although there is still a long way to go. The objective of this work is to present the challenges that the PROTAC strategy has very recently addressed in drug design and discovery by presenting extremely recent results from the literature and to provide guidelines in the drug design of new PROTACs as successful therapeutic modality for medicinal chemists.