総説・解説等

＜文献概要＞ポイント　◆手術標本より研究用組織検体を採取する際には,病理診断に支障をきたさないよう,出血・壊死巣を回避し,がん部・非がん部を採取する.◆臓器摘出後,室温で30分以内あるいは4℃保管3時間以内に研究用組織検体を採取し,2～3mm角に細切して急速凍結し,液体窒素保管容器あるいは超低温槽に保管する.◆ホルマリン固定・パラフィン包埋標本の品質は,固定までの時間・固定時間・ホルマリンの種類と濃度に依存する.

The use of anti-human signal molecules monoclonal antibodies (mAbs) for malignant tumors therapy has achieved considerable success in recent years. Antibody drug conjugates are powerful new clinical treatment options for lymphomas and solid tumors, and immunomodulatory antibodies have also recently achieved remarkable clinical success. The development of therapeutic antibodies requires a deep understanding of malignant tumor serology, protein-engineering techniques, mechanisms of action and resistance, and the interplay between the immune system and tumorigenesis. This review outlines the fundamental strategies, which are required to establish antibody therapies for patients with mesenchymal tumors through iterative approaches to target and antibody selection, extending from preclinical studies to human trials.

Epigenetic alterations consisting mainly of DNA methylation alterations and histone modification alterations are frequently observed in cancers associated with chronic inflammation and/or persistent infection with viruses or other pathogenic microorganisms, or with cigarette smoking. Accumulating evidence suggests that alterations of DNA methylation are involved even in the early and precancerous stages. On the other hand, in patients with cancers, aberrant DNA methylation is frequently associated with tumor aggressiveness and poor patient outcome. Recently, epigenome alterations have been attracting a great deal of attention from researchers who are focusing on not only cancers but also neuronal, immune and metabolic disorders. In order to accurately identify disease-specific epigenome profiles that could be potentially applicable for disease prevention, diagnosis and therapy, strict comparison with standard epigenome profiles of normal tissues is indispensable. However, epigenome mechanisms show heterogeneity among tissues and cell lineages. Therefore, it is not easy to obtain a comprehensive picture of standard epigenome profiles of normal tissues. In 2010, the International Human Epigenome Consortium (IHEC) was established to coordinate the production of reference maps of human epigenomes for key cellular states. In order to gain substantial coverage of the human epigenome, the IHEC has set an ambitious goal to decipher at least 1000 epigenomes within the next 7-10 years. We consider that pathway analysis using genes showing multilayer-omics abnormalities, including genome, epigenome, transcriptome, proteome and metabolome abnormalities, may be useful for elucidating the molecular background of pathogenesis and for exploring possible therapeutic targets for each disease. © 2014 Kanai and Arai.

© Annals of Translational Medicine. All rights reserved. Soft tissue sarcomas are neoplastic malignancies that typically arise in tissues of mesenchymal origin. The identification of novel molecular mechanisms leading to mesenchymal transformation and the establishment of new therapies and diagnostic biomarker has been hampered by several critical factors. First, malignant soft tissue sarcomas are rarely observed in the clinic with fewer than 15,000 newly cases diagnosed each year in the United States. Another complicating factor is that soft tissue sarcomas are extremely heterogeneous as they arise in a multitude of tissues from many different cell lineages. The scarcity of clinical materials coupled with its inherent heterogeneity creates a challenging experimental environment for clinicians and scientists. Faced with these challenges, there has been extremely limited advancement in clinical treatment options available to patients as compared to other malignant tumours. In order to glean insight into the pathobiology of soft tissue sarcomas, scientists are now using mouse models whose genomes have been specifically tailored to carry gene deletions, gene amplifications, and somatic mutations commonly observed in human soft tissue sarcomas. The use of these model organisms has been successful in increasing our knowledge and understanding of how alterations in relevant oncogenic and/or tumour suppressive signal cascades, i.e., interferon-γ (IFN-γ), tumour protein 53 (TP53) and/or retinoblastoma (RB) pathway directly impact sarcomagenesis. It is the goal of many in the physiological community that the use of several mouse models will serve as powerful in vivo tools for further understanding of sarcomagenesis and potentially identify new diagnostic biomarker and therapeutic strategies against human soft tissue sarcomas.