ABSTRACT
Recently, oxaliplatin(L-OHP)and irinotecan hydrochloride hydrate(CPT-11)have gained recognition as key drugs in the treatment of advanced colorectal cancer. In this article, we describe the results of a survey of medical institutions by pharmacists working at a pharmaceutical company. First, questions from medical institutions on L-OHP and CPT-11 were totaled and analyzed. The results showed that most of these questions concerned safety, with many of these addressing side effects. Next, a questionnaire on FOLFOX and FOLFIRI regimens was administered to medical institutions. The results indicated that staff are interested in the safety and critical path of these regimens. These results suggest that a lot of medical institutions require more information from pharmaceutical companies. This indicates that pharmacists should do more to take the needs of medical institutions into account in providing improved customer support.
Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Drug Industry , Neoplasms/drug therapy , Pharmacists/standards , Antineoplastic Agents/pharmacology , Humans , Japan , Societies, Medical , Surveys and QuestionnairesABSTRACT
MicroRNAs (miRNAs) control cell proliferation, differentiation and fate through modulation of gene expression by partially base-pairing with target mRNA sequences. Drosha is an RNase III enzyme that is the catalytic subunit of a large complex that cleaves pri-miRNAs with distinct structures into pre-miRNAs. Here, we show that both the p68 and p72 DEAD-box RNA helicase subunits in the mouse Drosha complex are indispensable for survival in mice, and both are required for primary miRNA and rRNA processing. Gene disruption of either p68 or p72 in mice resulted in early lethality, and in both p68(-/-) and p72(-/-) embryos, expression levels of a set of, but not all, miRNAs and 5.8S rRNA were significantly lowered. In p72(-/-) MEF cells, expression of p72, but not a mutant lacking ATPase activity, restored the impaired expression of miRNAs and 5.8S rRNA. Furthermore, we purified the large complex of mouse Drosha and showed it could generate pre-miRNA and 5.8S rRNA in vitro. Thus, we suggest that DEAD-box RNA helicase subunits are required for recognition of a subset of primary miRNAs in mDrosha-mediated processing.
