bortezomib

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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2015/01/02 21:47:08」(JST)

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英文文献

  • Reactive nucleolar and Cajal body responses to proteasome inhibition in sensory ganglion neurons.
  • Palanca A1, Casafont I1, Berciano MT1, Lafarga M2.Author information 1Department of Anatomy and Cell Biology, University of Cantabria-IFIMAV, Santander, Spain; "Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)", Santander, Spain.2Department of Anatomy and Cell Biology, University of Cantabria-IFIMAV, Santander, Spain; "Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)", Santander, Spain. Electronic address: lafargam@unican.es.AbstractThe dysfunction of the ubiquitin proteasome system has been related to a broad array of neurodegenerative disorders in which the accumulation of misfolded protein aggregates causes proteotoxicity. The ability of proteasome inhibitors to induce cell cycle arrest and apoptosis has emerged as a powerful strategy for cancer therapy. Bortezomib is a proteasome inhibitor used as an antineoplastic drug, although its neurotoxicity frequently causes a severe sensory peripheral neuropathy. In this study we used a rat model of bortezomib treatment to study the nucleolar and Cajal body responses to the proteasome inhibition in sensory ganglion neurons that are major targets of bortezomib-induced neurotoxicity. Treatment with bortezomib induced dose-dependent dissociation of protein synthesis machinery (chromatolysis) and nuclear retention of poly(A) RNA granules resulting in neuronal dysfunction. However, as a compensatory response to the proteotoxic stress, both nucleoli and Cajal bodies exhibited reactive changes. These include an increase in the number and size of nucleoli, strong nucleolar incorporation of the RNA precursor 5'-fluorouridine, and increased expression of both 45S rRNA and genes encoding nucleolar proteins UBF, fibrillarin and B23. Taken together, these findings appear to reflect the activation of the nucleolar transcription in response to proteotoxic stress Furthermore, the number of Cajal bodies, a parameter related to transcriptional activity, increases upon proteasome inhibition. We propose that nucleoli and Cajal bodies are important targets in the signaling pathways that are activated by the proteotoxic stress response to proteasome inhibition. The coordinating activity of these two organelles in the production of snRNA, snoRNA and rRNA may contribute to neuronal survival after proteasome inhibition. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.
  • Biochimica et biophysica acta.Biochim Biophys Acta.2014 Jun;1842(6):848-59. doi: 10.1016/j.bbadis.2013.11.016. Epub 2013 Nov 19.
  • The dysfunction of the ubiquitin proteasome system has been related to a broad array of neurodegenerative disorders in which the accumulation of misfolded protein aggregates causes proteotoxicity. The ability of proteasome inhibitors to induce cell cycle arrest and apoptosis has emerged as a powerfu
  • PMID 24269586
  • The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2.
  • Morelli MB1, Offidani M, Alesiani F, Discepoli G, Liberati S, Olivieri A, Santoni M, Santoni G, Leoni P, Nabissi M.Author information 1Section of Experimental Medicine, School of Pharmacy, University of Camerino, Camerino, Italy.AbstractMultiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the accumulation of a monoclonal PC population in the bone marrow (BM). Cannabidiol (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the transient receptor potential vanilloid type-2 (TRPV2) channel has been reported as a potential CBD receptor. TRPV2 activation by CBD decreases proliferation and increases susceptibility to drug-induced cell death in human cancer cells. However, no functional role has been ascribed to CBD and TRPV2 in MM. In this study, we identified the presence of heterogeneous CD138+TRPV2+ and CD138+TRPV2- PC populations in MM patients, whereas only the CD138+ TRPV2- population was present in RPMI8226 and U266 MM cell lines. Because bortezomib (BORT) is commonly used in MM treatment, we investigated the effects of CBD and BORT in CD138+TRPV2- MM cells and in MM cell lines transfected with TRPV2 (CD138+TRPV2+). These results showed that CBD by itself or in synergy with BORT strongly inhibited growth, arrested cell cycle progression and induced MM cells death by regulating the ERK, AKT and NF-κB pathways with major effects in TRPV2+ cells. These data provide a rationale for using CBD to increase the activity of proteasome inhibitors in MM.
  • International journal of cancer. Journal international du cancer.Int J Cancer.2014 Jun 1;134(11):2534-46. doi: 10.1002/ijc.28591. Epub 2013 Dec 2.
  • Multiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the accumulation of a monoclonal PC population in the bone marrow (BM). Cannabidiol (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the transient receptor potential vanilloid type-2 (TRPV2) channel has
  • PMID 24293211
  • Sequential treatment of HPV E6 and E7-expressing TC-1 cells with bortezomib and celecoxib promotes apoptosis through p-p38 MAPK-mediated downregulation of cyclin D1 and CDK2.
  • Kim JE1, Lee JI1, Jin DH2, Lee WJ3, Park GB4, Kim S4, Kim YS4, Wu TC5, Hur DY4, Kim D4.Author information 1Department of Anatomy, Chung-Ang University, College of Medicine, Seoul, Republic of Korea.2Institute for Innovate Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.3Department of Anatomy, Seoul National University, College of Medicine, Seoul, Republic of Korea.4Department of Anatomy and Laboratory for Cancer Immunotherapy, Inje University, College of Medicine, Busan, Republic of Korea.5Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.AbstractInterruption of the cell cycle is accompanied by changes in several related molecules that result in the activation of apoptosis. The present study was performed to verify the apoptotic effects of sequential treatment with bortezomib and celecoxib in TC-1 cells expressing the human papillomavirus (HPV) E6 and E7 proteins. In TC-1 cells sequentially treated with bortezomib and celecoxib, apoptosis was induced through decreased expression of signal transducer and activator of transcription-3 (STAT3), cyclin D1 and cyclin-dependent kinase (CDK) 2, which are major regulators of the G0/G1 cell cycle checkpoint. In addition, increased levels of p21, CHOP, BiP and p-p38 MAPK were identified in these cells. The treatment-induced apoptosis was effectively inhibited by treatment with SB203580, an inhibitor of p-p38. Moreover, the growth of tumors sequentially treated with bortezomib and celecoxib was retarded compared to the growth of tumors exposed to a single treatment with either bortezomib or celecoxib in vivo. We demonstrated that sequential treatment with bortezomib and celecoxib induced apoptosis via p-p38-mediated G0/G1 cell cycle arrest and endoplasmic reticulum (ER) stress. Sequential treatment with these two drugs could therefore be a useful therapy for cervical cancer.
  • Oncology reports.Oncol Rep.2014 May;31(5):2429-37. doi: 10.3892/or.2014.3082. Epub 2014 Mar 12.
  • Interruption of the cell cycle is accompanied by changes in several related molecules that result in the activation of apoptosis. The present study was performed to verify the apoptotic effects of sequential treatment with bortezomib and celecoxib in TC-1 cells expressing the human papillomavirus (H
  • PMID 24627094

和文文献

  • がんの最新治療 各論(5)多発性骨髄腫
  • 今井 陽一
  • 東京女子医科大学雑誌 83(3), 160-167, 2013-06-25
  • 形質細胞由来の造血器腫瘍である多発性骨髄腫は血清・尿中の単クローン性免疫グロブリンの産生を特徴とする。貧血などの造血障害、溶骨病変、腎機能障害、易感染性などの様々な臨床症状を伴いADLの低下を伴う場合がみられる難治・再発性の悪性腫瘍である。治療としては従来の化学療法であるMP (メルファラン・プレドニン)療法では完全寛解を得られることは困難で十分な生存期間を得られなかった。近年になって大量化学療法 …
  • NAID 110009605129
  • 多発性骨髄腫のこれまでの治療と最近の治療について
  • 高橋 正知,TAKAHASHI Masatomo
  • 東京女子医科大学雑誌 83(E2), E476-E484, 2013-03-31
  • 多発性骨髄腫(以下MM)は形質細胞の腫瘍性増殖による疾患で、一時的には治療に反応するものの再発が必須である。サリドマイドがMMに有効であることが明らかとなり、その後ボルテゾミブおよびレナリドマイドが治療に用いられ、これまでの標準治療とされてきたメルファラン、プレドニゾンによるMP療法からMMに対する治療が大きく変わりつつある。これまで予後不良因子としての染色体異常、例えば13番異常を持つMM患者は …
  • NAID 110009575055
  • 多発性骨髄腫の標準的な寛解導入療法-新薬を含む多剤併用療法の現況-
  • 和田 眞紀夫,WADA Makio
  • 東京女子医科大学雑誌 83(E2), E470-E475, 2013-03-31
  • 現在、米国、英国などから、多発性骨髄腫および類縁疾患の包括的な診療ガイドラインが公表されている。共通していることは、それぞれ独自に世界の臨床研究データを収集・分析して、高いエビデンスの得られた事項を中心に「根拠に基づいた治療ガイドライン」を組み立てていることである。具体的には(1)無症候性の骨髄腫にはすぐには治療をしないこと、(2)可能な症例では自家幹細胞移植を行う方がよいことなどがエビデンスレベ …
  • NAID 110009575054

関連リンク

プロテアソーム阻害剤 Bortezomibボルテゾミブ(商品名 VELCADE®ベルケード)の 多発性骨髄腫における有効性 ベルケード®とは? ベルケード®は、プロテアソーム阻害活性を利用した新しい作用機序をもつ抗がん剤です(1)。
Bortezomib is a highly selective, reversible inhibitor of the 26S proteasome. This drug is thought to inhibit many proteins (known as proteasomes) that cancer cells need to survive and multiply. It has ...

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