專題討論之中文報告與演講報告

S46924044

碩二李建勳

Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis

Abstract:

由數種蛋白酶造成的細胞外基質分解已知與腫瘤入侵和轉移有相關性。其中 cathepsin B 和 matrix metalloproteases (MMP)-9 在晚期的神經膠質瘤的轉移入侵扮有重要的角色(1)。Pro-Cathepsin B 被 tPA 與 cathepsin D 活化, 並接著激活MMPs 和 uPA 。這樣的連鎖反應會促進胞外基質的分解、血管新生和腫瘤轉移(2) 。在這個研究小組先前的研究中, cathepsin B 和MMP-9 的減少在降低了神經膠質瘤細胞的轉移和入侵。作者用了RNAi的方式來降低 SNB19 神經膠質瘤細胞中 cathepsin B 和MMP-9 的表現。除腫瘤轉移和入侵之外, 這兩個蛋白酶的減少亦導致腫瘤引發之血管新生被抑制。在裸鼠的顱內注射模型中, 兩個蛋白酶的siRNA質體有效的抑制並清除以生長出來的神經膠質瘤。晚期腦癌的惡性化可歸結於其轉移和入侵的特性。利用 RNAi 減少內源cathepsin B 和MMP-9 的表現, 在經過更多的研究後當可視為神經膠質瘤的一種新療法。

References:

1.      Lakka SS et al. Downregulation of MMP-9 in ERK-mutated stable transfectants inhibits glioma invasion in vitro. Oncogene, 21, 5601, 2002.

2.      Rao JS. Molecular mechanisms of glioma invasiveness: The role of proteases. Nat Rev Cancer, 3, 489-501, 2003.

3.      Lakka SS et al. Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis. Oncogene,23, 4681–4689, 2004.

Figures:

Fig. 1 Function of MMPs.

Fig.2 Molecular mechanism of cathepsin B and MMP-9.

演講記錄報告

BK(Ca) channel:an important target for cellular functionBK(Ca)離子通道：一個重要細胞功能調控之標的            94.01.04          二        12：30-13：30           吳勝男            基醫所/教授

The search for disease genes: genetic epidemiology and ENU mutagenesis approaches疾病基因的搜尋: 利用遺傳流行病學法及ENU基因突變法       94.01.06          四        12：30-14：30           陳垣崇            中央研究院生物醫學科學研究所/院士

Molecular Mechanism of Organ-Specific Tumor Metastasis         94.01.12          三        12：30-13：30　       鄭宏祺    Research Associate, Department of Molecular Medicine, New York State College of Veterinary Medicine, Cornell University /博士

Role of Reactive Oxygen Species Generated from Microglial NADPH Oxidase in Inflammation-mediated Neurodegeneration    93.12.02          四        12:30-14:00     洪昭雄            國家環境衛生研究院/教授

MAOA gene and alcoholismMAOA基因和酒隱   93.12.07          二        12:30-14:00     陸汝斌            行醫所/教授

The role of leptin in endometriosis瘦素於子宮內膜異位症伴演的角色           93.12.14          二        12:30-14:00            吳孟興            婦產科/助理教授

給世界醫學的禮物：台灣原住民痛風基因搜尋A Gift to World Medicine: Gout Gene Pursuit in Taiwan Aboriginals     93.12.16          四        12:30-14:00     葛應欽            國家衛生研究院環境衛生與職業醫學研究組/主任

Novel Autoregulatory Function HBV Middle Surface Protein on Surface Gene ExpressionＢ型肝炎病毒中表面蛋白在表面基因表現的自我調節功能            93.12.21          二       12:30-13:30     呂政展            病理科/副教授

Memory, navigation and hippocampus記憶, 認路與海馬            93.11.09          二        12:30-13:30     白明奇            神經科/副教授

Mechanisms of Anti-angiogenic Action in Endothelial Cells and its Clinical Application.抑制血管新生的分子機制之探討及其於臨床應用 93.11.16          二        12:30-13:30     吳梨華            分醫所/助理教授

Oxidative Stress Contributes to Neural Mechanisms of Hypertension氧化壓力在高血壓神經機制的角色            93.11.18          四        12:30-14:00     華  瑜  高雄榮民總醫院教學研究部/教授

Fly Brain Neurogenomics: Genes and Circuits Involving in Learning and Memory果蠅大腦之神經基因學            93.10. 07         四        12:30-13:30     江安世            國立清華大學生物科技研究所/教授

Prostaglandin E2: The master of masters in endometriosis前列腺素E2與子宮內膜異位症的分子機制            93.10.12          二        12:30-13:30     蔡少正            生理所/副教授

Bioinformatics基因與染色體之生物資訊學研究            93.9.21            四        12:30-13:30     何中良            病理科/助理教授

The Proteasome in Cancer Biology and Therapy蛋白質體在惡性腫瘤學上的應用       8/17    二      12:30 -14:00   Dr.  Dr. William H.McBride      Professor and Division Chief, Laboratory of Experimental Radiation Oncology, Department of Radiation Oncology, University of California, Los Angeles.

摘要與感想

吳勝男老師 : The BK channel might mediate more biological functions other than K ion transportation.

陳垣崇院士 : Very significant discovery.  Dr. Cheng must be a humble person that he described his novel findings published on Science without exaggerates.

鄭宏祺博士 : It seems that suspend tumor cells have a totally different pattern of fibronectin distribution comparing to adherent ones.

洪昭雄教授 :  Is the mouse that expresses low TNF for months an extreme case or an interesting finding?

陸汝斌教授 : I can barely understand the speech, the complicated and confusing terms were difficult to follow.

吳孟興老師 : Leptin also plays a role in occurrence of diabetes mellitus.  Is there any correlation between these two disorders?

葛應欽主任 : Will alcoholics bear higher predisposition of gout occurrence?

呂政展老師 : How about the interaction between M protein and host defensive factors?

白明奇老師 : I am quite disorientated, this makes me wonder if something happen to my hippocampus?

吳梨華老師 : Angiogenesis is a widely studied hot subject.  In our lab, a Ph.D student is working on how tumor cells attract endothelial cells to grow and form microvessels by using spheroid models.

華    瑜教授 : Surprising and significant discovery.  Very well organized and detailed speech.

江安世教授 : The fly model provides a great simulation of human, it is predictable that similar patterns will be observed on human bodies.

蔡少正教授 : Good animation provides great understanding of the speech.

何中良老師 : Bioinformatics is an upsurging scientific means foe gene and function analysis.  Dr. Ho’s humorous speech made me really interested in this special tool.

Dr. William H. McBride : The proteasome degrades excessive and hazardous proteins that accumulated in cytosol, such function might also implies a potential of tumor clearing.