泰福 前總經理(詹維康)退 /趙宇天親征

泰福今法說 蛋白質藥話題再起  黃文奇 / 報導 2015/08/12 11:12 生技天王、華生製藥（Watson）製藥趙宇天成立的泰福生技（6541），今日舉行興櫃前法說會，預計明日正式登興櫃，也將對產業注入一定的活水效應，包括永新、台康、喜康、瑞華等蛋白質藥廠，也將同步受到矚目。泰福是台灣神隆、潤泰集團共同投資，背後有大股東潤泰集團總裁尹衍樑加持，且趙宇天被國內尊為生技四大天王之一（其餘三位包括OPKO創辦人許照惠、安成藥董事長陳志明、益邦製藥創辦人許中強），今日可望正式面對投資大眾，也將引起一陣話題。泰福是蛋白質藥廠，主要經營項目為生技藥品研發及製造，擁有二家100%持有之子公司，台灣泰福著重在cell line研發與生物製程開發；美國聖地牙哥之La Jolla Biologics則專注於生物藥品之製程、量產技術開發與製造生產。泰福基地在聖地牙哥，最大股東為潤泰集團，目前產品線以蛋白質相似藥為主，速度最快的產品是白血球生長激素TX01，最快年底前商化，明年進入臨床三期。泰福生技兼「哺乳類動物細胞株開發」和「微生物發酵」兩大技術，是由細胞株開發、細胞培養、純化、製程放大到最終的商業化製劑量產的一條龍公司。該公司由神隆、潤泰共同轉投資、趙宇天創辦，原由神隆共同創辦人詹維康擔任總經理，現詹功遂身退。業界指出，近年來隨著多項專利暢銷生技藥品逐年到期，同時歐美各國有關Biosimilar之法規亦逐漸完善，致各國大藥廠莫不摩拳擦掌，積極布局，以搶食該產業巿場大餅。據統計，2011年全球生物相似藥藥品巿場約7億美元，約占生技藥品市場0.4%，估計至2016年將成長至20億到40億美元，規模繼續成長。泰福生技研發中的產品，除了白血球生長激素TX01產品，最快明年進入臨床三期，早期乳癌（EBC）單株抗體TX05，已獲美國食品藥物管理局（FDA）同意進入臨床試驗，目前正在臨床試驗進行中。另外，轉移性大腸直腸癌（mCRC）單株抗體TX16、乾癬性關節炎（Psoriasis）等，也持續開發中。

台大楊泮池團隊 建議基因YAP1單點突變 (高危險肺癌) 應定期低劑量CT檢查

楊泮池團隊 找到肺腺癌基因 2015-08-06 14:15:04 聯合晚報 記者／彭宣雅台灣每年新增一萬多名肺癌病例，肺癌是國人癌症死亡第一位，台灣大學校長楊泮池所帶領的研究團隊，利用全基因體組「高速定序」技術，發現位於基因「YAP1」上的一個位點異常與肺腺癌相關，YAP1基因有異常比無異常罹患肺腺癌的風險高出5.9倍；未來高危險族群提早篩檢，就可早期發現治療，研究成果發表在國際重要醫學期刊臨床腫瘤學雜誌(Journal of Clinical Oncology)上。楊泮池表示，研究團隊先找出多個高度發生肺癌的家族，把所有家族成員全進行基因定序，找出和肺腺癌相關的基因異常；再用1000多名肺腺癌患者、1000多名健康者對照，發現YAP1基因上一個位點異常與肺腺癌相關。研究團隊追蹤離病患者後發現，「YAP1」基因若帶有位點異常，具有早發(小於60歲發病)、遺傳的特性，帶有這基因位點異常的民眾，也比較容易罹患肺腺癌。楊泮池說，研究個案中有一個家族有七人，結果父母、四個女兒都罹患肺腺癌，唯一有抽菸喝酒習慣的兒子，是家族中目前唯一沒有發現得肺腺癌的人，他推測，這基因位點異常，在罹患肺腺癌的遺傳與性別上，都扮演著關鍵性的角色。楊泮池表示，台灣罹患肺癌的患者，有一半有抽菸喝酒習慣，但另外一半沒有抽菸習慣，罹癌的原因不明確，且大多數初期都沒有症狀，等到腫瘤已經長至4至5公分，侵犯到其他器官、開始咳嗽、積水，大都已經是癌症末期，治療起來相對棘手。楊泮池說，找出肺腺癌「 YAP1」基因位點異常後，未來檢測非常簡單，只要患者抽血檢驗，大約五個工作天就可以完成檢測；目前這項發現僅在研究階段，還沒有應用在臨床篩檢 ；未來包括台大及其他各醫院，都可以發展肺腺癌基因檢測，費用大約2000元。台大表示，未來民眾家族中若有人罹患肺癌或肺腺癌，家族其他親屬就能提早進行基因檢測，若同樣帶有這個基因位點異常，可在健檢時進行低劑量電腦斷層檢查，有機會早期發現病兆，小於一公分的肺癌腫瘤，只要透過內視鏡手術治療，95%的患者都可以完全治癒。

R331W Missense Mutation of Oncogene YAP1 Is a Germline Risk Allele for Lung Adenocarcinoma With Medical Actionability. J Clin Oncol. 2015 Jul PURPOSE: Adenocarcinoma is the most dominant type of lung cancer in never-smoker patients. The risk alleles from genome-wide association studies have small odds ratios and unclear biologic roles. Here we have taken an approach featuring suitable medical actionability to identify alleles with low population frequency but high disease-causing potential. PATIENTS AND METHODS: Whole-genome sequencing was performed for a family with an unusually high density of lung adenocarcinoma with available DNA from the affected mother, four affected daughters, and one nonaffected son. Candidate risk alleles were confirmed by matrix-assisted laser desorption ionization time of flight mass spectroscopy. Validation was conducted in an external cohort of 1,135 participants without cancer and 1,312 patients with lung adenocarcinoma. Family follow-ups were performed by genotyping the relatives of the original proband and the relatives of the identified risk-allele carriers. Low-dose computed tomography scans of the chest were evaluated for lung abnormalities. RESULTS: YAP1 R331W missense mutation from the original family was identified and validated in the external controls and the cohort with lung adenocarcinoma. The YAP1 mutant-allele carrier frequency was 1.1% in patients with lung adenocarcinoma compared with 0.18% in controls (P = .0095), yielding an odds ratio (adjusted for age, sex, and smoking status) of 5.9. Among the relatives, YAP1-mutant carriers have overwhelmingly higher frequencies of developing lung adenocarcinoma or ground-glass opacity lung lesions than those who do not carry the mutation (10:0 v 1:7; P < .001). YAP1 mutation was shown to increase the colony formation ability and invasion potential of lung cancer cells. CONCLUSION: These results implicated YAP1 R331W as an allele predisposed for lung adenocarcinoma with high familial penetrance. Low-dose computed tomography scans may be recommended to this subpopulation, which is at high risk for lung cancer, for personalized prevention and health management.

香港中文大學揭密YAP1/ miR-15a and miR-16-1於胃癌角色 !!

Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma. Mol Cancer. 2015 Feb 22;14:52 BACKGROUND: MicroRNAs (miRNAs) have been reported to play an important role in tumorigenesis. In this study, the role of miR-15a and miR-16-1 in gastric adenocarcinoma (GAC) was investigated. METHODS: The expression of miR-15a and miR-16-1 in cell lines and primary tumors was examined by miRNA qRT-PCR. Proliferative assays, colony formation, cell invasion and migration, flow cytometry analysis and in vivo study were performed by ectopic expression of miR-15a and miR-16-1. The putative target genes of miR-15a and miR-16-1 were explored by TargetScan and further validated. RESULTS: We found that miR-15a and miR-16-1 were down-regulated in GAC cell lines and primary tumor samples compared with normal gastric epithelium. Functional study demonstrated that ectopic expression of miR-15a and miR-16-1 suppressed cell proliferation, monolayer colony formation, invasion and migration, and xenograft formation in vivo. In addition, miR-15a and miR-16-1 induced G0/G1 cell cycle arrest which was further confirmed by Western blot and qRT-PCR of related cell cycle regulators. YAP1 was confirmed to be a functional target of miR-15a and miR-16-1 in GAC. YAP1 re-expression partly abrogated the inhibitory effect of miR-15a and miR-16-1 in GAC cells. In clinical samples, YAP1 protein expression shows negative correlation with miR-15a and miR-16-1 expression. CONCLUSION: In conclusion, targeting YAP1 by tumor suppressor miRNA miR-15a and miR-16-1 plays inhibitory effect and this might have a therapeutic potential in GAC.

哈佛團隊解密KRAS and YAP1互補癌化功能

KRAS and YAP1 converge to regulate EMT and tumor survival. Cell. 2014 Jul 3;158(1):171-84 Cancer cells that express oncogenic alleles of RAS typically require sustained expression of the mutant allele for survival, but the molecular basis of this oncogene dependency remains incompletely understood. To identify genes that can functionally substitute for oncogenic RAS, we systematically expressed 15,294 open reading frames in a human KRAS-dependent colon cancer cell line engineered to express an inducible KRAS-specific shRNA. We found 147 genes that promoted survival upon KRAS suppression. In particular, the transcriptional coactivator YAP1 rescued cell viability in KRAS-dependent cells upon suppression of KRAS and was required for KRAS-induced cell transformation. Acquired resistance to Kras suppression in a Kras-driven murine lung cancer model also involved increased YAP1 signaling. KRAS and YAP1 converge on the transcription factor FOS and activate a transcriptional program involved in regulating the epithelial-mesenchymal transition (EMT). Together, these findings implicate transcriptional regulation of EMT by YAP1 as a significant component of oncogenic RAS signaling.

老達利 (西園醫院/永越健康管理/芝利/東研實業/惠鼎醫管) 涉行賄 延押!!

涉行賄醫師換標案　老達利業務遭聲請延押  老達利業務許霓和經理劉仁釧因涉嫌行賄醫師，遭收押禁見。2015年08月12日11:32 台北地檢署指揮廉政署偵辦6名公立醫院醫師涉向醫材商老達利收回扣弊案，6月間發動搜索、約談後，業務許霓雯、經理劉仁釧2人遭收押禁見，據了解，由於2人羈押期將滿2個月，且仍有部分案情待釐清，檢方已向台北地院聲請延押，法官正在開庭決定是否延押2人。據了解，檢廉已陸續約談涉案醫師，並多次提訊許霓雯、劉仁釧，但醫師均否認收賄，許、劉2人對於關鍵案情，也多以「忘記了」、「不記得」帶過，矢口否認行賄。檢調追查，老達利為取得公立醫院的醫材標案，涉嫌自2003年至2013年間，夥同關係企業西園醫院、永越健康管理中心、芝利、東研實業、惠鼎醫院管理等5間公司，以贈送筆電、智慧型手機等3C產品籠絡醫師，另涉嫌以採購金額的3%到10%做為回扣行賄醫師，醫師再於醫院需要採購X光機、電腦斷層掃描、超音波掃描機等醫療器材時，幫老達利量身打造標案，讓老達利11年來順利得標至少9件標案。 涉收取回扣賄賂的醫師除和平醫院抗煞醫師方鶯珍外，還有北市聯醫仁愛院區放射科主任醫師杜興洋、中興院區放射線科楊展明、已退休的衛福部台中醫院放射科主任醫師陳昶男、國軍高雄總醫院腸胃肝膽科主任醫師蔡毓源、高雄榮總胸腔內科主任醫師賴瑞生。檢調6月間發動搜索、約談後，涉案醫師分別以10萬元到40萬元不等金額交保；老達利負責人林育良、副總蔡金蓀遭聲押禁見，獲法院各以300萬元、100萬元交保。(賴又嘉、張欽／台北報導)