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Perspectives on the combination of radiotherapy and targeted therapy with DNA repair inhibitors in the treatment of pancreatic cancer

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World Journal of Gastroenterology 2016年第32期22卷 7275-7288页

作者： Shih-Hung Yang Ting-Chun Kuo hsu Wu Jhe-Cyuan Guo chiun hsu Chih-Hung hsu Yu-Wen Tien Kun-Huei Yeh Ann-Lii Cheng Sung-Hsin Kuo Department of Oncology National Taiwan University Hospital and National Taiwan University Cancer Center Taipei 100 Taiwan Department of Internal Medicine National Taiwan University Hospital and National Taiwan University Cancer Center Taipei 100 Taiwan Institute of Clinical Medicine National Taiwan University Hospital and National Taiwan University Cancer Center Taipei 100 Taiwan Department of Traumatology National Taiwan University Hospital and National Taiwan University Cancer Center Taipei 100 Taiwan Department of Oncology National Taiwan University Hospital Yun-Lin Branch Yunlin 655 Taiwan Graduate Institute of Oncology National Taiwan University College of Medicine Taipei 100 Taiwan Department of Surgery National Taiwan University Hospital and National Taiwan University Cancer Center Taipei 100 Taiwan

Pancreatic cancer is highly lethal. Current research that combines radiation with targeted therapy may dramatically improve prognosis. Cancerous cells are characterized by unstable genomes and activation of DNA repair pathways, which are indicated by increased phosphorylation of numerous factors, including H2 AX, ATM, ATR, Chk1, Chk2, DNA-PKcs, Rad51, and Ku70/Ku80 heterodimers. Radiotherapy causes DNA damage. Cancer cells can be made more sensitive to the effects of radiation(radiosensitization) through inhibition of DNA repair pathways. The synergistic effects, of two or more combined non-lethal treatments, led to coadministration of chemotherapy and radiosensitization in BRCA-defective cells and patients, with promising results. ATM/Chk2 and ATR/Chk1 pathways are principal regulators of cell cycle arrest, following DNA doublestrand or single-strand breaks. DNA double-stranded breaks activate DNA-dependent protein kinase, catalytic subunit(DNA-PKcs). It forms a holoenzyme with Ku70/Ku80 heterodimers, called DNA-PK, which catalyzes the joining of nonhomologous ends. This is the primary repair pathway utilized in human cells after exposure to ionizing radiation. Radiosensitization, induced by inhibitors of ATM, ATR, Chk1, Chk2, Wee1, PP2 A, or DNA-PK, has been demonstrated in preclinical pancreatic cancer studies. Clinical trials are underway. Development of agents that inhibit DNA repair pathways to be clinically used in combination with radiotherapy is warranted for the treatment of pancreatic cancer.

关键词： Radiotherapy Pancreatic cancer DNA damage DNA repair Molecular targets

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Hepatitis B and C viruses are not risks for pancreatic adenocarcinoma

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World Journal of Gastroenterology 2014年第17期20卷 5060-5065页

作者： Ming-Chu Chang Chien-Hung Chen Ja-Der Liang Yu-Wen Tien chiun hsu Jau-Min Wong Yu-Ting Chang Department of Internal Medicine National Taiwan University HospitalCollege of MedicineNational Taiwan University Department of Surgery National Taiwan University HospitalCollege of MedicineNational Taiwan University Graduate Institute of Oncology College of MedicineNational Taiwan University

AIM: To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) increase risk of pancreatic ductal adenocarcinoma (PDAC).

关键词： Hepatitis B virus Hepatitis C virus Pancreatic ductal adenocarcinoma Risk Endemic disease Diabetes mellitus

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eTom/SOA的数字汇流运营支撑系统及流程实现

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北京邮电大学学报 2011年第2期34卷 39-44页

作者：黄振益徐俊傑台湾科技大学管理研究所

为了实现数字汇流业务融合的运营管理需求,符合未来数字融合业务导向的需求,以电信管理论坛的增强型电信运营图模型结构和面向服务的体系结构为设计核心,建构完整的运营支撑系统(OSS),分析说明了体系结构中的构成模块和相关子功能,利用... 详细信息

为了实现数字汇流业务融合的运营管理需求,符合未来数字融合业务导向的需求,以电信管理论坛的增强型电信运营图模型结构和面向服务的体系结构为设计核心,建构完整的运营支撑系统(OSS),分析说明了体系结构中的构成模块和相关子功能,利用web服务建立服务网络组件接口和信息传递标准化,并通过客户服务订单流程场景说明,对数字汇流网络下的服务OSS提供了架构面的建议与参考.

关键词：数字汇流面向服务的体系结构运营支撑系统 web服务网络融合

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Anti-CD 20 monoclonal antibodies and associated viral hepatitis in hematological diseases

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World Journal of Hematology 2014年第2期3卷 29-43页

作者： Shih-Hung Yang chiun hsu Ann-Lii Cheng Sung-Hsin Kuo Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Department of Oncology National Taiwan University Hospital Cancer Research Center National Taiwan University College of Medicine Graduate Institute of Oncology National Taiwan University College of Medicine Department of Internal Medicine National Taiwan University Hospital

Over the past decade, the administration of anti-CD20 monoclonal antibodies such as rituximab has demonstrated various degrees of effectiveness and has improved patients' outcomes during the treatment of autoimmune hematological disorders and hematological malignancies. However, the depletion of B-cells, the distribution of T-cell populations, and the reconstruction of host immunity resulting from the use of anti-CD20 monoclonal antibodies potentially lead to severe viral infections, such as hepatitis B virus(HBV), hepatitis C virus(HCV), parvovirus B19, and herpes viruses, in patients who are undergoing immune therapy or immunochemotherapy. Of these infections, HBV- and HCV-related hepatitis are a great concern in endemic areas because of the high morbidity and mortality rates in untreated patients. As a result, prophylaxis against HBV infection is becoming a standard of care in these areas. Parvovirus B19, a widespread pathogen that causes red blood cell aplasia in immunocompromised hosts, also causes hepatitis in healthy individuals. Recently, its association with hepatitis was recognized in a patient treated with rituximab. In addition, adenovirus, varicella-zoster virus hepatitis E virus, and rituximab itself have been linked to the occurrence of hepatitis during or after rituximab treatments. The epidemiologies and pathogeneses of these etiologies remain unknown. Because of the increasing use of anti-CD20 monoclonal antibodies for the treatment of hematological malignancies or autoimmune hematological disorders, it is imperative that physicians understand and balance the risks of hepatotropic virusassociated hepatitis against the benefits of using antiCD20 monoclonal antibodies.

关键词： CD20 Monoclonal antibody Hepatitis Hepatitis B virus Hepatitis C virus

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Long-term hepatic consequences of chemotherapy-related HBV reactivation in lymphoma patients

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World Journal of Gastroenterology 2005年第34期11卷 5283-5288页

作者： Chi-Chung Wen Chao A.Hsiung Ih-Jen Su Ann-Lii Cheng Ming-Chih Chang Chao-Jung Tsao Woei-Yao Kao Wu-Ching Uen chiun hsu Chih-Hung hsu Yen-Shen Lu Hwei-Fan Tien Tsu-Yi Chao Li-Tzong Chen Jacqueline Whang-Peng Pei-Jer Chen Division of Biostatics and Bioinformatics National Health Research Institutes Taipei Taiwan China Division of Clinical Research National Health Research Institutes Taipei Taiwan China Department of Oncology National Taiwan University Hospital Taipei Taiwan China Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan China Department of Internal Medicine Mackay Memorial Hospital Taipei Taiwan China Department of Internal Medicine Chi-Mei Hospital Tainan Taiwan China Department of Internal Medicine Tri-Service General Hospital Taipei Taiwan China Department of Internal Medicine Shin Kong Memorial Hospital Taipei Taiwan China Department of Oncology National Taiwan University Hospital Taipei Taiwan China Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan China Division of Cancer Research National Health Research Institutes Taipei Taiwan China

AIM: To investigate the long-term consequences of chemotherapy-related HBV reactivation in patients with ***: This study was based on the database of published prospective study evaluating HBV reactivation in HBV lymphoma patients during *** liver reserve (DLR) was defined as development of either one of the following conditions during follow-up: (1) newly onset parenchyma liver disease, splenomegaly or ascites without evidence of lymphoma involvement; (2) decrease of the ratio (albumin/globulin ratio) to less than 0.8 or increase of the ratio of INR of prothrombin time to larger than 1.2 without evidence of malnutrition or infection. Liver cirrhosis was diagnosed by imaging ***: A total of 49 patients were included. The median follow-up was 6.2 years (range, 3.9-8.1 years).There were 31 patients with and 18 patients without HBV reactivation. Although there was no difference of overall survival (OS) and chemotherapy response rate between the two groups, DLR developed more frequently in patients with HBV reactivation (48.4% vs 16.7%; P= 0.0342). Among the HBV reactivators, HBV genotype C was associated with a higher risk of developing DLR (P = 0.0768) and liver cirrhosis (P = 0.003). Four of five patients with sustained high titer of HBV DNA and two of three patients with multiple HBV reactivation developed DLR. Further, patients with a sustained high titer of HBV DNA had the shortest OS among the HBV reactivators (P= 0.0000). No patients in the non-HBV reactivation group developed hepatic failure or liver ***: Chemotherapy-related HBV reactivation is associated with the long-term effect of deterioration of hepatic function.

关键词： HBV reactivation Liver function Non-HodgkJn'slymphoma, Chemotherapy

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Rac 1 regulates peptidoglycan-induced nuclear factor-κB activation and cyclooxygenase-2 expression in RAW 264.7 macrophages by activating the phosphatidylinositiol 3-kinase/Akt pathway

Rac 1 regulates peptidoglycan-induced nuclear factor-κB act...

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第十五届国际药理学大会

作者： Chien-Huang Lin Ju-chiun Kang Ming-Jen hsu Graduate Institute of Medical Sciences. Graduate Institute of Pharmacology Graduate Institute of Medical Sciences.

＜正＞ In this study, we investigated the role of Rac 1. phosphatidylinositiol 3 - kinase （PI3K）, and Akt in peptidoglycan （PGN） - induced nuclear factor -κB （NF -κB） activation and cyclooxygenase - 2 （COX - 2） expression in RAW 264. 7 macrophages. PGN - induced COX - 2 expression was attenuated by a Racl dominant negative mutant （ RacN17）. PI3K inhibitors （ wortamanin and LY 294002）. and the Akt inhibitor. Treatmentof RAW 264. 7 macrophages with PGN caused the activation of Racl and Akt. The PGN - induced Akt activation was inhibited by RacN17. LY 294002. and the Akt inhibitor. Stimulation of RAW 264.7 macrophages with PGN resulted in the increase in IκB kinases α/β （IKKα/β） phosphorylation and p65 Ser536 phosphorylation;these effect were inhibited by RacN17. LY 294002. the Akt inhibitor, or an Akt dominant negative mutant （AktDN）. The PGN - induced increases in κB - luciferase activity was also inhibited by RacN17. wortmannin. LY 294002. the Akt inhibitor, and AktDN. Treatment of macrophages with PGN induced the recruitment of p85α and Racl to toll - like receptor 2 （TLR2） in a time - dependent manner. These results indicate that PGN may activate the Racl/PI3K/Akt pathway, which in turn initiates IKKα/β. p65Ser536 phosphorylation. and NF - κB activation, and ultimately induces COX - 2 expression in RAW 264.7 macrophages.

关键词： Cyclooxygenase-2. Racl. PI3K Akt Nuclear factor-κB. RAW 264.7 macrophages.

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Clinical application of dip-assisted endoscopic method for nasoenteric feeding in patients with gastroparesis and gastroesophageal wounds

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World Journal of Gastroenterology 2005年第24期11卷 3714-3718页

作者： Chung-Jen Wu Ping-I hsu Gin-Ho Lo Chang-Bih Shie Ching-Chu Lo E-Ming Wang chiun-Ku Lin Wen-Chi Chen Lung-Chin Cheng Hsien-Chung Yu Yi-Chun Chan Kwok-Hung Lai Division of Gastroenterology

AIM: To report the clinical experiences in the application of clip-assisted endoscopic method for nasoenteric feeding in patients with gastroparesis and patients with gastroesophageal wounds, and to compare the efficacy of nasoenteric feeding in these two indications. METHODS: From April 2002 to January 2004,21 consecutive patients with gastroparesis or gastroesophageal wounds were enrolled and received nasoenteric feeding for nutritional support. A clip-assisted method was used to place the nasoenteric tubes. Outcomes in the two groups were compared with respect to the successful rate of enteral feeding, percentage of recommended energy intake (REI), and complication rates. RESULTS: The gastroparesis group included 13 patients with major burns (n = 7), trauma (n = 2), congestive heart failure (n = 2) and post-surgery gastric stasis syndrome (n = 2). The esophageogastric wound group included eight patients with tracheoesophageal fistula (n = 2) and wound leakage following gastric surgery (n = 6). Two study groups were similar in feeding successful rates (84.6% vs 75.0%). There were also no differences in the percentage of REI between groups (79.4% vs 78.6%). Additionally, no complications occurred in any of the study groups. CONCLUSION: Nasoenteric feeding is a useful method to provide nutritional support to most of the patients with gastroparesis who cannot tolerate nasogastric tube feeding and to the cases who need bypass feeding for esophageogastric wounds.

关键词： Enteral feeding Nasoenteric tube Endoscopic Hemoclip

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Composition of common bile duct stones in Chinese patients during and after endoscopic sphincterotomy

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World Journal of Gastroenterology 2005年第27期11卷 4246-4249页

作者： Wei-Lun Tsai Kwok-Hung Lai chiun-Ku Lin Hoi-Hung Chan Ching-Chu Lo Ping-I hsu Wen-Chi Chen Jin-Shiung Cheng Gin-Ho Lo Division of Gastroenterology Department of InternalMedicine Kaohsiung Veterans General Hospital School of MedicineNational Yang Ming University Taiwan China

AIM： Endoscopic sphincterotomy （ES） is a well-established therapeutic modality for the removal of common bile duct （CBD） stones. Alter ES there are still around 10% of patients that experience recurrent CBD stones. The aim of this study is to investigate the composition of CBD stones before and alter ES and its clinical significance in Chinese ***： From January 1996 to December 2003, 735 patients with CBD stones received ES at Kaohsiung Veterans General Hospital and stone specimens from 266 patients were sent for analysis. Seventy-five patients had recurrent CBD stones and stone specimens from 44 patients were sent for analysis. The composition of the stones was analyzed by infrared （IR） spectrometry and they were classified as cholesterol or bilirubinate stones according to the predominant composition. Clinical data were ***： In the initial 266 stone samples, 217 （82%） were bilirubinate stones, 42 （16%） were cholesterol stones,3 were calcium carbonate stones, 4 were mixed cholesterol and bilirubinate stones. Patients with bilirubinate stones were significantly older than patients with cholesterol stones （66＋13 years vs 56＋17 years, P = 0.001）. In the 44 recurrent stone samples, 38 （86%） were bilirubinate stones, 3 （7%） were cholesterol stones, and 3 were mixed cholesterol and bilirubinate stones. In 27 patients, both initial and recurrent stone specimens can be obtained,23 patients had bilirubinate stones initially and 2 became cholesterol stones in the recurrent attack. In the four patients with initial cholesterol stones, three patients had bilirubinate stones and one patient had a cholesterol stone in the recurrent ***： Bilirubinate stone is the predominant composition of initial or recurrent CBD stone in Chinese patients, The composition of CBD stones may be different from initial stones afl：er ES,

关键词： Endoscopic sphincterotomy Common bile ductstone Bilirubinate stone Cholesterol stone

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Implications of anti-parietal cell antibodies and anti-Helicobacter pylori antibodies in histological gastritis and patient outcome

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World Journal of Gastroenterology 2005年第30期11卷 4715-4720页

作者： Ching-Chu Lo Ping-I hsu Gin-Ho Lo Kwok-Hung Lai Hui-Hwa Tseng chiun-Ku Lin Hoi-Hung Chan Wei-Lun Tsai Wen-Chi Chen Nan-Jing Peng Division of Gastroenterology Department of Internal Medicine Kaohsiung Veterans General Hospital and St. Martin De Porres HospitalNational Yang-Ming University Kaohsiung Taiwan China Department of Pathology Kaohsiung Veterans General Hospital and National Yang-Ming University KaohsiungTaiwan China Department of Nuclear Medicine Kaohsiung Veterans General Hospital and National Yang-Ming University Kaohsiung Taiwan China

AIM： To develop a serum or histological marker for early discovery of gastric atrophy or intestinal metaplasia. METHODS： This study enrolled 44 patients with gastric adenocarcinoma, 52 patients with duodenal ulcer, 14 patients with gastric ulcer and 42 consecutive healthy adults as controls. Each patient received an endoscopy and five biopsy samples were obtained. The degrees of histological parameters of gastritis were categorized following the Updated Sydney System. Anti-parietal cell antibodies （APCA） and anti- Helicobacter pylori （ H pylori） antibodies （AHPA） were analyzed by immunoassays. Hpyloriinfection was diagnosed by rapid unease test and histological examination. RESULTS： Patients with gastric cancer and gastric ulcer are significantly older than healthy subjects, while also displaying higher frequency of APCA than healthy controls. Patients with positive APCA showed higher scores in gastric atrophy and intestinal metaplasia of corpus than patients with negative APCA. Patients with positive AHPA had higher scores in gastric atrophy, intestinal metaplasia, and gastric inflammation of antrum than those patients with negative AHPA. Elderly patients had greater prevalence rates of APCA. Following multivariant logistic regression analysis, the only significant risk factor for antral atrophy is positive AHPA, while that for corpus atrophy is positive APCA. CONCLUSION： The existence of positive APCA correlates with glandular atrophy in corpus and the presence of positive AHPA correlates with glandular atrophy in antrum. The existence of serum APCA and AHPA betokens glandular atrophy and requires further examination for gastric cancer.

关键词： Glandular atrophy Intestinal metaplasia Gastriccancer Anti-parietal cell antibody Anti-Helicobacter pylori antibodies

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多粘杆菌中合成乙酰乳酸酶系的压制与诱导

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Acta Biochimica et Biophysica Sinica 1964年第3期 314-321页

作者：徐美琳沈善炯中国科学院植物生理研究所微生物研究室中国科学院植物生理研究所微生物研究室上海

多粘杆菌中合成乙酰乳酸酶系的合成,受其所催化的反应的终末产物,缬氨酸、异白氨酸和白氨酸所抑制。有些不属于合成乙酰乳酸酶系所参予催化的反应的终末产物如甲硫氨酸,赖氨酸,苏氨酸,半胱氨酸和高胱氨酸等,对该酶的合成亦有抑制作用。... 详细信息

多粘杆菌中合成乙酰乳酸酶系的合成,受其所催化的反应的终末产物,缬氨酸、异白氨酸和白氨酸所抑制。有些不属于合成乙酰乳酸酶系所参予催化的反应的终末产物如甲硫氨酸,赖氨酸,苏氨酸,半胱氨酸和高胱氨酸等,对该酶的合成亦有抑制作用。生长在豌豆汁营养培养基上的细菌内,测不出合成乙酰乳酸酶系的活力,当加入葡萄糖后,酶的合成速率显著增加。葡萄糖有抵制缬氨酸对合成乙酰乳酸酶系的合成的抑制作用。而葡萄糖对这个酶的去压制作用不能为甘油或丙酮酸所代替。作者对甲硫氨酸、赖氨酸和苏氨酸等对合成乙酰乳酸酶系的合成的抑制作用,以及葡萄糖对这个酶的诱导现象进行了讨论。

关键词：异白氨酸抑制作用乳酸异亮氨酸基因互作羟基羧酸营养培养基杆菌

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