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Hypofractionated particle beam therapy for hepatocellular carcinoma–a brief review of clinical effectiveness

World Journal of Gastrointestinal Oncology 2019年第8期11卷 579-588页

作者： Che-Yu Hsu Chun-Wei Wang Ann-Lii Cheng sung-hsin kuo Division of Radiation Oncology Department of OncologyNational Taiwan University Hospital and National Taiwan University College of MedicineTaipei 100Taiwan National Taiwan University Cancer Center National Taiwan University College of MedicineTaipei 100Taiwan Cancer Research Center National Taiwan University College of MedicineTaipei 100Taiwan Department of Internal Medicine and Department of Oncology National Taiwan University HospitalTaipei 100Taiwan Graduate Institute of Oncology National Taiwan University College of MedicineTaipei 100Taiwan

Hepatocellular carcinoma(HCC)is the fifth most common malignancy and the second leading cause of cancer mortality *** cornerstone to improving the prognosis of HCC patients has been the control of loco-regional disease progression and the lesser toxicities of local *** radiotherapy has not been considered a preferred treatment modality for HCC,charged particle therapy(CPT),including proton beam therapy(PBT)and carbon ion radiotherapy(CIRT),possesses advantages(for example,it allows ablative radiation doses to be applied to tumors but simultaneously spares the normal liver parenchyma from radiation)and has emerged as an alternative treatment option for *** the technological advancements in CPT,various radiation dosages of CPT have been used for HCC treatment via ***,the efficacy and safety of the evolving dosages remain *** assess the association between locoregional control of HCC and the dose and regimen of CPT,we provide a brief overview of selected literature on dose regimens from conventional to hypofractionated short-course CPT in the treatment of HCC and the subsequent determinants of clinical ***,CPT provides a better local control rate compared with photon beam therapy,ranging from 80%to 96%,and a 3-year overall survival ranging from 50%to 75%,and it results in rare grade 3 toxicities of the late gastrointestinal tract(including radiation-induced liver disease).Regarding CPT for the treatment of locoregional HCC,conventional CPT is preferred to treat central tumors of HCC to avoid late toxicities of the biliary *** contrast,the hypo-fractionation regimen of CPT is suggested for treatment of larger-sized tumors of HCC to overcome potential radio-resistance.

关键词： Hepatocellular carcinoma Proton beam therapy Carbon ion radiotherapy Local control Toxicity Overall survival

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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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Fractionated evaluation of immunohistochemical hormone receptor expression enhances prognostic prediction in breast cancer patients treated with tamoxifen as adjuvant therapy

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2010年第1期11卷 1-9页

作者： Ching-hung LIN Huang-chun LIEN Fu-chang HU Yen-shen LU sung-hsin kuo Ling-chu WE San-lin YOU Ann-lii CHENG King-jen CHANG Department of Oncology National Taiwan University Hospital Taiwan Taipei 10016 Department of Pathology National Taiwan University Hospital Taiwan Taipei 10016 National Center of Excellence for General Clinical Trial and Research National Taiwan University Hospital Taiwan Taipei 1001 6 Graduate Institute of Epidemiology College of Public Health National Taiwan University Taiwan Taipei 10055 Department of Surgery National Taiwan University Hospital Taiwan Taipei 10016

Objective： To compare the prognostic prediction between dichotomized and fractionated evaluations of hormone receptor expressions. Methods： Patients with stages Ⅰ-Ⅲ breast cancers, who received adjuvant tamoxifen, were enrolled. The expression of estrogen receptor （ER） and progesterone receptor （PR） was evaluated by immu- nohistochemistry （IHC）. A fractionated score （F score）, the percentage of positive-staining nuclei （0=none, 1=1%-10% 2= 11%-30%, 3=31%-50%, 4=51%-70%, and 5=71%-100%）, was assigned to each case. The dichotomized scoring method defines an F score 〉1 as positive. The prognostic values of both scores were compared by multiple Cox＇s proportional hazard models of disease-free survival （DFS） and overall survival （OS）. Results： Four hundred and six- teen patients with a median follow-up of 78.0 months were included. F scores for ER and PR correlated directly with DFS and OS. Although both the dichotomized and fractionated ER and PR scores were significantly associated with DFS and OS in univariate analyses, only fractionated ER and PR scores remained as independent prognostic factors of DFS and OS in the final multiple Cox＇s proportional hazard models. Conclusion： Fractionated IHC hormone receptor expression evaluation enhances the prognostic prediction compared with a dichotomized assessment.

关键词： Breast cancer Fractionated evaluation Estrogen receptor Progesterone receptor

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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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Effects of glucocorticoids on the growth and chemosensitivity of carcinoma cells are heterogeneous and require high concentration of functional glucocorticoid receptors

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World Journal of Gastroenterology 2005年第40期11卷 6373-6380页

作者： Yen-Shen Lu Huang-Chun Lien Pei-Yen Yeh Kun-Huei Yeh Min-Liang kuo sung-hsin kuo Ann-Lii Cheng Department ofOncology National Taiwan University Hospital Graduate Instituteof Clinical Medicine National Taiwan University College ofMedicine Taipei Taiwan China Departments of Pathology National TaiwanUniversity Hospital Taipei Taiwan China Department of Oncology National Taiwan UniversityHospital Taipei Taiwan Department of Oncology and Departments of InternalMedicine National Taiwan University Hospital Departments ofInternal Medicine and Medical Research Far Eastern MemorialHospital Taipei Taiwan China Department of Oncology and Department ofInternal Medicine National Taiwan University Hospital TaipeiTaiwan China

AIM： To determine how glucocorticoids （GCs） may affect the growth and chemosensitivity of common carcinoma cells. METHODS： The effect of dexamethasone （DEX） on growth and chemosensitivity was assessed in 14 carcinoma cell lines. The function of GC receptors （GR） was assessed by MMTV reporter assay. Overexpression of GR was done by in vitro transfection and expression of a GR-expressing vector. Immunohistochemical stain of tissues and ceils were done by PA1-511A, an anti-GR monodonal antibody. RESULTS： DEX inhibited cell growth of four （MCF-7, MCF- 7/MXR1, MCF-7/TPT300, and HeLa）, increased cisplatin cytoxicity of one （SiHa）, and decreased dsplatin cytotoxicity of two （H460 and Hep3B） cell lines. The GR content of the seven cell lines affected by DEX was significantly higher than those of the seven cell lines unaffected by DEX （5.2±2.5×10^4 sites/cell vs1.3±1.4×10^4 sites/cell, P= 0.005）. Only two DEX-unresponsive cell lines {NPC-TW01 and NPC- TW04） oontained high GR amounts in the range （1.9-8.1×10^4 sites/cell） of the seven DEX-responsive cell lines. The GR function of NPC-TW01 and NPC-TW04, however, was foundto be impaired. The importance of high cellular amount of GR in mediating DEX susceptibility of the cells was further exemplified by GR dose-dependent drug resistance to cisplatin of AGS, a cell line with low GR content and was unaffected by DEX before transfection of GR-expressing vector. Immunohistochemical studies of human cancer tissues showed that 5 of the 45 （11.1%） breast cancer and 43 of the 85 （50.6%） non-small cell lung cancer had high GR contents at the ranges of the GC-responsive carcinoma cell lines. CONCLUSION： The growth and chemosensitivity of human carcinomas with high GR contents may be affected by GC. However, in light of the heterogeneous and even contradictive effects of GC on these cells, routine examination of GR contents of human carcinoma tissues may not be clinically useful until other markers that help predict the ultimate effect of

关键词： Glucocorticoids Glucocorticoid receptor Carcinoma Cell growth Chemosensitivility Drug resistance

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Expression of CD86 and increased infiltration of NK cells are associated with Helicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma

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World Journal of Gastroenterology 2005年第28期11卷 4357-4362页

作者： sung-hsin kuo Li-Tzong Chen Chi-Long Chen Shin-Lian Doong Kun-Huei Yeh Hui-Chen Hsu Ming-Shiang Wu Jaw-Town Lin Hsiu-Po Wang Ann-Lii Cheng Departments of Oncology National Taiwan University Hospital Taipei Cancer Research Center and Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei Taiwan China Division of Cancer Research National Health Research Institutes Taipei Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taipei Taiwan China Department of Pathologyl Taipei MedicalUniversity Taipei Taiwan China Graduate Institute of Microbiology National Taiwan University College of Medicine Taipei Taiwan China Departments of Oncology National Taiwan University Hospital Taipei Cancer Research Center National Taiwan University College of Medicine Taipei Taiwan China Department of Internal Mcclicine National Taiwan University Hospital Taipei Taiwan China Department of Emergency Medicine National Taiwan University Hospital Taipei Taiwan China Department of internal Medicine and Department of Oncology National Taiwan University Hospital Taipei Cancer Research Center National Taiwan University College of MedicineTaipei Division of Cancer Research National Health Research Institutes Taipei Taiwan China

AIM： A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue （MALT） lymphomas remain Helicobacter pylori （ H pylori）-dependent. However,unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors. Proliferation of MALT lymphoma cells depends on cognate help and cell-to-cell contact of H pylori- spedfic intratumoral T-cells. To examine whether the expression of co-stimulatory marker CD86 （B7.2） and the infiltration of CD56 （＋） natural killer （NK） cells can be useful markers to predict Hpylori-dependent status of high-grade gastric MALT iymphoma.METHODS： Lymphoma biopsies from 26 patients who had participated in a prospective study of Hpylori-eradication for stage IE high-grade gastric MALT lymphomas were evaluated. Tumors that resolved to Wotherspoon grade Ⅱ or less alter H pylori eradication were dassified as H pylori-dependent; others were dassified as H *** infiltration of NK cells and the expression of CD86 in pre-treatment paraffin-embedded lymphoma tissues were determined by immunohistochemistry. RESULTS： There were 16 H pylori-dependent and 10 H pylori-independent cases. CD86 expression was detected in 11 （68.8%） of 16 H pylori-dependent cases but in none of 10 H pylori-independent cases （P = 0.001）.H pylori-dependent high-grade gastric MALT lymphomas contained significantly higher numbers of CD56 （＋） NK cells than H pylori-independent cases （2.8±1.4% vs 1.1±0.8%, P = 0.003）. CD86 positive MALT lymphomas also showed significantly increased infiltration of CD56 （＋） NK cells compared to CD86-negative cases （2.9±1.1% vs 1.4±1.3%; P= 0.005）.CONCLUSION： These results suggest that the expression of co-stimulatory marker CD86 and the increased infiltration of NK cells are associated with Hpylori-dependent state of early-stage high-grade gastric M

关键词： MALT lymphoma Hpylori CD86 CD56

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Malignant pleural mesothelioma mimics thoracic empyema: A case report

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World Journal of Clinical Cases 2023年第35期11卷 8372-8378页

作者： Ya-hsin Yao Yen-Shou kuo Department of General Medicine Tri-Service General HospitalNational Defense Medical CenterTaipei 114202Taiwan Division of Thoracic Surgery Department of SurgeryTri-Service General HospitalNational Defense Medical CenterTaipei 114202Taiwan

BACKGROUND Thoracic empyema and malignant pleural mesothelioma(MPM)are distinct medical conditions with similar symptoms,including cough,chest pain,and breathing *** present a rare MPM case mimicking thoracic *** must consider MPM risks for patients exposed to building material who exhibit lobulated pleural effusions,indicating thoracic *** SUMMARY A 68-year-old retired male construction worker suffered from shortness of breath and chest tightness over 10 d,particularly during physical activity.A poor appetite and 4 kg weight loss over the past 3 wk were also *** images and laboratory data concluded a tentative impression of empyema thoracis(right).Video-assisted thoracic surgery with decortication and delobulation(right)was *** pathological report yielded an MPM *** pleural bilateral effusions and respiratory failure developed postoperatively,and the patient died three weeks after the *** Thoracic empyema and MPM are distinct medical conditions that can present similar symptoms,and video-assisted thoracic surgery facilitates an accurate ***-mimicking presentations and postoperative refractory pleural effusion may indicate a poor MPM outcome.

关键词： Thoracic empyema Malignant pleural mesothelioma Video-assisted thoracic surgery Case report

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Composites of graphene and encapsulated silicon for practically viable high-performance lithium-ion batteries

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Nano Research 2014年第10期7卷 1429-1438页

作者： Xin Zhao Minjie Li kuo-hsin Chang Yu-Ming Lin Bluestone Global Tech 169 Myers Corners Road Wappingers Falls NY 12590 USA

A facile and scalable approach to synthesize silicon composite anodes has been developed by encapsulating Si particles via in situ polymerization and carbonization of phloroglucinol-formaldehyde gel, followed by incorporation of graphene nanoplatelets. As a result of its structural integrity, high packing density and an intimate electrical contact consolidated by the conductive networks, the composite anode yielded excellent electrochemical performance in terms of charge storage capability, cycling life and coulombic efficiency. A half cell achieved reversible capacities of 1,600 mAh·g-1 and 1,000 mAh·g-1 at 0.5 A·g-1 and 2.1 A·g-1, respectively, while retaining more than 70% of the initial capacities over 1,000 cycles. Complete lithium-ion pouch cells coupling the anode with a lithium metal oxide cathode demonstrated excellent cycling performance and energy output, representing significant advance in developing Si-based electrode for practical application in high-performance lithium-ion batteries.

关键词： silicon nanoparticles graphene nanoplatelets phloroglucinol-formaldehyde gel lithium-ion batteries

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A STUDY ON FACTORS FOR RETAILERS IMPLEMENTING CPFR-A FUZZY AHP ANALYSIS

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Journal of Systems Science and Systems Engineering 2010年第2期19卷 192-209页

作者： hsin-Pin FU kuo-Kuang CHU Sheng-Wei LIN Chi-Ren CHEN Department of Marketing and Distribution Management National Kaohsiung First University of Science and Technology Kaohsiung (811) Taiwan China Department of Tourism management Shih Chien University Kaohsiung campus (845) Taiwan China Department of Marketing and Logistics Management Far East University Tainan County (744) Taiwan China

Since collaborative, planning, forecasting, and replenishment （CPFR） was first proposed in 1998, numerous studies have focused on exploring its implementation in retailing contexts. While a considerable body of research has emphasized reduced costs, increased sales and improved forecasting ability, there has been a lack of research on the importance of each of the various factors which affect such implementations. In order to find out the critical success factors affecting CPFR implementation, this paper first collected related influence factors regarding adopting CPFR or business to business （B2B） information systems, and further constructed a factor table with a three-layer hierarchical structure. A pair wise analytic hierarchy process （AHP） questionnaire was designed and distributed to experts who were familiar with implementing CPFR in the retailing industry. After questionnaires were returned, we found out the weights of each impact factor by using a fuzzy analytic hierarchy process （fuzzy AHP） approach. The importance of each critical impact factor was investigated, and the paths of the critical success factors were also analyzed. The results of this study can provide more precise information with regard to allocating optimal resources for retailers implementing CPFR.

关键词： Collaborative planning forecasting and replenishment (CPFR) critical influence factors fuzzy analytic hierarchy process (fuzzy AHP)

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Phlegmonous gastritis after biloma drainage:A case report and review of the literature

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World Journal of Clinical Cases 2022年第33期10卷 12430-12439页

作者： Kai-Chun Yang hsin-Yu kuo Jui-Wen Kang Department of Internal Medicine National Cheng Kung University HospitalTainan 704Taiwan

BACKGROUND Phlegmonous gastritis(PG)is a rare bacterial infection of the gastric submucosa and is related to septicemia,direct gastric mucosal injury,or the direct influence of infection or inflammation in neighboring ***,we present a patient who had spontaneous biloma caused by choledocholithiasis and then PG resulting from bile leakage after biloma *** SUMMARY A 79-year-old man with a medical history of hypertension had persistent diffuse abdominal pain for 4 *** examination showed stable vital signs,icteric sclera,diffuse abdominal tenderness,and muscle *** tests showed hyperbilirubinemia and *** computed tomography(CT)of the abdomen showed a dilated common bile duct and left subphrenic *** subphrenic abscess drainage revealed bilious fluid,and infected biloma was *** abdominal CT for persistent epigastralgia after drainage showed gastric wall ***(EGD)showed an edematous,hyperemic gastric mucosa with poor *** gastric mucosal culture yielded Enterococcus *** was diagnosed based on imaging,EGD findings,and gastric mucosal *** patient recovered successfully with antibiotic *** PG should be considered in patients with intraabdominal infection,especially from infected organs adjacent to the stomach.

关键词： Phlegmonous gastritis Epigastric pain Choledocholithiasis Bile leakage Antibiotics Case report

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