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PI3K-AKT-mTOR signaling in prostate cancer progression and androgen deprivation therapy resistance

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Asian Journal of Andrology 2014年第3期16卷 378-386页

作者： Merritt P Edlind Andrew C hsieh Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Division of Hematology/Oncology and Department of Internal Medicine University of California San Francisco CA USA.

Prostate cancer （PCa） is the second most common malignancy among men in the world. Castration-resistant prostate cancer （CRPC） is the lethal form of the disease, which develops upon resistance to first line androgen deprivation therapy （ADT）. Emerging evidence demonstrates a key role for the PI3K-AKT-mTOR signaling axis in the development and maintenance of CRPC. This pathway, which is deregulated in the majority of advanced PCas, serves as a critical nexus for the integration of growth signals with downstream cellular processes such as protein synthesis, proliferation, survival, metabolism and differentiation, thus providing mechanisms for cancer cells to overcome the stress associated with androgen deprivation. Furthermore, preclinical studies have elucidated a direct connection between the PI3K-AKT-mTOR and androgen receptor （AR） signaling axes, revealing a dynamic interplay between these pathways during the development of ADT resistance. Thus, there is a clear rationale for the continued clinical development of a number of novel inhibitors of the PI3K pathway, which offer the potential of blocking CRPC growth and survival. In this review, we will explore the relevance of the PI3K-AKT-mTOR pathway in PCa progression and castration resistance in order to inform the clinical development of specific pathway inhibitors in advanced PCa. In addition, we will highlight current deficiencies in our clinical knowledge, most notably the need for biomarkers that can accurately predict for response to PI3K pathway inhibitors.

关键词： androgen receptor CRPC kinase inhibitors mTOR prostate cancer PI3K resistance

CD14 promoter polymorphism in Chinese alcoholic patients with cirrhosis of liver and acute pancreatitis

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World Journal of Gastroenterology 2005年第38期11卷 6043-6048页

作者： Hsin-Hung Huang Tsai-Yuan hsieh Division of Gastroenterology

AIM： To investigate the relationship between genetic polymorphism of the CD14 promoter and the occurrence of alcoholic cirrhosis and alcoholic pancreatitis, and to challenge the conclusion made earlier that the patients with acute alcoholic pancreatitis and patients with alcoholic cirrhosis of liver are two different subpopulations. METHODS： Using the polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method, we determined the polymorphism of CD14 gene and aldehyde dehydrogenase gene 2 （ALDH 2） in 335 alcoholic patients with different organ complications i.e., cirrhosis of liver （n = 100）, acute pancreatitis （n = 100）, esophageal cancer （n = 82） and avascular necrosis of hip joint （AVN）（n = 53） and 194 non-alcoholic controls in a Chinese group. RESULTS： The results showed that the carriage of T allele was not different among alcoholic patients with cirrhosis of liver, alcoholic patients with other complication and non-alcoholic controls. On the other hand, the carriage of the C allele was significantly more prevalent for alcoholic pancreatitis than for esophageal cancer （0.79 vs 0.60, P〈0.001）, alcoholic AVN （0.79 vsO.65, P〈0.025） and nonalcoholic controls （0.79 vs 0.68, P〈0.025）. Furthermore, when only subjects with ALDH2 1-1 genotype were examined, the C allele frequency was significantly more prevalent for alcoholic pancreatitis than for alcoholic liver cirrhosis （0.82 vs 0.69, P〈0.025）, esophageal cancer （0.82 vs 0.61, P〈0.01）, alcoholic AVN （0.82 vs 0.64, P〈0.01） and non-alcoholic controls （0.82 vs0.69, P〈0.05）. CONCLUSION： The C allele may be associated with some mechanism, which is important in the pathogenesis of alcoholic pancreatitis, and that alcoholic patients with acute pancreatitis and cirrhosis of liver are probably two different subpopulations.

关键词： CD14 promoter Polymorphism Alcoholic patients

Delayed diagnosis of pulmonary embolism

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Open Journal of Clinical Diagnostics 2012年第4期2卷 81-83页

作者： Chia-Jung hsieh meng-Jung Chen Department of Emergency Medicine Chi-Mei Medical Center Tainan Chinese Taipei Department of Medical Technology Chung-Hwa University of Medical Technology Tainan Chinese Taipei

Pulmonary embolism is a common and potentially life threatening condition. Delays in pulmonary embolism diagnosis represent an important problem. It is crucial to have early diagnosis of pulmonary embolism if one wishes to reduce its complication. We retrospectively reviewed our patients who visited our emergency department with a final diagnosis of pulmonary embolism. We found that delayed diagnosis of pulmonary embolism usually happened when patients did not present with the classical symptoms and signs leading to other medical diagnosis at first. Clinical signs and symptoms for pulmonary embolism are mostly non-specific;therefore, patients suspected of having pulmonary embolism—because of unexplained chest pain, shortness of breath or tachycardia with or without the risk factors for pulmonary embolism—must undergo diagnostic tests including D-dimer or CT pulmonary angiography if indicated until the diagnosis is ruled out.

关键词： Delayed Diagnosis Emergency Department Pulmonary Embolism

WATER WAVES IN AN ELASTIC VESSEL

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Acta Mechanica Sinica 1997年第4期13卷 289-303页

作者： D. Y. hsieh Department of Mathematics Hong Kong University of Science and Technology Hong Kong

Linear and nonlinear analyses of water waves in an elastic vessel are carried out to study the dramatic phenomena of Dragon Wash as well as related controllable experiments. It is proposed that the capillary edge waves are generated by parametric resonance, which is shown to be a possible mechanism for both rectangular an circular vessels. For circular vessel, the normal geometric resonance is also operating, thus greatly. enhance the dramatic effect. The mechanism of nonlinear mode-mode interaction is proposed far the generation of axisymmetric low-frequency gravity waves by the high-frequency external excitation. A simple model system is studied numerically to demonstrate explicitly this interaction mechanism.

关键词： water waves elastic vessel Dragon Wash

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Quantum speedup in adaptive boosting of binary classification

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Science China(Physics,Mechanics & Astronomy) 2021年第2期64卷 51-60页

作者： XiMing Wang YueChi Ma Min-Hsiu hsieh Man-Hong Yung School of Physics and Mathmatical Science Nanyang Technological UniversitySingaporeSingapore Department of Physics Southern University of Science and TechnologyShenzhen518055China Shenzhen Institute for Quantum Science and Engineering Southern University of Science and TechnologyShenzhen518055China Center for Quantum Information Institute for Interdisciplinary Information SciencesTsinghua UniversityBeijing100084China Center for Quantum Software and Information University of Technology SydneySydney2007Australia Guangdong Provincial Key Laboratory of Quantum Science and Engineering Southern University of Science and TechnologyShenzhen518055China

In classical machine learning,a set of weak classifiers can be adaptively combined for improving the overall performance,a technique called adaptive boosting(or AdaBoost).However,constructing a combined classifier for a large data set is typically resource *** we propose a quantum extension of AdaBoost,demonstrating a quantum algorithm that can output the optimal strong classifier with a quadratic speedup in the number of queries of the weak *** results also include a generalization of the standard AdaBoost to the cases where the output of each classifier may be *** prove that the query complexity of the non-deterministic classifiers is the same as those of deterministic classifiers,which may be of independent interest to the classical machine-learning ***,once the optimal classifier is determined by our quantum algorithm,no quantum resources are further *** fact may lead to applications on near term quantum devices.

关键词： AdaBoost quantum machine learning quantum algorithm

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Temporal patterns of dengue epidemics:The case of recent outbreaks in Kaohsiung

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Asian Pacific Journal of Tropical Medicine 2017年第3期10卷 275-279页

作者： Mattia Sanna Ying-Hen hsieh Department of Public Health China Medical University Taichung Taiwan 40402 Center for Infectious Disease Education and Research China Medical UniversityTaichung Taiwan 40402

Objective:To investigate whether major dengue outbreaks in the last two decades in Kaohsiung follow a precise temporal ***:Government daily lab-confirmed dengue case data from three major dengue outbreaks occurring during the last two decades in Kaohsiung in2002,2014 and 2015,is utilized to compute the corresponding weekly cumulative percentage of total case *** divide each of the three time series data into two periods to examine the corresponding weekly cumulative percentages of case numbers for each ***’s correlation coefficient was calculated to compare quantitatively the similarity between the temporal patterns of these three ***:Three cutoff points produce the most interesting comparisons and the most different ***’s correlation coefficient indicates quantitative discrepancies in the similarity between temporal patterns of the three years when using different cutoff ***:Temporal patterns in 2002 and 2014 are comparatively more similar in early *** 2015 outbreak started late in the year,but ended more like the outbreak in 2014,both with record-breaking number of *** retrospective analysis shows that the temporal dynamics of dengue outbreaks in Kaohsiung can strongly vary from one year to another,making it difficult to identify any common predictor.

关键词： Dengue Kaohsiung Temporal pattern Cumulative percentage Pearson's correlation coefficient

Tumor progression-dependent angiogenesis in gastric cancer and its potential application

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World Journal of Gastrointestinal Oncology 2019年第9期11卷 686-704页

作者： Hsi-Lung hsieh Ming-Ming Tsai Research Center for Chinese Herbal Medicine College of Human EcologyChang Gung University of Science and TechnologyTaoyuan 333Taiwan Department of Nursing Division of Basic Medical SciencesChang-Gung University of Science and TechnologyTaoyuan 333Taiwan Department of Neurology Chang Gung Memorial HospitalTaoyuan 333Taiwan Department of General Surgery Chang Gung Memorial HospitalChiayi 613Taiwan

Despite improvements in the early diagnosis,prognosis and therapeutic strategies for gastric cancer(GC),human GC remains one of the most frequently diagnosed malignant tumors in the world,and the survival rate of GC patients remains very ***,a suitable therapeutic strategy for GC is important for prolonging *** tumor cells themselves and the tumor microenvironment play an important role in tumorigenesis,including angiogenesis,inflammation,immunosuppression and ***,these cells contribute to gastric carcinogenesis by altering the angiogenic phenotype *** development,relapse and spreading of tumors depend on new vessels that provide the nutrition,growth factors and oxygen required for continuous tumor ***,a state of tumor dormancy could be induced by blocking tumor-associated ***,several antiangiogenic agents have been identified,and their potential for the clinical management of GC has been ***,we provide an up-to-date summary of angiogenesis and the angiogenic factors associated with tumor progression in *** also review antiangiogenic agents with a focus on the anti-vascular endothelial growth factor receptor(VEGFR)-mediated pathway for endothelial cell growth and their angiogenesis ability in ***,most antiangiogenic agents have reported no benefit to overall survival(OS)compared to chemotherapy alone in local or advanced *** phase III clinical trials,only ramucirumab(anti-VEGFR blocker)and apatinib(VEGFR-TKI blocker)have reported an improved median overall response rate and prolonged OS and progression-free survival outcomes as a 2 nd-line agent combined with chemotherapy treatment in advanced *** providing insights into the molecular mechanisms of angiogenesis associated with tumor progression in GC,this review will hopefully aid the optimization of antiangiogenesis strategies for GC therapy in combination with chemotherapy and adjuvant treatment.

关键词： Gastric cancer Angiogenesis Vascular endothelial cell Angiogenic phenotype switch Anti-angiogenesis Tumor dormancy

The Reduction of Thermal Nitrogen Oxides (NOx) Emission Using Staged Combustion in Furnace

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Journal of Thermal Science 1993年第1期2卷 61-69页

作者： H.K.Ma D.M.hsieh DepartmentofMechanicalEngineering NationalTaiwanUniversityTaiwanChina DepartmentofMechanicalEnginee

The experimental study described in this paper is to investigate the control of thermal nitrogen oxides emissions from a 2.28 MW gas-fired test furnace. Tests, including changing axial or radial air flow rate, adding cooling water, and adding staged air, were performed to characterize and opimize the fuel-rich burning zone and the fuel-lean burnout zone independently. Detailed measurements of O_2, CO_2, CO, NO and NOx were made at the fuel-rich burning zone and furnace exit. The influence of forming CO, NO and NOx was examined. Results indicated that adding staged air in the fuel-rich burning zone (75 cm from burner) will reduce the mawximum NO and NO_x emissions. Adding cooling water in a right position may further lower the NO and NO_x emissions. In addition, the least formation of thermal nitrogen oxides in the first stooge fuel-rich bunting zone will occur at the stoichiometric ratio's inverse value, (φ_1)^(-1), 0.65 to 0.7.

关键词： reduction of NO_x emission staged combustion furnace.

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Association between metabolic factors and chronic hepatitis B virus infection

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World Journal of Gastroenterology 2014年第23期20卷 7213-7216页

作者： Chien-hsieh Chiang Kuo-Chin Huang Department of Family Medicine National Taiwan University Hospital and College of Medicine Department of Community and Family Medicine National Taiwan University Hospital Yun-Lin Branch Graduate Institute of Clinical Medical Science China Medical University

There are limited data regarding the relationship between chronic hepatitis B virus(HBV)infection and metabolic *** article aims to highlight the link of metabolic factors with hepatitis B surface antigen(HBsAg)serostatus,HBV load,and HBV-related hepatocellular carcinoma(HCC).Although HBsAg-positive serostatus was positively correlated with a high risk of metabolic syndrome in students,chronic HBV-infected individuals have high serum adiponectin *** androgen pathway in HBV carriers with a low body mass index is more triggered which leads to enhanced HBV *** HBV load was inversely associated with obesity in hepatitis B e antigen(HBeAg)-seropositive HBV carriers;while in HBeAg-seronegative HBV carriers,high HBV load was inversely related to hypertriglyceridemia rather than *** overweight and obese HBV-infected patients,high HBV load was positively associated with serum adiponectin *** large cohort studies have revealed a positive link of diabetes with incidence of HBV-related ***,the association between incidence of HCC and metabolic factors other than diabetes is still *** long-term prospective studies should elucidate the association of chronic HBV infection and its outcomes with metabolic factors in clinical practice.

关键词： Hepatitis B surface antigen Hepatitis B viral load Hepatocellular carcinoma Diabetes Obesity Adiponectin