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Apple polyphenol phloretin inhibits type II glucose transporter and enhances anti-HER2 antibody drug binding as an adjuvant treatment for HER2-positive breast cancer

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Food Science and Human Wellness 2024年

作者： Han-Sheng Chang Tzu-Chun Cheng Shih-Hsin Tu Pei-Han Liao Yu-ching Lee Chi-tang Ho Min-Hsiung Pan Li-ching Chen Yuan-soon Ho Department of Biological Science & Technology， College of Life Sciences， China Medical University Institute of Biochemistry and Molecular Biology， College of Life Sciences， China Medical University Department of Surgery， School of Medicine， College of Medicine， Taipei Medical University Research Center of Cancer Translational Medicine， Taipei Medical University Department of Food Science， Rutgers University New Jersey， USA Institute of Food Sciences and Technology， Taiwan University

This study presents novel findings on the potential of phloretin， an apple polyphenol， to enhance the effectiveness of anti-HER2 antibody therapy in HER2-positive breast cancer patients. Our research reveals that phloretin inhibits type II glucose transporter (GLUT2) activity， significantly reducing cancer cell glucose uptake. We confirmed the overexpression of GLUT1 and GLUT2 mRNA in paired human breast tumor tissues， with GLUT2 overexpression associated explicitly with poorer survival rates in breast cancer patients. Treatment with phloretin was observed to increase the interaction between GLUT2 and HER2 proteins， attenuate glycolysis， and enhance the binding affinity of anti-HER2 antibody drugs to target human breast cancer cells. Furthermore， the efficacy of the combination therapy involving phloretin and antibody drugs was reaffirmed in a cell-derived xenograft (CDX) tumor animal model， particularly in suppressing the growth of Trastuzumab-resistant HER2+ breast cancer. These significant findings suggest that targeting GLUT2 activity with phloretin in combination with anti-HER2 antibody drugs may help mitigate the development of drug-resistant breast cancer， offering valuable insights for enhancing tumor treatment strategies and contributing to developing more effective therapies.

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Quercetin inhibits truncated isoform of dopamine-and cAMP-regulated phosphoprotein as adjuvant treatment for trastuzumab therapy resistance in HER2-positive breast cancer

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Food Science and Human Wellness 2024年第5期13卷 2653-2667页

作者： Han-Sheng Chang Tzu-Chun Cheng Shih-Hsin Tu Chih-Hsiung Wu You-Cheng Liao Jungshan Chang Min-Hsiung Pan Li-ching Chen Yuan-soon Ho Department of Biological Science&Technology College of Life SciencesChina Medical UniversityTaichung 406TaiwanChina Institute of Biochemistry and Molecular Biology College of Life SciencesChina Medical UniversityTaichung 406TaiwanChina Department of Surgery School of MedicineCollege of MedicineTaipei Medical UniversityTaipei 110TaiwanChina Department of Surgery Taipei Medical University HospitalTaipei 110TaiwanChina Graduate Institute of Medical Sciences College of MedicineTaipei Medical UniversityTaipei 110TaiwanChina Institute of Food Sciences and Technology National Taiwan UniversityTaipei 106TaiwanChina

Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosphoprotein(t-DARPP)has been reported to be involved in trastuzumab therapy resistance and promoting tumor *** evaluate the t-DARPP expression in BC,paired tumors and surrounding normal tissues were analyzed by real-time polymerase chain reaction and confirmed higher DARPP-32 kDa family mRNA expression in HER2+BC tumor *** established 2 patient-derived xenografts(PDX)mice models to test the efficacy of trastuzumab,named model 1(non-responder)and model 2(responder).t-DARPP and p95-HER2 protein-protein interactions were detected in PDX tumor tissue from non-responders using Förster resonance energy transfer ***,there is no response from the ***,mechanistic studies using transwell and western blot assays demonstrated that t-DARPP could upregulate epithelial-mesenchymal transition signaling proteins,enhance p95-HER2 expression and promote cell *** found that quercetin effectively reduced t-DARPP expression in HER2+BC *** t-DARPP ShRNA-suppressed cells,quercetin synergistically enhanced trastuzumab-induced apoptotic cell death and G2/M phase *** conclusion,the combination of quercetin and trastuzumab treatment by targeting t-DARPP in HER2+BC patients has the potential as a biomarker for mitigating drug resistance.

关键词： p95-Human epidermal growth factor receptor 2 (HER2) HER2-positive breast cancer Quercetin Trastuzumab resistance Truncated isoform of dopamine-and cAMPregulated phosphoprotein

INTERPRETATION OF COPPER AND ZINC CONTAMINATION IN THE AQUATIC ENVIRONMENT OF PENINSULAR MALAYSIA WITH SPECIAL REFERENCE TO A POLLUTED RIVER,SEPANG RIVER

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湿地科学 2007年第4期5卷 311-321页

作者： Chee Kong Yap Ahmad Ismail ching How Low soon Guan tan Department of Biology Faculty of ScienceUniversity Putra MalaysiaUPM 43400SerdangSelangorMalaysia

Three different aquatic ecosystems(an urban pond,Kelana Jaya Pond;a polluted river,Sepang River;and the intertidal and offshore areas of the west coast of Peninsular Malaysia)with different sets of ecological backgrounds and human activities were reviewed and assessed for the levels of Cu and Zn contamination with special reference to those found in polluted sediments collected from the Sepang *** discussion on the contamination levels of Cu and Zn in the aquatic environment of Peninsular Malaysia was based on a comparison of the metal contamination of 4 kinds of aquatic *** comparison of 4 different areas was based on ① total concentrations of 2 metals;② the concentrations and percentages of the nonresistant(EFLE,acid-reducible and oxidisable-organic)and resistant geochemical fractions;and ③ correlation coefficients(R-values)based on data of 4 areas separately and a combination of 4 *** Sepang River recorded nonresistant fractions of 63.1% for Zn and 55.8% for Cu in addition to slightly lower metal concentrations when compared to those(60%-70%)reported before the shutting down of the piggery activities in that *** nonresistant metal percentages(55%-63%)indicated that the metal concentrations were still dominated by anthropogenic sources since nonresistant fraction of metals were mostly contributed by anthropogenic *** positive results from the four different aquatic environments assessed here provided strong evidence to show that Malaysia's aquatic environment had received anthropogenic Cu and *** present study also showed that the percentage of the nonresistant fraction and the R-values based on correlation analysis of Cu and Zn could be used as indicators of Cu and Zn pollution in the Malaysian aquatic *** on the present data,the correlation coefficients(R-values)are potential indicators of EFLE Cu and acid-reducible Cu of the *** use of R-values as indicators of metal pollution is suggested and it

关键词：铜污染锌污染水生环境环境污染马来群岛沉积物

ENHANCEMENT OF SPEECH SIGNAL CORRUPTED BY HIGH ACOUSTIC NOISE

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ENHANCEMENT OF SPEECH SIGNAL CORRUPTED BY HIGH ACOUSTIC NOIS...

Molecular mechanisms of denbinobin-induced anti-tumorigenesis effect in colon cancer cells

计算机，通信，控制与电力工程国际会议

作者： Wee-soon ching Peng-Seng Toh School of Electrical and Electronic Engineering Nanyang Technological University

ISBN: (纸本)0780312333

Additive broad band noise is a common source of corruption in speech signals and often limits the effective operation of speech communication systems. This paper presents a new spectral-subtraction-based speech enhancement algorithm which exploits the correlation property of speech signal,the masking characteristic of the human ear,the speech redundancy property,and the frame-to-frame randomness of the noise that is present in the signal for the enhancement. Informal listening tests show that the proposed algorithm greatly improved the quality of the noisy speech even when the speech signal is corrupted by high acoustic *** the algorithm has low complexity and uses only a single input,it is well suited to a wide range of speech processing applications.

关键词： ENHANCEMENT OF SPEECH SIGNAL CORRUPTED BY HIGH ACOUSTIC NOISE

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World Journal of Gastroenterology 2005年第20期11卷 3040-3045页

作者： Kuo-ching Yang Yih-Huei Uen Fat-Moon Suk Yu-Chih Liang Ying-Jan Wang Yuan-soon Ho I-Hsuan Li Shyr-Yi Lin Department of Internal Medicine Shin Kong Wu Ho-Su Memorial Hospital Taipei Taiwan Department of Internal Medicine Taipei Medical University Taipei Taiwan China Department of Surgery Chi-Mei Foundational Medical Center Yung-Kane City Tainan Taiwan China Department of Internal Medicine Taipei Medical University Hospital Taipei Taiwan China School of Medical Technology Taipei Medical University Taipei Taiwan China Department of Environmental and Occupational Health National Cheng Kung University Medical College TainanTaiwan China Department of Internal Medicine School of Medicine Taipei Medical University Taipei Taiwan China Department of Internal Medicine School of Medicine and Department of Internal Medicine Taipei Medical University Hospital Taipei Medical University Taipei Taiwan China

AIM: To explore both the in vitro and in vivo effects of denbinobin against colon cancer cells and clarify its underlying signal pathways. METHODS: We used COLO 205 cancer cell lines and nude mice xenograft model to study the in vitro and in vivo anti-cancer effects of denbinobin. RESULTS: Denbinobin at concentration of 10-20 μmol/L dose-dependently suppressed COLO 205 cell proliferation by MTT test. Flow cytometry analysis and DNA fragmentation assay revealed that 10-20 μmol/L denbinobin treatment induced COLO 205 cells apoptosis. Western blot analysis showed that caspases 3,8,9 and Bid protein were activated by denbinobin treatment to COLO 205 cells accompanied with cytochrome c and apoptosis-inducing factor (AIF) translocation. Pretreatment of MEK 1 inhibitor (U10126), but not p38 inhibitor (SB203580) and JNK inhibitor (SP600125), reversed denbinobin-induced caspase 8, 9 and Bid activation in COLO 205 cells suggesting that extracellular signal-regulated kinase were involved in the denbinobin-induced apoptosis in COLO 205 cells. Significant regression of tumor up to 68% was further demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with denbinobin 50 mg/kg intraperitoneally. CONCLUSION: Our findings suggest that denbinobin could inhibit colon cancer growth both in vitro and in vivo. Activation of extrinsic and intrinsic apoptotic pathways and AIF were involved in the denbinobin-induced COLO 205 cell apoptosis.

关键词： Denbinobin Colon cancer Nude mice Apoptosis ERK pathway

Further analysis of PREVAIL： enzalutamide use in chemotherapy-naive men with metastatic castration- resistant prostate cancer

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Asian Journal of Andrology 2014年第6期16卷 803-804页

作者： Jeanny B Aragon-ching Department of Medicine Division of Hematology andOncology George Washington University MedicalCenter 2150 Pennsylvania Avenue NW WashingtonDC 20037 USA.

PREVAIL was a phase III multinational, double-blind, placebo-controlled trial that enrolled chemotherapy-naive men with metastatic castration-resistant prostate cancer （mCRPC）, which showed remarkable improvement in co-primary endpoints with an overall 81% reduction in the risk of radiographic progression, as well as 29% reduction in the risk of death in favor of the enzalutamide arm over placebo. All secondary endpoints including time to subsequent chemotherapy initiation and prostate specific antigen （PSA） progression were in favor of the enzalutamide arm. The results of PREVAIL shows the utility of enzalutamide that would likely soon expand the indication to asymptomatic or minimally symptomatic men with mCRPC not previously treated with chemotherapy.

关键词： ABIRATERONE DOCETAXEL

Cytogenetic and molecular aberrations of multiple myeloma patients： a single-center study in Singapore

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Chinese Medical Journal 2013年第10期126卷 1872-1877页

作者： LIM Alvin soon Tiong LIM Tse Hui SEE Karen Hsu Shien NG Yit Jun tan Yu Min CHO0 Natasha Swee Lian LIM Sherry Xin Er YEE Yenny LAU Lai ching TIEN Sim Leng Kumar Sathish tan Daryl Chen Lung Cytogenetics Laboratory Department of Pathology SingaporeGeneral Hospital Singapore School of Biological Sciences Nanyang Technological UniversitySingapore Temasek Applied Science School Temasek Polytechnic Singapore Department of Haematology Singapore General HospitalSingapore

Background Much is known about the cytogenetic lesions that characterize multiple myeloma （MM） patients from the USA, Europe, and East Asia. However, little has been published about the disease among Southeast Asians. The aim of this study was to determine the chromosomal abnormalities of MM patients in our Singapore population. Methods Forty-five newly-diagnosed, morphologically confirmed patients comprising 18 males and 27 females, aged 46-84 years （median 65 years） were investigated by karyotyping and fluorescence in situ hybridization （FISH）. FISH employing standard panel probes and lp36/lq21 and 6q21/15q22 probes was performed on diagnostic bone marrow samples. Results Thirty-four cases （75.6%） had karyotypic abnormalities. Including FISH, a total detection rate of 91.1% was at- tained. Numerical and complex structural aberrations were common to both hyperdiploid and non-hyperdiploid patients. Numerical gains of several recurring chromosomes were frequent among hyperdiploid patients while structural rear- rangements of several chromosomes including 8q24.1 and 14q32 characterized non-hyperdiploid patients. With FISH, immunoglobulin heavy chain （IGH） gene rearrangements, especially fibroblast growth factor receptor 3 （FGFR3）/IGH and RB1 deletion/monosomy 13 were the most common abnormalities （43.4%）. Amplification lq21 was 10 times more frequent （42.5%） than del（1p36） and del（6q21）. Conclusions We have successfully reported the comprehensive cytogenetic profiling of a cohort of newly-diagnosed myeloma patients in our population. This study indicates that the genetic and cytogenetic abnormalities, and their frequencies, in our study group are generally similar to other populations.

关键词： amp(l q21), del(13q) fluorescence in situ hybridization, immunoglobulin heavy chain, Southeast Asia

Acute pancreatitis and amiodarone:A case report

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World Journal of Gastroenterology 2007年第6期13卷 975-977页

作者： Yen-Yuan Chen ching-Yu Chen Kai-Kuen Leung Department of Family Medicine National Taiwan University Hospital Taipei Taiwan China

Amiodarone, a class Ⅲ antiarrhythmic drug, is one of the most effective drugs used in the treatment of ventricular and paroxysmal supraventricular tachyarrhythmia. Adverse effects of amiodarone including pulmonary toxicity, hepatotoxicity, aggravation of arrhythmia, and thyroid diseases are well understood. A 66-year old woman with acute pancreatitis was admitted to our hospital with the complaint of epigastralgia radiating to both flanks for two months. Her symptoms and elevation of pancreatic enzymes did not respond to conventional medical treatment of pancreatitis for 18 d. No known causal factors for pancreatitis such as biliary tract stone, hypertriglyceridemia and alcohol consumption could be identified. Under the suspicion of amiodarone-induced acute pancreatitis, amiodarone was substituted by propafenone. Her symptoms soon alleviated and serum lipase level declined. Three months after hospital discharge, the abdominal pain did not recur. Amiodarone was approved to treat recurrent ventricular fibrillation or sustained ventricular tachyarrhythmia that has been resistant to other medications since 1986. Pancreatitis is a very rare adverse effect associated with the use of amiodarone, and only four cases of amiodarone-induced pancreatitis have been reported in literature. We report a patient who developed acute pancreatitis during amiodarone therapy.

关键词： Acute pancreatitis Amiodarone Amylase Lipase

皮质类固醇治疗外伤性视神经病变的四天关键时期

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国际眼科杂志 2008年第3期8卷 452-455页

作者： soon Lek Yap Angeline Diong ching Nga Nadir Ali Mohamed Ali Visvaraja Subrayan 马来亚大学医学院眼科马来西亚吉隆坡50603

目的：评估静脉注射甲基强的松龙（IVMP）对外伤性视神经病变患者的疗效。方法：回顾性分析2000-01至2007-06我院收治的16例外伤性视神经病变（TON）患者的临床资料。1g甲基强的松龙分3d静脉应用，然后口服泼尼松龙11d，并逐渐减量。记... 详细信息

目的：评估静脉注射甲基强的松龙（IVMP）对外伤性视神经病变患者的疗效。方法：回顾性分析2000-01至2007-06我院收治的16例外伤性视神经病变（TON）患者的临床资料。1g甲基强的松龙分3d静脉应用，然后口服泼尼松龙11d，并逐渐减量。记录从损伤开始到治疗开始的时间。视力变化是本研究结果的主要功能评价指标。在入院时，治疗后1，2，3d；1wk和1mo时，分别记录最佳矫正视力（BCVA）。结果：共有16例患者纳入本研究，平均年龄为30岁，其中男性14例、女性2例。引起TON的主要原因有摩托车事故（占69％），打架斗殴（占19％）和体育运动（占12％）。所有患者都表现有相对传入性瞳孔障碍。在损伤后4d内开始静脉注射甲基强的松龙，采用Snellen视力表检查视力，绝大部分（56％）患者视力提高超过3行或大于等于0．5（6／12）。在损伤后5d以上才开始用类固醇治疗，视力则没有任何进步。结论：治疗TON，静脉注射中等到大剂量甲基强的松龙仍将起到重要作用。静脉注射甲基强的松龙治疗TON可能存在伤后4d的关键时期，超过了这个时期，该治疗可能就毫无效果。但还需要有更多的研究来为我们提供有明显统计学意义的数据。

关键词：外伤性视神经病变甲基强的松龙类固醇