Publications by authors named "Yin-Hsun Feng"

45 Publications

Myocardial Infarction and Azygos Vein Thrombosis After ChAdOx1 nCoV-19 Vaccination in a Hemodialysis Patient.

Cureus 2021 Sep 30;13(9):e18390. Epub 2021 Sep 30.

Department of Hematology and Oncology, Chi Mei Medical Center, Tainan, TWN.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication after vaccination of Oxford-AstraZeneca coronavirus disease 2019 (COVID-19) vaccine (AZD1222) or Janssen COVID-19 vaccine. It makes a rare complication of thrombosis at common and/or uncommon organs with thrombocytopenia after COVID-19 vaccination four to 28 days later and most patients were younger than 60 years of age. We reported the case of a 75-year-old female with end-stage renal disease who received regular hemodialysis. She received Oxford-AstraZeneca COVID-19 vaccination eight days ago and then she suffered from intermittent chest tightness and epigastric pain with tarry stool passage for two days. Severe thrombocytopenia with elevated D-dimer value was noted and computed tomography of the chest showed azygos vein thrombosis. Elevated cardiac enzyme with ST-T change in 12-lead electrocardiogram was also noted. For positive anti-platelet factor 4 antibodies, VITT with myocardial infarction and azygos vein thrombosis was diagnosed.
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http://dx.doi.org/10.7759/cureus.18390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489656PMC
September 2021

Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens.

Breast Cancer Res Treat 2021 Oct 23;189(3):665-676. Epub 2021 Sep 23.

Division of Breast Oncology and Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, No.100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.

Purpose: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein.

Methods: 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m bid, day 1-14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety.

Results: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity.

Conclusion: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted.

Clinical Trial Registration: NCT01808573.
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http://dx.doi.org/10.1007/s10549-021-06313-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505315PMC
October 2021

The impact of COVID-19 on cardio-oncology care in Taiwan.

J Formos Med Assoc 2021 Aug 23. Epub 2021 Aug 23.

Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan; Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:

COVID-19 has not only affected the respiratory but the cardiovascular system. Taiwan has encountered a less severe COVID-19 pandemic. We reported the current situation in Taiwan. In this study, we retrospectively analyzed the data from our cardio-oncology program since October of 2019 to April of 2020 (the initial months of COVID-19 pandemic). In our cardio-oncology program, newly diagnosed breast cancer patients preparing for epirubicin therapy were included. Echocardiography, 6-min walking distance and major adverse cardiovascular events (MACEs) were recorded. To evaluate whether the social atmosphere affects cardio-oncology care, we analyzed the objective (physical) and subjective (emotional) parameters before and after January 21, 2020, when the first case of COVID-19 was confirmed in Taiwan. There was no significant decrease in patients' return ratio and LVEFs. However, there was a trend of subjective shortness of breath reported by the patients but no decline in 6 MWT. Notably, none of the enrolled patients reported MACEs during the COVID pandemic. We observed an impact of anxiety on patients receiving epirubicin but it did not influence their return ratio.
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http://dx.doi.org/10.1016/j.jfma.2021.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380481PMC
August 2021

Assessment of pegylated arginine deiminase and modified FOLFOX6 in patients with advanced hepatocellular carcinoma: Results of an international, single-arm, phase 2 study.

Cancer 2021 Dec 20;127(24):4585-4593. Epub 2021 Aug 20.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Arginine starvation depletes the micronutrients required for DNA synthesis and interferes with both thymidylate synthetase activity and DNA repair pathways in preclinical models of hepatocellular carcinoma (HCC). Pegylated arginine deiminase (ADI-PEG 20), an arginine degrader, potentiates the cytotoxic activity of platinum and pyrimidine antimetabolites in HCC cellular and murine models.

Methods: This was a global, multicenter, open-label, single-arm, phase 2 trial of ADI-PEG 20 and modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in patients who had HCC with Child-Pugh A cirrhosis and disease progression on ≥2 prior lines of treatment. The primary objective was the objective response rate assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary objectives were to estimate progression-free survival, overall survival, safety, and tolerability. Eligible patients were treated with mFOLFOX6 intravenously biweekly at standard doses and ADI-PEG-20 intramuscularly weekly at 36 mg/m .

Results: In total, 140 patients with advanced HCC were enrolled. The median patient age was 62 years (range, 30-85 years), 83% of patients were male, 76% were of Asian race, 56% had hepatitis B viremia, 10% had hepatitis C viremia, 100% had received ≥2 prior lines of systemic therapy, and 39% had received ≥3 prior lines of systemic therapy. The objective response rate was 9.3% (95% confidence interval [CI], 5.0%-15.4%), with a median response duration of 10.2 months (95% CI, 5.8 months to not reached). The median progression-free survival was 3.8 months (95% CI, 1.8-6.3 months), and the median overall survival was 14.5 months (95% CI, 13.6-20.9 months). The most common grade ≥3 treatment-related events were neutropenia (32.9%), white blood cell count decrease (20%), platelet count decrease (19.3%), and anemia (9.3%).

Conclusions: Concurrent mFOLFOX6 plus ADI-PEG 20 exhibited limited antitumor activity in patients with treatment-refractory HCC. The study was terminated early, and no further evaluation of the combination will be pursued.

Lay Summary: Arginine is an important nutrient for hepatocellular carcinoma (HCC). The depletion of arginine with pegylated arginine deiminase (ADI-PEG 20), an arginine degrader, appeared to make chemotherapy (FOLFOX) work better in animal models of HCC and in patients with HCC on an early phase clinical trial. To formally test this hypothesis in the clinical setting, a large, global, phase 2 clinical trial was conducted of ADI-PEG 20 and FOLFOX in the treatment of patients with refractory HCC. The study showed limited activity of ADI-PEG 20 and FOLFOX in advanced HCC and was stopped early.
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http://dx.doi.org/10.1002/cncr.33870DOI Listing
December 2021

Atezolizumab plus Bevacizumab versus Sorafenib in the Chinese Subpopulation with Unresectable Hepatocellular Carcinoma: Phase 3 Randomized, Open-Label IMbrave150 Study.

Liver Cancer 2021 Jul 23;10(4):296-308. Epub 2021 Apr 23.

Department of Medical Oncology, National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan.

Introduction: Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety data from the Chinese subpopulation are reported.

Methods: IMbrave150, a global, randomized, open-label, phase 3 study in patients with systemic treatment-naive unresectable HCC, included an extension phase that enrolled additional patients from mainland China. Patients were randomized (2:1) to receive intravenous atezolizumab 1,200 mg plus bevacizumab 15 mg/kg once every 3 weeks or sorafenib 400 mg twice a day until unacceptable toxicity or loss of clinical benefit. Co-primary endpoints were OS and independent review facility-assessed PFS per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population.

Results: Of 194 Chinese patients enrolled from April 16, 2018, to April 8, 2019 (137 in the global study and 57 in the China extension phase), 133 received atezolizumab plus bevacizumab and 61 received sorafenib. At the data cutoff (August 29, 2019), the stratified hazard ratio for OS was 0.44 (95% CI, 0.25-0.76) and for PFS was 0.60 (95% CI, 0.40-0.90). The respective median OS and PFS with atezolizumab plus bevacizumab were not reached (NR; 95% CI, 13.5 months to NR) and 5.7 months (95% CI, 4.2-8.3) versus 11.4 months (95% CI, 6.7 to NR) and 3.2 months (95% CI, 2.6-4.8) with sorafenib. Grade 3-4 adverse events (AEs) occurred in 78 of 132 (59.1%) atezolizumab plus bevacizumab-treated and 27 of 58 (46.6%) sorafenib-treated patients. The most common grade 3-4 AE with atezolizumab plus bevacizumab was hypertension, occurring in 15.2% of patients; however, other high-grade AEs were infrequent.

Conclusion: Clinically meaningful improvements in OS and PFS observed with atezolizumab plus bevacizumab versus sorafenib suggest that atezolizumab plus bevacizumab may become a practice-changing treatment for Chinese patients with unresectable HCC.
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http://dx.doi.org/10.1159/000513486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339481PMC
July 2021

The Effectiveness and Safety of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Patients With Stage III/IV: A Multicenter Study.

Front Oncol 2021 7;11:671127. Epub 2021 Jul 7.

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, United States.

Immune checkpoint inhibitors (ICIs) have been approved to treat patients with various cancer types, including lung cancer, in many countries. This study aims to investigate the effectiveness and safety of ICIs under different treatment conditions of non-small cell lung cancer patients. A population-based retrospective cohort study was conducted using the electronic health records of three medical centers in Taiwan. From January 01, 2016, to November 30, 2018, a total of 91 ICIs and 300 traditional chemotherapy users who had undergone stage III and IV lung cancer treatment were included in the study. We performed the randomized matched pair design by selecting a Chemotherapy subject for each ICI patient in the sample population. All subjects were monitored from the date of taking ICIs or chemotherapy drugs until the event of death, loss to follow-up, or were occurred with any defined adverse events. Kaplan-Meier estimators and cox proportional hazard regression models were used to compute the overall survival, efficacy, and safety of the ICIs group. The median overall survival (OS) in the ICI and Chemo groups after matching was 11.2 months and 10.5 months, respectively. However, the results showed no significant OS differences between ICIs and chemo groups for both before and after matching (HR,1.30; 95%CI, 0.68-2.46; p=0.428 before matching and HR,0.96; 95CI%, 0.64-1.44; p=0.838 after matching). We observed that with the higher amount of PD-L1, the length of the patients' overall survival was (positive negative PD-L1, HR,0.21; 95%CI, 0.05-0.80; p=0.022). The incidences of serious adverse drug events above grade 3 in the ICIs and traditional chemo groups were 12.7% and 21.5%, respectively. We also found that the number of AEs was less in ICIs than in the Chemo group, and the AEs that occurred after treatments were observed earlier in the ICIs compared to the Chemo group. ICIs drugs were observed to be safer than traditional chemotherapy as they had a lower risk of serious adverse drug events. It is necessary to pay attention to immune-related side effects and provide appropriate treatment. Furthermore, the patient's physical status and PD-L1 test can be used to evaluate the clinical effectiveness of ICIs.
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http://dx.doi.org/10.3389/fonc.2021.671127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293991PMC
July 2021

The Expression of MicroRNA-21 in Bone Marrow Fluid is an Indicator of Hematological Disorders and Mortality.

Asian Pac J Cancer Prev 2020 Oct 1;21(10):2817-2821. Epub 2020 Oct 1.

Division of Hematology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.

Objective: Bone marrow fluid (BMF) consists of various components that establishes a microenvironment for cell differentiation and remodeling. MicroRNA-21 (miR-21) levels have recently emerged as novel biomarkers for different diseases. However, the conventional RNU6B (U6), used as the reference for intracellular miRNA, may not be appropriate for the normalization of circulating miRNAs.

Methods: We measured the levels of U6, spiked-in RNA, and miR-21 in the BMF of 13 healthy controls and 37 patients with hematological disorders to investigate the reliability of either U6 or spike-in RNA as an endogenous reference and also to study the correlation between miR-21, hematological disorders and mortality.

Results: Notably, the levels of U6 demonstrated a high variability in BMF of healthy controls and patients. In contrast, the levels of spiked-in RNA displayed a significantly higher stability in both cohorts. Compared with controls, the levels of miR-21 were significantly upregulated in BMF of patients with leukemia but not lymphoma. Also, using 21 as the cut-off value of miR-21, it differentiated the mortality of patients with hematologic disorders.

Conclusions: Collectively, using spiked-in RNA as a reference the upregulated miR-21 levels in BMF could be an indicator of the diagnosis of leukemia and a predictor of mortality.
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http://dx.doi.org/10.31557/APJCP.2020.21.10.2817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798149PMC
October 2020

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial.

J Clin Oncol 2020 09 17;38(27):3138-3149. Epub 2020 Jul 17.

Graduate School of Medicine, Gunma University, Gunma, Japan.

Purpose: NALA (ClinicalTrials.gov identifier: NCT01808573) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens.

Methods: Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL).

Results: A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank 0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; 2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% 29.2%; 043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; 1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; .0004). The most common all-grade adverse events were diarrhea (N+C 83% L+C 66%) and nausea (53% 42%). Discontinuation rates and HRQoL were similar between groups.

Conclusion: N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.
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http://dx.doi.org/10.1200/JCO.20.00147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499616PMC
September 2020

The impact of a multidisciplinary cardio-oncology programme on cardiovascular outcomes in Taiwan.

ESC Heart Fail 2020 10 4;7(5):2135-2139. Epub 2020 Jul 4.

Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center, 901, Zhonghua Road, Tainan, Taiwan.

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http://dx.doi.org/10.1002/ehf2.12840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524067PMC
October 2020

Oct4 promotes M2 macrophage polarization through upregulation of macrophage colony-stimulating factor in lung cancer.

J Hematol Oncol 2020 06 1;13(1):62. Epub 2020 Jun 1.

Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, 1, University Road, Tainan, Taiwan.

Background: Expression of Oct4 maintains cancer stem cell (CSC)-like properties in lung cancer cells and is correlated with poor prognosis of lung adenocarcinoma. M2-type tumor-associated macrophages (TAMs) promote cancer cell migration and metastasis. Tumor microenvironments promote monocyte differentiation into M2 TAMs via a complex cytokine-based connection. We explored the role of Oct4 in cytokine secretion in lung cancer and its impact on M2 TAM polarization.

Methods: Monocytes co-cultured with the conditioned medium from Oct4-overexpressing lung cancer cells were used to investigate M2 TAM differentiation. The inflammatory factors in the conditioned medium of Oct4-overexpressing A549 cells were examined using human inflammation antibody arrays. The correlations of Oct4, macrophage colony-stimulating factor (M-CSF), and M2 TAMs were validated in lung cancer cells, syngeneic mouse lung tumor models, and clinical samples of non-small cell lung cancer (NSCLC).

Results: Oct4-overexpressing A549 cells expressed elevated levels of M-CSF, which contributed to increased M2 macrophages and enhanced tumor migration. Overexpression of Oct4 enhanced tumor growth and reduced the survival of lung tumor-bearing mice, which was correlated with increased number of M2 macrophages in lung cancer. Notably, NSCLC patients with high expression levels of Oct4, M-CSF, and M2 TAMs had the poorest recurrence-free survival. A positive correlation between Oct4, M-CSF, and M2 TAMs was observed in the tumor tissue of NSCLC patient. Treatment with all-trans retinoic acid exerted anti-tumor effects and reduced M2 TAMs in tumor-bearing mice.

Conclusions: Our results indicate that Oct4 expressed by lung cancer cells promotes M2 macrophage polarization through upregulation of M-CSF secretion, leading to cancer growth and metastasis. Our findings also implicate that the Oct4/M-CSF axis in M2 macrophage polarization may be potential therapeutic targets for lung cancer.
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http://dx.doi.org/10.1186/s13045-020-00887-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268452PMC
June 2020

The Effectiveness of Dignity Therapy as Applied to End-of-Life Patients with Cancer in Taiwan: A Quasi-Experimental Study.

Asian Nurs Res (Korean Soc Nurs Sci) 2020 Oct 23;14(4):189-195. Epub 2020 Apr 23.

College of Nursing, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Purpose: The aim of the study was to determine the effectiveness of dignity therapy for end-of-life patients with cancer.

Methods: This study used a quasi-experimental study design with a nonrandomized controlled trial. Dignity therapy was used as an intervention in the experimental group, and general visit was used in the control group. Thirty end-of-life patients with cancer were recruited, with 16 in the experimental group and 14 in the control group. Outcome variables were the participants' dignity, demoralization, and depression. Measurements were taken at the following time points: pre-test (before intervention), post-test 1 (the 7th day), and post-test 2 (the 14th day). The effectiveness of the intervention in the two groups was analyzed using the generalized estimating equation, with the p value set to be less than .05.

Results: After dignity therapy, the end-of-life patients with cancer reflected increased dignity significantly [β = -37.08, standard error (SE) = 7.43, Wald χ = 24.94, p < .001], whereas demoralization (β = -39.55, SE = 6.42, Wald χ = 37.95, p < .001) and depression (β = -12.01, SE = 2.17, Wald χ = 30.71, p < .001) were both reduced significantly.

Conclusion: Clinical nurses could be adopting dignity therapy to relieve psychological distress and improve spiritual need in end-of-life patients with cancer. Future studies might be expanded to looking at patients vis-à-vis end-of-life patients without cancer to improve their psychological distress. These results provide reference data for the care of end-of-life patients with cancer for nursing professionals.
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http://dx.doi.org/10.1016/j.anr.2020.04.003DOI Listing
October 2020

Differential Inhibitory Actions of Multitargeted Tyrosine Kinase Inhibitors on Different Ionic Current Types in Cardiomyocytes.

Int J Mol Sci 2020 Feb 29;21(5). Epub 2020 Feb 29.

Department of Physiology, National Cheng Kung University Medical College 70101, Tainan, Taiwan.

Lapatinib (LAP) and sorafenib (SOR) are multitargeted tyrosine kinase inhibitors (TKIs) with antineoplastic properties. In clinical observations, LAP and SOR may contribute to QTc prolongation, but the detailed mechanism for this has been largely unexplored. In this study, we investigated whether LAP and SOR affect the activities of membrane ion channels. Using a small animal model and primary cardiomyocytes, we studied the impact of LAP and SOR on Na and K currents. We found that LAP-induced QTc prolongation in mice was reversed by isoproterenol. LAP or SOR suppressed the amplitude of the slowly activating delayed-rectifier K current () in H9c2 cells in a time- and concentration-dependent fashion. The LAP-mediated inhibition of was reversed by adding isoproterenol or meclofenamic acid, but not by adding diazoxide. The steady-state activation curve of during exposure to LAP or SOR was shifted toward a less negative potential, with no change in the gating charge required to activate the current. LAP shortened the recovery from deactivation. As rapid repetitive stimuli, the amplitude decreased; however; the LAP-induced inhibition of remained effective. LAP or SOR alone also suppressed inwardly rectifying K and voltage-gated Na current in neonatal rat ventricular myocytes. The inhibition of ionic currents during exposure to TKIs could be an important mechanism underlying changes in QTc intervals.
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http://dx.doi.org/10.3390/ijms21051672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084345PMC
February 2020

Layer-specific distribution of myocardial deformation from anthracycline-induced cardiotoxicity in patients with breast cancer-From bedside to bench.

Int J Cardiol 2020 07 16;311:64-70. Epub 2020 Jan 16.

Department of Cardiology, Chi Mei Medical Center, Tainan, Taiwan; Department of Pharmacy, Chia Nan University of Pharmacy & Science, Tainan, Taiwan. Electronic address:

Background: Anthracycline anticancer drugs such as epirubicin and doxorubicin may induce myocardial dysfunction, leading to poor prognosis. Early detection of minor left ventricular (LV) myocardial dysfunction is important for the prevention of anthracylcine-induced cardiotoxicity. Using layer-specific speckle tracking echocardiography (STE), we investigated the progressive distribution of myocardial dysfunction in both breast cancer patients and an animal toxicity model.

Methods: Patients with preserved LV ejection fraction (LVEF) preparing for epirubicin chemotherapy (N = 125) were prospectively enrolled. Layer-specific STE, including LV longitudinal and circumferential strains on subepicardium and subendocardium, were evaluated at baseline and after the first cycle, third cycle and six months of epirubicin therapy. A decline of LVEF above 10% to <55% at six months was defined as cardiotoxicity. These same strain measures were obtained in doxorubicin-treated rats and the distribution of myocardial fibrosis evaluated.

Results: In patients developing cardiotoxicity, LV longitudinal strain on subendocardium (LVLSendo) was significantly reduced after three cycles of therapy despite no significant changes in conventional LV systolic, diastolic parameters as well as LV circumferential strains at that moment. Compared to conventional echocardiographic parameters, LVLSendo was significantly predictive of cardiotoxicity. Declines in LVLSendo were also observed in doxorubicin-treated rats at an early stage. These reductions also predicted significant fibrosis in the subendocardial layer.

Conclusion: LVLSendo is useful for the early detection of minor cardiac dysfunction during chemotherapy, thereby implicating endocardial involvement in the development of cardiotoxicity.
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http://dx.doi.org/10.1016/j.ijcard.2020.01.036DOI Listing
July 2020

Proteomic Profile of Sorafenib Resistance in Hepatocellular Carcinoma; GRP78 Expression Is Associated With Inferior Response to Sorafenib.

Cancer Genomics Proteomics 2019 Nov-Dec;16(6):569-576

Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan, R.O.C.

Background/aim: The outcome of patients with advanced hepatocellular carcinoma (HCC) remains poor and therapeutic options, including sorafenib, the first anti-cancer drug proved to prolong survival in patients with advanced HCC, are limited. However, no clinically useful predictive biomarker for sorafenib has been reported.

Materials And Methods: We exploited two-dimensional gel electrophoresis coupled with mass spectrometry to find de-regulated proteins by using conditioning of a sorafenib-resistant HCC cell line, Huh7. Tumor samples from 60 patients with HCC treated with sorafenib were analyzed and correlated with survival outcome.

Results: Comparative proteomics indicated three proteins including, 78 kDa glucose related protein (GRP78), 14-3-3ε, and heat shock protein 90β (HSP90β). The three proteins were over-expressed in sorafenib-resistant Huh7 cells. In HCC tumor samples from patients treated with sorafenib, 73% of tumor samples had a high expression of GRP78, 18% had high 14-3-3ε expression and 85% had high HSP90β expression. Among these, GRP78 was associated with the shortest progression-free survival of HCC patients treated with sorafenib.

Conclusion: GRP78 can be a predictive biomarker in HCC patients treated with sorafenib. Strategies designed to inhibit the GRP78-related pathway may overcome sorafenib resistance.
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http://dx.doi.org/10.21873/cgp.20159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885357PMC
March 2020

Concurrent chemoradiotherapy in patients with non-metastatic upper urinary tract urothelial carcinoma: Report from a single institution in Taiwan.

Int J Urol 2020 Jan 12;27(1):83-84. Epub 2019 Sep 12.

Division of Hematology and Oncology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.

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http://dx.doi.org/10.1111/iju.14112DOI Listing
January 2020

Oct4 upregulates osteopontin via Egr1 and is associated with poor outcome in human lung cancer.

BMC Cancer 2019 Aug 9;19(1):791. Epub 2019 Aug 9.

Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, 70101, Taiwan.

Background: Roles of cancer stem cells and early growth response gene 1 (Egr1) in carcinogenesis have been extensively studied in lung cancer. However, the role of Egr1 in the metastasis of lung cancer remains undetermined, especially in regard to stem cell-related pathways.

Methods: Egr1, osteopontin (OPN) and Oct4 expression in human lung cancer was determined by performing immunohistochemistry. Immunoblotting, ELISA, luciferase reporter assay, chromatin immunoprecipitation assay and RT-PCR were performed to validate the regulation of Oct4-Egr1-OPN axis. Moreover, the effect of Oct4-Egr1-OPN axis on lung cancer progression was evaluated by cell migration assay and mice study.

Results: We detected Oct4, Egr1, and OPN expression in clinical specimens from 79 lung cancer patients, including 72 adenocarcinomas and 7 squamous cell carcinomas. High expression of Oct4, Egr1, and OPN accounted for 53, 51, and 57% of the patients, respectively. All of the three biomarkers were positively correlated in clinical human lung cancer. Patients with high expression of OPN were significantly associated with shorter disease-free survivals than those with low expression of OPN (p < 0.05). In lung cancer cells, Oct4 transactivated the Egr1 promoter and upregulated Egr1 expression. In a human lung cancer xenograft model, Oct4-overexpressing tumors expressed elevated levels of Egr1. Furthermore, overexpression of Oct4 in lung cancer cells increased the metastatic potential.

Conclusions: Egr1 exerts a promoting effect on cancer metastasis in Oct4-overexpressing lung cancer. Thus, therapeutic strategies targeting the Oct4/Egr1/OPN axis may be further explored for the treatment of lung cancer, especially when lung cancer is refractory to conventional treatment due to cancer stem cells.
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http://dx.doi.org/10.1186/s12885-019-6014-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688208PMC
August 2019

Expression of prothymosin α in lung cancer is associated with squamous cell carcinoma and smoking.

Oncol Lett 2019 Jun 12;17(6):5740-5746. Epub 2019 Apr 12.

Institute of Reproductive and Developmental Biology, Imperial College London, London W12 ONN, UK.

Prothymosin α (ProTα) is a nuclear protein that serves a role in oncogenesis, by promoting proliferation and inhibiting apoptosis in various malignancies. The present study was designed to investigate ProTα expression in resected human non-small cell lung cancer to define the clinicopathological associations of ProTα-positive lung cancer. Immunohistochemical staining of ProTα was performed using tumor sample slides from 149 patients with non-small cell lung cancer, who underwent surgical resection. Association between the expression of ProTα and the following clinicopathological parameters was accessed: Age, sex, stage, lymph node involvement, pathological subtype, recurrence and cigarette smoking. A total of 85 tumors (57%) were classified as ProTα-positive lung cancer by staining intensity and 73 tumors (49%) were regarded as ProTα-positive by scoring index. The majority of patients with ProTα-positive tumors were younger (P=0.05) and had squamous cell carcinoma (P<0.01) compared with older and adenocarcinoma. Positive expression of ProTα by staining intensity was associated with a higher incidence rate of cancer recurrence (P=0.05) compared with negative ProTα expression. ProTα was also associated with cigarette smoking, particularly in the group with squamous cell carcinoma. Therefore, the present data suggested that ProTα-positive non-small cell lung cancer was associated with younger patients, squamous cell carcinoma, cigarette smoking and a higher incidence recurrence rate, subsequently indicating a subtype consisting of patients with smoking-associated inferior outcomes.
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http://dx.doi.org/10.3892/ol.2019.10248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507549PMC
June 2019

Subsequent thyroid disorders associated with treatment strategy in head and neck cancer patients: a nationwide cohort study.

BMC Cancer 2019 May 16;19(1):461. Epub 2019 May 16.

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, 138, Shengli Road, Tainan, Taiwan.

Background: We investigated the risk of thyroid disorders, namely hypothyroidism, thyrotoxicosis and thyroiditis, in head and neck cancer patients undergoing multimodal treatment.

Methods: A cohort study design using Taiwan's National Health Insurance Research Database was used to assess head and neck cancer patients over 20 years old. The cohort was divided into one group who underwent primary tumor excision only (PTE) and another with additional neck dissection (PTE + ND). The tumor sites were stratified to estimate the tumor-site-specific risk of thyroid disorders. The effect of subsequent resurgery, radiotherapy (RT), chemotherapy (CT), and concomitant (CCRT) or sequential chemoradiation therapy (sequential CT+ RT) on the risk of thyroid disorders was explored.

Results: For 1999-2012, 7460 patients who underwent PTE + ND and 3730 who underwent PTE were enrolled and followed-up until the end of 2013. There were 122 and 50 patients in the two groups, respectively, who developed thyroid disorders, with no statistical difference between the groups. Patients with hypopharyngeal, oropharyngeal, or laryngeal cancer in the PTE + ND group had a higher risk of thyroid disorders (adjusted HR: 1.50, 95% CI: 0.67-3.38) than those in the PTE group when adjusted for covariates and mortality. Patients who underwent subsequent RT (adjusted HR: 3.64, 95% CI: 1.05-2.77) and CCRT (adjusted HR: 1.70, 95% CI: 1.05-2.77) after PTE + ND had a significantly higher risk of thyroid disorders.

Conclusion: RT results in a major risk of subsequent thyroid disorders, and ND may exacerbate this effect. Physicians should monitor thyroid function from two years after treatment initiation, especially in patients who undergo ND and subsequent RT.
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http://dx.doi.org/10.1186/s12885-019-5697-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524259PMC
May 2019

A Phase I/Randomized Phase II Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Nintedanib versus Sorafenib in Asian Patients with Advanced Hepatocellular Carcinoma.

Liver Cancer 2018 May 15;7(2):165-178. Epub 2018 Mar 15.

National Taiwan University Hospital, Taipei, Taiwan.

Background: Nintedanib is an oral, triple angiokinase inhibitor of vascular endothelial growth factor/platelet-derived growth factor/fibroblast growth factor receptors. This randomized, multicenter, open-label, phase I/II study evaluated the safety, pharmacokinetics, maximum tolerated dose (MTD) in terms of dose-limiting toxicities (DLTs), and efficacy of nintedanib versus sorafenib in Asian patients with unresectable advanced hepatocellular carcinoma (HCC).

Patients And Methods: For the phase I portion, patients were stratified into two groups according to their alanine aminotransferase/aspartate aminotransferase (ALT/AST) and Child-Pugh score at baseline. For phase I, the primary endpoint was determination of the MTD in terms of DLTs. For phase II, patients with a Child-Pugh score of 5-6, an Eastern Cooperative Oncology Group performance score ≤2, and an ALT/AST ≤2× the upper limit of normal were enrolled and randomized 2: 1 to nintedanib 200 mg twice daily (b.i.d.) (the MTD determined in phase I) or sorafenib 400 mg b.i.d. continuously in 28-day cycles until intolerable adverse events (AEs) or disease progression (PD); treatment beyond PD was allowed if clinical benefit was perceived. The primary endpoint for phase II was time to progression (TTP) by central independent review (CIR; by Response Evaluation Criteria in Solid Tumors v1.0); the secondary endpoints included overall survival (OS). All analyses were exploratory.

Results: The MTD was 200 mg in both groups. For phase II, 95 patients were randomized to nintedanib ( = 63) or sorafenib ( = 32). For nintedanib and sorafenib, respectively, the median CIR TTP was 2.8 vs. 3.7 months (hazard ratio [HR] = 1.21, 95% confidence interval [CI] 0.73-2.01) and the median OS 10.2 vs. 10.7 months (HR = 0.94, 95% CI 0.59-1.49). Nintedanib-treated patients had fewer grade 3 or higher AEs (56 vs. 84%), serious AEs (46 vs. 56%), and AEs leading to dose reduction (19 vs. 59%) and drug discontinuation (24 vs. 34%). AEs associated more frequently with nintedanib were vomiting and nausea, whereas those associated more frequently with sorafenib were ALT/AST increases, diarrhea, rash, and palmar-plantar erythrodysesthesia syndrome.

Conclusions: Nintedanib showed numerically similar efficacy to sorafenib for CIR TTP and OS in Asian patients with advanced HCC and adequate liver function. AEs were generally manageable.
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http://dx.doi.org/10.1159/000486460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985414PMC
May 2018

Elovl6 is a negative clinical predictor for liver cancer and knockdown of Elovl6 reduces murine liver cancer progression.

Sci Rep 2018 04 26;8(1):6586. Epub 2018 Apr 26.

Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

The elongation of long-chain fatty acids family member 6 (Elovl6) is a key enzyme in lipogenesis that catalyzes the elongation of saturated and monounsaturated fatty acids. Insulin resistance involves upregulation of Elovl6, which has been linked to obesity-related malignancies, including hepatocellular carcinoma (HCC). However, the role of Elovl6 in cancer progression remains unknown. In this study, we analyzed the expression of Elovl6 in 61 clinical HCC specimens. Patients with Elovl6 high-expressing tumors were associated with shorter disease-free survival and overall survival compared to those with Elovl6 low-expressing tumors. Knockdown of Elovl6 in HCC cells reduced cell proliferation and Akt activation, as well as sensitivity to fatty acids. Inhibition of Elovl6 reduced tumor growth and prolonged survival in mice bearing tumors. Taken together, our results indicate that Elovl6 enhances oncogenic activity in liver cancer and is associated with poor prognosis in patients with HCC. Elovl6 may be a therapeutic target for HCC; thus, further studies to confirm this strategy are warranted.
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http://dx.doi.org/10.1038/s41598-018-24633-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920119PMC
April 2018

Associations between interventions for urolithiasis and urinary tract cancer among patients in Taiwan: The effect of early intervention.

Medicine (Baltimore) 2016 Dec;95(49):e5594

Division of Hematology and Oncology Division of Urology, Chi-Mei Medical Center, Liouying Campus Min-Hwei Junior College of Health Care Management Department of Nursing Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Biostatistics Consulting Center, National Cheng Kung University Hospital, Tainan, Taiwan.

The aim of this study was to investigate cancer risk in patients with a history of urolithiasis and to determine whether intervention for calculi attenuated the risk of subsequent urinary tract cancer (UTC).Using data from the National Health Insurance Research Database in Taiwan, we performed a nationwide cohort study enrolling participants (n = 42,732) aged > 30 years who were diagnosed with urinary tract calculi between 2000 and 2009. Age- and gender-matched insured individuals (n = 213,660) found in the health service records over the same period were recruited as the control group. The Cox proportional hazards model and competing risks regression model were used to examine the relationship between urolithiasis and UTC, as well as whether early intervention for urolithiasis decreased the subsequent cancer risk relative to late intervention.Participants with a previous diagnosis of urolithiasis (n = 695) had a 1.82-fold (95% CI: 1.66-1.99, P < 0.001) increased risk of developing UTC. Furthermore, the risk of UTC associated with urolithiasis was higher in women (adjusted HR: 2.43, 95% CI: 1.94-3.05) than in men (adjusted HR: 1.72, 95% CI: 1.55-1.90). When stratified by cancer site, the adjusted HR for bladder, renal pelvis/ureter, renal, and prostate cancers were 1.94 (95% CI: 1.62-2.33), 2.94 (95% CI: 2.24-3.87), 2.94 (95% CI: 2.29-3.77), and 1.45 (95% CI: 1.27-1.65), respectively. Patients who received interventions for urolithiasis within 3 months of detection had a decreased risk of subsequent UTC (adjusted HR: 0.53, 95% CI: 0.40-0.71, P < 0.001).The present study demonstrated that urolithiasis increased the risk of subsequent UTC, especially upper UTC. Hence, it is recommended that physicians administer the appropriate interventions as early as possible upon diagnosis of urolithiasis.
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http://dx.doi.org/10.1097/MD.0000000000005594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266053PMC
December 2016

Impact of Adjuvant Chemotherapy in Elderly Breast Patients in Taiwan, A Hospital-Based Study

Asian Pac J Cancer Prev 2016 10 1;17(10):4591-4597. Epub 2016 Oct 1.

Department of Internal Medicine, Chi-Mei Medical Center, Yong Kang, Tainan, Taiwan, Email:

Purpose: Decisions as to whether to provide adjuvant treatment in older breast cancer patients remains challenging. Side effects of chemotherapy have to be weighed against life expectancy, comorbidities, functional status, and frailty. To aid decision-making, we retrospectively analyzed 110 women with breast cancer treated with a curative intention from 2006 to 2012. Survival data with clinical and pathological parameters were evaluated to address the role of adjuvant chemotherapy in this study population. Method: A total of 110 elderly (>70 years) patients that received mastectomy at two hospitals in Taiwan were observed retrospectively for a medium of 51 months. After mastectomy, patients received conservative treatment or adjuvant chemotherapy, or hormone therapy following clinical guidelines or physician’s preference. Data were collected from the cancer registry system. Results: Median age at diagnosis was 75.7 years. Thirty-five percent of patients received adjuvant chemotherapy, these having a significantly younger age (mean=74.0±5.3 vs 77.5±5.3, p<0.001) and higher tumor staging (p=0.003) compared with their non-chemotherapy counterparts.Five-year overall survival was non-significantly higher in patients who received adjuvant chemotherapy (with chemotherapy 64.2% vs without chemotherapy 62.6%, p=0.635), while five-year recurrence free survival was non-significantly lower (with chemotherapy 64.1% vs without chemotherapy 90.5%, p=0.80). Conclusions: In this analysis, adjuvant chemotherapy tended to be given to patients with a younger age and higher tumor staging at our institute. It was not associated with any statistically significant improvement in survival and recurrence rate. Until age specific recommendations are available, physicians must use their clinical judgment and assess the tumor biology with the patient’s comorbidities to make the best choice. Clinical trials focusing on this critical issue are warranted.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454603PMC
http://dx.doi.org/10.22034/apjcp.2016.17.10.4591DOI Listing
October 2016

Malignant Peripheral Nerve Sheath Tumor of Prostate: A Rare Case Report and Literature Review.

Case Rep Urol 2016 30;2016:9317567. Epub 2016 Oct 30.

Divisions of Urology, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.

A mid-aged male presented with progressive lower urinary tract symptoms (LUTS) for years. Huge prostate with low serum prostate-specific antigen (PSA) level was detected. The specimen from transurethral resection revealed surprising pathology finding as malignant peripheral nerve sheath tumor (MPNST). Considering its huge size (more than 300 gm) and location, we prescribed neoadjuvant chemotherapy firstly. The tumor became regressive and then radical surgical resection was achieved. Adjuvant multimodality treatment including concurrent chemoradiotherapy (CCRT) and target therapy was given. However, he expired about one year later. MPNST originating from prostate is very rare and seldom reported before. We here present this extremely rare disease and share our treatment experience.
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http://dx.doi.org/10.1155/2016/9317567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107239PMC
October 2016

The Early Predictive Value of Right Ventricular Strain in Epirubicin-Induced Cardiotoxicity in Patients with Breast Cancer.

Acta Cardiol Sin 2016 Sep;32(5):550-559

Division of Cardiology, Department of Internal Medicine, Chi-Mei Medical Center; ; Department of Pharmacy, Chia Nan University of Pharmacy & Science, Tainan, Taiwan.

Background: As cancer therapies have improved, patient life spans have been extended but quality of life has been threatened by chemotherapy induced cardiotoxicity. Most cardiac complications remain unobserved until specific symptoms develop. Speckle-tracking echocardiography is a sensitive imaging modality in detecting early occult myocardial dysfunction.

Methods: A total number of 35 patients newly diagnosed with breast cancer and preparing for epirubicin therapy were prospectively recruited. Echocardiography, including speckle-tracking echocardiography, was performed sequentially at baseline (T1), after the first cycle (T2) and after the third cycle (T3) of epirubicin. At each visit, the severity of dyspnea was evaluated by the assessment scale.

Results: Compared with the baseline, right ventricular longitudinal strain (RVLS_FW) at T2 significantly declined (-22.49 ± 4.97 vs. -18.48 ± 4.46, p = 0.001), which was also positively associated with the development of dyspnea (R = 0.8, p = 0.01). At T3, both the left ventricular global longitudinal strain and RVLS_FW were significantly impaired (-21.4 ± 4.12 vs. -16.94 ± 6.81%; -22.49 ± 4.97 vs. -16.86 ± 7.27%, p = 0.01; 0.001, respectively). Also, the accumulating dose of epirubicin positively correlated with the development of dyspnea (R = 0.38, p = 0.04) and the decline of RVLS_FW (R = 0.53, p = 0.02). Notably, compared with the other echocardiographic parameters only RVLS_FW at the early stage (T2) significantly correlated with the development of dyspnea (odds ratio: 1.84, 95% confidence interval: 1.22-2.78, p = 0.04).

Conclusions: RVLS_FW sensitively predicts dyspnea development in breast cancer patients receiving epirubicin therapy. However, larger scale studies are required to validate its role in long-term patient survival.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052473PMC
http://dx.doi.org/10.6515/acs20151023aDOI Listing
September 2016

Emerging role of microRNA-21 in cancer.

Biomed Rep 2016 Oct 26;5(4):395-402. Epub 2016 Aug 26.

Department of Hematology and Oncology, Chi-Mei Medical Center, Tainan 73657, Taiwan, R.O.C.

MicroRNAs (miRs) are a class of single-stranded RNA molecules of 15-27 nucleotides in length that regulate gene expression at the post-translational level. miR-21 is one of the earliest identified cancer-promoting 'oncomiRs', targeting numerous tumor suppressor genes associated with proliferation, apoptosis and invasion. The regulation of miR-21 and its role in carcinogenesis have been extensively investigated. Recent studies have focused on the diagnostic and prognostic value of miR-21 as well as its implication in the drug resistance of human malignancies. The further use of miR-21 as a biomarker and target for cancer treatments is likely to improve the outcome for patients with cancer. The present review highlights recent findings associated with the importance of miR-21 in hematological and non-hematological malignancies.
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http://dx.doi.org/10.3892/br.2016.747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038362PMC
October 2016

Elovl6 is a poor prognostic predictor in breast cancer.

Oncol Lett 2016 Jul 16;12(1):207-212. Epub 2016 May 16.

Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan R.O.C.

Elongation of long chain fatty acids family member 6 (Elovl6) has been demonstrated to be involved in insulin resistance, obesity and lipogenesis. In addition, it has been reported that the protein is upregulated in human hepatocellular carcinoma and is implicated in nonalcoholic steatohepatitis-associated liver carcinogenesis. Excess body weight has been associated with an increased risk of postmenopausal breast cancer and poor prognosis. However, the connection between Elovl6 expression and outcome of breast cancer remains uncertain. Therefore, the present study used immunohistochemical analysis to investigate the expression of Elovl6 in breast cancer tissues from patients who had undergone curative mastectomy. Out of a total of 70 patients, 37.1% of patients exhibited positive Elovl6 expression in breast cancer tissue, whilst 62.9% were considered as negative. Positive Elov16 expression correlated with positive lymph node involvement and shorter recurrence-free survival. However, Elovl6 expression had no association with primary tumor size, lymph node metastasis, stage, grade, estrogen receptor, progesterone receptor, HER2 and age. Therefore, positive Elovl6 expression is a poor prognostic factor in patients with breast cancer that have previously undergone surgery, and may function as a potential therapeutic approach in the future, particularly in the scope of obesity related disease.
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http://dx.doi.org/10.3892/ol.2016.4587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907155PMC
July 2016

Multiple abdominal papules and plaques and mild lymphocytosis.

Int J Dermatol 2016 Aug 13;55(8):845-8. Epub 2015 Oct 13.

Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.

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http://dx.doi.org/10.1111/ijd.13078DOI Listing
August 2016

An Effective and Well Tolerated Strategy of Bladder Preservation Therapy in Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer.

Clin Genitourin Cancer 2016 Feb 29;14(1):e67-74. Epub 2015 Aug 29.

Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan. Electronic address:

Unlabelled: To investigate bladder preservation therapy with a well tolerated strategy, 30 patients with bladder cancer underwent concomitant chemoradiotherapy with weekly carboplatin. The 2-year overall survival was 75% for all patients, 43% and 95% for patients without adjuvant chemotherapy or with adjuvant chemotherapy separately. This strategy was well tolerated with 7% of Grade 3/4 late bladder toxicity.

Background: The purpose of this study was to determine the feasibility and clinical effectiveness of concurrent weekly carboplatin chemotherapy in conjunction with definite radiation with or without adjuvant chemotherapy in the treatment of muscle-invasive bladder cancer.

Patients And Methods: Between April 2010 and December 2013, 30 patients with muscle-invasive bladder cancer were evaluated retrospectively in this study. Concurrent chemoradiotherapy (CCRT) with weekly carboplatin was initiated. CCRT was followed by 2 courses of carboplatin and gemcitabine limited to patients with Eastern Cooperative Oncology Group performance status < 3 and age < 80 years.

Results: Thirty patients were treated and all completed the CCRT protocol. Seven of 8 patients (88%) achieved a pathological complete response (pCR) with CCRT alone, and 18 of 22 patients (82%) treated with CCRT followed by adjuvant chemotherapy had a pCR. The median follow-up was 23.2 (range, 8.3-40.7) months. The median progression-free survival was 15.9 months for the CCRT group, and not sufficient to evaluate CCRT followed by adjuvant chemotherapy. The median overall survival with CCRT was 18.8 months, and had not yet been reached for CCRT with adjuvant chemotherapy. The protocol was well tolerated for adverse events.

Conclusion: Our study has shown that concomitant chemotherapy using weekly carboplatin in the management of muscle-invasive bladder cancer is feasible and well tolerated, even in older patients. Additional adjuvant chemotherapy with 2 cycles of carboplatin and gemcitabine should be encouraged in physically fit patients. These results provide a basis for randomized studies to compare this approach with conventional therapy for patients who wish to preserve the bladder.
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http://dx.doi.org/10.1016/j.clgc.2015.08.005DOI Listing
February 2016

Adiponectin is down-regulated in bone marrow interstitial fluid in hematological malignancy.

Int J Hematol 2015 Sep 27;102(3):312-7. Epub 2015 Jun 27.

Department of Internal Medicine, Chi-Mei Medical Center, Yong Kang, Tainan, Taiwan.

Adipokines play a role in carcinogenesis in a variety of malignancies. These findings were established with regard to serum adipokines and malignancies. However, the expression of adipokines in bone marrow fluid remains unclear, and an investigation of the correlation between bone marrow adipokines and hematological malignancy is needed. The present study was designed to detect adipokine concentrations, including adiponectin, leptin and resistin, in bone marrow interstitial fluid from patients with hematological malignancy and controlled counterparts. The correlations between adipokines, body mass index, clinical parameters, and hematological malignancy were assessed. A total of 80 bone marrow samples were assessed for values of adipokines, adiponectin, leptin and resistin. Patients with hematological malignancy had lower levels of adiponectin. Adiponectin from leukemia bone marrow expressed significantly low values. The adiponectin levels were inversely correlated with body mass index. In conclusion, adiponectin was decreased in bone marrow from patients with leukemia and negatively correlated with body mass index.
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http://dx.doi.org/10.1007/s12185-015-1831-zDOI Listing
September 2015

Sprouty2 protein is downregulated in human squamous cell carcinoma of the head and neck and suppresses cell proliferation in vitro.

Mol Med Rep 2015 Jan 20;11(1):547-54. Epub 2014 Oct 20.

Department of Hematology and Oncology, Chi-Mei Medical Center, Tainan 71004, Taiwan, R.O.C.

Sprouty2 is known for its tumor-suppressing effect in various human malignant diseases. In head and neck squamous cell carcinoma (HNSCC), the role of sprouty2 in tumorigenesis and clinical implication remains elusive. The aim of the present study was to investigate the expression of sprouty2 in patients with HNSCC and its function in vitro. Quantitative analysis of mRNA expression of sprouty2 was performed on frozen tumor samples from 42 patients with HNSCC and 19 with oral verrucous hyperplasia (OVH) with paired counterparts of normal mucosa. Downregulation of sprouty2 expression was demonstrated in 79% of HNSCC samples and in 58% of OVH samples compared with paired samples of normal mucosa. Enhanced expression of sprouty2 protein suppressed the growth of HNSCC cells and signaling of the phosphorylated AKT pathway. Following transfection of the sprouty2 plasmid, HNSCC cells were more sensitive to sorafenib, a tyrosine kinase inhibitor of Raf and vascular endothelial growth factor receptor. The present study suggested that sprouty2 expression was downregulated and behaved as a tumor suppressor in HNSCC. Sprouty2 expression in tumor cells enhanced sensitivity to sorafenib. Further studies are required to define the clinical impact of sprouty2 in patients with HNSCC.
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http://dx.doi.org/10.3892/mmr.2014.2700DOI Listing
January 2015
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