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Kung cancer

Yu-Tang Chang, Hsiang-Lin Tsai, Ya-Ting Kung, Yung-Sung Yeh, Ching-Wen Huang, Cheng-Jen Ma, Herng-Chia Chiu, Jaw-Yuan Wang
BACKGROUND: Increasing bodies of evidence suggest that metformin may be beneficial in the primary prevention of colorectal cancer (CRC), and a dose-response relationship has been reported. However, long-term epidemiological observations between the treatment period, cumulative dose, and intensity of metformin and CRC are rarely reported. The aim of this study was to identify the association between the effect of metformin and CRC development in a nationwide cohort study. METHODS: This nationwide population-based study examined a cohort of 1,000,000 patients randomly sampled from individuals enrolled in the Taiwan National Health Insurance system...
March 7, 2018: Translational Oncology
Florence F Wagner, Lina Benajiba, Arthur J Campbell, Michel Weïwer, Joshua R Sacher, Jennifer P Gale, Linda Ross, Alexandre Puissant, Gabriela Alexe, Amy Conway, Morgan Back, Yana Pikman, Ilene Galinsky, Daniel J DeAngelo, Richard M Stone, Taner Kaya, Xi Shi, Matthew B Robers, Thomas Machleidt, Jennifer Wilkinson, Olivier Hermine, Andrew Kung, Adam J Stein, Damodharan Lakshminarasimhan, Michael T Hemann, Edward Scolnick, Yan-Ling Zhang, Jen Q Pan, Kimberly Stegmaier, Edward B Holson
Glycogen synthase kinase 3 (GSK3), a key regulatory kinase in the wingless-type MMTV integration site family (WNT) pathway, is a therapeutic target of interest in many diseases. Although dual GSK3α/β inhibitors have entered clinical trials, none has successfully translated to clinical application. Mechanism-based toxicities, driven in part by the inhibition of both GSK3 paralogs and subsequent β-catenin stabilization, are a concern in the translation of this target class because mutations and overexpression of β-catenin are associated with many cancers...
March 7, 2018: Science Translational Medicine
Subhasree Basu, Keerthana Gnanapradeepan, Thibaut Barnoud, Che-Pei Kung, Michele Tavecchio, Jeremy Scott, Andrea Watters, Qing Chen, Andrew V Kossenkov, Maureen E Murphy
Mutant forms of p53 protein often possess protumorigenic functions, conferring increased survival and migration to tumor cells via their "gain-of-function" activity. Whether and how a common polymorphism in TP53 at amino acid 72 (Pro72Arg; referred to here as P72 and R72) impacts this gain of function has not been determined. We show that mutant p53 enhances migration and metastasis of tumors through the ability to bind and regulate PGC-1α and that this regulation is markedly impacted by the codon 72 polymorphism...
February 20, 2018: Genes & Development
Zhihao Zha, Karl Ploessl, Seok Rye Choi, Zehui Wu, Lin Zhu, Hank F Kung
INTRODUCTION: Prostate specific membrane antigen (PSMA) is a well-established target for diagnostic and therapeutic applications for prostate cancer. It is know that [68 Ga]PSMA 11 ([68 Ga]Glu-NH-CO-NH-Lys(Ahx)-HBED-CC) is the most well studied PET imaging agent for detecting over expressed PSMA binding sites of tumors in humans. In an effort to provide new agents with improved characteristics for PET imaging, we report a novel [68 Ga]-Glu-NH-CO-NH-Lys(Ahx)-linker-HBED-CC conjugate with a novel O-(carboxymethyl)-L-tyrosine, as the linker group...
December 27, 2017: Nuclear Medicine and Biology
Jing-Hui Chiou, Li-Kuo Liu, Wei-Ju Lee, Li-Ning Peng, Liang-Kung Chen
OBJECTIVES: The main aim was to investigate the complex inter-relationship between frailty and pain, and the mediating roles of cognitive function, morbidity and mood in this nexus. DESIGN: A cross-sectional analysis. SETTING: A prospective community-dwelling population-based cohort. PARTICIPANTS: 1682 adults age ≥50 years without evident cognitive or functional impairment, or history of cancer. PRIMARY AND SECONDARY OUTCOME MEASURES: The mediating effect of depression, cognitive function and comorbidity on the nexus between pain and frailty among older and middle-aged adults...
February 16, 2018: BMJ Open
Amer Alam, Raphael Küng, Julia Kowal, Robert A McLeod, Nina Tremp, Eugenia V Broude, Igor B Roninson, Henning Stahlberg, Kaspar P Locher
The multidrug transporter ABCB1 (P-glycoprotein) is an ATP-binding cassette transporter that has a key role in protecting tissues from toxic insult and contributes to multidrug extrusion from cancer cells. Here, we report the near-atomic resolution cryo-EM structure of nucleotide-free ABCB1 trapped by an engineered disulfide cross-link between the nucleotide-binding domains (NBDs) and bound to the antigen-binding fragment of the human-specific inhibitory antibody UIC2 and to the third-generation ABCB1 inhibitor zosuquidar...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Mark P S Dunphy, James J Harding, Sriram Venneti, Hanwen Zhang, Eva M Burnazi, Jacqueline Bromberg, Antonio M Omuro, James J Hsieh, Ingo K Mellinghoff, Kevin Staton, Christina Pressl, Bradley J Beattie, Pat B Zanzonico, John F Gerecitano, David P Kelsen, Wolfgang Weber, Serge K Lyashchenko, Hank F Kung, Jason S Lewis
Purpose To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods This study was approved by the institutional review board and conducted under a U.S. Food and Drug Administration-approved Investigational New Drug application in accordance with the Helsinki Declaration and the Health Insurance Portability and Accountability Act. All patients provided written informed consent...
January 31, 2018: Radiology
Wenyan Zhang, Rui Duan, Jian Zhang, William K C Cheung, Xiaoge Gao, Raymond Zhang, Qing Zhang, Mengxue Wei, Gang Wang, Qian Zhang, Peng-Jin Mei, Hong-Lin Chen, Hsiangfu Kung, Marie C Lin, Zan Shen, Junnian Zheng, Longzhen Zhang, Hong Yao
BACKGROUND: The therapeutic resistance to ionising radiation (IR) and anti-angiogenesis mainly impair the prognosis of patients with glioblastoma. The primary and secondary MET aberrant activation is one crucial factor for these resistances. The kringle 1 domain of hepatocyte growth factor (HGFK1), an angiogenic inhibitor, contains a high-affinity binding domain of MET; however, its effects on glioblastoma remain elusive. METHODS: We formed the nanoparticles consisting of a folate receptor-targeted nanoparticle-mediated HGFK1 gene (H1/pHGFK1) and studied its anti-tumoural and radiosensitive activities in both subcutaneous and orthotopic human glioma cell-xenografted mouse models...
January 18, 2018: British Journal of Cancer
Mário L de Lemos, Carrie Kung, Victoria Kletas, Nadine Badry, Isabell Kang
Since the introduction of regulatory drug approval guidance on the evaluation of QT interval prolongation, an increasing number of drug monographs has included cautions on the risk of QT prolongation. For example, QT prolongation is mentioned in the Canadian product monographs of 29 drugs commonly seen in oncology practice. This presents two major challenges. First, most guidelines and risk predictive tools for QT prolongation have been developed for hospitalized patients in acute care settings. In contrast, most QT-prolonging oncology drugs are used in medically stable patients in the ambulatory setting...
January 1, 2018: Journal of Oncology Pharmacy Practice
Shih-Wei Chen, Yen-Kung Chen
BACKGROUND: Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its value in the surveillance of post-operative colorectal cancer is well established. Fluorodeoxyglucose-positron emission tomography (FDG-PET) has been clinically used in colorectal cancer imaging including preoperative staging, evaluation of therapeutic response, detection of disease recurrence, and investigation of unexplained rising tumor markers. CASE PRESENTATION: We report a case of resected colorectal cancer presented with rising CEA levels in 5 years, and FDG-PET revealed no definitive evidence of recurrence except abnormal focal FDG uptake in the right thyroid lobe...
December 29, 2017: World Journal of Surgical Oncology
Cheng-Yu Yang, Cheng-Chih Hsieh, Chih-Kung Lin, Chun-Shu Lin, Bo Peng, Gu-Jiun Lin, Huey-Kang Sytwu, Wen-Liang Chang, Yuan-Wu Chen
BACKGROUND: Danshen is a common traditional Chinese medicine used to treat neoplastic and chronic inflammatory diseases in China. However, the effects of Danshen on human oral cancer cells remain relatively unknown. This study investigated the antiproliferative effects of a Danshen extract on human oral cancer SAS, SCC25, OEC-M1, and KB drug-resistant cell lines and elucidated the possible underlying mechanism. METHODS: We investigated the anticancer potential of the Danshen extract in human oral cancer cell lines and an in vivo oral cancer xenograft mouse model...
December 29, 2017: BMC Complementary and Alternative Medicine
Kenly Wuputra, Chang-Shen Lin, Ming-Ho Tsai, Chia-Chen Ku, Wen-Hsin Lin, Ya-Han Yang, Kung-Kai Kuo, Kazunari K Yokoyama
The cancer stem cell (CSC) hypothesis postulates that cancer originates from the malignant transformation of stem/progenitor cells and is considered to apply to many cancers, including liver cancer. Identification that CSCs are responsible for drug resistance, metastasis, and secondary tumor appearance suggests that these populations are novel obligatory targets for the treatment of cancer. Here, we describe our new method for identifying potential CSC candidates. The reprogramming of cancer cells via induced pluripotent stem cell (iPSC) technology is a novel therapy for the treatment and for the study of CSC-related genes...
2017: Inflammation and Regeneration
Shun-Mu Wang, Jung-Chen Chang, Shu-Chuan Weng, Ming-Kung Yeh, Chau-Shoun Lee
The association of the risk of suicide with cancer at different time points after a new cancer diagnosis is unclear. This study explored the suicide hazard at different time points after a first cancer diagnosis during the 1-year period before suicide. This case-crossover study included 2,907 suicide cases from 2002 to 2012 in Taiwan and compared the odds of suicide risk at different time points during one year after any cancer diagnosis with self-matched periods. The 13th month preceding the suicide date was used as the control period, and the hazard period was the duration from the 1st to 12th month in the conditional logistic regression for case-crossover comparisons...
December 18, 2017: International Journal of Cancer. Journal International du Cancer
Kuang-Tzu Huang, I-Ying Kuo, Ming-Chao Tsai, Chun-Hsien Wu, Li-Wen Hsu, Li-Yu Chen, Chao-Pin Kung, Yu-Fan Cheng, Shigeru Goto, Yu-Wei Chou, Chao-Long Chen, Chih-Che Lin, Kuang-Den Chen
Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignancies worldwide. Treatment outcomes remain poor mainly due to lack of good diagnostic/prognostic markers and limited therapeutic strategies. We previously characterized aberrant activation of the TF/FVII/PAR2 pathway, which subsequently results in decreased autophagy, as a crucial event in malignant progression of HCC. Here, we identified miR-135a as a highly upregulated miRNA in HCC in response to TF/FVII/PAR2 activation. Analyzing 103 HCC patient specimens, we confirmed that miR-135a was frequently elevated in HCC tissues with higher FVII expression compared to adjacent non-cancerous counterparts...
December 15, 2017: Molecular Therapy. Nucleic Acids
Sumanta Chatterjee, Pratima Basak, Edward Buchel, Janice Safneck, Leigh C Murphy, Michael Mowat, Sam K Kung, Peter Eirew, Connie J Eaves, Afshin Raouf
Human breast cancer cells are known to activate adjacent "normal-like" cells to enhance their own growth, but the cellular and molecular mechanisms involved are poorly understood. We now show by both phenotypic and functional measurements that normal human mammary progenitor cells are significantly under-represented in the mammary epithelium of patients' tumor-adjacent tissue (TAT). Interestingly, fibroblasts isolated from TAT samples showed a reduced ability to support normal EGF-stimulated mammary progenitor cell proliferation in vitro via their increased secretion of transforming growth factor β...
January 9, 2018: Stem Cell Reports
Fiona Tsui-Fen Cheng, Fu Ou-Yang, Nina Lapke, Kai-Che Tung, Yen-Kung Chen, Yuh-Yu Chou, Shu-Jen Chen
Treatment options for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer and resistance to endocrine therapy remain limited. An interesting therapeutic target in these patients is fibroblast growth factor receptor 1 ( FGFR1 ). FGFR1 is amplified in approximately 11% of patients with breast cancer, especially those with HR+ disease. This report presents a patient with metastatic HR+ HER2- breast cancer harboring an FGFR1 amplification who was resistant to endocrine therapy but responded to pazopanib, a multi-tyrosine kinase inhibitor with FGFR -inhibiting activity...
December 2017: Journal of the National Comprehensive Cancer Network: JNCCN
Yong Li, Zhi-Cheng He, Xiao-Ning Zhang, Qing Liu, Cong Chen, Zheng Zhu, Qian Chen, Yu Shi, Xiao-Hong Yao, You-Hong Cui, Xia Zhang, Yan Wang, Hsiang-Fu Kung, Yi-Fang Ping, Xiu-Wu Bian
Glioblastoma (GBM) is a fatal tumor and comprises heterogeneous cells in which a subpopulation with stem cell-like properties is included. Cancer cells with stem cell-like properties account for tumor initiation, drug resistance and recurrence. To identify and characterize specific factors in regulating stem-like traits is critical for GBM therapeutic. Here, we showed that Stanniocalcin-1 (STC1), a secretory glycoprotein, functions as a novel stimulator for stem-like traits of GBM cells. We found STC1 was prominently expressed in glioma spheres which are mainly comprised of glioma stem-like cells...
March 1, 2018: Cancer Letters
Mengnuo Chen, Lai Wei, Cheuk-Ting Law, Felice Ho-Ching Tsang, Jialing Shen, Carol Lai-Hung Cheng, Long-Hin Tsang, Daniel Wai-Hung Ho, David Kung-Chun Chiu, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng, Chun-Ming Wong
Epigenetic alterations immensely contributed to human carcinogenesis. Conventional epigenetic studies predominantly focused on DNA methylation, histone modifications, and chromatin remodeling. Recently, diverse and reversible chemical modifications on RNAs emerge as a new layer of epigenetic regulation. N6-methyladenosine (m6A) is the most abundant chemical modification on eukaryotic mRNA and is important to the regulation of mRNA stability, splicing, and translation. Using transcriptome sequencing, we discovered that METTL3 (methyltransferase like 3), a major RNA N6-adenosine methyltransferase, was significantly up-regulated in human hepatocellular carcinoma (HCC) and multiple solid tumors...
November 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Cong Chen, Yu Shi, Yong Li, Zhi-Cheng He, Kai Zhou, Xiao-Ning Zhang, Kai-Di Yang, Jin-Rong Wu, Hsiang-Fu Kung, Yi-Fang Ping, Xiu-Wu Bian
Reprogrammed metabolism is a hallmark of cancer. Glioblastoma (GBM) tumor cells predominantly utilize aerobic glycolysis for the biogenesis of energy and intermediate nutrients. However, in GBM, the clinical significance of glycolysis and its underlying relations with the molecular features such as IDH1 mutation and subtype have not been elucidated yet. Herein, based on glioma datasets including TCGA (The Cancer Genome Atlas), REMBRANDT (Repository for Molecular Brain Neoplasia Data) and GSE16011, we established a glycolytic gene expression signature score (GGESS) by incorporating ten glycolytic genes...
November 20, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
Giovanni Roti, Jun Qi, Samuel Kitara, Marta Sanchez-Martin, Amy Saur Conway, Anthony C Varca, Angela Su, Lei Wu, Andrew L Kung, Adolfo A Ferrando, James E Bradner, Kimberly Stegmaier
On-target drug delivery remains a challenge in cancer precision medicine; it is difficult to deliver a targeted therapy to cancer cells without incurring toxicity to normal tissues. The SERCA (sarco-endoplasmic reticulum Ca2+ ATPase) inhibitor thapsigargin inhibits mutant NOTCH1 receptors compared with wild type in T cell acute lymphoblastic leukemia (T-ALL), but its administration is predicted to be toxic in humans. Leveraging the addiction of ALL to folic acid, we conjugated folate to an alcohol derivative of thapsigargin via a cleavable ester linkage...
November 20, 2017: Journal of Experimental Medicine
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