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Cancer drug resistence

Faezeh Ghasemi, Parisa Zia Sarabi, Seyyed Shamsadin Athari, Abdulreza Esmaielzadeha
Breast cancer is known as a most prevalent cancer and second deadly cancer, among women worldwide. Due to the high incidence rate of breast cancer and limitations of conventional therapy it seemed essential to look for new targets in cancer cells and directly target them such as target therapy on breast cancer stem cells. In this review we indicate some of therapeutic uses of cancer stem cells in breast cancer. Some strategies are targeting surface specific markers and activated signaling pathways in their microenvironment such as Notch, Hedgehog, Wnt/b-catenin, PI3K/Akt, NF-kB, BMP and TGF-β and their maintenance and drug resistance, using various miRNAs, enhancement of CSCs apoptosis, differentiation therapy, blocking epithelial to mesenchymal transition and using different natural compounds...
February 14, 2019: International Journal of Biochemistry & Cell Biology
Ran Su, Xinyi Liu, Leyi Wei, Quan Zou
The identification of therapeutic biomarkers predictive of drug response is crucial in personalized medicine. A number of computational models to predict response of anti-cancer drugs have been developed as the establishment of several pharmacogenomics screening databases. In our study, we proposed a deep cascaded forest model, Deep-Resp-Forest, to classify the anti-cancer drug response as "sensitive" or "resistant". We made three contributions in this study. Firstly, diverse molecular data could be effectively integrated to provide more information than single type of data for the classification...
February 14, 2019: Methods: a Companion to Methods in Enzymology
Agnieszka Kotlarz, Małgorzata Przybyszewska, Paweł Swoboda, Jacek Neska, Joanna Miłoszewska, Monika Anna Grygorowicz, Andrzej Kutner, Sergiusz Markowicz
Conventional cytotoxic drugs preferentially eliminate differentiated cancer cells but spare relatively more resistant stem-like cancer cells capable to initiate recurrence. Due to cancer cell plasticity, the stem-like phenotype can be also acquired by cancer cells refractory to treatment with cytotoxic drugs. We investigated whether drugs inhibiting receptor tyrosine kinases could be used to target human colon cancer cells initiating cancer regrowth following conventional cytotoxic treatment. The moderately differentiated cell line HT-29 and poorly differentiated cell line HCT-116 were exposed to 5-fluorouracil (5-FU)...
February 14, 2019: Journal of Steroid Biochemistry and Molecular Biology
Sirichat Kaowinn, Natpaphan Yawut, Sang Seok Koh, Young-Hwa Chung
Although our previous studies have showed that a novel oncogene, cancer upregulated gene (CUG)2 induced epithelial-mesenchymal transition (EMT), the detailed molecular mechanism remains unknown. Because several lines of evidence documented that Yes-Associated Protein (YAP)1 is closely associated with cancer stem cell (CSC)-like phenotypes including EMT, stemness, and drug resistance, we wondered if YAP1 is involved in CUG2-induced EMT. We herein found that the overexpression of CUG2 increased YAP1 expression at the transcriptional as well as protein levels...
February 13, 2019: Biochemical and Biophysical Research Communications
James Nyagwange, Elias Awino, Edwin Tijhaar, Nicholas Svitek, Roger Pelle, Vishvanath Nene
Chemotherapy of East Coast fever, a lymphoproliferative cancer-like disease of cattle causing significant economic losses in Africa, is largely dependent on the use of buparvaquone, a drug that was developed in the late 1980's. The disease is caused by the tick-borne protozoan pathogen Theileria parva. Buparvaquone can be used prophylactically and it is also active against tropical theileriosis, caused by the related parasite Theileria annulata. Recently, drug resistance was reported in T. annulata, and could occur in T...
January 25, 2019: International Journal for Parasitology, Drugs and Drug Resistance
Hsin-Hung Chen, I-Lin Lu, Te-I Liu, Yuan-Chung Tsai, Wen-Hsuan Chiang, Sung-Chyr Lin, Hsin-Cheng Chiu
To overcome low therapeutic efficacy of chemotherapy against multidrug resistance (MDR) breast cancer, a combination therapy system based upon functionalized polymer nanoparticles comprising poly(γ-glutamic acid)-g-poly(lactic-co-glycolic acid) (γ-PGA-g-PLGA) as the major component was developed. The NPs were loaded with doxorubicin (DOX) and indocyanine green (ICG) for dual modality cancer treatment and coated with cholesterol-PEG (C-PEG) for MDR abrogation in treatment of human MDR breast cancer. The in vitro cellular uptake of the DOX/ICG loaded nanoparticles (DI-NPs) by MDR cancer cells was significantly enhanced owing to effective inhibition of the P-gp activity by C-PEG and γ-PGA receptor-mediated endocytosis...
February 5, 2019: Colloids and Surfaces. B, Biointerfaces
Wei-Hsun Hsu, Xiaoliang Zhao, Jianquan Zhu, In-Kyu Kim, Guanhua Rao, Justine McCutcheon, Shuo-Tse Hsu, Beverly Teicher, Bhaskar Kallakury, Afshin Dowlati, Yu-Wen Zhang, Giuseppe Giaccone
INTRODUCTION: Platinum-based chemotherapy remains the standard treatment for patients with small cell lung cancer (SCLC), but the benefit of the treatment is often hampered by rapid development of drug resistance. Thus far, there is no targeted therapy available for SCLC. Over 90% of SCLC tumors harbor mutations in the tumor suppressor gene p53, an important DNA damage checkpoint regulator, and these tumor cells rely predominantly on the checkpoint kinases to control DNA damage response...
February 13, 2019: Journal of Thoracic Oncology
Sharad S Singhal, Ravi Salgia, Sulabh Singhal, David Horne, Sanjay Awasthi
Breast cancer (BC) is the most common cancer among women worldwide. Due to its complexity in nature, effective BC treatment can encounter many challenges. The human RALBP1 gene encodes a 76-kDa splice variant protein, RLIP (ral-binding protein1, RalBP1), a stress-protective mercapturic acid pathway (MAP) transporter protein, that also plays a key role in regulating clathrin-dependent endocytosis (CDE) as a Ral effector. Growing evidence shows that targeting RLIP may be an effective strategy in cancer therapy, as RLIP is over-expressed in multiple cancers and is known to induce resistance to apoptosis and chemotherapeutic drugs...
February 13, 2019: Biochimica et biophysica acta. Reviews on cancer
Jinhuan Wu, Yuping Chen, Guohe Geng, Lei Li, Ping Yin, Somaira Nowsheen, Yunhui Li, Chenming Wu, Jiaqi Liu, Fei Zhao, Wootae Kim, Qin Zhou, Jinzhou Huang, Guijie Guo, Chao Zhang, Xinyi Tu, Xiumei Gao, Zhenkun Lou, Kuntian Luo, Haixuan Qiao, Jian Yuan
The serine/threonine kinase, CHK2 (checkpoint kinase 2), is a key mediator in DNA damage response and a tumor suppressor, which is implicated in promoting cell cycle arrest, apoptosis and DNA repair. Accumulating evidence suggests that these functions are primarily exerted through phosphorylation downstream factors such as p53 and BRCA1. Recent studies have shown that ubiquitination is an important mode of regulation of CHK2. However, it remains largely unclear whether deubiquitinases participate in regulation of CHK2...
February 13, 2019: Cancer Letters
Min-Kyue Shin, Jae-Ho Cheong
Metabolic and genotoxic stresses that arise during tumor progression and anti-cancer treatment, respectively, can impose a selective pressure to promote cancer evolution in the tumor microenvironment. This process ultimately selects for the most "fit" clones, which generally have a cancer stem cell like phenotype with features of drug resistance, epithelial-mesenchymal transition, invasiveness, and high metastatic potential. From a bioenergetics perspective, these cancer stem-like cells (CSCs) exhibit mitochondria-centric energy metabolism and are capable of opportunistically utilizing available nutrients such as fatty acids to generate ATP and other metabolic substances, providing a selective advantage for their survival in an impermissible environment and metabolic context...
February 15, 2019: Archives of Pharmacal Research
D Merino, T S Weber, A Serrano, F Vaillant, K Liu, B Pal, L Di Stefano, J Schreuder, D Lin, Y Chen, M L Asselin-Labat, T N Schumacher, D Cameron, G K Smyth, A T Papenfuss, G J Lindeman, J E Visvader, S H Naik
Primary triple negative breast cancers (TNBC) are prone to dissemination but sub-clonal relationships between tumors and resulting metastases are poorly understood. Here we use cellular barcoding of two treatment-naïve TNBC patient-derived xenografts (PDXs) to track the spatio-temporal fate of thousands of barcoded clones in primary tumors, and their metastases. Tumor resection had a major impact on reducing clonal diversity in secondary sites, indicating that most disseminated tumor cells lacked the capacity to 'seed', hence originated from 'shedders' that did not persist...
February 15, 2019: Nature Communications
Tingting Wang, Gang Chen, Xuemei Ma, Yao Yang, Yali Chen, Yihan Peng, Zhigang Bai, Zhongtao Zhang, Huadong Pei, Wei Guo
Despite gemcitabine being the leading chemotherapeutic drug for pancreatic cancer, many patients still relapse due to the drug resistance. We previously reported the molecular link between FKBP51 mediated AKT inhibition and gemcitabine response in pancreatic cancers. However, the upstream regulator of this pathway, especially the involvement of non-coding RNAs in gemcitabine response is still not clear. Here we delineated the miRNA expression profile and key signaling pathways associated with gemcitabine response...
February 15, 2019: Cell Death & Disease
Xiaolan Zhu, Huiling Shen, Xinming Yin, Meiling Yang, Hong Wei, Qi Chen, Fan Feng, Yueqin Liu, Wenlin Xu, Yuefeng Li
BACKGROUND: How exosomal microRNAs (miRNAs) derived from macrophages contribute to the development of drug resistance in the context of the hypoxic tumor microenvironment in epithelial ovarian cancer (EOC) remains poorly understood. METHODS: The miRNA levels were detected by qRT-PCR. Protein levels of HIF-1α, CD163 and PTEN-PI3K/AKT pathway were assessed by Western blot (WB) and Immunohistochemistry (IHC). Exosomes were isolated, and then confirmed by Transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and WB...
February 15, 2019: Journal of Experimental & Clinical Cancer Research: CR
Yalei Yin, Mingju Sun, Xi Zhan, Changqing Wu, Pengyu Geng, Xiaoyan Sun, Yunsong Wu, Shuijun Zhang, Jianhua Qin, Zhengping Zhuang, Yang Liu
BACKGROUND: The bromodomain and extra-terminal domain (BET) inhibitor is a type of anti-tumor agent, currently being evaluated in phase I and II clinical trials for cancer therapy. It can decrease MYC expression levels and cause effective anti-tumor effects in diverse human cancers. However, its cytotoxic effect and related mechanisms of drug resistance are poorly understood in hepatocellular carcinomas (HCC). Here, we investigated the anti-tumor effects of BET inhibitor on HCC and the molecular mechanisms involved in its associated drug resistance...
February 15, 2019: Journal of Experimental & Clinical Cancer Research: CR
Reza Mohammadinejad, Zahra Ahmadi, Shima Tavakol, Milad Ashrafizadeh
Today, pharmacognosy is considered a valuable science in the prevention and treatment of diseases. Among herbals, Berberine is an isoquinoline alkaloid found in the Berberis species. Surprisingly, it shows antimicrobial, antiviral, antidiarrheal, antipyretic, and anti-inflammatory potential. Furthermore, it diminishes drug resistance in cancer therapy and enhances tumor suppression in part through autophagy and cell cycle arrest mechanisms. In the present review, we discuss the effect of berberine on diverse cellular pathways and describe how berberine acts as an autophagy modulator to adjust physiologic and pathologic conditions and diminishes drug resistance in cancer therapy...
February 15, 2019: Journal of Cellular Physiology
Neil E Bhola, Valerie M Jansen, James P Koch, Hua Li, Luigi Formisano, Janice A Williams, Jennifer R Grandis, Carlos L Arteaga
No abstract text is available yet for this article.
February 15, 2019: Cancer Research
Longbing Ling, Muhammad Ismail, Yawei Du, Chen Yao, Xinsong Li
Liposomes have emerged as a fascinating nanocarriers for the delivery of cancer therapeutics. However, their efficacy for cancer therapy is reduced because of the serum-instability and incomplete drug release. In this study, a novel disulfide cross-linked liposomes (CLs) assembled from dimeric lipoic acid-derived glycerophosphorylcholine (di-LA-PC) conjugate was developed. The conjugate was synthesized by a facial esterification of lipoic acid (LA) and glycerophosphorylcholine (GPC) and characterized by MS, 1 H NMR and 13 C NMR...
February 12, 2019: International Journal of Pharmaceutics
Chunlai Feng, Haisheng Zhang, Jiaming Chen, Siqi Wang, Yuanrong Xin, Yang Qu, Qi Zhang, Wei Ji, Fumiyoshi Yamashita, Mengjie Rui, Ximing Xu
Combination therapy is a promising treatment for certain advanced drug-resistant cancers. Although effective inhibition of various tumor cells was reported in vitro, combination treatment requires improvement in vivo due to uncontrolled ratiometric delivery. In this study, a tumor-targeting lipodisk nanoparticle formulation was developed for ratiometric loading and the transportation of two hydrophobic model drugs, doxorubicin (DOX) and paclitaxel (PTX), in one single platform. Furthermore, a slightly acidic pH-sensitive peptide (SAPSP) incorporated into lipodisks effectively enhanced the tumor-targeting and cell internalization...
February 12, 2019: International Journal of Pharmaceutics
Shipeng Gong, Yongning Chen, Fanliang Meng, Yadi Zhang, Huan Wu, Chanyuan Li, Guangping Zhang
Currently, cisplatin (DDP) is the first-line chemotherapeutic agent used for treatment of ovarian cancer, but gradually acquired drug resistance minimizes its therapeutic outcomes. We aimed to identify crucial genes associated with DDP resistance in ovarian cancer and uncover potential mechanisms. Two sets of gene expression data were downloaded from Gene Expression Omnibus, and bioinformatics analysis was conducted. In our study, the differentially expressed genes between DDP-sensitive and DDP-resistant ovarian cancer were screened in GSE15709 and GSE51373 database, and chromosome condensation 2 regulator (RCC2) and nucleoporin 160 were identified as 2 genes that significantly up-regulated in DDP-resistant ovarian cancer cell lines compared with DDP-sensitive cell lines...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Lei Huang, David Brunell, Clifford Stephan, James Mancuso, Bin He, Timothy C Thompson, Ralph Zinner, Jeri Kim, Peter Davies, Stephen T C Wong
MOTIVATION: Drug combinations that simultaneously suppress multiple cancer driver signaling pathways increase therapeutic options and may reduce drug resistance. We have developed a computational systems biology tool, DrugComboExplorer, to identify driver signaling pathways and predict synergistic drug combinations by integrating the knowledge embedded in vast amounts of available pharmacogenomics and omics data. RESULTS: This tool generates driver signaling networks by processing DNA sequencing, gene copy number, DNA methylation, and RNA-seq data from individual cancer patients using an integrated pipeline of algorithms, including bootstrap aggregating-based Markov random field, weighted co-expression network analysis, and supervised regulatory network learning...
February 15, 2019: Bioinformatics
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