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Molecular analysis of chemotherapy resistance

Chao Xu, Yue Yu, Fei Ding
Pancreatic cancer (PC) is one of the most malignant tumors of the digestive system due to its rapid progression, metastasis and resistance to chemotherapy. Gemcitabine (GEM) chemotherapy is the first‑choice treatment for advanced PC. However, the effect of GEM‑based chemotherapy on PC is limited due to the development of chemoresistance, and the molecular mechanisms underlying this resistance have yet to be investigated. Circular RNAs (circRNAs), which can function as microRNA sponges, have been found to be involved in the development of several types of cancer...
May 17, 2018: Oncology Reports
Rajnee Kanwal, Sanjeev Shukla, Ethan Walker, Sanjay Gupta
The role of CD133 (Prominin-1) as a cancer stem cell marker may be useful for therapeutic approaches and prognostication in prostate cancer patients. We investigated the stem-cell-related function and biological features of a subpopulation of CD133+ cells isolated from established primary human prostate cancer cell lines. The CD133+ cells sorted from human prostate cancer 22Rv1 exhibited high clonogenic and tumorigenic capabilities, sphere forming capacity and serially reinitiated transplantable tumors in NOD-SCID mice...
May 15, 2018: Cancer Letters
Jun Bai, Xin Luo
BACKGROUND Chemotherapy has been assuring more important roles in the treatment of carcinoma. Developing new types of drugs with less adverse effects and low drug resistance has become an important researching focus. The present study aimed to investigate the anticancer effects of 5-hydroxy-4'-nitro-7-propionyloxy-genistein (HNPG) and to elucidate its underlying molecular mechanism. MATERIAL AND METHODS The inhibitory effects of cell viability of HNPG were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flat plate clone formation method, and Transwell assay...
May 17, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Qilai Cheng, Meixiang Liao, Haibo Hu, Hongliang Li, Longhuo Wu
BACKGROUND/AIMS: P-glycoprotein (P-gp, i.e., MDR1) is associated with the phenotype of multidrug resistance (MDR) and causes chemotherapy failure in the management of cancers. Searching for effective MDR modulators and combining them with anticancer drugs is a promising strategy against MDR. Asiatic acid (AA), a natural triterpene isolated from the plant Centella asiatica, may have an antitumor activity. The present study assessed the reversing effect of AA on MDR and possible molecular mechanisms of AA action in MDR1-overexpressing cisplatin (DDP)-resistant lung cancer cells, A549/DDP...
May 11, 2018: Cellular Physiology and Biochemistry
Xin Zhang, Suping Zhang, Xingui Liu, Yingying Wang, Jianhui Chang, Xuan Zhang, Samuel G Mackintosh, Alan J Tackett, Yonghan He, Dongwen Lv, Remi-Martin Laberge, Judith Campisi, Jianrong Wang, Guangrong Zheng, Daohong Zhou
The selective depletion of senescent cells (SCs) by small molecules, termed senolytic agents, is a promising therapeutic approach for treating age-related diseases and chemotherapy- and radiotherapy-induced side effects. Piperlongumine (PL) was recently identified as a novel senolytic agent. However, its mechanism of action and molecular targets in SCs was unknown and thus was investigated. Specifically, we used a PL-based chemical probe to pull-down PL-binding proteins from live cells and then mass spectrometry-based proteomic analysis to identify potential molecular targets of PL in SCs...
May 15, 2018: Aging Cell
Zongjing Chen, Liang Zhao, Keqing Shi, Bicheng Chen
BACKGROUND: Pancreatic cancer is one of the most lethal cancers with limited treatment options. Gemcitabine has been the standard drug for patients with advanced pancreatic cancer. Dasatinib is a competitive inhibitor of Src kinase, which has shown promise in treatment of pancreatic cancer. Several studies have revealed the drug resistant mechanism of gemcitabine or dasatinib in human cancers; however, few reports focused on the different mechanisms of gemcitabine and dasatinib resistance in pancreatic cancer...
May 1, 2018: Clinical Laboratory
Xiao-Lin Luo, Chengcheng Deng, Xiao-Dong Su, Fang Wang, Zhen Chen, Xing-Ping Wu, Shao-Bo Liang, Jihong Liu, Liwu Fu
A high rate of disease relapse makes epithelial ovarian cancer (EOC) the leading cause of death among all gynecological malignancies. These relapses are often due to tumor dormancy. Here we identify the RNA polymerase II transcriptional Mediator subunit 12 (MED12) as an important molecular regulator of tumor dormancy. MED12 knockout (KO) induced dormancy of EOC cells in vitro and in vivo, and microarray analysis showed that MED12 KO decreased expression of EGFR. Restoration of EGFR expression in MED12 KO cells restored proliferation...
May 7, 2018: Cancer Research
Sang Cheul Oh, Bo Hwa Sohn, Jae-Ho Cheong, Sang-Bae Kim, Jae Eun Lee, Ki Cheong Park, Sang Ho Lee, Jong-Lyul Park, Yun-Yong Park, Hyun-Sung Lee, Hee-Jin Jang, Eun Sung Park, Sang-Cheol Kim, Jeonghoon Heo, In-Sun Chu, You-Jin Jang, Young-Jae Mok, WonKyung Jung, Baek-Hui Kim, Aeree Kim, Jae Yong Cho, Jae Yun Lim, Yuki Hayashi, Shumei Song, Elena Elimova, Jeannelyn S Estralla, Jeffrey H Lee, Manoop S Bhutani, Yiling Lu, Wenbin Liu, Jeeyun Lee, Won Ki Kang, Sung Kim, Sung Hoon Noh, Gordon B Mills, Seon-Young Kim, Jaffer A Ajani, Ju-Seog Lee
Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy...
May 3, 2018: Nature Communications
Jinshuai Shan, Yang Liu, Yukun Wang, Yimiao Li, Xiaochun Yu, Chen Wu
GALNT14 is a member of N-acetylgalactosaminyltransferase enzyme family and mediates breast cancer cell development. Here, we find that GALNT14 regulates multidrug resistance (MDR) in breast cancer. The expression of GALNT14 is associated with MDR in breast cancer. Higher level of GALNT14 facilitates MCF-7 cells to resist Adriamycin, whereas knockdown of GALNT14 sensitizes cells to Adriamycin. Moreover, the expression of GALNT14 associates with the expression of P-gp, the efflux pump localized on the cell membrane, which could be the underlying mechanism of how GALNT14 induces MDR...
April 23, 2018: Translational Oncology
Jeffrey W Clark, Dan L Longo
PURPOSE OF REVIEW: We intend to highlight progress made in 2017 to lung cancer molecular nosology and application of new knowledge to treatment. RECENT FINDINGS: Studies have shown that agents targeting specific molecular defects in lung cancers such as epidermal growth factor receptor(egfr) mutations, alk or ros1 gene rearrangements, are more effective than conventional combination chemotherapy as primary treatment for various lung cancer subgroups. Identification of mechanisms of drug resistance has guided development of improved agents and effective salvage regimens...
April 24, 2018: Current Opinion in Pulmonary Medicine
Megan H Cox, Parth Kapoor, Deborah A Briggs, Ian D Kerr
Multidrug binding and transport by the ATP binding cassette transporter ABCG2 is a factor in the clinical resistance to chemotherapy in leukaemia, and a contributory factor to the pharmacokinetic profiles of many other prescribed drugs. Despite its importance, the structural basis of multidrug transport, i.e. the ability to transport multiple distinct chemicals, has remained elusive. Previous research has shown that at least two residues positioned towards the cytoplasmic end of transmembrane helix 3 (TM3) of the transporter play a role in drug transport...
April 16, 2018: Biochemical Journal
Emilie Moati, Valérie Taly, Audrey Didelot, Géraldine Perkins, Hélène Blons, Julien Taieb, Pierre Laurent-Puig, Aziz Zaanan
Colorectal cancer is a major health burden with a prognosis that has been improved with the progresses in diagnosis and the advance of chemotherapy and personalized medicine. However, because of intra-tumor heterogeneity, clonal evolution and selection, tumors often develop resistance to treatments. "Liquid biopsy" is a minimally invasive method, based on analysis of tumor-specific material in peripheral blood samples of patients. Analysis of tumor specific genetic or epigenetic alterations in cell-free circulating nucleic acids may reflect the molecular heterogeneity of the underlying disease process and serial testing could allow to monitor its temporal genomic changing without using re-biopsy...
April 4, 2018: Clinics and Research in Hepatology and Gastroenterology
Bao G Vu, W Scott Moye-Rowley
Candida glabrata is the second most common species causing candidiasis. C. glabrata can also readily acquire resistance to azole drugs, complicating its treatment. Here we add to the collection of disruption markers to aid in genetic analysis of this yeast. This new construct is marked with a nourseothricin resistance cassette that produces an estrogen-activated form of Cre recombinase in a methionine-regulated manner. This allows eviction and reuse of this cassette in a facile manner. Using this new disruption marker, we have constructed a series of strains lacking different members of the major facilitator superfamily (MFS) of membrane transporter proteins...
March 2018: MSphere
Murugesan Palaniappan, David Edwards, Chad J Creighton, Daniel Medina, Orla M Conneely
The tumor suppressor gene p53 is frequently mutated in human breast cancer and is a marker for poor prognosis and resistance to chemotherapy. Transplantation of p53 null mouse mammary epithelium into syngeneic wild-type mice leads to normal mammary gland development followed by spontaneous mammary tumors that recapitulate many of the phenotypic, molecular and genetic features of human breast cancer. Transient exposure of p53 null mice to the anti-estrogen, tamoxifen leads to sustained and robust protection against tumor development...
2018: PloS One
Huijuan Xiao, Yihe Liu, Pan Liang, Bo Wang, Hongna Tan, Yonggao Zhang, Xianzheng Gao, Jianbo Gao
Background: The acquisition of drug resistance has been considered as a main obstacle for cancer chemotherapy. Tumor protein 53 target gene 1 (TP53TG1), a p53-induced lncRNA, plays a vital role in the progression of human cancers. However, little is known about the detailed function and molecular mechanism of TP53TG1 in cisplatin resistance of NSCLC. Methods: qRT-PCR analysis was used to detect the expression of TP53TG1, miR-18a and PTEN mRNA in NSCLC tissues and cells...
2018: Cell & Bioscience
Ida Kappel Buhl, Eric Santoni-Rugiu, Jesper Ravn, Anker Hansen, Ib Jarle Christensen, Thomas Jensen, Bruce Pratt, Jon Askaa, Peter Buhl Jensen, Steen Knudsen, Jens Benn Sørensen
INTRODUCTION: Effective predictive biomarkers for selection of patients benefiting from adjuvant platinum-based chemotherapy in non-small cell lung cancer (NSCLC) are needed. Based on a previously validated methodology, molecular profiles of predicted sensitivity in two patient cohorts are presented. METHODS: The profiles are correlations between in vitro sensitivity to cisplatin and vinorelbine and baseline mRNA expression of the 60 cell lines in the National Cancer Institute panel...
2018: PloS One
Yaming Xi, Zhuanzhen Ma, Hao Zhang, Maowen Yuan, Lina Wang
The aim of the present study was to investigate the cytotoxic effect and multi-drug resistance (MDR) of Clostridium difficile toxin A (TcdA) on K562/A02 cells, and understand its underlying molecular pathways. K562/A02 cells were treated with TcdA at different concentrations for 24, 48 and 72 h, and the inhibition effect and drug resistance of TcdA on K562/A02 cell proliferation was assessed by methyl thiazolyl tetrazolium colorimetric assay. Furthermore, cell cycle-apoptosis was analyzed by flow cytometry, P-glycoprotein (P-gp) expression was determined by western blot analysis and caspase-3 activity was measured using a caspase-3 activity kit...
April 2018: Oncology Letters
Nora M Gerhards, Sven Rottenberg
Despite substantial advances in the treatment of various cancers, many patients still receive anti-cancer therapies that hardly eradicate tumor cells but inflict considerable side effects. To provide the best treatment regimen for an individual patient, a major goal in molecular oncology is to identify predictive markers for a personalized therapeutic strategy. Regarding novel targeted anti-cancer therapies, there are usually good markers available. Unfortunately, however, targeted therapies alone often result in rather short remissions and little cytotoxic effect on the cancer cells...
January 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
T Ouchi, S Morikawa, S Shibata, M Takahashi, M Yoshikawa, T Soma, H Miyashita, W Muraoka, K Kameyama, H Kawana, Y Arima, H Saya, H Okano, T Nakagawa, S Asoda
This study investigated a case of spindle cell carcinoma (SpCC) in tongue pathological lesions. The patient experienced a local recurrence and distant metastasis after surgical intervention. Although standard chemotherapy was administered, a granulomatous mass continued to develop. This aggressive growth led to survival of the tumor. Secondary debulking surgery was performed to improve the patient's quality of life at the request of the patient. Using a tissue sample derived from the secondary debulking surgery, we performed an analysis of the tumor's cell surface antigens, differentiation potential, metastatic ability, and inhibition potential by anticancer reagents...
February 1, 2018: Journal of Dental Research
Marta Michalska, Susanne Schultze-Seemann, Irina Kuckuck, Arndt Katzenwadel, Philipp Wolf
BACKGROUND: Cisplatin-based chemotherapy is the treatment of choice for advanced bladder cancer. Since many tumor cells show inherent or acquired cisplatin resistance, research is needed to improve the therapeutic efficacy. Since the analgesic methadone is discussed as being a sensitizer for chemotherapy, we tested its effects on the cisplatin treatment of bladder cancer cells. MATERIALS AND METHODS: T24 and HT-1376 bladder cancer cells were incubated with cisplatin in combination with methadone...
March 2018: Anticancer Research
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