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Molecular analysis of chemotherapy resistance

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https://www.readbyqxmd.com/read/28063788/response-to-chemotherapy-and-prognosis-in-metastatic-colorectal-cancer-with-dna-deficient-mismatch-repair
#1
Alexandra Khichfy Alex, Sheila Siqueira, Renata Coudry, Juliana Santos, Michel Alves, Paulo M Hoff, Rachel P Riechelmann
BACKGROUND: DNA deficient mismatch repair (dMMR) genes are associated with microsatellite instability and good prognosis in early-stage colorectal cancer (CRC). However dMMR is rare in metastatic CRC (mCRC) and little is known about its influence on treatment response rate (RR). The primary objective of this study was to compare the RR of patients with mCRC according to dMMR status. METHODS: This was a retrospective study that compared the RR by Response Evaluation Criteria In Solid Tumors 1...
November 26, 2016: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28062800/novel-allosteric-pathway-of-eg5-regulation-identified-through-multivariate-statistical-analysis-of-hx-ms-ligand-screening-data
#2
Joey G Sheff, Farshad Farshidfar, Oliver F Bathe, Karen Kopciuk, Francesco Gentile, Jack Tuszynski, Khaled Barakat, David C Schriemer
The mitotic kinesin Eg5 is an important target in cancer chemotherapy. A structurally diverse collection of canonical loop L5 inhibitors engage an allosteric pathway that includes elements of its microtubule binding region. However, recent evidence suggests that Eg5 may permit alternative allosteric mechanisms. Terpendole E, a natural-product Eg5 inhibitor, is active against mutants resistant to canonical loop L5 inhibitors and appears to offer a unique mode of inhibition. To investigate the variety of inhibitor responses, the structure-function properties of eighteen kinesin inhibitors were quantified with hydrogen-exchange mass spectrometry (HX-MS), functional analysis and molecular modeling...
January 5, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28009971/dacomitinib-a-new-pan-egfr-inhibitor-is-effective-in-killing-ovarian-cancer-cells
#3
Lei Xu, Huini Wu, Chao Jiang, Hongcai Wang, Bei Gao, Shumei Yan, Yushu Qi, Shufeng Zhou
OBJECTIVE: Aberrant epidermal growth factor receptor (EGFR) is involved in a variety of cancers and its inhibitors have been studied for over a decade. We aim to investigate the effects of dacomitinib, a second generation pan-EGFR inhibitor, on ovarian cancer cells. METHODS: By immunohistochemistry, we studied the clinical significance of EGFR expression in epithelial ovarian cancer (EOC). The correlations between EGFR expression and the clinicopathological variables of patients with EOC were assessed using Pearson's X2 test...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27974547/molecular-epidemiology-of-clostridium-difficile-infection-in-hospitalized-patients-in-eastern-china
#4
Dazhi Jin, Yun Luo, Chen Huang, Jian Cai, Julian Ye, Yi Zheng, Liqian Wang, Peng Zhao, Anbing Liu, Weijia Fang, Xianjun Wang, Shichang Xia, Jianmin Jiang, Yi-Wei Tang
Few studies on risk factors and transmission of Clostridium difficile infection (CDI) have been reported from China. A cross-sectional study was conducted for three years in Eastern China. Consecutive stool specimens from hospitalized patients with diarrhea were cultured for C. difficile C. difficle isolates from these patients then were analyzed for toxin genes, genotypes and antimicrobial resistance. Severity of CDI was determined in each patient by a blinded review of the medical record and ranged from 1 to 6...
December 14, 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/27959427/inhibiting-the-cytoplasmic-location-of-hmgb1-reverses-cisplatin-resistance-in-human-cervical-cancer-cells
#5
Jiyi Xia, Xiaolan Yu, Xueqin Song, Gang Li, Xiguang Mao, Yujiao Zhang
Cervical cancer is the fourth most common malignancy in women worldwide, and resistance to chemotherapy drugs is the biggest obstacle in the treatment of cervical cancers. In the present study, the molecular mechanisms underlying cisplatin resistance in human cervical cancer cells were investigated. When human cervical cancer cells were treated with 10 µg/ml of cisplatin for 24 and 48 h, high mobility group box 1 (HMGB1) protein expression levels significantly increased in a time‑dependent manner. Comparisons between cisplatin‑sensitive HeLa cells and cisplatin‑resistant HeLa/DDP cells revealed higher levels of HMGB1 in HeLa/DDP cells than in HeLa cells...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27926740/a-17-gene-stemness-score-for-rapid-determination-of-risk-in-acute-leukaemia
#6
Stanley W K Ng, Amanda Mitchell, James A Kennedy, Weihsu C Chen, Jessica McLeod, Narmin Ibrahimova, Andrea Arruda, Andreea Popescu, Vikas Gupta, Aaron D Schimmer, Andre C Schuh, Karen W Yee, Lars Bullinger, Tobias Herold, Dennis Görlich, Thomas Büchner, Wolfgang Hiddemann, Wolfgang E Berdel, Bernhard Wörmann, Meyling Cheok, Claude Preudhomme, Herve Dombret, Klaus Metzeler, Christian Buske, Bob Löwenberg, Peter J M Valk, Peter W Zandstra, Mark D Minden, John E Dick, Jean C Y Wang
Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories. However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27899771/-perspectives-of-individualized-treatment-by-genome-wide-analyses-in-ovarian-cancer
#7
Noriomi Matsumura, Ken Yamaguchi, Ryusuke Murakami, Masaki Mandai, Ikuo Konishi
Genome-wide analyses have recently been reported for ovarian cancer. High-grade serous ovarian carcinoma(HGSOC) almost exclusively harbor TP53 mutations and prominent copy number aberrations. Approximately 20% of HGSOCs harbor BRCA mutations, in which case PARP inhibitors may be effective. HGSOCs are classified into 4 molecular subtypes with distinct histopathological features by transcriptional profiling. These subtypes differ in prognosis and drug sensitivity. Additionally, a whole-genome analysis for HGSOC has revealed various factors that can induce resistance to chemotherapy...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27895763/small-cell-lung-cancer-transformation-and-the-t790m-mutation-a-case-report-of-two-acquired-mechanisms-of-tki-resistance-detected-in-a-tumor-rebiopsy-and-plasma-sample-of-egfr-mutant-lung-adenocarcinoma
#8
Greta Alì, Rossella Bruno, Mirella Giordano, Irene Prediletto, Letizia Marconi, Simonetta Zupo, Franco Fedeli, Alessandro Ribechini, Antonio Chella, Gabriella Fontanini
The present study describes the case of a 45-year-old man diagnosed with metastatic lung adenocarcinoma, which harbored a deletion within exon 19 of the epidermal growth factor receptor (EGFR) gene. The patient was subsequently treated with gefitinib (250 mg/day orally from May 2013 to March 2014), but developed acquired resistance to the drug following 11 months of treatment. Tumor burden molecular analysis was performed on a tumor rebiopsy and plasma sample, and histological analysis was also performed on the tumor rebiopsy...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27891677/staurosporine-scaffold-based-rational-discovery-of-the-wild-type-sparing-reversible-inhibitors-of-egfr-t790m-gatekeeper-mutant-in-lung-cancer-with-analog-sensitive-kinase-technology
#9
Xiaoyun Song, Xingcai Liu, Xi Ding
The human epidermal growth factor receptor (EGFR) has been established as an attractive target for lung cancer therapy. However, an acquired EGFR T790M gatekeeper mutation is frequently observed in patients treated with first-line anticancer agents such as gefitinib and erlotinib to cause drug resistance, largely limiting the application of small-molecule kinase inhibitors in EGFR-targeted chemotherapy. Previously, the reversible pan-kinase inhibitor staurosporine and its several analogs such as Gö6976 and K252a have been reported to selectively inhibit the EGFR T790M mutant (EGFR(T790M) ) over wild-type kinase (EGFR(WT) ), suggesting that the staurosporine scaffold is potentially to develop the wild-type sparing reversible inhibitors of EGFR(T790M) ...
November 28, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27881732/metronomic-chemotherapy-prevents-therapy-induced-stromal-activation-and-induction-of-tumor-initiating-cells
#10
Tze-Sian Chan, Chung-Chi Hsu, Vincent C Pai, Wen-Ying Liao, Shenq-Shyang Huang, Kok-Tong Tan, Chia-Jui Yen, Shu-Ching Hsu, Wei-Yu Chen, Yan-Shen Shan, Chi-Rong Li, Michael T Lee, Kuan-Ying Jiang, Jui-Mei Chu, Gi-Shih Lien, Valerie M Weaver, Kelvin K Tsai
Although traditional chemotherapy kills a fraction of tumor cells, it also activates the stroma and can promote the growth and survival of residual cancer cells to foster tumor recurrence and metastasis. Accordingly, overcoming the host response induced by chemotherapy could substantially improve therapeutic outcome and patient survival. In this study, resistance to treatment and metastasis has been attributed to expansion of stem-like tumor-initiating cells (TICs). Molecular analysis of the tumor stroma in neoadjuvant chemotherapy-treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximum-tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-κB activity in carcinoma-associated fibroblasts...
December 12, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27879115/preface
#11
Avner Friedman, Mirosław Lachowicz, Urszula Ledzewicz, Monika Joanna Piotrowska, Zuzanna Szymanska
This volume was inspired by the topics presented at the international conference "Micro and Macro Systems in Life Sciences" which was held on Jun 8-12, 2015 in Będlewo, Poland. System biology is an approach which tries to understand how micro systems, at the molecular and cellular levels, affect macro systems such as organs, tissue and populations. Thus it is not surprising that a major theme of this volume evolves around cancer and its treatment. Articles on this topic include models for tumor induced angiogenesis, without and with delays, metastatic niche of the bone marrow, drug resistance and metronomic chemotherapy, and virotherapy of glioma...
February 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/27878398/hsp90-is-a-promising-target-in-gemcitabine-and-5-fluorouracil-resistant-pancreatic-cancer
#12
Tarik Ghadban, Judith L Dibbern, Matthias Reeh, Jameel T Miro, Tung Y Tsui, Ulrich Wellner, Jakob R Izbicki, Cenap Güngör, Yogesh K Vashist
Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution...
November 22, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27865367/circulating-tumor-stem-like-cells-in-oral-squamous-cell-carcinoma-an-unresolved-paradox
#13
Shanaya Patel, Kavan Shah, Sheefa Mirza, Kanisha Shah, Rakesh Rawal
OBJECTIVE: Circulating tumor cells (CTCs) are increasingly gaining importance due to their immense potential in enhancing diagnosis, prognosis and response to therapy in solid malignancies. Therefore, we aimed to comprehend the molecular diversity and critical role of this disseminated tumor population in OSCC. METHODOLOGY: CD44+ subpopulation was isolated using immuno-magnetic cell separation and their purity was validated using flow cytometry. Characterisation of self renewal potential and resistance to chemotherapy was assessed using tumor sphere forming and cytotoxicity assay...
November 2016: Oral Oncology
https://www.readbyqxmd.com/read/27847566/metallothinein-1e-enhances-glioma-invasion-through-modulation-matrix-metalloproteinases-2-and-9-in-u87mg-mouse-brain-tumor-model
#14
Hyuk Hur, Hyang-Hwa Ryu, Chun-Hao Li, In Young Kim, Woo-Youl Jang, Shin Jung
Malignant glioma cells invading surrounding normal brain are inoperable and resistant to radio- and chemotherapy, and eventually lead to tumor regrowth. Identification of genes related to motility is important for understanding the molecular biological behavior of invasive gliomas. According to our previous studies, Metallothionein 1E (MT1E) was identified to enhance migration of human malignant glioma cells. The purpose of this study was to confirm that MT1E could modulate glioma invasion in vivo. Firstly we established 2 cell lines; MTS23, overexpressed by MT1E complementary DNA construct and pV12 as control...
November 2016: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/27835695/reference-genes-for-addressing-gene-expression-of-bladder-cancer-cell-models-under-hypoxia-a-step-towards-transcriptomic-studies
#15
Luís Lima, Cristiana Gaiteiro, Andreia Peixoto, Janine Soares, Manuel Neves, Lúcio Lara Santos, José Alexandre Ferreira
Highly aggressive, rapidly growing tumors contain significant areas of hypoxia or anoxia as a consequence of inadequate and/or irregular blood supply. During oxygen deprivation, tumor cells withstand a panoply of adaptive responses, including a shift towards anaerobic metabolism and the reprogramming of the transcriptome. One of the major mediators of the transcriptional hypoxic response is the hypoxia-inducible factor 1 (HIF-1), whose stabilization under hypoxia acts as an oncogenic stimulus contributing to chemotherapy resistance, invasion and metastasis...
2016: PloS One
https://www.readbyqxmd.com/read/27831559/decreased-expression-of-microrna-17-and-microrna-20b-promotes-breast-cancer-resistance-to-taxol-therapy-by-upregulation-of-ncoa3
#16
Xiang Ao, Peipei Nie, Baoyan Wu, Wei Xu, Tao Zhang, Songmao Wang, Haocai Chang, Zhengzhi Zou
Chemoresistance is a major obstacle to effective breast cancer chemotherapy. However, the underlying molecular mechanisms remain unclear. In this study, nuclear receptor coactivator 3 (NCOA3) was found to be significantly increased in taxol-resistant breast cancer tissues and cells. Moreover, overexpression of NCOA3 enhanced breast cancer cell resistance to taxol, whereas depletion of NCOA3 decreased taxol resistance. Subsequently, we investigated whether NCOA3 expression was regulated by miRNAs in breast cancer...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27825341/essential-oils-in-vitro-activity-against-leishmania-amazonensis-cytotoxicity-and-chemical-composition
#17
Milene Aparecida Andrade, Clênia Dos Santos Azevedo, Flávia Nader Motta, Maria Lucília Dos Santos, Camila Lasse Silva, Jaime Martins de Santana, Izabela M D Bastos
BACKGROUND: The current chemotherapy for cutaneous leishmaniosis (CL) has a series of drug limitations such as toxic side effects, long duration, high costs and drug resistance, which requires the development of new drugs or effective alternatives to the CL treatment. Essential oils (EOs) are complex mixtures of secondary metabolites from various plants. It has been shown that several EOs, or their constituents, have inhibitory activity against protozoa. Thus, this study aims to evaluate the biological activity of different essential oils (EOs) on Leishmania (L...
November 8, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27806319/ammonium-tetrathiomolybdate-treatment-targets-the-copper-transporter-atp7a-and-enhances-sensitivity-of-breast-cancer-to-cisplatin
#18
Cristine L Chisholm, Haitao Wang, Ada Hang-Heng Wong, Guelaguetza Vazquez-Ortiz, Weiping Chen, Xiaoling Xu, Chu-Xia Deng
Cisplatin is an effective breast cancer drug but resistance often develops over prolonged chemotherapy. Therefore, we performed a candidate approach RNAi screen in combination with cisplatin treatment to identify molecular pathways conferring survival advantages. The screen identified ATP7A as a therapeutic target. ATP7A is a copper ATPase transporter responsible for intercellular movement and sequestering of cisplatin. Pharmaceutical replacement for ATP7A by ammonium tetrathiomolybdate (TM) enhanced cisplatin treatment in breast cancer cells...
October 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27783307/therapeutic-effects-of-aicar-and-dox-conjugated-multifunctional-nanoparticles-in-sensitization-and-elimination-of-cancer-cells-via-survivin-targeting
#19
Cenk Daglioglu, Burcu Okutucu
PURPOSE: Resistance to chemotherapy is one of the major problems facing current cancer research. Enhancing tumor cell response to anticancer agents increases chemotherapeutic effectiveness. We have recently addressed this issue and reported on producing multifunctional nanoparticles (Fe3O4@SiO2(FITC)-FA/AICAR/DOX) aiming to overcome chemoresistance with synergetic effect of AICAR and DOX. In the present study, we demonstrated that these nanoparticles not only show enhanced cellular uptake and cytotoxic effect but can also show enhanced pro-apoptotic and anti-proliferative effects in five different tumor-derived cell lines (A549, HCT-116, HeLa, Jurkat and MIA PaCa-2)...
January 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/27767100/ccne1-copy-number-gain-and-overexpression-identify-ovarian-clear-cell-carcinoma-with-a-poor-prognosis
#20
Ayse Ayhan, Elisabetta Kuhn, Ren-Chin Wu, Hiroshi Ogawa, Asli Bahadirli-Talbott, Tsui-Lien Mao, Haruhiko Sugimura, Ie-Ming Shih, Tian-Li Wang
Ovarian clear cell carcinoma is a unique type of ovarian cancer, often derived from endometriosis, and advanced-stage disease has a dismal prognosis primarily due to the resistance to conventional chemotherapy. Previous studies have shown frequent somatic mutations in ARID1A, PIK3CA, hTERT promoter, and amplification of ZNF217; however, the molecular alterations that are associated with its aggressiveness remain largely unknown. This study examined and compared cyclin E1 expression in endometriosis-related ovarian tumors, with the aim of determining the relationship between hTERT mutations and ARID1A expression and evaluating the effects of these molecular alterations on patient survival...
October 21, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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