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Molecular analysis of chemotherapy resistance

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https://www.readbyqxmd.com/read/29125238/lncrna-uca1-promotes-proliferation-and-cisplatin-resistance-of-oral-squamous-cell-carcinoma-by-sunppressing-mir-184-expression
#1
Zheng Fang, Junfang Zhao, Weihong Xie, Qiang Sun, Haibin Wang, Bin Qiao
Chemotherapy resistance has become the main obstacle for the effective treatment of human cancers. Long non-coding RNA urothelial cancer associated 1 (UCA1) is generally regarded as an oncogene in some cancers. However, the function and molecular mechanism of UCA1 implicated in cisplatin (CDDP) chemoresistance of oral squamous cell carcinoma (OSCC) is still not fully established. UCA1 expression in tumor tissues and cells was tested by qRT-PCR. MTT, flow cytometry and caspase-3 activity analysis were explored to evaluate the CDDP sensitivity in OSCC cells...
November 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29116143/risk-factors-and-molecular-features-of-sequence-type-st-131-extended-spectrum-%C3%AE-lactamase-producing-escherichia-coli-in-community-onset-bacteremia
#2
Hyunsoo Kim, Young Ah Kim, Yoon Soo Park, Min Hyuk Choi, Gyeong In Lee, Kyungwon Lee
Due to the spread of a single CTX-M-type extended-spectrum β-lactamase (ESBL) clone of sequence type (ST) 131, community-onset bacteremia caused by ESBL-producing Escherichia coli has increased dramatically. We evaluated the risk factors and molecular features of ESBL-producing E. coli ST131 clones isolated from Korean patients with community-onset bacteremia. We collected a total of 124 ESBL-producing E. coli isolates from blood in patients with community-onset bacteremia over a 2 year-period. Among 124 patients, the number of community-associated bacteremia cases was 57 (46%)...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29100359/the-conjugated-antimetabolite-5-fdu-ecyd-and-its-cellular-and-molecular-effects-on-platinum-sensitive-vs-resistant-ovarian-cancer-cells-in-vitro
#3
Sarah Schott, Pauline Wimberger, Barbara Klink, Konrad Grützmann, Julian Puppe, Ulrike Sophie Wauer, Daniel Martin Klotz, Evelin Schröck, Jan Dominik Kuhlmann
Background: Resistance to platinum-based chemotherapy is a clinical challenge in the treatment of ovarian cancer (OC) and limits survival. Therefore, innovative drugs against platinum-resistance are urgently needed. Our therapeutic concept is based on the conjugation of two chemotherapeutic compounds to a monotherapeutic pro-drug, which is taken up by cancer cells and cleaved into active cytostatic metabolites. We explore the activity of the duplex-prodrug 5-FdU-ECyd, covalently linking 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), on platinum-resistant OC cells...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048400/cd10-aldh-cells-are-the-sole-cisplatin-resistant-component-of-a-novel-ovarian-cancer-stem-cell-hierarchy
#4
Brendan Ffrench, Claudia Gasch, Karsten Hokamp, Cathy Spillane, Gordon Blackshields, Thamir Mahmoud Mahgoub, Mark Bates, Louise Kehoe, Aoibhinn Mooney, Ronan Doyle, Brendan Doyle, Dearbhaile O'Donnell, Noreen Gleeson, Bryan T Hennessy, Britta Stordal, Ciaran O'Riain, Helen Lambkin, Sharon O'Toole, John J O'Leary, Michael F Gallagher
It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CSC hierarchies and chemoresistance in an ovarian cancer model. Using a single cell-based approach to CSC discovery and validation, we report a novel, four-component CSC hierarchy based around the markers cluster of differentiation 10 (CD10) and aldehyde dehydrogenase (ALDH)...
October 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28992456/prediction-of-new-chromene-based-inhibitors-of-tubulin-using-structure-based-virtual-screening-and-molecular-dynamics-simulation-methods
#5
Hassan Aryapour, Maryam Dehdab, Farzin Sohraby, Afshar Bargahi
Multidrug resistance (MDR) is one of the serious problems in cancer research that causes failure in chemotherapy. Chromene-based compounds have been proven to be the novel anti-MDR agents for inhibiting proliferation of tumor cells through tubulin polymerization inhibition of by binding at the colchicine binding site. In this study, we screened a chromene-based database of small molecules using physicochemical, ADMET properties and molecular docking to identify potential hit compounds. In order to validate our hit compounds, molecular dynamics simulations and related analysis were carried out and the results suggest that our hit compounds (PubChem CIDs: 16814409, 17594471, 57367244 and 69899719) can prove to be potential inhibitors of tubulin...
September 27, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28985022/endocrine-sensitivity-of-estrogen-receptor-positive-breast-cancer-is-negatively-correlated-with-aspartate-%C3%AE-hydroxylase-expression
#6
Masafumi Shimoda, Ami Hori, Jack R Wands, Ryo Tsunashima, Yasuto Naoi, Tomohiro Miyake, Tomonori Tanei, Naofumi Kagara, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
Although prognostic markers for early estrogen receptor (ER)-positive breast cancer have been extensively developed, predictive markers for adjuvant endocrine therapy are still lacking. Focusing on the mechanisms underlying endocrine resistance, we investigated whether the endocrine sensitivity of ER-positive breast cancer cells was correlated with the expression of aspartate-β-hydroxylase (ASPH), which is involved in the development of hepatocellular carcinoma. ASPH expression in ER-positive and tamoxifen-resistant breast cancer cells was upregulated by the MAPK and phosphoinositide-3 kinase (PI3K) pathways, which both play pivotal roles in endocrine resistance...
October 6, 2017: Cancer Science
https://www.readbyqxmd.com/read/28975890/identification-and-validation-of-novel-prognostic-markers-in-renal-cell-carcinoma
#7
Maj Rabjerg
Kidney cancer (Renal Cell Carcinoma (RCC)) is one of the most deadly malignancies due to frequent late diagnosis and poor treatment options. Histologically, RCC embraces a wide variety of different subtypes with the clear cell variant (ccRCC) being the most common, accounting for 75-90% of all RCCs. At present, the surveillance protocols for follow-up of RCC patients after radical nephrectomy are based on the American Joint Committee on Cancers (AJCC) pathological tumor-node-metastasis (TNM) classification system...
October 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/28969635/impact-of-mesenchymal-stem-cells-secretome-on-glioblastoma-pathophysiology
#8
Joana Vieira de Castro, Eduardo D Gomes, Sara Granja, Sandra I Anjo, Fátima Baltazar, Bruno Manadas, António J Salgado, Bruno M Costa
BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain cancer, for which curative therapies are not available. An emerging therapeutic approach suggested to have potential to target malignant gliomas has been based on the use of multipotent mesenchymal stem cells (MSCs), either unmodified or engineered to deliver anticancer therapeutic agents, as these cells present an intrinsic capacity to migrate towards malignant tumors. Nevertheless, it is still controversial whether this innate tropism of MSCs towards the tumor area is associated with cancer promotion or suppression...
October 2, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28968955/integrated-analysis-profiles-of-long-non-coding-rnas-reveal-potential-biomarkers-of-drug-resistance-in-lung-cancer
#9
Wenhua Xue, Lifeng Li, Xin Tian, Zhirui Fan, Ying Yue, Chaoqi Zhang, Xianfei Ding, Xiaoqin Song, Bingjun Ma, Yunkai Zhai, Jingli Lu, Quancheng Kan, Jie Zhao
Lung cancer is one of the leading causes of cancer-related death. Resistance to chemotherapy and molecularly targeted therapies is a major problem that can contribute substantially to high mortality. The roles of long non-coding RNAs (lncRNAs) in drug resistance of lung cancer are insufficiently understood. Here, we identified a distinct drug resistance-related transcriptional signature and constructed a functional lncRNA-mRNA co-expression network. We found that 34 lncRNAs and 103 mRNAs have differential expression in drug resistance of lung cancer, in which 10 lncRNAs were down regulated and 24 up regulated; 49 mRNAs were down regulated and 54 up regulated...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938919/mir-19b-3p-promotes-colon-cancer-proliferation-and-oxaliplatin-based-chemoresistance-by-targeting-smad4-validation-by-bioinformatics-and-experimental-analyses
#10
Tao Jiang, Ling Ye, Zhongbo Han, Yuan Liu, Yinxue Yang, Zhihai Peng, Junwei Fan
BACKGROUND: As a disease with extremely complex molecular mechanisms, many deregulated miRNAs have been identified in colon cancer. Few studies have been performed by using Ingenuity Pathways Analysis (IPA) to predict miRNAs specifically expressed in colon cancer. METHODS: A characteristic microRNA-target network of colon cancer was explored using IPA. Then the clinical significance of miR-19b-3p was evaluated in 211 colon cancer patients. The roles of miR-19b-3p and its candidate target gene, SMAD4, in colon cancer progression were examined both in vitro and in vivo...
September 22, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28928839/analysis-of-resistance-associated-gene-expression-in-docetaxel-resistant-prostate-cancer-cells
#11
Sangchul Lee, Kwangtaek Kim, Jin-Nyoung Ho, Hyunjin Jin, Seok-Soo Byun, Eunsik Lee
Docetaxel-based chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (CRPC). However, a number of patients with metastatic CRPC are refractory to docetaxel or develop docetaxel resistance. The underlying molecular mechanisms of docetaxel resistance remain unclear, which is a significant burden to the management of metastatic prostate cancer. In the present study, the differential gene expression between docetaxel-sensitive (PC3) and docetaxel-resistant (PC3DR2) prostate cancer cells was identified using DNA microarrays, western blot analysis and reverse transcription-quantitative polymerase chain reaction...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28906153/investigational-drugs-in-phase-ii-clinical-trials-for-the-treatment-of-neuroblastoma
#12
REVIEW
Loredana Amoroso, Riccardo Haupt, Alberto Garaventa, Mirco Ponzoni
Neuroblastoma (NB) is an embryonal tumor originating from undifferentiated neural crest cell, highly heterogeneous ranging from spontaneous regression to progression despite multimodal treatments. Approximately, 20% of patients are refractory to frontline therapy and 50% will relapse/progress after an initial response. The overall five year survival for high-risk neuroblastoma ranges from 35-45%. Despite enhanced understanding of NB biology and the addition of myeloablative chemotherapy, isotretinoin and immunotherapy, survival for high risk NB remains less than 50%...
November 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28903376/improving-circulating-tumor-cells-enumeration-and-characterization-to-predict-outcome-in-first-line-chemotherapy-mcrpc-patients
#13
Luis León-Mateos, Helena Casas, Alicia Abalo, María Vieito, Manuel Abreu, Urbano Anido, Antonio Gómez-Tato, Rafael López, Miguel Abal, Laura Muinelo-Romay
INTRODUCTION: There is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28884043/preclinical-and-clinical-applications-of-specific-molecular-imaging-for-her2-positive-breast-cancer
#14
Wei Chen, Xiaofeng Li, Lei Zhu, Jianjing Liu, Wengui Xu, Ping Wang
Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2 (HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment...
August 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28880970/optimization-of-western-blotting-analysis-for-the-isolation-and-detection-of-membrane-xenobiotic-transporter-abcg2
#15
Małgorzata Szczygieł, Marcin Markiewicz, Milena Szafraniec, Roxana Zuziak, Krystyna Urbańska, Leszek Fiedor
All organisms are exposed to numerous stress factors, which include harmful xenobiotics. The diversity of these compounds is enormous, thus in the course of evolution diverse biological defense mechanisms at various levels of organization have developed. One of them engages an evolutionarily conserved family of transporters from the ABC superfamily, found in most species - from bacteria to humans. An important example of such a transporter is the breast cancer resistance protein (BCRP/ABCG2), a typical integral membrane protein...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28874593/egfr-exon-19-deletion-in-pancreatic-adenocarcinoma-responds-to-erlotinib-followed-by-t790m-mediated-resistance
#16
Michael Cecchini, Jeffrey Sklar, Jill Lacy
The prognosis of metastatic pancreatic cancer remains poor despite recent advances in treatment with multidrug chemotherapy regimens. Use of immune checkpoint inhibitors and molecular targeted therapies has so far been disappointing. This report describes a patient with chemotherapy-refractory metastatic pancreatic ductal adenocarcinoma (PDAC) whose tumor was characterized by an activating mutation in exon 19 of the epidermal growth factor receptor (EGFR). He experienced response to erlotinib for 10 months, and then developed disease progression in association with emergence of the T790M mutation...
September 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28851888/the-prognostic-97-chemoresponse-gene-signature-in-ovarian-cancer
#17
Abel Matondo, Yong Hwa Jo, Muhammad Shahid, Tae Gyu Choi, Minh Nam Nguyen, Ngoc Ngo Yen Nguyen, Salima Akter, Insug Kang, Joohun Ha, Chi Hoon Maeng, Si-Young Kim, Ju-Seog Lee, Jayoung Kim, Sung Soo Kim
Patient diagnosis and care would be significantly improved by understanding the mechanisms underlying platinum and taxane resistance in ovarian cancer. Here, we aim to establish a gene signature that can identify molecular pathways/transcription factors involved in ovarian cancer progression, poor clinical outcome, and chemotherapy resistance. To validate the robustness of the gene signature, a meta-analysis approach was applied to 1,020 patients from 7 datasets. A 97-gene signature was identified as an independent predictor of patient survival in association with other clinicopathological factors in univariate [hazard ratio (HR): 3...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819699/cudc-907-a-dual-hdac-and-pi3k-inhibitor-reverses-platinum-drug-resistance
#18
Kenneth K W To, Li-Wu Fu
Platinum (Pt)-based anticancer drugs are the mainstay of treatment for solid cancers. However, resistance to Pt drugs develops rapidly, which can be caused by overexpression of multidrug resistance transporters and activation of DNA repair. CUDC-907 is a potent molecular targeted anticancer agent, rationally designed to simultaneously inhibit histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K). We investigated the potentiation effect of CUDC-907 on Pt drugs in resistant cancer cells. ABCC2 stably-transfected HEK293 cells and two pairs of parental and Pt-resistant cancer cell lines were used to test for the circumvention of resistance by CUDC-907...
August 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28802152/comparison-and-analysis-of-the-structures-and-binding-modes-of-antifungal-se-and-cyp51-inhibitors
#19
Bin Sun, Wanxu Huang, Min Liu, Kang Lei
With the abuse of clinical broad-spectrum antimicrobial agents, immunosuppressive agents, chemotherapy drugs, the emergence of pathogenic fungi resistance is more and more frequent. However, there is still no effective treatment for the fungal resistance. Squalenee epoxidase (SE) and 14 α-demethylase (CYP51) are important antifungal drug targets. In order to achieve a deeper insight into the structural characteristics and the action modes of SE and CYP51inhibitors, the homology model of SE (Candida albicans) was constructed using monooxygenase of Pseudomonas aeruginosa as template, and the reliability of model was confirmed by Ramachandran plots and Verify 3D...
August 1, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28796930/recurrence-associated-gene-signature-optimizes-recurrence-free-survival-prediction-of-colorectal-cancer
#20
Xianglong Tian, Xiaoqiang Zhu, Tingting Yan, Chenyang Yu, Chaoqin Shen, Ye Hu, Jie Hong, Haoyan Chen, Jing-Yuan Fang
High throughput gene expression profiling has showed great promise in providing insight into molecular mechanisms. Metastasis-related mRNAs may potentially enrich genes with the ability to predict cancer recurrence, therefore we attempted to build a recurrence-associated gene signature to improve prognostic prediction of colorectal cancer (CRC). We identified 2848 differentially expressed mRNAs by analyzing CRC tissues with or without metastasis. For the selection of prognostic genes, a LASSO Cox regression model (least absolute shrinkage and selection operator method) was employed...
November 2017: Molecular Oncology
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