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Molecular analysis of chemotherapy resistance

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https://www.readbyqxmd.com/read/28928839/analysis-of-resistance-associated-gene-expression-in-docetaxel-resistant-prostate-cancer-cells
#1
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
#2
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%...
September 14, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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 was employed...
August 10, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28763753/the-anti-proliferative-and-apoptotic-effects-of-crocin-on-chemosensitive-and-chemoresistant-cervical-cancer-cells
#11
Homa Mollaei, Reza Safaralizadeh, Esmaeil Babaei, Mohamad Reza Abedini, Reyhane Hoshyar
Cervical cancer is the fourth cause of cancer-related mortality among females worldwide. Although current therapies reduce disease symptoms, resistance of tumor cells to chemotherapy agents after a while is a serious problem. Therefore, utilization of novel adjuvant agents to increase efficiency of chemotherapy is essential. In the last two decades, botanicals with effective anticancer activities have been studied. Among them, the anticancer properties of crocin have been more attended. In this study, the molecular mechanism of crocin action was investigated in sensitive human cervical cancer cell line (OV2008) in comparison with the resistant one (C13)...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28750358/antitumor-potential-of-1-thiocarbamoyl-3-5-diaryl-4-5-dihydro-1h-pyrazoles-in-human-bladder-cancer-cells
#12
Josiane Weber Tessmann, Julieti Buss, Karine Rech Begnini, Lucas Moraes Berneira, Favero Reisdorfer Paula, Claudio Martin Pereira de Pereira, Tiago Collares, Fabiana Kömmling Seixas
Bladder cancer is a genitourinary malignant disease common worldwide. Current chemotherapy is often limited mainly due to toxicity and drug resistance. Thus, there is a continued need to discover new therapies. Recently evidences shows that pyrazoline derivatives are promising antitumor agents in many types of cancers, but there are no studies with bladder cancer. In order to find potent and novel chemotherapy drugs for bladder cancer, a series of pyrazoline derivatives 2a-2d were tested for their antitumor activity in two human bladder cancer cell lines 5647 and T24...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28744141/the-translational-expression-of-abca2-and-abca3-is-a-strong-prognostic-biomarker-for-multidrug-resistance-in-pediatric-acute-lymphoblastic-leukemia
#13
Narges Aberuyi, Soheila Rahgozar, Zohreh Khosravi Dehaghi, Alireza Moafi, Andrea Masotti, Alessandro Paolini
PURPOSE: The aim of this work was to study the correlation between the expressions of the ABCA2 and ABCA3 genes at the mRNA and protein levels in children with acute lymphoblastic leukemia (ALL) and the effects of this association on multidrug resistance (MDR). MATERIALS AND METHODS: Sixty-nine children with de novo ALL and 25 controls were enrolled in the study. Mononuclear cells were isolated from the bone marrow. The mRNA levels of ABCA2 and ABCA3 were measured by real-time polymerase chain reaction (PCR)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28735518/the-possible-prognostic-role-of-histone-deacetylase-and-transforming-growth-factor-%C3%AE-smad-signaling-in-high-grade-gliomas-treated-by-radio-chemotherapy-a-preliminary-immunohistochemical-study
#14
Roberta Sferra, Simona Pompili, Claudio Festuccia, Francesco Marampon, Giovanni L Gravina, Luca Ventura, Ernesto Di Cesare, Sara Cicchinelli, Eugenio Gaudio, Antonella Vetuschi
Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system. Unfortunately, patients affected by this disease have a very poor prognosis, due to high level of invasiveness and resistance to standard therapies. Although the molecular profile of GBM has been extensively investigated, the events responsible for its pathogenesis and progression remain largely unknown. Histone Deacetylases (HDAC) dependent epigenetic modifications and transforming growth factor (TGF)-β/Smad pathway seem to play an important role in GBM tumorigenesis, resistance to common therapies and poor clinical outcome...
May 16, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28729771/microarray-gene-expression-analysis-of-chemosensitivity-for-docetaxel-cisplatin-and-5-fluorouracil-tpf-combined-chemotherapeutic-regimen-in-hypopharyngeal-squamous-cell-carcinoma
#15
Meng Lian, Haizhou Wang, Jugao Fang, Jie Zhai, Ru Wang, Xixi Shen, Yifan Yang, Zhihong Ma, Honggang Liu
OBJECTIVE: To screen out a set of candidate genes which could help to determine whether patients with hypopharyngeal squamous cell carcinoma (HSCC) could benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy. METHODS: Gene-expression profiles in 12 TPF-sensitive patients were compared to 9 resistant controls by microarray analysis. Subsequently, expression levels of potential biomarkers in chemosensitive cell line FaDu after TPF treatment were observed by quantitative real-time polymerase chain reaction (qRT-PCR)...
June 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28728166/whole-genome-sequencing-revealed-novel-prognostic-biomarkers-and-promising-targets-for-therapy-of-ovarian-clear-cell-carcinoma
#16
Hiroaki Itamochi, Tetsuro Oishi, Nao Oumi, Satoshi Takeuchi, Kosuke Yoshihara, Mikio Mikami, Nobuo Yaegashi, Yasuhisa Terao, Kazuhiro Takehara, Kimio Ushijima, Hidemichi Watari, Daisuke Aoki, Tadashi Kimura, Toshiaki Nakamura, Yoshihito Yokoyama, Junzo Kigawa, Toru Sugiyama
BACKGROUND: Ovarian clear cell carcinoma (OCCC) is mostly resistant to standard chemotherapy that results in poor patient survival. To understand the genetic background of these tumours, we performed whole-genome sequencing of OCCC tumours. METHODS: Tumour tissue samples and matched blood samples were obtained from 55 Japanese women diagnosed with OCCC. Whole-genome sequencing was performed using the Illumina HiSeq platform according to standard protocols. RESULTS: Alterations to the switch/sucrose non-fermentable (SWI/SNF) subunit, the phosphatidylinositol-3-kinase (PI3K)/Akt signalling pathway, and the receptor tyrosine kinase (RTK)/Ras signalling pathway were found in 51%, 42%, and 29% of OCCC tumours, respectively...
August 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28714013/glioblastoma-entities-express-subtle-differences-in-molecular-composition-and-response-to-treatment
#17
Joana Balça-Silva, Diana Matias, Anália Do Carmo, Luiz Gustavo Dubois, Ana Cristina Gonçalves, Henrique Girão, Nathalie Henriques Silva Canedo, Ana Helena Correia, Jorge Marcondes De Souza, Ana Bela Sarmento-Ribeiro, Maria Celeste Lopes, Vivaldo Moura-Neto
Glioblastoma (GBM) is a grade IV astrocytoma. GBM patients show resistance to chemotherapy such as temozolomide (TMZ), the gold standard treatment. In order to simulate the molecular mechanisms behind the different chemotherapeutic responses in GBM patients we compared the cellular heterogeneity and chemotherapeutic resistance mechanisms in different GBM cell lines. We isolated and characterized a human GBM cell line obtained from a GBM patient, named GBM11. We studied the GBM11 behaviour when treated with Tamoxifen (TMX) that, among other functions, is a protein kinase C (PKC) inhibitor, alone and in combination with TMZ in comparison with the responses of U87 and U118 human GBM cell lines...
July 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28698581/gtse1-promotes-cell-migration-and-invasion-by-regulating-emt-in-hepatocellular-carcinoma-and-is-associated-with-poor-prognosis
#18
Xiaojuan Wu, Hongbo Wang, Yifan Lian, Lubiao Chen, Lin Gu, Jialiang Wang, Yanlin Huang, Meihai Deng, Zhiliang Gao, Yuehua Huang
G2 and S phase-expressed-1 (GTSE1) regulates G1/S cell cycle transition. It was recently reported to be overexpressed in certain human cancers, but its significance and mechanism(s) in hepatocellular carcinoma (HCC) remain unknown. Here, we showed preferential GTSE1 upregulation in human HCC tissues and cell lines that positively correlated with Ki67. GTSE1 knockdown by short hairpin RNA resulted in deficient colony-forming ability and depleted capabilities of HCC cells to migrate and invade. Conversely, exogenous GTSE1 overexpression enhanced colony formation and stimulated HCC cell migration and invasion...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28685087/heterogeneity-in-the-colorectal-primary-tumor-and-the-synchronous-resected-liver-metastases-prior-to-and-after-treatment-with-an-anti-egfr-monoclonal-antibody
#19
Daniela Adua, Francesca Di Fabio, Giorgio Ercolani, Michelangelo Fiorentino, Elisa Gruppioni, Annalisa Altimari, Fabiola Lorena Rojas Limpe, Nicola Normanno, Antonio Daniele Pinna, Carmine Pinto
Molecular heterogeneity between primary tumors (PTs) and synchronous resected liver metastasis in colorectal cancer (CRC) has potential relevance in treatment strategies. Next-generation sequencing (NGS) may be able to increase the chances of identifying multiple molecular driver alterations, calling for therapy. The aim of the present study was to evaluate mutations in PT and synchronous resected liver metastases for patients with Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) exon 2 wild-type metastatic (m)CRC who underwent chemotherapy (CT) featuring an anti-epidermal growth factor receptor (EGFR) monoclonal antibody...
July 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28681829/molecular-characterisation-of-uropathogenic-escherichia-coli-isolates-at-a-tertiary-care-hospital-in-south-india
#20
Arindam Chakraborty, Prabha Adhikari, Shalini Shenoy, Vishwas Saralaya
Uropathogenic Escherichia coli (UPEC) express a multitude of virulence factors (VFs) to break the inertia of the mucosal barrier of the urinary tract. The aim of the present study was undertaken to characterised the UPEC strains and to correlate carriage of specific virulence markers with different phylogroups and also to correlate these findings with clinical outcome of patients. A total of 156 non-repeated, clinically significant UPEC isolates were studied. Virulent genes were determined by two set of multiplex polymerase chain reaction (PCR)...
April 2017: Indian Journal of Medical Microbiology
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