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Chemotherapy resistance

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https://www.readbyqxmd.com/read/29352488/understanding-intratumor-heterogeneity-by-combining-genome-analysis-and-mathematical-modeling
#1
REVIEW
Atsushi Niida, Satoshi Nagayama, Satoru Miyano, Koshi Mimori
Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy...
January 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29352327/limk-cofilin-pathway-and-slingshot-are-implicated-in-human-colorectal-cancer-progression-and-chemoresistance
#2
Helen Aggelou, Panagiota Chadla, Sofia Nikou, Sofia Karteri, Ioannis Maroulis, Haralabos P Kalofonos, Helen Papadaki, Vasiliki Bravou
Cofilin phospho-regulation is important for actin filament turnover and is implicated in cancer. Phosphorylation of cofilin is mediated by LIM kinases (LIMKs) and dephosphorylation by Slingshot phosphatases (SSH). LIMKs and SSH promote cancer cell invasion and metastasis and represent novel anti-cancer targets. However, little is known regarding LIMK/cofilin and SSH in human colorectal cancer (CRC). In this study, we aimed to address their expression and significance in human CRC. We evaluated expression of non-phosphorylated (active) and phosphorylated cofilin, LIMK1, LIMK2, and SSH1 by immunohistochemistry in 143 human CRC samples in relation to clinicopathologic parameters, response of metastatic disease to chemotherapy, and epithelial-mesenchymal transition (EMT) markers β-catenin, E-cadherin, and ZEB...
January 19, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29352306/prognostic-and-predictive-role-of-egfr-pathway-alterations-in-biliary-cancer-patients-treated-with-chemotherapy-and-anti-egfr
#3
Caterina Peraldo-Neia, Giuliana Cavalloni, Elisabetta Fenocchio, Celeste Cagnazzo, Loretta Gammaitoni, Stefano Cereda, Guglielmo Nasti, Maria Antonietta Satolli, Giuseppe Aprile, Michele Reni, Antonio Avallone, Rosella Spadi, Tiziana Venesio, Vittoria Martin, Claudio Doglioni, Milo Frattini, Massimo Aglietta, Francesco Leone
The association of anti-EGFR to gemcitabine and oxaliplatin (GEMOX) chemotherapy did not improve survival in biliary tract carcinoma (BTC) patients. Multiple mechanisms might be involved in the resistance to anti-EGFR. Here, we explored the mutation profile of EGFR extracellular domain (ECD), of tyrosine kinase domain (TKD), and its amplification status. EGFR mutational status of exons 12, 18-21 was analyzed in 57 tumors by Sanger sequencing. EGFR amplification was evaluated in 37 tumors by Fluorescent In Situ Hybridization (FISH)...
2018: PloS One
https://www.readbyqxmd.com/read/29352235/systems-modeling-accurately-predicts-responses-to-genotoxic-agents-and-their-synergism-with-bcl-2-inhibitors-in-triple-negative-breast-cancer-cells
#4
Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen H M Prehn
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352223/zeb1-confers-chemotherapeutic-resistance-to-breast-cancer-by-activating-atm
#5
Xiang Zhang, Zhen Zhang, Qing Zhang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Guosheng Ren, Shuang Yang
Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351920/exceptional-response-to-pembrolizumab-in-a-metastatic-chemotherapy-radiation-resistant-ovarian-cancer-patient-harboring-a-cd274-pd-l1-genetic-rearrangement
#6
Stefania Bellone, Natalia Buza, Jungmin Choi, Luca Zammataro, Laurie Gay, Julia A Elvin, David L Rimm, Yuting Liu, Elena Ratner, Peter E Schwartz, Alessandro D Santin
PURPOSE: Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed. EXPERIMENTAL DESIGN: We describe a heavily pretreated ovarian cancer patient with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune check-point inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (ie, automated quantitative analysis, AQUA) and whole exome sequencing (WES) techniques...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29350467/alveolar-soft-part-sarcoma-in-children-and-young-adults-a-report-of-69-cases
#7
Ricardo J Flores, Douglas J Harrison, Noah C Federman, Wayne L Furman, Winston W Huh, Emily G Broaddus, Mehmet F Okcu, Rajkumar Venkatramani
BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor characterized by ASPL-TFE3 translocation. Apart from complete surgical resection, there is no standard management strategy. PROCEDURE: The clinical data of 69 children and young adults less than 30 years old with ASPS diagnosed from 1980-2014 were retrospectively collected from four major institutions. RESULTS: Median age at diagnosis was 17 years (range: 1.5-30). Forty-four (64%) were female...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29350064/comparison-of-hyaluronic-acid-based-micelles-and-polyethylene-glycol-based-micelles-on-reversal-of-multidrug-resistance-and-enhanced-anticancer-efficacy-in-vitro-and-in-vivo
#8
Jinling Wang, Ying Li, Lifang Wang, Xiaohui Wang, Pengfei Tu
Polyethylene glycol (PEG)-based block copolymer micelles and hyaluronic acid (HA)-based grafted copolymer micelles have been widely investigated in chemotherapy. In this study, to evaluate the differences among HA-based grafted polymer micelles, PEG-based block polymer micelles and the mixed of these two micelles in enhancing antitumor effects and overcoming MDR, two amphiphilic vitamin E succinate (VES) derivatives, HA VES (HA-g-VES) and PEG 2000 VES (TPGS2k), were applied as nanocarriers to prepare HA-VES micelles (HA-PMs), TPGS2k micelles (TPGS2k-PMs) and the mixed micelles (HA/TPGS2k-PMs) for the co-delivery of doxorubicin (DOX) and curcumin (Cur)...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29349762/advances-in-endocrine-therapy-for-postmenopausal-metastatic-breast-cancer
#9
Lisa E Flaum, William J Gradishar
A majority of breast cancers are hormone receptor (HR) positive and are responsive to various types of hormone manipulation. Endocrine therapy is the preferred first-line therapy for patients with advanced estrogen receptor (ER) positive, HER2-negative breast cancer who do not have symptomatic visceral disease. Endocrine therapy is often continued in the second- and third-line setting, with chemotherapy deferred until tumor becomes endocrine therapy refractory and/or a visceral crisis in imminent. Therapeutic options vary based on clinical presentation and include single-agent therapies such as tamoxifen, aromatase inhibitors and fulvestrant, and combination therapies options...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349712/highly-favorable-physiological-responses-to-concurrent-resistance-and-high-intensity-interval-training-during-chemotherapy-the-optitrain-breast-cancer-trial
#10
Sara Mijwel, Malin Backman, Kate A Bolam, Emil Olofsson, Jessica Norrbom, Jonas Bergh, Carl Johan Sundberg, Yvonne Wengström, Helene Rundqvist
BACKGROUND: Advanced therapeutic strategies are often accompanied by significant adverse effects, which warrant equally progressive countermeasures. Physical exercise has proven an effective intervention to improve physical function and reduce fatigue in patients undergoing chemotherapy. Effects of high-intensity interval training (HIIT) in this population are not well established although HIIT has proven effective in other clinical populations. The aim of the OptiTrain trial was to examine the effects of concurrent resistance and high-intensity interval training (RT-HIIT) or concurrent moderate-intensity aerobic and high-intensity interval training (AT-HIIT), to usual care (UC) on pain sensitivity and physiological outcomes in patients with breast cancer during chemotherapy...
January 18, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29349597/drug-repurposing-screening-identifies-bortezomib-and-panobinostat-as-drugs-targeting-cancer-associated-fibroblasts-cafs-by-synergistic-induction-of-apoptosis
#11
Hak-Min Lee, Eunmyong Lee, So-Young Yeo, Sang Shin, Hyun-Kyu Park, Do-Hyun Nam, Seok-Hyung Kim
Cancer associated fibroblasts (CAFs) are the most abundant components of cancer-microenvironment. They play important roles in cancer initiation, progression, and metastasis. In addition, CAFs can confer drug-resistance to cancer cells. Considering their pro-tumorigenic roles, it is recommended to remove CAFs to prevent cancer recurrence after chemotherapy. Despite their clinical significance, few anti-CAF drugs have been developed. The objective of this study was to find a drug that could suppress the viability of patient-derived CAFs through repurposed screening of 51 drugs that were in clinical trials or received FDA approval...
January 18, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29348856/prognostic-value-of-diametrically-polarized-tumor-associated-macrophages-in-multiple-myeloma
#12
Xinyi Chen, Jin Chen, Wenyan Zhang, Ruixue Sun, Ting Liu, Yuhuan Zheng, Yu Wu
Tumor-associated macrophages (TAMs) are correlated with the prognosis of different types of solid tumors and lymphoma, according to many clinical studies. In vitro experiments have demonstrated the roles of these cells in myeloma cell survival, angiogenesis, immunomodulation, drug resistance, and the interaction between malignant myeloma cells and the microenvironment. Here, we investigated the prognostic significance of TAMs in patients with multiple myeloma (MM). We evaluated the polarized functional status of bone marrow infiltrated by TAMs by immunohistochemical staining of CD68, iNOS, and CD163 in 240 patients with MM from January 2009 to December 2014...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348854/acid-ceramidase-and-its-inhibitors-a-de-novo-drug-target-and-a-new-class-of-drugs-for-killing-glioblastoma-cancer-stem-cells-with-high-efficiency
#13
Ninh B Doan, Hisham Alhajala, Mona M Al-Gizawiy, Wade M Mueller, Scott D Rand, Jennifer M Connelly, Elizabeth J Cochran, Christopher R Chitambar, Paul Clark, John Kuo, Kathleen M Schmainda, Shama P Mirza
Glioblastoma remains the most common, malignant primary cancer of the central nervous system with a low life expectancy and an overall survival of less than 1.5 years. The treatment options are limited and there is no cure. Moreover, almost all patients develop recurrent tumors, which typically are more aggressive. Therapeutically resistant glioblastoma or glioblastoma stem-like cells (GSCs) are hypothesized to cause this inevitable recurrence. Identifying prognostic biomarkers of glioblastoma will potentially advance knowledge about glioblastoma tumorigenesis and enable discovery of more effective therapies...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348850/novel-indazole-based-small-compounds-enhance-trail-induced-apoptosis-by-inhibiting-the-mkk7-tiprl-interaction-in-hepatocellular-carcinoma
#14
Ji-Yong Yoon, Jeong-Ju Lee, Sujin Gu, Myoung Eun Jung, Hyun-Soo Cho, Jung Hwa Lim, Soo Young Jun, Jun-Ho Ahn, Ju-Sik Min, Min-Hyuk Choi, Su-Jin Jeon, Yong-Jae Lee, Areum Go, Yun-Jeong Heo, Cho-Rok Jung, Gildon Choi, Kwangho Lee, Moon-Kook Jeon, Nam-Soon Kim
Hepatocellular carcinoma (HCC) is one of the most malignant tumors. Although various treatments, such as surgery and chemotherapy, have been developed, a novel alternative therapeutic approach for HCC therapy is urgently needed. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising anti-cancer agent, but many cancer cells are resistant to TRAIL-induced apoptosis. To help overcome TRAIL resistance in HCC cancer cells, we have identified novel chemical compounds that act as TRAIL sensitizers...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348804/lysine-analogue-of-polymyxin-b-as-a-significant-opportunity-for-photodynamic-antimicrobial-chemotherapy
#15
Florent Le Guern, Tan-Sothea Ouk, Catherine Ouk, Regis Vanderesse, Yves Champavier, Emilie Pinault, Vincent Sol
In order to highlight the potential of photodynamic antimicrobial chemotherapy in case of infections by antibiotic resistant-strains, a new antimicrobial peptide conjugate has been synthesized, consisting of a derivative of polymyxin B and a cationic porphyrin covalently attached together to a spacer. A polymyxin-derived moiety was subjected to a primary structural modification in the replacement of four diaminobutyrate residues with lysine ones. This modification was done in order to strongly reduce bactericidal activity, with the aim to eliminate the potential rise of polymyxin-resistant strains...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348495/preclinical-evaluation-of-antitumor-activity-of-the-proteasome-inhibitor-mln2238-ixazomib-in-hepatocellular-carcinoma-cells
#16
Giuseppa Augello, Martina Modica, Antonina Azzolina, Roberto Puleio, Giovanni Cassata, Maria Rita Emma, Caterina Di Sano, Antonella Cusimano, Giuseppe Montalto, Melchiorre Cervello
Hepatocellular carcinoma (HCC) is one of the common malignancies and is an increasingly important cause of cancer death worldwide. Surgery, chemotherapy, and radiation therapy extend the 5-year survival limit in HCC patients by only 6%. Therefore, there is a need to develop new therapeutic approaches for the treatment of this disease. The orally bioavailable proteasome inhibitor MLN2238 (ixazomib) has been demonstrated to have anticancer activity. In the present study, we investigated the preclinical therapeutic efficacy of MLN2238 in HCC cells through in vitro and in vivo models, and examined its molecular mechanisms of action...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348387/cancer-stem-cells-and-molecular-biology-test-in-colorectal-cancer-therapeutic-implications
#17
Rustam Effendi-Ys
Colorectal cancer (CRC) is the third most frequent cancer in males, the second in females, and is the second leading cause of cancer related death worldwide. Within Indonesia's 250 million population, the incidence rates for CRC per 100,000 population were 15.2 for males and 10.2 for females, and estimated 63,500 cases per year.  More than 50% of colorectal cancer patients will develop metastasis. CRC is still the main cause of tumor-related death, and although most CRC patients are treated with surgery to remove the tumor tissue, some of the CRC patients recurred...
October 2017: Acta Medica Indonesiana
https://www.readbyqxmd.com/read/29346433/vault-rnas-partially-induces-drug-resistance-of-human-tumor-cells-mcf-7-by-binding-to-the-rna-dna-binding-protein-psf-and-inducing-oncogene-gage6
#18
Jianjun Chen, Hui OuYang, Xuemei An, Shixi Liu
BACKGROUND: Vault is the largest nonicosahedral cytosolic nucleoprotein particle, which is widely involved in induction of chemoresistance and lead to failure in long-term chemotherapy. Vault contains three different major vault proteins (MVPs) and four vault RNAs paralogues (vtRNAs, vtRNA1-1, vtRNA1-2, vtRNA1-3 and vtRNA2-1). Disruption of the MVPs do not induce hypersensitivity while expression of vtRNAs contributes to cells' drug resistance, indicates that vtRNAs, but not MVPs play an important role in causing drug resistance...
2018: PloS One
https://www.readbyqxmd.com/read/29345574/role-of-cd73-in-disease-promising-prognostic-indicator-and-therapeutic-target
#19
Jiayin Yang, Xiaohong Liao, Jerry Yu, Ping Zhou
CD73, also known as ecto-5'-nucleotidase (eN, NT5E, EC3.13.5), is the rate-limiting enzyme for adenosine generation and is expressed on multiple cells. Its expression is significantly influenced by hypoxia and inflammatory factors. During inflammation, CD73 protects endothelial barrier function and inhibits leukocyte trafficking. CD73 also promotes M2 macrophages (anti-inflammatory phenotype). In addition, CD73 is expressed on Treg cells and mediates immune suppression through adenosine. CD73 serves as an essential regulator for the immunity and inflammation...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345284/quantitative-proteomics-analysis-of-the-role-of-tetraspanin-8-in-the-drug-resistance-of-gastric-cancer
#20
Lan Li, Daping Yang, Dejun Cui, Yu Li, Zhao Nie, Jinglin Wang, Li Liang
Gastric cancer, due to its high incidence rate, is the second leading cause of cancer-related mortality worldwide. Chemotherapy is an important component of the multimodal treatment for gastric cancer; however, a significant impediment to successful treatment is multidrug resistance (MDR) in patients with gastric cancer. In the present study, the protein profiles of the MDR cell line, SGC7901/DDP, and its parental cell line, SGC7901, were comparatively analyzed through an iTRAQ-based quantitative proteomics technique...
February 2018: International Journal of Oncology
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