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https://www.readbyqxmd.com/read/28938696/the-molecular-mechanisms-of-chemoresistance-in-cancers
#1
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938541/differential-expression-of-circulating-biomarkers-of-tumor-phenotype-and-outcomes-in-previously-treated-non-small-cell-lung-cancer-patients-receiving-erlotinib-vs-cytotoxic-chemotherapy
#2
Mary Jo Fidler, Casey Frankenberger, Richard Seto, Gabriela C Lobato, Cristina L Fhied, Selina Sayidine, Sanjib Basu, Mark Pool, Reem Karmali, Marta Batus, Wen-Rong Lie, David Hayes, Jehangir Mistry, Philip Bonomi, Jeffrey A Borgia
BACKGROUND: The objective of this study was to identify serum biomarkers capable of predicting clinical outcomes in previously-treated NSCLC patients with wild-type for EGFR activating mutations or insufficient tissue for mutation status determination. METHODS: Sixty-six Luminex immunoassays representative of biological themes that emerged from a re-analysis of transcriptome data from the Cancer Genome Atlas (TCGA) were evaluate against pretreatment serum specimens from previously-treated advanced NSCLC patients received either cytotoxic chemotherapy (n=32) or erlotinib (n=79)...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938477/growth-hormone-and-the-epithelial-to-mesenchymal-transition
#3
Alison L Brittain, Reetobrata Basu, Yanrong Qian, John J Kopchick
Context: Previous studies have implicated growth hormone (GH) in the progression of several cancers, including breast, colorectal and pancreatic. A mechanism by which GH may play this role in cancer is through the induction of the epithelial-to-mesenchymal transition (EMT). During the EMT process, epithelial cells lose their defining phenotypes causing loss of cellular adhesion and increased cell migration. This review aims to carefully summarize the previous two decades of research that points to GH as an initiator of EMT, in both cancerous and non-cancerous tissues...
August 4, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938159/lunatic-fringe-and-p53-cooperatively-suppress-mesenchymal-stem-like-breast-cancer
#4
Wen-Cheng Chung, Shubing Zhang, Lavanya Challagundla, Yunyun Zhou, Keli Xu
Claudin-low breast cancer (CLBC) is a poor prognosis molecular subtype showing stemness and mesenchymal features. We previously discovered that deletion of a Notch signaling modulator, Lunatic Fringe (Lfng), in the mouse mammary gland induced a subset of tumors resembling CLBC. Here we report that deletion of one copy of p53 on this background not only accelerated mammary tumor development but also led to a complete penetrance of the mesenchymal stem-like phenotype. All mammary tumors examined in the Lfng/p53 compound mutant mice displayed a mesenchymal/spindloid pathology...
September 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28937318/the-crosstalk-between-p38-and-akt-signaling-pathways-orchestrates-emt-by-regulating-satb2-expression-in-nsclc-cells
#5
Hakan Kucuksayan, Hakan Akca
Epithelial-mesenchymal transition is a crucial event for metastasis and could be mediated by several pathways such as phosphoinositide 3-kinase/Akt, mitogen-activated protein kinases, as well as many epigenetic regulators. Special AT-rich sequence-binding protein 2 is an epigenetic regulator involved in epithelial-mesenchymal transition and osteoblastic differentiation. It has been reported that the crosstalk between several pathways is responsible for the regulation of epithelial-mesenchymal transition in cancer cells...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28936799/proteomic-features-of-colorectal-cancer-identify-tumor-subtypes-independent-of-oncogenic-mutations-and-independently-predict-relapse-free-survival
#6
Callisia N Clarke, Michael S Lee, Wei Wei, Ganiraju Manyam, Zhi-Qin Jiang, Yiling Lu, Jeffrey Morris, Bradley Broom, David Menter, Eduardo Vilar-Sanchez, Kanwal Raghav, Cathy Eng, George J Chang, Iris Simon, Rene Bernards, Michael Overman, Gordon B Mills, Dipen Maru, Scott Kopetz
BACKGROUND: The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear. METHODS: We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis...
September 21, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28936481/controlling-epithelial-to-mesenchymal-transition-through-acetylation-of-histone-h2bk5
#7
Robert J Mobley, Amy N Abell
Large-scale epigenetic changes take place when epithelial cells with cell-cell adhesion and apical-basal polarity transition into invasive, individual, mesenchymal cells through a process known as epithelial to mesenchymal transition (EMT). Importantly, cancers with stem cell properties disseminate and form distant metastases by reactivating the developmental EMT program. Recent studies have demonstrated that the epigenetic histone modification, H2BK5 acetylation (H2BK5Ac), is important in the regulation of EMT...
September 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28935466/morphomechanical-and-structural-changes-induced-by-rock-inhibitor-in-breast-cancer-cells
#8
Mariafrancesca Cascione, Valeria De Matteis, Chiara Cristina Toma, Paolo Pellegrino, Stefano Leporatti, Rosaria Rinaldi
The EMT phenomenon is based on tumour progression. The cells lose their physiologic phenotype and assumed a mesenchymal phenotype characterized by an increased migratory capacity, invasiveness and high resistance to apoptosis. In this process, RHO family regulates the activation or suppression of ROCK (Rho-associated coiled-coil containing protein kinase) which in turn regulates the cytoskeleton dynamics. However, while the biochemical mechanisms are widely investigated, a comprehensive and careful estimation of biomechanical changes has not been extensively addressed...
September 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28935391/extracellular-vesicles-released-by-mesenchymal-like-prostate-carcinoma-cells-modulate-emt-state-of-recipient-epithelial-like-carcinoma-cells-through-regulation-of-ar-signaling
#9
Ihsan Y El-Sayed, Ahmad Daher, Damien Destouches, Virginie Firlej, Enis Kostallari, Pascale Maillé, Eric Huet, Nathaline Haidar-Ahmad, Guido Jenster, Alexandre de la Taille, Raghida Abou Merhi, Stéphane Terry, Francis Vacherot
Extracellular vesicles released from cancer cells may play an important role in cancer progression by shuttling oncogenic information into recipient cells. However, our knowledge is still fragmentary and there remain numerous questions regarding the mechanisms at play and the functional consequences of these interactions. We have recently established a mesenchymal-like prostate cancer cell line (22Rv1/CR-1; Mes-PCa). In this study, we assessed the effects of the extracellular vesicles released by these cells on recipient androgen-dependent epithelial VCaP prostate cancer cells...
September 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28934754/cntn-1-enhances-chemoresistance-in-human-lung-adenocarcinoma-through-induction-of-epithelial-mesenchymal-transition-by-targeting-the-pi3k-akt-pathway
#10
Ruijie Zhang, Shenghua Sun, Fuyun Ji, Chun Liu, Hua Lin, Lihua Xie, Honghui Yang, Wenxiang Tang, Yan Zhou, Jianping Xu, Pei Li
BACKGROUND/AIMS: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. METHODS: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28934238/a-tool-to-automatically-analyze-electromagnetic-tracking-data-from-high-dose-rate-brachytherapy-of-breast-cancer-patients
#11
Th I Götz, G Lahmer, V Strnad, Ch Bert, B Hensel, A M Tomé, E W Lang
During High Dose Rate Brachytherapy (HDR-BT) the spatial position of the radiation source inside catheters implanted into a female breast is determined via electromagnetic tracking (EMT). Dwell positions and dwell times of the radiation source are established, relative to the patient's anatomy, from an initial X-ray-CT-image. During the irradiation treatment, catheter displacements can occur due to patient movements. The current study develops an automatic analysis tool of EMT data sets recorded with a solenoid sensor to assure concordance of the source movement with the treatment plan...
2017: PloS One
https://www.readbyqxmd.com/read/28934230/e-cadherin-a-determinant-molecule-associated-with-ovarian-cancer-progression-dissemination-and-aggressiveness
#12
Marina Rosso, Blanca Majem, Laura Devis, Lara Lapyckyj, María José Besso, Marta Llauradó, María Florencia Abascal, María Laura Matos, Lucia Lanau, Josep Castellví, José Luis Sánchez, Asunción Pérez Benavente, Antonio Gil-Moreno, Jaume Reventós, Anna Santamaria Margalef, Marina Rigau, Mónica Hebe Vazquez-Levin
Ovarian cancer (OC) is the fifth cancer death cause in women worldwide. The malignant nature of this disease stems from its unique dissemination pattern. Epithelial-to-mesenchymal transition (EMT) has been reported in OC and downregulation of Epithelial cadherin (E-cadherin) is a hallmark of this process. However, findings on the relationship between E-cadherin levels and OC progression, dissemination and aggressiveness are controversial. In this study, the evaluation of E-cadherin expression in an OC tissue microarray revealed its prognostic value to discriminate between advanced- and early-stage tumors, as well as serous tumors from other histologies...
2017: PloS One
https://www.readbyqxmd.com/read/28931648/targeting-epithelial-mesenchymal-plasticity-in-cancer-clinical-and-preclinical-advances-in-therapy-and-monitoring
#13
REVIEW
Sugandha Bhatia, James Monkman, Alan Kie Leong Toh, Shivashankar H Nagaraj, Erik W Thompson
The concept of epithelial-mesenchymal plasticity (EMP), which describes the dynamic flux within the spectrum of phenotypic states that invasive carcinoma cells may reside, is being increasingly recognised for its role in cancer progression and therapy resistance. The myriad of events that are able to induce EMP, as well as the more recently characterised control loops, results in dynamic transitions of cancerous epithelial cells to more mesenchymal-like phenotypes through an epithelial-mesenchymal transition (EMT), as well as the reverse transition from mesenchymal phenotypes to an epithelial one...
September 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28930565/role-of-fibroblast-growth-factor-receptor-2-splicing-in-normal-and-cancer-cells
#14
Toshiyuki Ishiwata
Types 1-4 of fibroblast growth factor receptors (FGFR) are all expressed in various cancers. Because of its prominent role in carcinogenesis and cancer progression, FGFR-2, is being considered as a novel target in cancer treatment. Owing to the alternative splicing of its extracellular domain, FGFR-2 exists in two variants: IIIb and IIIc. FGFR-2 IIIb is mainly expressed in normal epithelial cells, as well as in oral mucosal, esophageal, gastric, colorectal, pancreatic, pulmonary, breast, endometrial, cervical, and prostate cancers...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28930561/immune-ligands-for-cytotoxic-t-lymphocytes-ctls-in-cancer-stem-cells-cscs
#15
Ioannis A Voutsadakis
   The immune system has come to the forefront of cancer therapeutics in recent years with the success of immune blockade inhibitors in a variety of cancers whose list is increasing with a quick pace. Despite the efficacy of these drugs across a significant part of the cancer spectrum, responses are still seen only in a minority of patients, that implies that most patients are refractory or promptly develop resistance to these agents. Mechanisms of this resistance are important to decipher as this knowledge may lead to the introduction of additional therapies or manipulations to modulate resistance...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28929494/crhr2-ucn2-signaling-is-a-novel-regulator-of-mir-7-yy1-fas-circuitry-contributing-to-reversal-of-colorectal-cancer-cell-resistance-to-fas-mediated-apoptosis
#16
Charalabos Pothoulakis, Monica Torre-Rojas, Marco A Duran-Padilla, Jonathan Gevorkian, Odysseas Zoras, Emmanuel Chrysos, George Chalkiadakis, Stavroula Baritaki
Colorectal cancer (CRC) responds poorly to immuno-mediated cytotoxicity. Underexpression of Corticotropin-releasing-hormone-receptor-2 (CRHR2) in CRC, promotes tumor survival, growth and Epithelial to Mesenchymal Transition (EMT), in vitro and in vivo. We explored the role of CRHR2 downregulation in CRC cell resistance to Fas/FasL-mediated apoptosis and the underlying molecular mechanism. CRC cell sensitivity to CH11-induced apoptosis was compared between Urocortin-2 (Ucn2)-stimulated parental and CRHR2-overexpressing CRC cell lines and targets of CRHR2/Ucn2 signaling were identified through in vitro and ex vivo analyses...
September 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28929255/carbonic-anhydrase-ix-inhibition-affects-viability-of-cancer-cells-adapted-to-extracellular-acidosis
#17
Elena Andreucci, Silvia Peppicelli, Fabrizio Carta, Giulia Brisotto, Eva Biscontin, Jessica Ruzzolini, Francesca Bianchini, Alessio Biagioni, Claudiu T Supuran, Lido Calorini
Among the players of the adaptive response of cancer cells able to promote a resistant and aggressive phenotype, carbonic anhydrase IX (CAIX) recently has emerged as one of the most relevant drug targets. Indeed, CAIX targeting has received a lot of interest, and selective inhibitors are currently under clinical trials. Hypoxia has been identified as the master inductor of CAIX, but, to date, very few is known about the influence that another important characteristic of tumor microenvironment, i.e., extracellular acidosis, exerts on CAIX expression and activity...
September 19, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28928908/epithelial-plasticity-and-cancer-stem-cells-major-mechanisms-of-cancer-pathogenesis-and-therapy-resistance
#18
REVIEW
Minal Garg
Epithelial-mesenchymal transition (EMT) has been linked with aggressive tumor biology and therapy resistance. It plays central role not only in the generation of cancer stem cells (CSCs) but also direct them across the multiple organ systems to promote tumor recurrence and metastasis. CSCs are reported to express stem cell genes as well as specific cell surface markers and allow aberrant differentiation of progenies. It facilitates cancer cells to leave primary tumor, acquire migratory characteristics, grow into new environment and develop radio-chemo-resistance...
August 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28928869/hes1-promotes-colorectal-cancer-cell-resistance-to-5-fu-by-inducing-of-emt-and-abc-transporter-proteins
#19
Lei Sun, Jia Ke, Zhen He, Zexian Chen, Qinghua Huang, Wenjia Ai, Guoqiang Wang, Yisheng Wei, Xiangcai Zou, Shi Zhang, Ping Lan, Chuyuan Hong
Background and Aim: Hairy enhancer of split-1 (HES1) is a downstream transcriptional factor of Notch signaling pathway, which was found to be related to chemoresistance. This study was aimed to investigate the role of HES1 in chemoresistance of colorectal cancer (CRC). Methods: Tissue microarray was used to analyze the clinical significance of HES1 in radical resected (R0) stage II/III CRC patients that received adjuvant chemotherapy. 5-fluorouracil (5-Fu) chemoresistance was examined in CRC cell lines (RKO and HCT8, LOVO) with stable over-expression and inhibition of HES1 gene by cytotoxicity test...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928831/park2-negatively-regulates-the-metastasis-and-epithelial-mesenchymal-transition-of-glioblastoma-cells-via-zeb1
#20
Haiyang Wang, Zhenfeng Jiang, Meng Na, Haitao Ge, Chongyang Tang, Hong Shen, Zhiguo Lin
Glioblastoma multiforme (GBM), one of the most aggressive human malignant brain tumors, is induced by multiple complex pathological mechanisms. The main cause of mortality in patients with GBM is the invasion-metastasis cascade of tumor cells. The dysfunction of Parkinson protein 2 E3 ubiquitin protein ligase (PARK2) is closely linked with the development of certain human cancers. However, whether PARK2 is associated with metastasis in GBM remains unknown. The present study demonstrated that the metastasis and invasion of U87 cells were significantly repressed by PARK2 overexpression...
September 2017: Oncology Letters
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