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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/28938159/lunatic-fringe-and-p53-cooperatively-suppress-mesenchymal-stem-like-breast-cancer
#2
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/28936481/controlling-epithelial-to-mesenchymal-transition-through-acetylation-of-histone-h2bk5
#3
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/28934561/epigenetic-mechanisms-regulating-adaptive-responses-to-targeted-kinase-inhibitors-in-cancer
#4
Steven P Angus, Jon S Zawistowski, Gary L Johnson
Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance...
September 15, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28934230/e-cadherin-a-determinant-molecule-associated-with-ovarian-cancer-progression-dissemination-and-aggressiveness
#5
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/28933990/influence-of-salinomycin-treatment-on-division-and-movement-of-individual-cancer-cells-cultured-in-normoxia-or-hypoxia-evaluated-with-time-lapse-digital-holographic-microscopy
#6
Sofia Kamlund, Daniel Strand, Birgit Janicke, Kersti Alm, Stina Oredsson
Most studies on new cancer drugs are based on population-derived data, where the absence of response of a small population may pass unnoticed. Thus, individual longitudinal tracking of cells is important for the future development of efficient cancer treatments. We have used digital holographic microscopy to track individual JIMT-1 human breast cancer cells and L929 mouse fibroblast cultivated in normoxia or hypoxia. In addition, JIMT-1 cells were treated with salinomycin, a cancer stem cell targeting compound...
September 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28933253/the-role-of-p53-microrna-200-moesin-axis-in-invasion-and-drug-resistance-of-breast-cancer-cells
#7
Farheen Alam, Fatima Mezhal, Hussain El Hasasna, Vidhya A Nair, S R Aravind, Maha Saber Ayad, Ahmed El-Serafi, Wael M Abdel-Rahman
This study aimed to analyze the expression of microRNAs in relation to p53 status in breast cancer cells and to delineate the role of Moesin in this axis. We used three isogenic breast carcinoma cell lines MCF7 (with wild-type p53), 1001 (MCF7 with mutated p53), and MCF7-E6 (MCF7 in which p53 function was disrupted). MicroRNA expression was analyzed using microarray analysis and confirmed by real-time polymerase chain reaction. The 1001 clone with mutant p53 showed 22 upregulated and 25 downregulated microRNAs...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28932171/the-role-of-ppar%C3%AE-and-autophagy-in-ros-production-lipid-droplets-biogenesis-and-its-involvement-with-colorectal-cancer-cells-modulation
#8
José Antonio Fagundes Assumpção, Kelly Grace Magalhães, José Raimundo Corrêa
BACKGROUND: In cancer cells, autophagy can act as both tumor suppressor, when autophagic event eliminates cellular contends which exceeds the cellular capacity of regenerate promoting cell death, and as a pro-survival agent removing defective organelles and proteins and helping well-established tumors to maintain an accelerated metabolic state while still dealing with harsh conditions, such as inflammation. Many pathways can coordinate the autophagic process and one of them involves the transcription factors called PPARs, which also regulate cellular differentiation, proliferation and survival...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28931648/targeting-epithelial-mesenchymal-plasticity-in-cancer-clinical-and-preclinical-advances-in-therapy-and-monitoring
#9
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/28931539/detachment-induced-e-cadherin-expression-promotes-3d-tumor-spheroid-formation-but-inhibits-tumor-formation-and-metastasis-of-lung-cancer-cells
#10
Phattrakorn Powan, Sudjit Luanpitpong, Xiaoqing He, Yon Rojanasakul, Pithi Chanvorachote
The interconversion between epithelial and mesenchymal is proposed to be a key machinery responsible for metastasis-related deaths. Likewise, cancer stem cells (CSCs) have been proposed to be a key driver of tumor metastasis. However, the linkage between the two events and their control mechanisms are unclear. We used a 3D tumor spheroid assay and other CSC-indicating assays to investigate the role of E-cadherin in CSC regulation and its association to epithelial to mesenchymal transition in lung cancer cells...
September 20, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28930684/tumor-derived-mesenchymal-stem-cells-use-distinct-mechanisms-to-block-the-activity-of-natural-killer-cell-subsets
#11
Sabine Galland, Joanna Vuille, Patricia Martin, Igor Letovanec, Anne Caignard, Giulia Fregni, Ivan Stamenkovic
Mesenchymal stem cells (MSCs) display pleiotropic functions, which include secretion of soluble factors with immunosuppressive activity implicated in cancer progression. We compared the immunomodulatory effects on natural killer (NK) cells of paired intratumor (T)- and adjacent non-tumor tissue (N)-derived MSCs from patients with squamous cell lung carcinoma (SCC). We observed that T-MSCs were more strongly immunosuppressive than N-MSCs and affected both NK function and phenotype, as defined by CD56 expression...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930561/immune-ligands-for-cytotoxic-t-lymphocytes-ctls-in-cancer-stem-cells-cscs
#12
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/28928908/epithelial-plasticity-and-cancer-stem-cells-major-mechanisms-of-cancer-pathogenesis-and-therapy-resistance
#13
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/28928657/colocynth-extracts-prevent-epithelial-to-mesenchymal-transition-and-stemness-of-breast-cancer-cells
#14
Kaushik Chowdhury, Ankit Sharma, Suresh Kumar, Gyanesh K Gunjan, Alo Nag, Chandi C Mandal
Modern treatment strategies provide better overall survival in cancer patients, primarily by controlling tumor growth. However, off-target and systemic toxicity, tumor recurrence, and resistance to therapy are still inadvertent hurdles in current treatment regimens. Similarly, metastasis is another deadly threat to patients suffering from cancer. This has created an urgent demand to come up with new drugs having anti-metastatic potential and minimum side effects. Thus, this study was aimed at exploring the anti-proliferative and anti-metastatic potential of colocynth medicinal plant...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28927233/fibroblast-growth-factor-2-mediated-fgfr-erk-signaling-supports-maintenance-of-cancer-stem-like-cells-in-esophageal-squamous-cell-carcinoma
#15
Osamu Maehara, Goki Suda, Mitsuteru Natsuizaka, Shunsuke Ohnishi, Yoshito Komatsu, Fumiyuki Sato, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Tomoe Shimazaki, Megumi Kimura, Ayaka Asano, Yoshiyuki Fujimoto, Shinya Ohashi, Shingo Kagawa, Hideaki Kinugasa, Seiji Naganuma, Kelly A Whelan, Hiroshi Nakagawa, Koji Nakagawa, Hiroshi Takeda, Naoya Sakamoto
In esophageal squamous cell carcinoma (ESCC), a subset of cells defined by high expression of CD44 and low expression of CD24 has been reported to possess characteristics of cancer stem-like cells (CSCs). Novel therapies directly targeting CSCs have the potential to improve prognosis of ESCC patients. Although fibroblast growth factor-2 (FGF-2) expression correlates with recurrence and poor survival in ESCC patients, the role of FGF-2 in regulation of ESCC CSCs has yet to be elucidated. We report that FGF-2 is significantly upregulated in CSCs and significantly increases CSC content in ESCC cell lines by inducing epithelial-mesenchymal transition (EMT)...
September 13, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28927099/interleukin-6-identified-as-an-important-factor-in-hypoxia-and-aldehyde-dehydrogenase-based-gefitinib-adaptive-resistance-in-non-small-cell-lung-cancer-cells
#16
Shi-Min An, Hui-Min Lei, Xu-Ping Ding, Fan Sun, Chun Zhang, Ya-Bin Tang, Hong-Zhuan Chen, Ying Shen, Liang Zhu
Gefitinib resistance and relapse of the disease were the greatest challenges facing clinical therapy of non-small-cell lung cancer (NSCLC). Of note, regarding the hypoxia condition in solid tumor tissues in vivo, roles of hypoxia in gefitinib adaptive resistance and its association with lung cancer stem cells (LCSCs) have not been fully elucidated. In the present study, the role of hypoxia in gefitinib adaptive resistance and its association with aldehyde dehydrogenase (ALDH)-based LCSC gefitinib resistance were comparatively studied using RNA-sequencing (RNA-seq) technology...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926122/stem-cells-and-differentiated-cells-differ-in-their-sensitivity-to-urine-in-vitro
#17
Marta Pokrywczyńska, Tomasz Kloskowski, Daria Balcerczyk, Monika Buhl, Arkadiusz Jundziłł, Maciej Nowacki, Kaja Męcińska-Jundziłł, Tomasz Drewa
INTRODUCTION: Urinary tract regeneration using tissue engineering is one of the most challenging issues in the field of reconstructive urology. Cells seeded on scaffold are exposed to urine immediately after the implantation. The outcome of urinary bladder regeneration is depended on the ability of these cells to survive, proliferate and regenerate. The aim of this study was to compare a sensitivity of three different cell lines to urine in vitro. MATERIAL AND METHODS: Three different cell lines were isolated from porcine bladder (urothelial cells, UCs and smooth muscle cells, SMCs) and adipose tissue (adipose-derived stem cells, ADSCs)...
September 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28925549/biomaterial-substrate-mediated-multicellular-spheroid-formation-and-their-applications-in-tissue-engineering
#18
REVIEW
Ting-Chen Tseng, Chui-Wei Wong, Fu-Yu Hsieh, Shan-Hui Hsu
Three-dimentional (3D) multicellular aggregates (spheroids), compared to the traditional 2D monolayer cultured cells, are physiologically more similar to the cells in vivo. So far there are various techniques to generate 3D spheroids. Spheroids obtained from different methods have already been applied to regenerative medicine or cancer research. Among the cell spheroids created by different methods, the substrate-derived spheroids and their forming mechanism are unique. This review focuses on the formation of biomaterial substrate-mediated multicellular spheroids and their applications in tissue engineering and tumor models...
September 19, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28922619/identification-of-angiogenesis-inhibitors-using-a-co-culture-cell-model-in-a-high-content-and-high-throughput-screening-platform
#19
Shuaizhang Li, Chia-Wen Hsu, Srilatha Sakamuru, Chaozhong Zou, Ruili Huang, Menghang Xia
Angiogenesis is an important hallmark of cancer, contributing to tumor formation and metastasis. In vitro angiogenesis models for analyzing tube formation serve as useful tools to study these processes. However, current in vitro co-culture models using primary cells have limitations in usefulness and consistency. Therefore, in the present study, an in vitro co-culture assay system was optimized in a 1536-well format for high-throughput screening using human telomerase reverse transcriptase (hTERT)-immortalized mesenchymal stem cells and aortic endothelial cells...
September 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28921309/lung-cancer-associated-brain-metastasis-molecular-mechanisms-and-therapeutic-options
#20
REVIEW
Meysam Yousefi, Tayyeb Bahrami, Arash Salmaninejad, Rahim Nosrati, Parisa Ghaffari, Seyed H Ghaffari
BACKGROUND: Lung cancer is the most common cause of cancer-related mortality in humans. There are several reasons for this high rate of mortality, including metastasis to several organs, especially the brain. In fact, lung cancer is responsible for approximately 50% of all brain metastases, which are very difficult to manage. Understanding the cellular and molecular mechanisms underlying lung cancer-associated brain metastasis brings up novel therapeutic promises with the hope to ameliorate the severity of the disease...
September 18, 2017: Cellular Oncology (Dordrecht)
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