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https://www.readbyqxmd.com/read/27935869/the-involvement-of-bcl-2-family-proteins-in-akt-regulated-cell-survival-in-cisplatin-resistant-epithelial-ovarian-cancer
#1
Yan Dai, Shiguang Jin, Xueping Li, Daxin Wang
Many studies involving patients with cisplatin-resistant ovarian cancer have shown that AKT activation leads to inhibition of apoptosis. The aim of this study was to examine the potential involvement of the Bcl-2 family proteins in AKT-regulated cell survival in response to cisplatin treatment. Cisplatin-sensitive (PEO1) and cisplatin-resistant (PEO4) cells were taken from ascites of patients with ovarian cancer before cisplatin treatment and after development of chemoresistance. It was found that cisplatin treatment activated the AKT signaling pathway and promoted cell proliferation in cisplatin-resistant EOC cells...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935336/rrx-001-a-systemically-non-toxic-m2-to-m1-macrophage-stimulating-and-prosensitizing-agent-in-phase-ii-clinical-trials
#2
Bryan Oronsky, Ramasamy Paulmurugan, Kira Foygel, Jan Scicinski, Susan J Knox, Donna Peehl, Hongjuan Zhao, Shoucheng Ning, Pedro Cabrales, Thomas A Summers, Tony R Reid, William L Fitch, Michelle M Kim, Jane B Trepel, Min-Jung Lee, Santosh Kesari, Nacer D Abrouk, Regina M Day, Arnold Oronsky, Carolyn M Ray, Corey A Carter
According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: 1) self-sufficiency in growth signals, 2) insensitivity to growth-inhibitory signals, 3) evasion of programmed cell death, 4) limitless replicative potential, 5) sustained angiogenesis, and 6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes...
December 9, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27934900/corrigendum-pak1-confers-chemoresistance-and-poor-outcome-in-non-small-cell-lung-cancer-via-%C3%AE-catenin-mediated-stemness
#3
Ming-Jenn Chen, De-Wei Wu, Yao-Chen Wang, Chi-Yi Chen, Huei Lee
No abstract text is available yet for this article.
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27933604/chemoresistant-lung-cancer-stem-cells-display-high-dna-repair-capability-to-remove-cisplatin-dna-damage
#4
Wai-Kin Yu, Zhigang Wang, Chi-Chun Fong, Dandan Liu, Tak-Chun Yip, Siu-Kie Au, Guangyu Zhu, Mengsu Yang
BACKGROUND AND PURPOSE: The persistence of lung cancer stem cells (LCSCs) has been proposed to be the main factor of lung cancer recurrence due to their high resistance to conventional chemotherapy. The underlying mechanisms, however, have not been fully addressed. EXPERIMENTAL APPROACH: In this study, we examined the cellular response of a human lung cancer stem cell line upon treatment with cisplatin, a DNA-damaging anticancer drug that is extensively applied in clinics...
December 9, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27929731/autophagic-homeostasis-is-required-for-the-pluripotency-of-cancer-stem-cells
#5
Tanveer Sharif, Emma Martell, Cathleen Dai, Barry E Kennedy, Patrick Murphy, Derek Clements, Youra Kim, Patrick W K Lee, Shashi Gujar
Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate limiting enzyme in the NAD(+) synthesis pathway NAMPT (nicotinamide phosphoribosyltransferase) and the transcription factor POU5F1/OCT4 (POU class 5 homeobox 1)...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27929538/downregulation-of-aspp2-improves-hepatocellular-carcinoma-cells-survival-via-promoting-becn1-dependent-autophagy-initiation
#6
Rui Chen, Hao Wang, Beibei Liang, Guoke Liu, Min Tang, Rongjie Jia, Xiaoyu Fan, Wei Jing, Xuyu Zhou, Huajing Wang, Yang Yang, Huafeng Wei, Bohua Li, Jian Zhao
Autophagy is an important catabolic process, which sustains intracellular homeostasis and lengthens cell survival under stress. Here we identify the ankyrin-repeat-containing, SH3-domain-containing, and proline-rich region-containing protein 2 (ASPP2), a haploinsufficient tumor suppressor, as a molecular regulator of starvation-induced autophagy in hepatocellular carcinoma (HCC). ASPP2 expression is associated with an autophagic response upon nutrient deprivation and downregulation of ASPP2 facilitates autophagic flux, whereas overexpression of ASPP2 blocks this starvation-induced autophagy in HCC cells...
December 8, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27926520/inhibiting-the-mnk-eif4e-%C3%AE-catenin-axis-increases-the-responsiveness-of-aggressive-breast-cancer-cells-to-chemotherapy
#7
Zhiqiang Li, Yang Sun, Miao Qu, Hongxing Wan, Fang Cai, Peng Zhang
Advanced breast cancer (eg. stage IV) is resistant to chemotherapy. In this work, we identified potentially druggable targets that are critically involved in chemoresistance. We showed that eIF4E is highly phosphorylated at serine 209 in breast cancer patients in response to chemotherapy, which significantly correlated with poorer clinical responses and outcomes. Depletion of eIF4E enhanced the anti-proliferative and pro-apoptotic effects of chemotherapeutic drugs in breast cancer cells. Chemotherapy activated the Wnt/β-catenin signaling in an eIF4E-dependent manner...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925198/cancer-cell-plasticity-rapid-reversal-of-chemosensitivity-and-expression-of-stemness-markers-in-lung-and-breast-cancer-tumorspheres
#8
Juan Sebastian Yakisich, Neelam Azad, Vivek Kaushik, Anand Krishnan V Iyer
In cancer cells, the reversible nature of the stemness status in terms of chemoresistance has been poorly characterized. In this study, we have simulated on cycle of environmental conditions to study such reversibility by first generating floating tumorspheres (FTs) from lung and breast cancer cells by culturing them in serum-free media without the addition of any external mitogenic stimulation, and subsequently (after two weeks) re-incubating them back in serum-containing media to simulate routine culture conditions (RCCs)...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924308/ph-sensitive-pt-nanocluster-assembly-overcomes-cisplatin-resistance-and-heterogeneous-stemness-of-hepatocellular-carcinoma
#9
Hongping Xia, Fangyuan Li, Xi Hu, Wooram Park, Shuaifei Wang, Youngjin Jang, Yang Du, Seungmin Baik, Soojeong Cho, Taegyu Kang, Dong-Hyun Kim, Daishun Ling, Kam Man Hui, Taeghwan Hyeon
Response rates to conventional chemotherapeutics remain unsatisfactory for hepatocellular carcinoma (HCC) due to the high rates of chemoresistance and recurrence. Tumor-initiating cancer stem-like cells (CSLCs) are refractory to chemotherapy, and their enrichment leads to subsequent development of chemoresistance and recurrence. To overcome the chemoresistance and stemness in HCC, we synthesized a Pt nanocluster assembly (Pt-NA) composed of assembled Pt nanoclusters incorporating a pH-sensitive polymer and HCC-targeting peptide...
November 23, 2016: ACS Central Science
https://www.readbyqxmd.com/read/27923654/zeb1-is-neither-sufficient-nor-required-for-epithelial-mesenchymal-transition-in-ls174t-colorectal-cancer-cells
#10
Sabine Jägle, Annika Dertmann, Monika Schrempp, Andreas Hecht
Epithelial-mesenchymal transition (EMT) is implicated in metastases formation and acquired therapy resistance in several tumor entities. The two transcription factors SNAIL1 and ZEB1 are thought to be master regulators of EMT and to form a core regulatory network required for EMT-associated transcriptional reprogramming. Yet, inducible EMT models show the sequential upregulation first of SNAIL1 and only subsequently of ZEB1. Therefore, SNAIL1 and ZEB1 might be differentially needed for the onset and propagation of EMT...
December 3, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27922681/cxcr4-promotes-cisplatin-resistance-of-non-small-cell-lung-cancer-in-a-cyp1b1-dependent-manner
#11
Songping Xie, Zhenbo Tu, Jie Xiong, Ganjun Kang, Lina Zhao, Weidong Hu, Haiyan Tan, Kingsley Miyanda Tembo, Qianshan Ding, Xinzhou Deng, Jie Huang, Qiuping Zhang
Chemoresistance is the main cause of treatment failure and high mortality in advanced lung cancer. Cisplatin, an important chemotherapeutic agent for lung cancer, has been observed to show enormously reduced chemotherapeutic efficacy owing to the development of chemoresistance. CXCR4, a stromal-derived-factor-1 specific chemokine receptor, is highly expressed in non-small cell lung cancer (NSCLC) tissues and participates in cancer progression by regulating cell growth, apoptosis or invasion. In this study, we therefore investigated whether CXCR4 plays a role in the cisplatin associated resistance in NSCLC...
December 2, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27922075/cancer-associated-fibroblasts-treated-with-cisplatin-facilitates-chemoresistance-of-lung-adenocarcinoma-through-il-11-il-11r-stat3-signaling-pathway
#12
Leilei Tao, Guichun Huang, Rui Wang, Yan Pan, Zhenyue He, Xiaoyuan Chu, Haizhu Song, Longbang Chen
Cancer-associated fibroblasts (CAF) are recognized as one of the key determinants in the malignant progression of lung adenocarcinoma. And its contributions to chemoresistance acquisition of lung cancer has raised more and more attention. In our study, cancer associated fibroblasts treated with cisplatin conferred chemoresistance to lung cancer cells. Meanwhile, Interleukin-11(IL-11) was significantly up-regulated in the CAF stimulated by cisplatin. As confirmed in lung adenocarcinoma cells in vivo and in vitro, IL-11 could protect cancer cells from cisplatin-induced apoptosis and thus promote their chemoresistance...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920054/researchers-find-new-chemoresistance-mechanism-in-brca-deficient-tumors
#13
Vijay Shankar Balakrishnan
No abstract text is available yet for this article.
November 2016: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27919951/rho-associated-protein-kinase-rock-inhibitors-inhibit-survivin-expression-and-sensitize-pancreatic-cancer-stem-cells-to-gemcitabine
#14
Hiroyuki Takeda, Masashi Okada, Shuhei Suzuki, Kenta Kuramoto, Hirotsugu Sakaki, Hikaru Watarai, Tomomi Sanomachi, Shizuka Seino, Takashi Yoshioka, Chifumi Kitanaka
BACKGROUND: Targeting pathways regulating survivin expression, which has been implicated in multidrug resistance of cancer cells, is a promising strategy to overcome cancer chemoresistance. To date, the role of rho-associated protein kinases (ROCKs) in survivin expression remains largely unknown. MATERIALS AND METHODS: The effects of ROCK inhibitors Y-27632 and fasudil on survivin expression and cell viability were determined by immunoblot analysis and dye exclusion, respectively, in PANC-1 CSLC, a cancer stem cell line derived from a serum-cultured, gemcitabine-sensitive pancreatic cancer cell line, PANC-1...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919680/aldh1a1-induces-resistance-to-chop-in-diffuse-large-b-cell-lymphoma-through-activation-of-the-jak2-stat3-pathway
#15
Jinqiong Jiang, Yiping Liu, Youhong Tang, Li Li, Ruolan Zeng, Shan Zeng, Meizuo Zhong
Although the majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), chemoresistance is a common cause of treatment failure. This study aims to investigate the significance of aldehyde dehydrogenase (ALDH) 1A1 expression and the mechanism by which ALDH1A1 is involved in chemoresistance of DLBCL cells. ALDH1A1 expression levels were upregulated in patients with stable or progressive disease after CHOP treatment and positively correlated with expression of STAT3 and p-STAT3...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27919217/drug-delivery-nanoparticles-in-treating-chemoresistant-tumor-cells
#16
Giuseppina Barrera, Martina Daga, Benedetta Ferrara, Chiara Dianzani, Stefania Pizzimenti, Monica Argenziano, Roberta Cavalli, Francesco Trotta
Intrinsic or acquired chemoresistance represents the main obstacle to the successful treatment of cancer patients. Several mechanisms are involved in multidrug resistance: decreased uptake of hydrophilic drugs, increase of energy dependent efflux, alteration of the redox state, alteration of apoptotic pathways, and modification of the tumor microenvironment. In recent years, several types of nanoparticles have been developed to overcome these obstacles and improve the accumulation and release of drugs at the pathological site...
December 5, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27916693/comparison-of-2-strategies-to-enhance-pyridoclax-solubility-nanoemulsion-delivery-system-versus-salt-synthesis
#17
A-C Groo, M De Pascale, A-S Voisin-Chiret, S Corvaisier, M Since, A Malzert-Fréon
Pyridoclax is an original oligopyridine lead, very promising in treatment of chemoresistant cancers. However, from solubility measurement and permeability evaluation, it appeared that this compound can be considered as a BCS II drug, with a poor water solubility. To overcome this unfavorable property, two strategies were proposed and compared: pyridoclax di-hydrochloride salt synthesis and formulation of pyridoclax-loaded nanoemulsions (PNEs) efficiently performed by transposing the spontaneous emulsification process previously developed by our team...
December 1, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27916539/inhibiting-the-sumo-pathway-represses-the-cancer-stem-cell-population-in-breast-and-colorectal-carcinomas
#18
Maria V Bogachek, Jung M Park, James P De Andrade, Allison W Lorenzen, Mikhail V Kulak, Jeffrey R White, Vivian W Gu, Vincent T Wu, Ronald J Weigel
Many solid cancers have an expanded CD44(+/hi)/CD24(-/low) cancer stem cell (CSC) population, which are relatively chemoresistant and drive recurrence and metastasis. Achieving a more durable response requires the development of therapies that specifically target CSCs. Recent evidence indicated that inhibiting the SUMO pathway repressed tumor growth and invasiveness, although the mechanism has yet to be clarified. Here, we demonstrate that inhibition of the SUMO pathway repressed MMP14 and CD44 with a concomitant reduction in cell invasiveness and functional loss of CSCs in basal breast cancer...
November 24, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27916347/new-treatment-strategy-with-nuclear-factor-%C3%AE%C2%BAb-inhibitor-for-pancreatic-cancer
#19
Takashi Horiuchi, Tadashi Uwagawa, Yoshihiro Shirai, Nobuhiro Saito, Ryota Iwase, Koichiro Haruki, Hiroaki Shiba, Toya Ohashi, Katsuhiko Yanaga
BACKGROUND: Because of difficulties with early diagnosis, most patients with pancreatic cancer receive chemotherapy. The National Comprehensive Cancer Network guidelines (version 2.2015) suggest therapy with gemcitabine (GEM) plus nab-paclitaxel (nPTX) as a category 1 recommendation for metastatic pancreatic ductal adenocarcinoma. According to the results of many studies, the activation of chemotherapeutic agents-induced nuclear factor-κB (NF-κB) causes chemoresistance. Hence, we hypothesized that the addition of nafamostat mesilate (NM), a potent NF-κB inhibitor, to GEM/nPTX therapy could enhance the antitumor effect in the treatment of pancreatic ductal adenocarcinoma...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27913491/prognostic-factors-in-follicular-lymphoma-new-tools-to-personalize-risk
#20
Carla Casulo
Follicular lymphoma (FL) is the most common indolent lymphoma, and it has a long median overall survival (OS). However, the recent discovery of clinical and biological prognostic biomarkers in FL is shedding light on FL heterogeneity and the need for a precise and risk-stratified individual approach at diagnosis and relapse. Many FL patients who are asymptomatic with indolent disease can be vulnerable to the toxicity, emotional distress, and financial burden of overtreatment. Yet a subset of FL patients develop chemoresistance to standard chemoimmunotherapy, experience transformation to aggressive lymphoma and rapid progression, and represent the population most in need of novel therapies and curative approaches...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
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