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Autophagy and chemoresistance

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https://www.readbyqxmd.com/read/28537902/endoplasmic-reticulum-stress-promotes-autophagy-and-apoptosis-and-reverses-chemoresistance-in-human-ovarian-cancer-cells
#1
Jin-Long Hu, Xin-Long Hu, Ai-Ye Guo, Chao-Jie Wang, Yi-Yang Wen, Shun-Dong Cang
Ovarian cancer presents the highest mortality rate among gynecological tumors. Here, we measured cell viability, proliferation, apoptosis, autophagy, and expression of endoplasmic reticulum stress (ERS)-related proteins, PI3K/AKT/mTOR pathway-related proteins, and apoptosis- and autophagy-related proteins in SKOV3 and SKOV3/CDDP cells treated with combinations of CDDP, tunicamycin, and BEZ235 (blank control, CDDP, CDDP + tunicamycin, CDDP + BEZ235, and CDDP + tunicamycin + BEZ235). Increasing concentrations of tunicamycin and CDDP activated ERS in SKOV3 cells, reduced cell viability and proliferation, increased apoptosis and autophagy, enhanced expression of ERS-related proteins, and inhibited expression of PI3K/AKT/mTOR pathway-related proteins...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534965/cucurbitacin%C3%A2-b-induces-autophagy-and-apoptosis-by-suppressing-cip2a-pp2a-mtorc1-signaling-axis-in-human-cisplatin-resistant-gastric-cancer-cells
#2
Xuewen Liu, Chao Duan, Juanli Ji, Te Zhang, Xiaoning Yuan, Yunfei Zhang, Wenjing Ma, Jingyuan Yang, Linsen Yang, Zhiguo Jiang, Huiliang Yu, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of tumors including gastric cancer (GC). Mammalian target of rapamycin complex 1 (mTORC1) over-activation is detected in GC and many other cancers. Previous study found that CIP2A/mTORC1 controls cell growth and autophagy through direct association. CIP2A plays an 'oncogenic nexus' in several cancer types to participate in the tumorigenic transformation and chemoresistance. In the present study, we investigated whether Cucurbitacin B (CuB), a natural compound found in Cucurbitaceae, can be used in cisplatin (DDP)-resistant human GC cell line SGC7901/DDP...
May 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28529574/knockdown-of-stmn1-enhances-osteosarcoma-cell-chemosensitivity-through-inhibition-of-autophagy
#3
Zili Wang, Rongzhen He, Hansong Xia, Yu Wei, Song Wu
Chemoresistance is a major cause for the poor prognosis of osteosarcoma (OS) patients. However, our understanding of mechanisms underlying chemoresistance in OS are limited. The present study aimed to investigate the effect of stathmin 1 (STMN1) on paclitaxel-induced chemoresistance, as well as the underlying mechanism. Western blot analysis data revealed that the expression level of STMN1 was dramatically increased in OS cell lines (HOS, Saos-2, U-2OS and MG-63), when compared to normal osteoblast hFOB1.19 cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28528979/sensitization-of-breast-cancer-cells-to-paclitaxel-by-dichloroacetate-through-inhibiting-autophagy
#4
Minghao Wang, Cuiwei Liao, Ying Hu, Wenqin Pan, Jun Jiang
Chemotherapy is still the main adjuvant strategy in the treatment of cancer, however, chemoresistance is also frequently encountered. Autophagy inhibition has been widely accepted as a promising therapeutic strategy in cancer, while the lack of effective and specific autophagy inhibitors hinders its application. Here we found that dichloroacetate (DCA), a small molecule compound, could significantly inhibit the autophagy induced by Doxorubicin in breast cancer cells. And DCA markedly enhances Doxorubicin-induced breast cancer cell death and anti-proliferation in vitro...
May 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28527723/activation-of-nrf2-signaling-augments-vesicular-stomatitis-virus-oncolysis-via-autophagy-driven-suppression-of-antiviral-immunity
#5
David Olagnier, Rassin R Lababidi, Samar Bel Hadj, Alexandre Sze, Yiliu Liu, Sharadha Dayalan Naidu, Matteo Ferrari, Yuan Jiang, Cindy Chiang, Vladimir Beljanski, Marie-Line Goulet, Elena V Knatko, Albena T Dinkova-Kostova, John Hiscott, Rongtuan Lin
Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28514219/science-to-practice-killing-dormant-cells-is-targeting-autophagy-the-key-to-complete-tumor-response-in-transarterial-chemoembolization
#6
Lynn Jeanette Savic, Julius Chapiro, Jean-François Geschwind
In this issue of Radiology, Gade et al ( 1 ) describe a unique mechanism of hepatocellular carcinoma (HCC) cells for surviving ischemia induced by transarterial embolization (TAE)/transarterial chemoembolization (TACE) in a state of cell cycle arrest-a function that may serve as a defensive shield against conventional chemotherapeutic agents. This finding adds to our knowledge and establishes a previously poorly understood mechanism of chemoresistance in HCC. As the Achilles heel in terms of this process, a concurrent upregulation of autophagic flux as an adaptive response to TAE-like ischemia was found by the authors...
June 2017: Radiology
https://www.readbyqxmd.com/read/28514207/circadian-gene-clock-affects-drug-resistant-gene-expression-and-cell-proliferation-in-ovarian-cancer-skov3-ddp-cell-lines-through-autophagy
#7
Yang Sun, Long Jin, Yu-Xia Sui, Li-Li Han, Jia-Hua Liu
Abnormal autophagy regulation affects the chemoresistance of ovarian cancer, during which the circadian gene clock may play a major role. In this study, RNA interference plasmid pSUPER-Clock and overexpression plasmid pcDNA3.1-Clock of CLOCK were used to stably transfect the SKOV3/DDP cells by lipofection. Upon screening, the in vitro transfected cell lines with pSUPER-Clock, the autophagy level, and G0/G1 phase cells were significantly reduced, and the expression levels of Clock, LC3, P-gp, and MRP2 were inhibited...
May 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28499919/long-non-coding-rna-ac023115-3-suppresses-chemoresistance-of-glioblastoma-by-reducing-autophagy
#8
Binbin Ma, Zhongbo Yuan, Li Zhang, Peng Lv, Ting Yang, Jinxia Gao, Ning Pan, Qiong Wu, Jiacheng Lou, Chuanchun Han, Bo Zhang
Malignant glioma is an aggressive brain cancer that responds poorly to chemotherapy. However, the molecular mechanism underlying the development of chemoresistance in glioma is not well-understood. In this study, we show that long non-coding RNA AC023115.3 is induced by cisplatin in human glioblastoma cells and that elevated AC023115.3 promotes cisplatin-induced apoptosis by inhibiting autophagy. Further mechanistic studies revealed that AC023115.3 acts as a competing endogenous RNA for miR-26a and attenuates the inhibitory effect of miR-26a on GSK3β, a proline-directed serine-threonine kinase that promotes the degradation of Mcl1, leading to an increase in GSK3β and a decrease in autophagy...
May 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28445132/targeting-autophagic-cancer-stem-cells-to-reverse-chemoresistance-in-human-triple-negative-breast-cancer
#9
Guilhem Bousquet, Morad El Bouchtaoui, Tan Sophie, Christophe Leboeuf, Cédric de Bazelaire, Philippe Ratajczak, Sylvie Giacchetti, Anne de Roquancourt, Philippe Bertheau, Laurence Verneuil, Jean-Paul Feugeas, Marc Espié, Anne Janin
There is growing evidence for the role of cancer stem-cells in drug resistance, but with few in situ studies on human tumor samples to decipher the mechanisms by which they resist anticancer agents.Triple negative breast cancer (TNBC) is the most severe sub-type of breast cancer, occurring in younger women and associated with poor prognosis even when treated at a localized stage.We investigated here the relationship between complete pathological response after chemotherapy and breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women with triple negative breast carcinoma (TNBC)...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431397/sensitization-of-tamoxifen-resistant-breast-cancer-cells-by-z-ligustilide-through-inhibiting-autophagy-and-accumulating-dna-damages
#10
Hongyi Qi, Zhuyun Jiang, Chengqiang Wang, Yi Yang, Li Li, Hui He, Zanyang Yu
Autophagy plays a pro-survival role in the tamoxifen-resistant breast cancer cells. Herein we found that autophagy was concomitantly induced in tamoxifen-resistant MCF-7 (MCF-7TR5) cells through the dissociation of Bcl-2 from Beclin 1 and subsequent enhancement of interaction among the ATG14-Beclin1-PI3KC3 complex. Moreover, higher level of DNA damage was observed in MCF-7TR5 cells with the decreased BRCA1 and RAD51 level and the increased Ku80 level. Interestingly, Nur77 was selectively degraded by autophagy, which causes the release of Ku80 from the Nur77-Ku80 complex, resulting in the increase of the DNA binding of Ku80 and DNA-PKcs...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415557/long-non-coding-rna-cta-sensitizes-osteosarcoma-cells-to-doxorubicin-through-inhibition-of-autophagy
#11
Zhengguang Wang, Zhendong Liu, Song Wu
Recently, several long non-coding RNAs (lncRNAs) have been implicated in osteosarcoma (OS). However, the regulatory roles of lncRNAs in chemotherapy resistance of OS still remain unclear. This study aimed to screen a novel lncRNA that contributes to chemotherapeutic resistance of OS, and to explore the underlying mechanisms. Our data showed that lncRNA CTA was markedly downregulated in OS tissues compared to their matched non-tumor tissues, and low expression of lncRNA CTA was significantly associated with the advanced clinical stage and tumor size...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408137/4-acetylantroquinonol-b-suppresses-autophagic-flux-and-improves-cisplatin-sensitivity-in-highly-aggressive-epithelial-cancer-through-the-pi3k-akt-mtor-p70s6k-signaling-pathway
#12
Mingche Liu, Oluwaseun Adebayo Bamodu, Wen-Chien Huang, Muhammad Ary Zucha, Yen-Kuang Lin, Alexander T H Wu, Chun-Chih Huang, Wei-Hwa Lee, Chiou-Chung Yuan, M Hsiao, Li Deng, Yew-Min Tzeng, Chi-Tai Yeh
Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg)...
April 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28404910/thalidezine-a-novel-ampk-activator-eliminates-apoptosis-resistant-cancer-cells-through-energy-mediated-autophagic-cell-death
#13
Betty Yuen Kwan Law, Flora Gordillo-Martínez, Yuan Qing Qu, Ni Zhang, Su Wei Xu, Paolo Saul Coghi, Simon Wing Fai Mok, Jianru Guo, Wei Zhang, Elaine Lai Han Leung, Xing Xing Fan, An Guo Wu, Wai Kit Chan, Xiao Jun Yao, Jing Rong Wang, Liang Liu, Vincent Kam Wai Wong
Cancers illustrating resistance towards apoptosis is one of the main factors causing clinical failure of conventional chemotherapy. Innovative therapeutic methods which can overcome the non-apoptotic phenotype are needed. The AMP-activated protein kinase (AMPK) is the central regulator of cellular energy homeostasis, metabolism, and autophagy. Our previous study showed that the identified natural AMPK activator is able to overcome apoptosis-resistant cancer via autophagic cell death. Therefore, AMPK is an ideal pharmaceutical target for chemoresistant cancers...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28382796/inhibition-of-autophagy-protein-lc3a-as-a-therapeutic-target-in-ovarian-clear-cell-carcinomas
#14
Morikazu Miyamoto, Masashi Takano, Tadashi Aoyama, Hiroaki Soyama, Tomoyuki Yoshikawa, Hitoshi Tsuda, Kenichi Furuya
OBJECTIVE: Ovarian clear cell carcinoma (CCC) is one of histological subtypes showing poor prognosis due to chemoresistance. The association of autophagy-related proteins and clinical implementation in CCC has not been determined. METHODS: The present study investigated whether expression of autophagy-related protein, light chain 3A (LC3A), was related with prognoses in the patients with CCC using immuno-histochemical stainings, and whether inhibition of autophagy modified the sensitivity to cisplatin in CCC cells in vitro...
May 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/28375488/a-combination-of-pterostilbene-with-autophagy-inhibitors-exerts-efficient-apoptotic-characteristics-in-both-chemosensitive-and-chemoresistant-lung-cancer-cells
#15
Ming-Ju Hsieh, Chiao-Wen Lin, Shun-Fa Yang, Gwo-Tarng Sheu, Ya-Yen Yu, Mu-Kuan Chen, Hui-Ling Chiou
No abstract text is available yet for this article.
April 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28373437/salinomycin-induces-reactive-oxygen-species-and-apoptosis-in-aggressive-breast-cancer-cells-as-mediated-with-regulation-of-autophagy
#16
Kwang-Youn Kim, Kwang Il Park, Sang-Hun Kim, Sun-Nyoung Yu, Deokjae Lee, Young Woo Kim, Kyung Tae Noh, Jin Yeul Ma, Young-Kyo Seo, Soon-Cheol Ahn
BACKGROUND/AIM: Chemotherapy is a critical option for cancer treatment. However, consistent exposure to chemotherapeutic drugs promotes chemoresistance in cancer cells through diverse mechanisms. Accordingly, we investigated whether salinomycin, a monocarboxylic ionophore, could induce apoptosis in aggressive breast cancer cells or not, as well as its underlying mechanism. MATERIALS AND METHODS: Using salinomycin on two breast cancer cell lines, MCF-7 cells and MDA-MB-231 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, caspase-3/9 activity, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assayed...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28356957/autophagy-impacts-on-oxaliplatin-induced-hepatocarcinoma-apoptosis-via-the-il-17-il-17r-jak2-stat3-signaling-pathway
#17
Jinghua Wu, Jiapei Guo, Qing Cao, Yi Wang, Junmao Chen, Zhigang Wang, Zhiyong Yuan
The interleukin (IL)-17/IL-17 receptor (IL-17R) complex has been shown to be important for the regulation of inflammation; however, its role in the regulation of tumor processes has recently emerged as a research focus. The present study demonstrated that oxaliplatin was able to increase the levels of IL-17/IL-17R in hepatocellular carcinoma (HCC) patients and cells lines, and that it had important roles in reducing the susceptibility of the cells to oxaliplatin-induced apoptosis. Furthermore, the expression of autophagy-related proteins was induced by IL-17/IL-17R and autophagy was shown to induce resistance to oxaliplatin in HCC...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28351381/the-role-of-stromal-cancer-associated-fibroblasts-in-pancreatic-cancer
#18
REVIEW
Dagny von Ahrens, Tushar D Bhagat, Deepak Nagrath, Anirban Maitra, Amit Verma
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer generally refractory to conventional treatments. Cancer-associated fibroblasts (CAFs) are cellular components of the desmoplastic stroma characteristic to the tumor that contributes to this treatment resistance. Various markers for CAFs have been explored including palladin and CD146 that have prognostic and functional roles in the pathobiology of PDAC. Mechanisms of CAF-tumor cell interaction have been described including exosomal transfer and paracrine signaling mediated by cytokines such as GM-CSF and IL-6...
March 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28349991/antiproliferative-effects-of-ruthenium-based-nucleolipidic-nanoaggregates-in-human-models-of-breast-cancer-in-vitro-insights-into-their-mode-of-action
#19
Carlo Irace, Gabriella Misso, Antonella Capuozzo, Marialuisa Piccolo, Claudia Riccardi, Alessandra Luchini, Michele Caraglia, Luigi Paduano, Daniela Montesarchio, Rita Santamaria
Looking for new metal-based anticancer treatments, in recent years many ruthenium complexes have been proposed as effective and safe potential drugs. In this context we have recently developed a novel approach for the in vivo delivery of Ru(III) complexes, preparing stable ruthenium-based nucleolipidic nanoaggregates endowed with significant antiproliferative activity. Herein we describe the cellular response to our ruthenium-containing formulations in selected models of human breast cancer. By in vitro bioscreens in the context of preclinical studies, we have focused on their ability to inhibit breast cancer cell proliferation by the activation of the intrinsic apoptotic pathway, possibly via mitochondrial perturbations involving Bcl-2 family members and predisposing to programmed cell death...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28347245/cancer-stem-cells-the-potential-role-of-autophagy-proteolysis-and-cathepsins-in-glioblastoma-stem-cells
#20
REVIEW
Joachim Bischof, Mike-Andrew Westhoff, Johanna Elisabeth Wagner, Marc-Eric Halatsch, Stephanie Trentmann, Uwe Knippschild, Christian Rainer Wirtz, Timo Burster
One major obstacle in cancer therapy is chemoresistance leading to tumor recurrence and metastasis. Cancer stem cells, in particular glioblastoma stem cells, are highly resistant to chemotherapy, radiation, and immune recognition. In case of immune recognition, several survival mechanisms including, regulation of autophagy, proteases, and cell surface major histocompatibility complex class I molecules, are found in glioblastoma stem cells. In different pathways, cathepsins play a crucial role in processing functional proteins that are necessary for several processes and proper cell function...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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