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Autophagy and chemotherapy resistance

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https://www.readbyqxmd.com/read/28454274/role-of-endoplasmic-reticulum-stress-on-cisplatin-resistance-in-ovarian-carcinoma
#1
Jing Tian, Rong Liu, Quanxin Qu
Endoplasmic reticulum (ER) is an essential site of cellular homeostasis regulation. ER stress (ERS) may induce autophagy in tumor cells that escape from apoptosis. The present study examined the effects and mechanism of ERS on cisplatin (DDP) sensitivity in ovarian carcinoma. SKOV3 tumor cells treated with Saquinavir were subjected to western blot and reverse transcription-quantitative polymerase chain reaction analysis to determine protein and messenger RNA (mRNA) expression levels of mechanistic target of rapamycin (mTOR) and Beclin 1...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28445132/targeting-autophagic-cancer-stem-cells-to-reverse-chemoresistance-in-human-triple-negative-breast-cancer
#2
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)...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28438108/17-aag-and-apoptosis-autophagy-and-mitophagy-in-canine-osteosarcoma-cell-lines
#3
M Massimini, C Palmieri, R De Maria, M Romanucci, D Malatesta, M De Martinis, L Maniscalco, A Ciccarelli, L Ginaldi, P Buracco, L Bongiovanni, L Della Salda
Canine osteosarcoma is highly resistant to current chemotherapy; thus, clarifying the mechanisms of tumor cell resistance to treatments is an urgent need. We tested the geldanamycin derivative 17-AAG (17-allylamino-17-demethoxygeldanamycin) prototype of Hsp90 (heat shock protein 90) inhibitors in 2 canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic tumors, respectively. With the aim to understand the interplay between cell death, autophagy, and mitophagy, in light of the dual effect of autophagy in regulating cancer cell viability and death, D22 and D17 cells were treated with different concentrations of 17-AAG (0...
May 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28433739/dual-functional-drug-liposomes-in-treatment-of-resistant-cancers
#4
REVIEW
Li-Min Mu, Rui-Jun Ju, Rui Liu, Ying-Zi Bu, Jing-Ying Zhang, Xue-Qi Li, Fan Zeng, Wan-Liang Lu
Efficacy of regular chemotherapy is significantly hampered by multidrug resistance (MDR) and severe systemic toxicity. The reduced toxicity has been evidenced after administration of drug liposomes, consisting of the first generation of regular drug liposomes, the second generation of long-circulation drug liposomes, and the third generation of targeting drug liposomes. However, MDR of cancers remains as an unsolved issue. The objectives of this article are to review the dual-functional drug liposomes, which demonstrate the potential in overcoming MDR...
April 19, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28415557/long-non-coding-rna-cta-sensitizes-osteosarcoma-cells-to-doxorubicin-through-inhibition-of-autophagy
#5
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...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404910/thalidezine-a-novel-ampk-activator-eliminates-apoptosis-resistant-cancer-cells-through-energy-mediated-autophagic-cell-death
#6
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...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401013/resistin-confers-resistance-to-doxorubicin-induced-apoptosis-in-human-breast-cancer-cells-through-autophagy-induction
#7
Zhenyu Liu, Aiping Shi, Dong Song, Bing Han, Zhiru Zhang, Le Ma, Dongxu Liu, Zhimin Fan
Clear evidence has linked obesity to a high risk of incidence as well as poor clinical outcome of breast cancer. It has been proven that changes in the levels of adipokines caused by obesity are associated with the initiation and progression of breast cancer. Resistin is a novel adipokine that is upregulated in breast cancer patients and promotes breast cancer cell growth, invasion, and migration. The aim of the study was to investigate whether resistin affected the efficacy of doxorubicin (Dox), one of the most effective anthracycline chemotherapeutic agents in the treatment of breast cancer...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28381160/insights-into-the-involvement-of-noncoding-rnas-in-5-fluorouracil-drug-resistance
#8
REVIEW
Jun Deng, Yi Wang, Jun Lei, Wan Lei, Jian Ping Xiong
5-Fluorouracil is a classic chemotherapeutic drug that is widely used to treat various cancers. However, patients often exhibit primary or acquired drug resistance during treatment with 5-fluorouracil chemotherapy. 5-Fluorouracil resistance is a multifactorial event that involves abnormal enzyme metabolism, transport deregulation, cell cycle disorders, apoptosis resistance, and mismatch repair deficiency. Despite advancements in bioresearch technologies in the past several decades, the molecular mechanisms of 5-fluorouracil resistance have not been completely clarified...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28379541/resistance-to-apoptosis-and-autophagy-leads-to-enhanced-survival-in-sertoli-cells
#9
Ferial Aslani, Tim Sebastian, Miguel Keidel, Suada Fröhlich, Hans-Peter Elsässer, Hans-Christian Schuppe, Jörg Klug, Poornima Mahavadi, Monika Fijak, Martin Bergmann, Andreas Meinhardt, Sudhanshu Bhushan
STUDY QUESTION: What is the underlying mechanism of Sertoli cell (SC) resistance to cell death? SUMMARY ANSWER: High expression of pro-survival B cell lymphoma-2 (BCL2) proteins and inhibition of apoptosis and autophagy prolongs SC survival upon exposure to stress stimuli. WHAT IS KNOWN ALREADY: In human and in experimental models of orchitis, tolerogenic SC survive stress conditions, while germ cells undergo massive apoptosis. In general, non-dividing highly differentiated cells tend to resist stress conditions for a longer time by favoring activation of pro-survival mechanisms and inhibition of cell death pathways...
April 3, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28378028/up-regulation-of-autophagy-is-a-mechanism-of-resistance-to-chemotherapy-and-can-be-inhibited-by-pantoprazole-to-increase-drug-sensitivity
#10
Qian Tan, A M Joshua, M Wang, R G Bristow, B G Wouters, C J Allen, Ian F Tannock
BACKGROUND: Autophagy is a survival mechanism that allows recycling of cellular breakdown products, particularly in stressed cells. Here we evaluate the hypotheses that up-regulation of autophagy is a common mechanism of resistance to chemotherapy, and that drug resistance can be reversed by inhibiting autophagy with a proton pump inhibitor. METHODS: We exposed human PC3, LNCaP and MCF7 cells to seven clinically-used chemotherapy drugs ± pantoprazole, examined the up-regulation of autophagy and the effect on cellular proliferation by Western Blots, MTS assay and colony-forming assay...
April 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28377355/-role-of-beclin-1-gene-in-autophagy-and-apoptosis-of-sw620-cells
#11
Meng Lv, Hang Lu
OBJECTIVE: To study the role of Beclin1 gene in autophagy and apoptosis of SW620 cells. METHODS: RNA interference was used to knockdown the expression of Beclin 1 in SW620 cells, and the cell viability was measured by MTT assays. The autophagic activity in serum-starved SW620 CRC cells was evaluated by assessing endogenous microtubule-associated protein 1 light chain 3 (LC3) protein levels using immunofluorescence assay. Flow cytometry was used to measure the apoptosis rate of SW620 cells treated with serum deprivation, staurosporine or etoposide, and the protein expression of Beclin1 was detected using Western blotting...
March 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28364003/multi-drug-analyses-in-patients-distinguish-efficacious-cancer-agents-based-on-both-tumor-cell-killing-and-immunomodulation
#12
Jason Frazier, Jessica A Bertout, William S Kerwin, Alicia Moreno-Gonzalez, Joey R Casalini, Marc O Grenley, Emily Beirne, Kori L Watts, Andy Keener, Derek J Thirstrup, Ilona Tretyak, Sally Ditzler, Chelsea D Tripp, Kevin Choy, Sarah Gillings, Megan N Breit, Karri A Meleo, Vanessa Rizzo, Chamisa L Herrera, James A Perry, Ravi K Amaravadi, James M Olson, Richard Klinghoffer
The vision of a precision medicine-guided approach to novel cancer drug development is challenged by high intra-tumor heterogeneity and interpatient diversity. This complexity is rarely modeled accurately during preclinical drug development, hampering predictions of clinical drug efficacy. To address this issue, we developed CIVO (Comparative In Vivo Oncology) arrayed microinjection technology to test tumor responsiveness to simultaneous microdoses of multiple drugs directly in a patient's tumor. Here, in a study of 18 canine patients with soft tissue sarcoma (STS), CIVO captured complex, patient-specific tumor responses encompassing both cancer cells and multiple immune infiltrates following localized exposure to different chemotherapy agents...
March 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28360820/the-effect-of-tetrandrine-combined-with-cisplatin-on-proliferation-and-apoptosis-of-a549-ddp-cells-and-a549-cells
#13
Ling-Yun Ye, Song Hu, Hua-E Xu, Rong-Rong Xu, Hui Kong, Xiao-Ning Zeng, Wei-Ping Xie, Hong Wang
BACKGROUND: Non-small cell lung cancer comprises the majority of lung cancer cases and is insensitive to chemotherapy. Most patients develop drug resistance. Recently, tetrandrine (TET), a bis-benzylisoquinoline alkaloid, was identified as a novel anti-cancer agent. However, the effect of tetrandrine combined with cisplatin on lung cancer has not yet been studied. We aimed to identify a possible synergistic effect between tetrandrine and cisplatin, besides, to investigate the effects of TET in combination with DDP on proliferation and apoptosis in cisplatin-resistant and cisplatin-sensitive A549 cell lines, and to study the underlying mechanism...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28347245/cancer-stem-cells-the-potential-role-of-autophagy-proteolysis-and-cathepsins-in-glioblastoma-stem-cells
#14
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
https://www.readbyqxmd.com/read/28341864/microrna-140-5p-regulates-osteosarcoma-chemoresistance-by-targeting-hmgn5-and-autophagy
#15
Yichen Meng, Rui Gao, Jun Ma, Jianquan Zhao, Enjie Xu, Ce Wang, Xuhui Zhou
Chemotherapy is an important treatment modality for osteosarcoma. However, it often fails because of chemoresistance, especially multidrug resistance. Previously, we found several genes were involved in chemoresistance development. In this report, we used high-throughput microRNA (miRNA) expression analysis to reveal that expression of miR-140-5p was associated with chemosensitivity in osteosarcoma. The exact roles of miR-140-5p in the chemoresistance of osteosarcoma were then investigated, we found that knockdown of miR-140-5p enhanced osteosarcoma cells resistance to multiple chemotherapeutics while overexpression of miR-140-5p sensitized tumors to chemotherapy in vitro...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28338617/egfr-family-members-regulation-of-autophagy-is-at-a-crossroads-of-cell-survival-and-death-in-cancer
#16
REVIEW
Elizabeth Henson, Yongqiang Chen, Spencer Gibson
The epidermal growth factor receptor (EGFR) signaling pathways are altered in many cancers contributing to increased cell survival. These alterations are caused mainly through increased expression or mutation of EGFR family members EGFR, ErbB2, ErbB3, and ErbB4. These receptors have been successfully targeted for cancer therapy. Specifically, a monoclonal antibody against ErbB2, trastuzumab, and a tyrosine kinase inhibitor against EGFR, gefitinib, have improved the survival of breast and lung cancer patients...
March 24, 2017: Cancers
https://www.readbyqxmd.com/read/28325600/synthesis-and-anti-cancer-activities-of-new-sulfonamides-4-substituted-triazolyl-nucleosides
#17
Soukaina Alaoui, Maeva Dufies, Mohsine Driowya, Luc Demange, Khalid Bougrin, Guillaume Robert, Patrick Auberger, Gilles Pagès, Rachid Benhida
Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action. Indeed, AICAR induced autophagy cell death and is able, following this mechanism, to circumvent resistance to apoptotic drugs including kinase inhibitors currently on the market...
May 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28298203/methylene-blue-photodynamic-therapy-induces-selective-and-massive-cell-death-in-human-breast-cancer-cells
#18
Ancély F Dos Santos, Letícia F Terra, Rosangela A M Wailemann, Talita C Oliveira, Vinícius de Morais Gomes, Marcela Franco Mineiro, Flávia Carla Meotti, Alexandre Bruni-Cardoso, Maurício S Baptista, Leticia Labriola
BACKGROUND: Breast cancer is the main cause of mortality among women. The disease presents high recurrence mainly due to incomplete efficacy of primary treatment in killing all cancer cells. Photodynamic therapy (PDT), an approach that causes tissue destruction by visible light in the presence of a photosensitizer (Ps) and oxygen, appears as a promising alternative therapy that could be used adjunct to chemotherapy and surgery for curing cancer. However, the efficacy of PDT to treat breast tumours as well as the molecular mechanisms that lead to cell death remain unclear...
March 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28292022/the-effects-of-the-long-non-coding-rna-malat-1-regulated-autophagy-related-signaling-pathway-on-chemotherapy-resistance-in-diffuse-large-b-cell-lymphoma
#19
Li-Juan Li, Ye Chai, Xiao-Jia Guo, Song-Lin Chu, Lian-Sheng Zhang
OBJECTIVE: Our study aimed to investigate the effects of the long non-coding RNA MALAT-1 (lncRNA MALAT-1) regulated autophagy-related signaling pathway on chemotherapy resistance in diffuse large B-cell lymphoma (DLBCL). METHODS: Human normal B lymphocytes (IM-9I) and DLBCL cell lines (Farage, Pfeiffer, Raji, Daud, Ly1, Ly3, Ly8 and Ly10) were chosen for our experiment. qRT-PCR was applied to detect the expression of lncRNA MALAT-1 in each DLBCL cell line. Farage and Daud cells were induced to be drug-resistant using 0...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28283035/inhibition-of-autophagy-enhances-the-selective-anti-cancer-activity-of-tigecycline-to-overcome-drug-resistance-in-the-treatment-of-chronic-myeloid-leukemia
#20
Ziyuan Lu, Na Xu, Bolin He, Chengyun Pan, Yangqing Lan, Hongsheng Zhou, Xiaoli Liu
BACKGROUND: Drug resistance and disease progression are still the major obstacles in the treatment of chronic myeloid leukemia (CML). Increasing researches have demonstrated that autophagy becomes activated when cancer cells are subjected to chemotherapy, which is involved in the development of drug resistance. Therefore, combining chemotherapy with inhibition of autophagy serves as a new strategy in cancer treatment. Tigecycline is an antibiotic that has received attention as an anti-cancer agent due to its inhibitory effect on mitochondrial translation...
March 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
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