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Autophagy and chemoresistance

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https://www.readbyqxmd.com/read/27912844/heparanase-from-basic-research-to-therapeutic-applications-in-cancer-and-inflammation
#1
Israel Vlodavsky, Preeti Singh, Ilanit Boyango, Lilach Gutter-Kapon, Michael Elkin, Ralph D Sanderson, Neta Ilan
Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27902471/autophagy-autophagy-associated-adaptive-immune-responses-and-its-role-in-hematologic-malignancies
#2
REVIEW
Liangshun You, Shenhe Jin, Li Zhu, Wenbin Qian
Autophagy is a tightly regulated catabolic process that leads to the degradation of cytoplasmatic components such as aggregated/misfolded proteins and organelles through the lysosomal machinery. Recent studies suggest that autophagy plays such a role in the context of the anti-tumor immune response, make it an attractive target for cancer immunotherapy. Defective autophagy in hematopoietic stem cells may contribute to the development of hematologic malignancies, including leukemia, myelodysplastic syndrome, and lymphoproliferative disorder...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27895792/microrna-199a-5p-inhibits-cisplatin-induced-drug-resistance-via-inhibition-of-autophagy-in-osteosarcoma-cells
#3
Yusheng Li, Wei Jiang, Yuling Hu, Zixun Da, Chao Zeng, Min Tu, Zhenhan Deng, Wenfeng Xiao
Osteosarcoma (OS) is the most common cancer of the bone. Chemotherapy is commonly used for the clinical treatment of OS. However, chemoresistance to cisplatin [also known as diamminedichloridoplatinum (II) (DDP)] is a major obstacle for OS therapy, the underlying mechanism of which is not fully understood. The present study aimed to investigate the role of microRNA (miR)-199a-5p in the regulation of chemoresistance to DDP in OS cells. Reverse transcription-quantitative polymerase chain reaction demonstrated that the expression level of miR-199a-5p was significantly reduced in human OS MG63 cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27878958/inhibition-of-orai1-mediated-ca-2-entry-enhances-chemosensitivity-of-hepg2-hepatocarcinoma-cells-to-5-fluorouracil
#4
Bao-Dong Tang, Xin Xia, Xiao-Fei Lv, Bei-Xin Yu, Jia-Ni Yuan, Xiao-Yi Mai, Jin-Yan Shang, Jia-Guo Zhou, Si-Jia Liang, Rui-Ping Pang
Increasing evidence supports that activation of store-operated Ca(2+) entry (SOCE) is implicated in the chemoresistance of cancer cells subjected to chemotherapy. However, the molecular mechanisms underlying chemoresistance are not well understood. In this study, we aim to investigate whether 5-FU induces hepatocarcinoma cell death through regulating Ca(2+) -dependent autophagy. [Ca(2+) ]i was measured using fura2/AM dye. Protein expression was determined by Western blotting and immunohistochemistry. We found that 5-fluorouracil (5-FU) induced autophagic cell death in HepG2 hepatocarcinoma cells by inhibiting PI3K/AKT/mTOR pathway...
November 23, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27867537/aquaporin-3-facilitates-chemoresistance-in-gastric-cancer-cells-to-cisplatin-via-autophagy
#5
Xuqiang Dong, Yao Wang, Yangchun Zhou, Jianfei Wen, Shoulin Wang, Lizong Shen
Cisplatin (cDDP) remains one of the first-line chemotherapeutic agents for gastric cancer (GC) treatment, and resistance to cDDP is the major limitation in its clinical application. Mechanisms of cDDP resistance have been shown to be varied and complicated. Aquaporin 3 (AQP3) has been demonstrated to be overexpressed in GC tissues and is thought to be involved in GC carcinogenesis and progression. However, the role of AQP3 in chemosensitivity of GC to cytotoxic agents remains unknown. In this study, we show that AQP3 overexpression induced resistance to cDDP in AGS cells (P<0...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27846885/autophagy-is-associated-with-chemoresistance-in-neuroblastoma
#6
Assila Belounis, Carine Nyalendo, Roxane Le Gall, Tina V Imbriglio, Mohamed Mahma, Pierre Teira, Mona Beaunoyer, Sonia Cournoyer, Elie Haddad, Gilles Vassal, Hervé Sartelet
BACKGROUND: Neuroblastoma (NB) is a frequent pediatric tumor characterized by a poor prognosis where a majority of tumors progress despite intensive multimodality treatments. Autophagy, a self-degradative process in cells, could be induced by chemotherapy and be associated with chemoresistance. The aim of this study was to determine whether: 1) autophagy is present in NB, 2) chemotherapy modified its levels, and 3) its inhibition decreased chemoresistance. METHODS: Immunohistochemical stainings were performed on samples from 184 NB patients in order to verify the expression of LC3B, a specific marker for autophagy, and Beclin 1, a positive regulator of autophagy...
November 15, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27812982/ampk-and-cancer
#7
Zhiyu Wang, Neng Wang, Pengxi Liu, Xiaoming Xie
This chapter focuses on the role of AMPK as a stress-response molecule with an emphasis on its duplex implication in carcinogenesis and cancer drug resistance. AMPK is closely correlated to the tumor-suppressive functions of LKB1 and P53, consequently modulating the activity of cellular survival signaling such as mTOR and Akt, leading to cell growth inhibition and cell cycle arrest. On the contrary, AMPK is tightly involved in cancer drug resistance via interacting with multiple known mechanisms of chemoresistance such as ABCG2 expression, autophagy induction, and cancer stem cells enrichment...
2016: EXS
https://www.readbyqxmd.com/read/27765907/activation-of-endoplasmic-reticulum-stress-promotes-autophagy-and-apoptosis-and-reverses-chemoresistance-of-human-small-cell-lung-cancer-cells-by-inhibiting-the-pi3k-akt-mtor-signaling-pathway
#8
Xin-Shuang Yu, Juan Du, Yu-Jun Fan, Feng-Jun Liu, Li-Li Cao, Ning Liang, De-Guo Xu, Jian-Dong Zhang
OBJECTIVE: This study aims to investigate the effects of endoplasmic reticulum stress (ERS) on autophagy, apoptosis and chemoresistance of human small cell lung cancer (SCLC) cells via the PI3K/AKT/mTOR signaling pathway. RESULTS: The expressions of ERS-related proteins (PEAK, eIF2α and CHOP) up-regulated, autophagy-related proteins (LC3, LC3-II and Beclin1) and apoptosis-related proteins (Bax and procaspase-3) down-regulated in NCI-H446 and H69 cells after tunicamycin treatment for 24 h...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27758044/heparanase-regulation-of-cancer-autophagy-and-inflammation-new-mechanisms-and-targets-for-therapy
#9
REVIEW
Ralph D Sanderson, Michael Elkin, Alan C Rapraeger, Neta Ilan, Israel Vlodavsky
Because of its impact on multiple biological pathways, heparanase has emerged as a major regulator of cancer, inflammation and other disease processes. Heparanase accomplishes this by degrading heparan sulfate which regulates the abundance and location of heparin-binding growth factors thereby influencing multiple signaling pathways that control gene expression, syndecan shedding and cell behavior. In addition, heparanase can act via nonenzymatic mechanisms that directly activate signaling at the cell surface...
October 18, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27754745/gfra1-promotes-cisplatin-induced-chemoresistance-in-osteosarcoma-by-inducing-autophagy
#10
Mihwa Kim, Ji-Yeon Jung, Seungho Choi, Hyunseung Lee, Liza D Morales, Jeong-Tae Koh, Sun Hun Kim, Yoo-Duk Choi, Chan Choi, Thomas J Slaga, Won Jae Kim, Dae Joon Kim
Recent progress in chemotherapy has significantly increased its efficacy, yet the development of chemoresistance remains a major drawback. In this study, we show that GFRA1/GFRα1 (GDNF family receptor α 1), contributes to cisplatin-induced chemoresistance by regulating autophagy in osteosarcoma. We demonstrate that cisplatin treatment induced GFRA1 expression in human osteosarcoma cells. Induction of GFRA1 expression reduced cisplatin-induced apoptotic cell death and it significantly increased osteosarcoma cell survival via autophagy...
October 18, 2016: Autophagy
https://www.readbyqxmd.com/read/27692344/autophagy-inhibition-upregulates-cd4-tumor-infiltrating-lymphocyte-expression-via-mir-155-regulation-and-trail-activation
#11
Paul Zarogoulidis, Savvas Petanidis, Kalliopi Domvri, Efrosini Kioseoglou, Doxakis Anestakis, Lutz Freitag, Konstantinos Zarogoulidis, Wolfgang Hohenforst-Schmidt, Wilfried Eberhardt
Chemoresistance is a major challenge in lung cancer treatment. Recent findings have revealed that autophagic mechanism contributes significantly to immunosuppressive related chemoresistance. For that reason, targeting autophagy-related immunosuppression is an important approach to reverse tumor drug resistance. In this study, we report for the first time that autophagy inhibition triggers upregulation of CD4(+), Foxp3(+) tumor infiltrating lymphocytes in late metastatic lung cancer tissues. Furthermore, autophagy blockage induces chemosensitization to carboplatin, immune activation and cell cycle arrest...
September 16, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27666552/-advances-in-the-research-of-autophagy-in-egfr-tki-treatment-and-resistance-%C3%A2-in-lung-cancer
#12
Qicheng Zhang, Ke Xu
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a group of targeted-drugs which effectively inhibits the growth of tumor cells with sensitive mutations in EGFR. However, the innate and acquired resistance are major obstacles of the efficiency. Autophagy is a highly conserved self-digesting process in cells, which is considered to be associated with cancer development andchemoresistance. The activation of EGFR may regulate autophagy through multiple signal pathways. EGFR-TKIs can induce autophagy, however, the function of the inducted autophagy remains biphasic...
September 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/27626179/noncanonical-sqstm1-p62-nrf2-pathway-activation-mediates-proteasome-inhibitor-resistance-in-multiple-myeloma-cells-via-redox-metabolic-and-translational-reprogramming
#13
Irene Riz, Teresa S Hawley, Jeffrey W Marsal, Robert G Hawley
Multiple Myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal plasma cells in the bone marrow, with drug resistance being a major cause of therapeutic failure. We established a carfilzomib-resistant derivative of the LP-1 MM cell line (LP-1/Cfz) and found that the transcription factor NF-E2 p45-related factor 2 (Nrf2; gene symbol NFE2L2) contributes to carfilzomib resistance. The mechanism of Nrf2 activation involved enhanced translation of Nrf2 as well as its positive regulator, the autophagy receptor sequestosome 1 (SQSTM1)/p62...
September 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27613096/human-rad23a-plays-a-regulatory-role-in-autophagy
#14
Xiaotong Tan, Hsin-Chiao Wang, Ruei-Yue Liang, Show-Mei Chuang
Chemotherapeutic agents can upregulate autophagy which contributes to the acquisition of chemoresistance and the recurrence of cancer. The involvement of hHR23A in chemoresistance is unknown. In this study, we provide evidence suggesting that hHR23A may regulate autophagy. Knockdown of hHR23A decreased cell growth and increased the resistance in A549 cells to the DNA-damaging agents, cisplatin and oxaliplatin. Measurement of EGFP-LC3 puncta (a marker of autophagy) revealed that autophagy was increased in hHR23A-depleted cells...
September 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27582507/mir-140-5p-attenuates-chemotherapeutic-drug-induced-cell-death-by-regulating-autophagy-through-inositol-1-4-5-trisphosphate-kinase-2-ip3k2-in-human-osteosarcoma-cells
#15
Renxiong Wei, Gang Cao, Zhouming Deng, Jiajia Su, Lin Cai
Acquisition of drug-resistant phenotypes is often associated with chemotherapy in osteosarcoma. A number of studies have demonstrated a critical role for autophagy in osteosarcoma development, therapy and drug resistance. However, the molecular mechanisms underlying the autophagy-mediated chemotherapy resistance of osteosarcoma cells remain largely unknown. In the present study, we determined the autophagy and microRNA-140 (miR-140-5p, miRBase ID: MIMAT0000431) expression induced by chemotherapeutic drugs in osteosarcoma cells...
October 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27537898/tumor-protein-tp-p53-members-as-regulators-of-autophagy-in-tumor-cells-upon-marine-drug-exposure
#16
Edward A Ratovitski
Targeting autophagic pathways might play a critical role in designing novel chemotherapeutic approaches in the treatment of human cancers, and the prevention of tumor-derived chemoresistance. Marine compounds were found to decrease tumor cell growth in vitro and in vivo. Some of them were shown to induce autophagic flux in tumor cells. In this study, we observed that the selected marine life-derived compounds (Chromomycin A2, Psammaplin A, and Ilimaquinone) induce expression of several autophagic signaling intermediates in human squamous cell carcinoma, glioblastoma, and colorectal carcinoma cells in vitro through a transcriptional regulation by tumor protein (TP)-p53 family members...
2016: Marine Drugs
https://www.readbyqxmd.com/read/27525970/blockage-of-ssrp1-ets-1-pim-3-signalling-enhances-chemosensitivity-of-nasopharyngeal-carcinoma-to-docetaxel-in-vitro
#17
Jingang Ai, Wei Li, Ruifang Zeng, Zuozhong Xie, Honghui Liu, Minghua Hou, Guolin Tan
Nasopharyngeal carcinoma (NPC) is a rare cancer in most parts of the world, but is prevalent in South China area. Besides, therapeutic outcome is still unsatisfactory for patients with refractory and relapsed NPC, even though receiving a second line of docetaxel-based chemotherapy. These reasons require a better understanding of mechanisms underlying the carcinogenesis, malignancy and chemoresistance. In the basis of our previous finding of SSRP1 over-expression in NPC cell lines, this study continuously discovered up-regulated Ets-1, phosphor-Ets-1 and Pim-3 in NPC tissues with immunohistochemistry assay and revealed a close correlation of these up-regulated proteins with NPC proliferation and invasion...
August 12, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27474203/jak-mediated-autophagy-regulates-stemness-and-cell-survival-in-cisplatin-resistant-bladder-cancer-cells
#18
R Ojha, S K Singh, S Bhattacharyya
BACKGROUND: Autophagy is a critical process in acquiring drug resistance in solid tumors. However, the mechanisms by which autophagy modulate resistance to chemotherapy in bladder cancer remains poorly understood. MATERIAL AND METHODS: We have established cisplatin resistant patient derived primary cultured cells as well as T24 bladder cancer cells. The autophagy flux as well as the effect of chemotherapeutic agents, gemcitabine (GC) and mitomycin (MM) were evaluated in these cells...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27473470/rlip76-depletion-enhances-autophagic-flux-in-u251-cells
#19
Chenran Zhang, Zheng Cai, Qiang Liang, Qi Wang, Yicheng Lu, Liuhua Hu, Guohan Hu
Our previous study showed that RalA-binding protein 1 (RLIP76) is overexpressed in gliomas and is associated with higher tumour grade and decreased patient survival. Furthermore, RLIP76 downregulation increases chemosensitivity of glioma cells to temozolomide by inducing apoptosis. However, other mechanisms underlying RLIP76-associated chemoresistance are unknown. In this study, we investigated the effect of RLIP76 depletion on autophagy. RLIP76 was knocked down in U251 glioma cells using shRNA and autophagy-related proteins, and PI3K/Akt signalling components were evaluated...
July 29, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27470344/inhibition-of-autophagy-sensitizes-mdr-phenotype-ovarian-cancer-skvcr-cells-to-chemotherapy
#20
Bing Liang, Xiaodong Liu, Yang Liu, Dejuan Kong, Xiaomei Liu, Rui Zhong, Shumei Ma
UNLABELLED: AUTOPHAGY: is an intracellular lysosomal degradation pathway where its primary function is to allow cells to survive under stressful conditions. Autophagy is, however, a double-edge sword that can either promote cell survival or cell death. CHEMORESISTANCE: is a major challenge in the clinical treatment of ovarian cancer, of which the underlying mechanisms remain unknown. OBJECTIVE: The aim of the present study was to explore the role of autophagy in vincristine (VCR) resistant ovarian cancer cells...
August 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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