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Autophagy and chemotherapy resistance

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https://www.readbyqxmd.com/read/28726781/autophagy-inhibition-reduces-chemoresistance-and-tumorigenic-potential-of-human-ovarian-cancer-stem-cells
#1
Anna Pagotto, Giorgia Pilotto, Elena Laura Mazzoldi, Maria Ornella Nicoletto, Simona Frezzini, Anna Pastò, Alberto Amadori
Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors with a high mortality rate owing to tumor relapse after anticancer therapies. It is widely accepted that a rare tumor cell population, known as cancer stem cells (CSC), is responsible for tumor progression and relapse; intriguingly, these cells are able to survive nutrient starvation (such as in vitro culture in the absence of glucose) and chemotherapy treatment. Recent data also indicated that chemotherapy resistance is associated with autophagy activation...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28707966/targeted-molecular-ablation-of-cancer-stem-cells-for-curing-gastrointestinal-cancers
#2
Yong Seok Kim, Ho Jae Lee, Jong-Min Park, Young-Min Han, Napapan Kangwan, Ji Young Oh, Dong Yoon Lee, Ki Baik Hahm
Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis...
July 14, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28701590/new-perspectives-of-cobalt-tris-bipyridine-system-anti-cancer-effect-and-its-collateral-sensitivity-towards-multidrug-resistant-mdr-cancers
#3
Betty Yuen Kwan Law, Yuan Q Qu, Simon Wing Fai Mok, Hauwei Liu, Zeng Wu, Yu Han, Flora Gordillo-Martinez, Wai-Kit Chan, Keith M Wong, Vincent Kam Wai Wong
Platinating compounds including cisplatin, carboplatin, and oxaliplatin are common chemotherapeutic agents, however, patients developed resistance to these clinical agents after initial therapeutic treatments. Therefore, different approaches have been applied to identify novel therapeutic agents, molecular mechanisms, and targets for overcoming drug resistance. In this study, we have identified a panel of cobalt complexes that were able to specifically induce collateral sensitivity in taxol-resistant and p53-deficient cancer cells...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28692436/andrographolide-enhances-cisplatin-mediated-anticancer-effects-in-lung-cancer-cells-through-blockade-of-autophagy
#4
Daolu Yuwen, Shanwei Mi, Yuzhu Ma, Wenjie Guo, Qiang Xu, Yan Shen, Yongqian Shu
Lung cancer is the most common cause of cancer-related death worldwide and the platinum-based drugs such as cisplatin have been used as the first line of the treatment. However, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance. In this study, we found that cisplatin induced autophagy that attenuated the sensitivity of both A549 and Lewis lung cancer (LLC) cells to cisplatin. In contrast, the clinical drug andrographolide (Andro) suppressed autophagy and enhanced cisplatin-mediated apoptosis in these cells...
July 7, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28678319/mir-146a-5p-level-in-serum-exosomes-predicts-therapeutic-effect-of-cisplatin-in-non-small-cell-lung-cancer
#5
D-L Yuwen, B-B Sheng, J Liu, W Wenyu, Y-Q Shu
OBJECTIVE: Lung cancer is the most common cause of death in cancer worldwide, and cisplatin plays an important role in its treatment. However, the response to chemotherapy is poorly attributable to drug resistance. Our present study aimed to investigate the relation of the exosomal miR-146a-5p level with the chemosensitivity of NSCLC to cisplatin and the molecular mechanism that miR-146a-5p mediated to effect on chemotherapy response. PATIENTS AND METHODS: The exosomes were isolated by ExoQuick kit...
June 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28677749/long-non%C3%A2-coding-rna-meg3-contributes-to-cisplatin%C3%A2-induced-apoptosis-via-inhibition-of-autophagy-in-human-glioma-cells
#6
Binbin Ma, Zebin Gao, Jiacheng Lou, Hongqiang Zhang, Zhongbo Yuan, Qiong Wu, Xinyu Li, Bo Zhang
Long non-coding RNAs (lncRNAs) function as oncogenes or tumor suppressors, and are involved in mediating tumorigenesis and resistance to chemotherapy by altering the expression of genes at various levels. Accumulating evidence suggests that the maternally expressed gene 3 (MEG3) lncRNA serves an important role in a number of cancers. However, its functional role in mediating cisplatin‑induced apoptosis of glioma cells is unknown. To investigate the role of MEG3, the mRNA levels of MEG3 under cisplatin treatment were investigated by reverse transcription‑quantitative polymerase chain reaction, and the cell viability and apoptosis were examined by MTT assay, and flow cytometry analysis and western blotting, respectively...
June 30, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28670281/n-desmethyldauricine-induces-autophagic-cell-death-in-apoptosis-defective-cells-via-ca-2-mobilization
#7
Betty Y K Law, Simon W F Mok, Juan Chen, Francesco Michelangeli, Zhi-Hong Jiang, Yu Han, Yuan Q Qu, Alena C L Qiu, Su-Wei Xu, Wei-Wei Xue, Xiao-Jun Yao, Jia Y Gao, Masood-Ul-Hassan Javed, Paolo Coghi, Liang Liu, Vincent K W Wong
Resistance of cancer cells to chemotherapy remains a significant problem in oncology. Mechanisms regulating programmed cell death, including apoptosis, autophagy or necrosis, in the treatment of cancers have been extensively investigated over the last few decades. Autophagy is now emerging as an important pathway in regulating cell death or survival in cancer therapy. Recent studies demonstrated variety of natural small-molecules could induce autophagic cell death in apoptosis-resistant cancer cells, therefore, discovery of novel autophagic enhancers from natural products could be a promising strategy for treatment of chemotherapy-resistant cancer...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28656199/wnt-%C3%AE-catenin-signaling-pathway-activation-reverses-gemcitabine-resistance-by-attenuating-beclin1-mediated-autophagy-in-the-mg63-human-osteosarcoma-cell-line
#8
Hao Tao, Feng Chen, Haifei Liu, Yanling Hu, Yingzhen Wang, Haiyan Li
Anaberrant Wnt/β-catenin signaling pathway is frequently implicated in tumorigenesis. However, whether the Wnt/β‑catenin pathway plays a role in resistance to antitumor chemotherapy drugs remains unknown. In the present study, the process of autophagy was assessed following overexpression of the autophagy‑associated gene Beclin 1 in gemcitabine‑induced MG63 human osteosarcoma cells. Autophagy‑associated gene expression was measured following activation or inhibition of the Wnt/β‑catenin pathway in gemcitabine‑induced MG63 cells using reverse transcription‑quantitative polymerase chain reaction...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28656197/autophagy-plays-an-important-role-in-stemness-mediation-and-the-novel-dual-function-of-eig121-in-both-autophagy-and-stemness-regulation-of-endometrial-carcinoma-jec-cells
#9
Xiaomin Ran, Ping Zhou, Keqiang Zhang
Endometrial cancer (EC) is the third most common gynecologic malignancy in the world, and is considered a chemotherapy poor responding cancer. There are two underlying mechanisms on chemoresistance: the stemness of cancer stem cells (CSCs) and activation of pro-survival autophagy. It was found that autophagy is one of the main factors of cancer stem cell survival, multidrug resistance and maintenance of the homeostasis of cancer stem cells and normal cancer cells. However, the relationship between CSCs and autophagy of EC cells is still unknown...
June 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28650662/glucose-restriction-combined-with-autophagy-inhibition-and-chemotherapy-in-hct-116-spheroids-decreases-cell-clonogenicity-and-viability-regulated-by-tumor-suppressor-genes
#10
Monica M Schroll, Gabriel J LaBonia, Katelyn R Ludwig, Amanda B Hummon
Drug resistance is a prevalent phenomenon that decreases the efficacy of cancer treatments and contributes to cancer progression and metastasis. Weakening drug-resistant cancer cells prior to chemotherapy is a potential strategy to combat chemoresistance. One approach to damage resistant cancer cells is modulation of nutritional intake. The combination of nutrient restriction with targeted compound treatment results in pronounced molecular changes. This study provides valuable information about augmenting existing chemotherapeutic regimes with simultaneous glucose restriction and autophagy inhibition in colorectal cancer cells...
July 3, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28650490/hypoxia-induced-tumor-cell-resistance-is-overcome-by-synergistic-gapdh-sirna-and-chemotherapy-co-delivered-by-long-circulating-and-cationic-interior-liposomes
#11
Jibin Guan, Jin Sun, Feilong Sun, Bo Lou, Dong Zhang, Vida Mashayekhi, Negar Sadeghi, Gert Storm, Enrico Mastrobattista, Zhonggui He
Chemotherapeutic drug resistance of tumor cells under hypoxic conditions is caused by the inhibition of apoptosis by autophagy and drug efflux via adenosine triphosphate (ATP)-dependent transporter activation, among other factors. Here, we demonstrate that disrupting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression can reduce the autophagy and ATP levels in tumor cells. To test whether GAPDH knockdown is sufficient to overcome drug resistance, a nanocarrier (asymmetry-membrane liposome) was designed to encapsulate GAPDH-siRNA with a low dose of paclitaxel (PTX)...
July 6, 2017: Nanoscale
https://www.readbyqxmd.com/read/28646911/autophagy-and-multidrug-resistance-in-cancer
#12
REVIEW
Ying-Jie Li, Yu-He Lei, Nan Yao, Chen-Ran Wang, Nan Hu, Wen-Cai Ye, Dong-Mei Zhang, Zhe-Sheng Chen
Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal...
June 24, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28628188/silencing-of-bag3-promotes-the-sensitivity-of-ovarian-cancer-cells-to-cisplatin-via-inhibition-of-autophagy
#13
Shuang Qiu, Liang Sun, Ye Jin, Qi An, Changjiang Weng, Jianhua Zheng
Ovarian cancer is the most lethal disease among all gynecological malignancies. Interval cytoreductive surgery and cisplatin‑based chemotherapy are the recommended therapeutic strategies. However, acquired resistance to cisplatin remains a big challenge for the overall survival and prognosis in ovarian cancer. Complicated molecular mechanisms are involved in the process. At present, increasing evidence indicates that autophagy plays an important role in the prosurvival and resistance against chemotherapy...
July 2017: Oncology Reports
https://www.readbyqxmd.com/read/28618969/penfluridol-induces-endoplasmic-reticulum-stress-leading-to-autophagy-in-pancreatic-cancer
#14
Alok Ranjan, Nadezhda German, Constantinos Mikelis, Kalkunte Srivenugopal, Sanjay K Srivastava
Pancreatic cancer is one of the most aggressive and difficult to treat cancers. Experimental and clinical evidence suggests that high basal state autophagy in pancreatic tumors could induce resistance to chemotherapy. Recently, we have demonstrated that penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis both in vitro and in vivo; however, the mechanism of autophagy induction by penfluridol was not clear. Several studies have established that endoplasmic reticulum stress could lead to autophagy and inhibit tumor progression...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28605878/an-oasis-in-the-desert-of-cancer-chemotherapeutic-resistance-the-enlightenment-from-reciprocal-crosstalk-between-signaling-pathways-of-upr-and-autophagy-in-cancers
#15
REVIEW
Yuhang Zhang, Xianjun Qu, Lingfan Jiang
Endoplasmic reticulum (ER), principal but complex, functions as the pleiotropic organelle for proper protein folding, Ca(2+) storage as well as lipid and carbohydrate metabolisms. Diverse microenviromental insults including, but not limited to, inflammatory reaction, glucose imbalance and hypoxia, elicit the accumulation of potentially toxic unfolded proteins in the ER lumen. Under the condition of these cellular threats, the autophagy with the well-orchestrated program containing over 30 autophagy-related genes (ATGs) might be initiated for degrading and recycling of the cumulative misfolded proteins and other related abnormal cytoplasmic components...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28601065/mazes-of-nrf2-regulation
#16
REVIEW
N K Zenkov, P M Kozhin, A V Chechushkov, G G Martinovich, N V Kandalintseva, E B Menshchikova
Nrf2 transcription factor plays a key role in maintaining cellular redox balance under stress and is a perspective target for oxidative stress-associated diseases. Under normal conditions, Nrf2 transcriptional activity is low due to its rapid ubiquitination and degradation in the 26S proteasome, as well as through various modifications of amino acid residues of this transcription factor that regulate its transport to the nucleus and binding to DNA. Continuous activation of Nrf2 is possible due to autophagy and epigenetic regulation that may underlie the increased resistance of tumor cells to radiotherapy and chemotherapy...
May 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28600513/trpc5-induced-autophagy-promotes-drug-resistance-in-breast-carcinoma-via-camkk%C3%AE-ampk%C3%AE-mtor-pathway
#17
Peng Zhang, Xiaoyu Liu, Hongjuan Li, Zhen Chen, Xiaoqiang Yao, Jian Jin, Xin Ma
Adriamycin is a first-line chemotherapy agent against cancer, but the development of resistance has become a major problem. Although autophagy is considered to be an adaptive survival response in response to chemotherapy and may be associated with chemoresistance, its inducer and the underlying molecular mechanisms remain unclear. Here, we demonstrate that adriamycin up-regulates the both levels of TRPC5 and autophagy, and the increase in autophagy is mediated by TRPC5 in breast cancer cells. Blockade of TRPC5 or autophagy increased the sensitivity to chemotherapy in vitro and in vivo...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28598229/autophagy-in-natural-and-therapy-driven-anticancer-immunosurveillance
#18
Federico Pietrocola, José Manuel Bravo-San Pedro, Lorenzo Galluzzi, Guido Kroemer
Autophagy is primordial for the maintenance of metabolic and genetic homeostasis in all eukaryotic organisms. Owing to its cell-intrinsic effects, autophagy robustly inhibits malignant transformation, yet can support the progression of established neoplasms as well as their resistance to conventional treatments. The notion that autophagy inhibition sensitizes neoplastic cells to chemotherapy and radiation therapy rivals with the capacity of autophagy to contribute to natural and therapy-driven anticancer immunosurveillance via a multitude of mechanisms...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28590019/afatinib-decreases-p-glycoprotein-expression-to-promote-adriamycin-toxicity-of-a549t-cells
#19
Yan Zhang, Chang-Yuan Wang, Ying-Jie Duan, Xiao-Kui Huo, Qiang Meng, Zhi-Hao Liu, Hui-Jun Sun, Xiao-Dong Ma, Ke-Xin Liu
We investigated the reversal effect of afatinib (AFT) on activity of adriamycin (ADR) in A549T cells and clarified the related molecular mechanisms. A549T cells overexpressing P-glycoprotein (P-gp) were resistant to anticancer drug ADR. AFT significantly increased the antitumor activity of ADR in A549T cells. AFT increased the intracellular concentration of ADR by inhibiting the function and expression of P-gp at mRNA and protein levels in A549T cells. Additionally, the reversal effect of AFT on P-gp mediated multidrug resistance (MDR) might be related to the inhibition of PI3K/Akt pathway...
June 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28587939/temozolomide-and-sorafenib-as-programmed-cell-death-inducers-of-human-glioma-cells
#20
Joanna Jakubowicz-Gil, Dorota Bądziul, Ewa Langner, Iwona Wertel, Adrian Zając, Wojciech Rzeski
BACKGROUND: Gliomas are aggressive brain tumors with very high resistance to chemotherapy. Therefore, the aim of the present study was to investigate the effectiveness of sorafenib and Temozolomide in elimination of human glioma cells through apoptosis and autophagy. METHODS: MOGGCCM (anaplastic astrocytoma) and T98G (glioblastoma multiforme) cell lines incubated with sorafenib and/or Temozolomide were used in the experiments. Cell morphology (ER stress, apoptosis, autophagy, and necrosis) was analyzed microscopically while apoptosis and mitochondrial membrane potential were assessed with flow cytometry...
March 14, 2017: Pharmacological Reports: PR
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