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Autophagy and chemoresistance

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https://www.readbyqxmd.com/read/29137236/the-nucleocytoplasmic-translocation-and-up-regulation-of-ing5-protein-in-breast-cancer-a-potential-target-for-gene-therapy
#1
Xiao-Qing Ding, Shuang Zhao, Lei Yang, Xin Zhao, Gui-Feng Zhao, Shu-Peng Zhao, Zhi-Jie Li, Hua-Chuan Zheng
Here, we found that ING5 overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial-transition of breast cancer cells. It also suppressed the tumor growth of breast cancer cells by inhibiting proliferation, inducing apoptosis and autophagy. ING5-mediated chemoresistance was positively linked to Akt and NF-κB activation, MRP1 and GST-π overexpression, and FBXW7 hypoexpression...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29130102/knockdown-of-lncrna-xist-enhances-the-chemosensitivity-of-nsclc-cells-via-suppression-of-autophagy
#2
Wei Sun, Yukun Zu, Xiangning Fu, Yu Deng
Drug resistance is the major factor contributing to the failure of chemotherapy in non-small cell lung cancer (NSCLC) patients. Emerging evidence suggests that autophagy plays a vital role in the chemoresistance of many types of tumors. However, the exact mechanism underlying the chemoresistance of NSCLC is still elusive, and it is unclear whether lncRNA-XIST is involved in autophagy and chemoresistance of NSCLC. In the present study, we demonstrated that lncRNA-XIST was overexpressed in NSCLC tumor samples, and knockdown of lncRNA-XIST significantly decreased autophagy by regulation of ATG7 as determined by qPCR and by western blotting...
December 2017: Oncology Reports
https://www.readbyqxmd.com/read/29100291/hinokitiol-up-regulates-mir-494-3p-to-suppress-bmi1-expression-and-inhibits-self-renewal-of-breast-cancer-stem-progenitor-cells
#3
Shih-Ming Chen, Bing-Yen Wang, Che-Hsin Lee, Hsueh-Te Lee, Jung-Jung Li, Guan-Ci Hong, Yu-Chieh Hung, Peng-Ju Chien, Che-Ying Chang, Li-Sung Hsu, Wen-Wei Chang
Hinokitiol (β-thujaplicin) is a tropolone-related compound that has anti-microbe, anti-inflammation, and anti-tumor effects. Cancer stem/progenitor cells (CSCs) are a subpopulation of cancer cells with tumor initiation, chemoresistant, and metastatic properties and have been considered the important therapeutic target in future cancer therapy. Previous studies reported that hinokitiol exhibits an anti-cancer activity against murine tumor cells through the induction of autophagy. The current research revealed that hinokitiol suppressed the self-renewal capabilities of human breast CSCs (BCSCs) and inhibited the expression of BMI1 at protein level without suppressing its mRNA...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099265/analysis-of-defective-protein-ubiquitylation-associated-to-adriamycin-resistant-cells
#4
Valérie Lang, Fabienne Aillet, Wendy Xolalpa, Sonia Serna, Laurie Ceccato, Rosa G Lopez-Reyes, Maria Paz Lopez-Mato, Radosław Januchowski, Niels-Christian Reichardt, Manuel S Rodriguez
DNA damage activated by Adriamycin (ADR) promotes ubiquitin-proteasome system-mediated proteolysis by stimulating both the activity of ubiquitylating enzymes and the proteasome. In ADR-resistant breast cancer MCF7 (MCF7(ADR)) cells, protein ubiquitylation is significantly reduced compared to the parental MCF7 cells. Here, we used tandem ubiquitin-binding entities (TUBEs) to analyze the ubiquitylation pattern observed in MCF7 or MCF7(ADR) cells. While in MCF7, the level of total ubiquitylation increased up to six-fold in response to ADR, in MCF7(ADR) cells only a two-fold response was found...
November 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29080702/glioblastoma-and-chemoresistance-to-alkylating-agents-involvement-of-apoptosis-autophagy-and-unfolded-protein-response
#5
REVIEW
Sabine Hombach-Klonisch, Maryam Mehrpour, Shahla Shojaei, Craig Harlos, Marshall Pitz, Ahmed Hamai, Krzysztof Siemianowicz, Wirginia Likus, Emilia Wiechec, Brian D Toyota, Reyhane Hoshyar, Amir Seyfoori, Zahra Sepehri, Sudharsana R Ande, Forough Khadem, Mohsen Akbari, Adrienne M Gorman, Afshin Samali, Thomas Klonisch, Saeid Ghavami
Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB...
November 8, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29073720/malat1-modulates-the-autophagy-of-retinoblastoma-cell-through-mir-124-mediated-stx17-regulation
#6
Jun Huang, Yuting Yang, Fang Fang, Ke Liu
The retinoblastoma is the most common intraocular malignant tumor in infants and children; it is one of the deadliest forms of cancer due to its limited sensitivity to chemotherapy and radiotherapy. In several cancers, chemoresistance is associated with autophagy induction. Non-coding RNAs, including long non-coding RNAs (lncRNA) and microRNAs (miRNAs) have been reported to regulate physiological activities of the cells, including proliferation, apoptosis, migration, as well as autophagy. MALAT1, a well-established lncRNA acts as an oncogene, promotes cancer proliferation and metastasis via the stimulation of autophagy...
October 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29069735/hmgb1-mediated-autophagy-attenuates-gemcitabine-induced-apoptosis-in-bladder-cancer-cells-involving-jnk-and-erk-activation
#7
Hubin Yin, Xiaoyu Yang, Wen Gu, Yan Liu, Xinyuan Li, Xiaolong Huang, Xin Zhu, Yong Tao, Xin Gou, Weiyang He
High-mobility group box 1 (HMGB1) has been found to mediate autophagy during chemotherapy in several cancers. However, whether HMGB1plays a role in autophagy and chemoresistance in bladder cancer is elusive. In this report, HMGB1 expression was found to be increased in 30 primary bladder cancer tissue specimens compared to their matched adjacent non-tumor tissues. While gemcitabine induced apoptotic cell death, it also induced HMGB1 expression and autophagy in bladder cancer T24 and BIU-87 cells. Suppressing HMGB1 expression with siRNA strongly potentiated gemcitabine-induced apoptosis...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027991/n6-isopentenyladenosine-dual-targeting-of-ampk-and-rab7-prenylation-inhibits-melanoma-growth-through-the-impairment-of-autophagic-flux
#8
Roberta Ranieri, Elena Ciaglia, Giuseppina Amodio, Paola Picardi, Maria Chiara Proto, Patrizia Gazzerro, Chiara Laezza, Paolo Remondelli, Maurizio Bifulco, Simona Pisanti
Targeting the autophagic process is considered a promising therapeutic strategy in cancer since a great number of tumors, including melanoma, show high basal levels of protective autophagy that contributes to tumor progression and chemoresistance. Here, exploiting both in vitro and in vivo approaches, we identified N6-isopentenyladenosine (iPA), an end product of the mevalonate pathway, as a novel autophagy inhibitor with an interesting anti-melanoma activity. iPA, after being phosphorylated by adenosine kinase into 5'-iPA-monophosphate, induces autophagosome accumulation through AMPK activation, measured by increased fluorescent GFP-LC3 puncta and enhanced conversion into the lipidated autophagosome-associated LC3-II...
October 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29022200/high-expression-of-the-mitophagy-related-protein-pink1-is-associated-with-a-poor-response-to-chemotherapy-and-a-poor-prognosis-for-patients-treated-with-neoadjuvant-chemotherapy-for-esophageal-squamous-cell-carcinoma
#9
Kotaro Yamashita, Hiroshi Miyata, Tomoki Makino, Yasunori Masuike, Haruna Furukawa, Koji Tanaka, Yasuhiro Miyazaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Shuji Takiguchi, Eiichi Morii, Masaki Mori, Yuichiro Doki
BACKGROUND: Autophagy plays a major role in cellular homeostasis and is implicated in cancer progression. Damaged mitochondria are scavenged and eliminated by mitochondrial autophagy, referred to as mitophagy, which can promote cancer cell survival. This study investigated the expression and effects of the autophagy-related protein LC3 and the mitophagy-related protein Pink1 in human esophageal squamous cell carcinoma (ESCC). METHODS: Both LC3 and Pink1 were analyzed by immunohistochemistry in tissues from 217 ESCC patients, including 159 patients undergoing neoadjuvant chemotherapy...
October 11, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28978341/mab-mdr1-modified-chitosan-nanoparticles-overcome-acquired-egfr-tki-resistance-through-two-potential-therapeutic-targets-modulation-of-mdr1-and-autophagy
#10
Yan Zheng, Chang Su, Liang Zhao, Yijie Shi
BACKGROUND: Tyrosine kinase inhibitors (TKIs) that act against the epithelial growth factor receptor (EGFR) were once widely used in chemotherapy for many human cancers. However, acquired chemoresistance occurred in almost all patients, limiting the clinical application of EGFR-TKI. Thus far, no effective methods existing can resolve this problem. Designing a therapeutic treatment with a specific multi-target profile has been regarded as a possible strategy to overcome acquired EGFR-TKI resistance...
October 4, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28977798/intensified-beclin-1-mediated-by-low-expression-of-mir-30a-5p-promotes-chemoresistance-in-human-small-cell-lung-cancer
#11
Xiang Yang, Fan Bai, Yichen Xu, Yitian Chen, Longbang Chen
BACKGROUND/AIMS: Although small cell lung cancer (SCLC) is sensitive to initial chemotherapy, patients experience tumor recurrence and metastasis, leading to treatment failure. Autophagy as a protective pattern for cell survival in the harsh environment plays an important role in chemoresistance. However, the role of Beclin-1, a key regulator of autophagy in the drug-resistance of SCLC cells is still poorly understood. In the current study, we focused on the effect and regulation of Beclin-1 in chemoresistance of SCLC cells...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28962872/ucp2-inhibition-induces-ros-akt-mtor-axis-role-of-gapdh-nuclear-translocation-in-genipin-everolimus-anticancer-synergism
#12
Ilaria Dando, Raffaella Pacchiana, Elisa Dalla Pozza, Ivana Cataldo, Stefano Bruno, Paola Conti, Marco Cordani, Anna Grimaldi, Giovanna Butera, Michele Caraglia, Aldo Scarpa, Marta Palmieri, Massimo Donadelli
Several studies indicate that mitochondrial uncoupling protein 2 (UCP2) plays a pivotal role in cancer development by decreasing reactive oxygen species (ROS) produced by mitochondrial metabolism and by sustaining chemoresistance to a plethora of anticancer drugs. Here, we demonstrate that inhibition of UCP2 triggers Akt/mTOR pathway in a ROS-dependent mechanism in pancreatic adenocarcinoma cells. This event reduces the antiproliferative outcome of UCP2 inhibition by genipin, creating the conditions for the synergistic counteraction of cancer cell growth with the mTOR inhibitor everolimus...
September 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28962169/microrna-320-regulates-autophagy-in-retinoblastoma-by-targeting-hypoxia-inducible-factor-1%C3%AE
#13
Yong Liang, Xi Chen, Zhu Liang
Retinoblastoma (RB) is the most common malignancy in children. Due to refractory mechanisms of chemoresistance and the toxicity of chemotherapies, novel therapies for RB treatment are urgently required. MicroRNA-320 (miR-320) is believed to be associated with the tumorigenesis of RB, although the mechanism remains unclear. Considering the hypoxic intratumoral region, the roles of miR-320 and hypoxia inducible factor-1α (HIF-1α) in the regulation of autophagy were investigated in 30 human RB samples and WERI-RB1 cells...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28949455/autophagy-inhibition-upregulates-cd4-tumor-infiltrating-lymphocyte-expression-via-mir-155-regulation-and-trail-activation
#14
(no author information available yet)
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...
December 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28945807/modulating-lysosomal-function-through-lysosome-membrane-permeabilization-or-autophagy-suppression-restores-sensitivity-to-cisplatin-in-refractory-non-small-cell-lung-cancer-cells
#15
Magdalena Circu, James Cardelli, Martin Barr, Kenneth O'Byrne, Glenn Mills, Hazem El-Osta
Lung cancer is the leading cause of cancer-related deaths. Most patients develop resistance to platinum within several months of treatment. We investigated whether triggering lysosomal membrane permeabilization (LMP) or suppressing autophagy can restore cisplatin susceptibility in lung cancer with acquired chemoresistance. Cisplatin IC50 in A549Pt (parental) and A549cisR (cisplatin resistant) cells was 13 μM and 47 μM, respectively. Following cisplatin exposure, A549cisR cells failed to elicit an apoptotic response...
2017: PloS One
https://www.readbyqxmd.com/read/28938696/the-molecular-mechanisms-of-chemoresistance-in-cancers
#16
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28906492/ndrg1-inhibition-sensitizes-osteosarcoma-cells-to-combretastatin-a-4-through-targeting-autophagy
#17
Hongsheng Wang, Wen Li, Jing Xu, Tao Zhang, Dongqing Zuo, Zifei Zhou, Binhui Lin, Gangyang Wang, Zhuoying Wang, Wei Sun, Mengxiong Sun, Shimin Chang, Zhengdong Cai, Yingqi Hua
Combretastatin A-4 (CA-4), a tubulin-depolymerizing agent, shows promising antitumor efficacy and has been under several clinical trials in solid tumors for 10 years. Autophagy has an important pro-survival role in cancer therapy, thus targeting autophagy may improve the efficacy of antitumor agents. N-myc downstream-regulated gene 1 (NDRG1) is a significant stress regulatory gene, which mediates cell survival and chemoresistance. Here we reported that CA-4 could induce cell-protective autophagy, and combination treatment of CA-4 and autophagy inhibitor chloroquine (CQ) exerted synergistic cytotoxic effect on human osteosarcoma (OS) cells...
September 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28899456/clc5-decreases-the-sensitivity-of-multiple-myeloma-cells-to-bortezomib-via-promoting-pro-survival-autophagy
#18
Huimin Zhang, Yuhui Pang, Chuanbao Ma, Jianying Li, Huaquan Wang, Zonghong Shao
Resistance to bortezomib (BZ) is the major problem that largely limits its clinical application in multiple myeloma treatment. In current study, we investigated whether ClC5, a member of the chloride channel family, involved in this process. The results of MTT assay showed that BZ treatment decreased cell viability in three multiple myeloma cell lines (ARH77, U266 and SKO-007), with the IC50 value of 2.83 nM, 4.37 nM and 1.91 nM, respectively. Moreover, BZ increased the conversion of LC3B-I to LC3B-II and expressions of Beclin-1 and ATG5, concomitantly with decreased p62 expression...
September 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28861639/repositioning-of-proton-pump-inhibitors-in-cancer-therapy
#19
REVIEW
Zhen-Ning Lu, Bing Tian, Xiu-Li Guo
Drug repositioning, as a smart way to exploit new molecular targets of a known drug, has been gaining increasing attention in the discovery of anti-cancer drugs. Proton pump inhibitors (PPIs) as benzimidazole derivatives, which are essentially H(+)-K(+)-ATPases inhibitors, are commonly used in the treatment of acid-related diseases such as gastric ulcer. In recent years, exploring the new application of PPIs in anti-cancer field has become a hot research topic. Interestingly, cancer cells display an alkaline intracellular pH and an acidic extracellular pH...
August 31, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28807161/phytochemical-modulation-of-apoptosis-and-autophagy-strategies-to-overcome-chemoresistance-in-leukemic-stem-cells-in-the-bone-marrow-microenvironment
#20
Helen C Owen, Sandra Appiah, Noor Hasan, Lucy Ghali, Ghada Elayat, Celia Bell
Advances in scientific research and targeted treatment regimes have improved survival rates for many cancers over the past few decades. However, for some types of leukemia, including acute lymphoblastic and acute myeloid leukemia, mortality rates have continued to rise, with chemoresistance in leukemic stem cells (LSCs) being a major contributing factor. Most cancer drug therapies act by inducing apoptosis in dividing cells but are ineffective in targeting quiescent LSCs. Niches in the bone marrow, known as leukemic niches, behave as "sanctuaries" where LSCs acquire drug resistance...
2017: International Review of Neurobiology
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