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Autophagy and cancer

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https://www.readbyqxmd.com/read/28327651/inhibition-of-cathepsin-s-confers-sensitivity-to-methyl-protodioscin-in-oral-cancer-cells-via-activation-of-p38-mapk-jnk-signaling-pathways
#1
Ming-Ju Hsieh, Chiao-Wen Lin, Mu-Kuan Chen, Su-Yu Chien, Yu-Sheng Lo, Yi-Ching Chuang, Yi-Ting Hsi, Chia-Chieh Lin, Jui-Chieh Chen, Shun-Fa Yang
Oral cancer is one of the most common cancers in the world. Approximately 90% of oral cancers are subtyped to oral squamous cell carcinoma (OSCC). Despite advances in diagnostic techniques and improvement in treatment modalities, the prognosis remains poor. Therefore, an effective chemotherapy mechanism that enhances tumor sensitivity to chemotherapeutics is urgently needed. Methyl protodioscin (MP) is a furostanol bisglycoside with a wide range of beneficial effects, including anti-inflammatory and anti-cancer properties...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325820/autophagy-and-vitamin-d
#2
Alexandra A Mushegian
Vitamin D receptor represses basal autophagy in breast tissue, which is derepressed by vitamin D, slowing cancer progression.
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325600/synthesis-and-anti-cancer-activities-of-new-sulfonamides-4-substituted-triazolyl-nucleosides
#3
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...
March 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28324486/mitopho8%C3%AE-60-assay-as-a-tool-to-quantitatively-measure-mitophagy-activity
#4
Zhiyuan Yao, Xu Liu, Daniel J Klionsky
Mitophagy, a selective type of macroautophagy (hereafter referred to as autophagy), specifically mediates the vacuole/lysosome-dependent degradation of damaged or surplus mitochondria. Because this process regulates the number and quality of mitochondria, it is vital for proper cellular homeostasis. Mitophagy also plays critical roles in the clearance of paternal mitochondria in C. elegans embryos, in erythroid cell maturation, and in the prevention of neurodegenerative disease and cancer. In order to study the molecular mechanism and regulation of mitophagy, sensitive assays are necessary to quantitatively measure mitophagy activity...
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28323034/co-targeting-of-egfr-and-autophagy-signaling-is-an-emerging-treatment-strategy-in-metastatic-colorectal-cancer
#5
Evangelos Koustas, Michalis V Karamouzis, Chrysovalantou Mihailidou, Dimitrios Schizas, Athanasios G Papavassiliou
The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic Colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR moAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28323020/metabolic-reprogramming-in-cancer-cells-consequences-on-ph-and-tumour-progression-integrated-therapeutic-perspectives-with-dietary-lipids-as-adjuvant-to-anticancer-treatment
#6
REVIEW
Jean-François Dumas, Lucie Brisson, Stéphan Chevalier, Karine Mahéo, Gaëlle Fromont, Driffa Moussata, Pierre Besson, Sébastien Roger
While tumours arise from acquired mutations in oncogenes or tumour-suppressor genes, it is clearly established that cancers are metabolic diseases characterized by metabolic alterations in tumour cells, and also non-tumour cells of the host organism resulting in tumour cachexia and patient weakness. In this review, we aimed at delineating details by which metabolic alterations in cancer cells, characterized by mitochondrial bioenergetics deregulations and the preference for aerobic glycolysis, are critical parameters controlling the aggressive progression of tumours...
March 17, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28320471/influence-of-autophagy-on-the-efficacy-of-radiotherapy
#7
REVIEW
Shing Yau Tam, Vincent Wing Cheung Wu, Helen Ka Wai Law
Autophagy is an important catabolic process in which cells digest and recycle their own cytoplasmic contents for maintaining cellular homeostasis. Interestingly, autophagy could play both pro-death and pro-survival roles in influencing the development of cancer via various signal pathways. As radiotherapy is one of the main treatment modalities for cancer, we reviewed the effect of autophagy modulations on radiosensitivity and radiotherapy efficacy in various cancer types. The future development of autophagy modifications for improving radiotherapy efficacy and cancer prognosis will also be discussed...
March 21, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28319090/a-single-copy-sleeping-beauty-transposon-mutagenesis-screen-identifies-new-pten-cooperating-tumor-suppressor-genes
#8
Jorge de la Rosa, Julia Weber, Mathias Josef Friedrich, Yilong Li, Lena Rad, Hannes Ponstingl, Qi Liang, Sandra Bernaldo de Quirós, Imran Noorani, Emmanouil Metzakopian, Alexander Strong, Meng Amy Li, Aurora Astudillo, María Teresa Fernández-García, María Soledad Fernández-García, Gary J Hoffman, Rocío Fuente, George S Vassiliou, Roland Rad, Carlos López-Otín, Allan Bradley, Juan Cadiñanos
The overwhelming number of genetic alterations identified through cancer genome sequencing requires complementary approaches to interpret their significance and interactions. Here we developed a novel whole-body insertional mutagenesis screen in mice, which was designed for the discovery of Pten-cooperating tumor suppressors. Toward this aim, we coupled mobilization of a single-copy inactivating Sleeping Beauty transposon to Pten disruption within the same genome. The analysis of 278 transposition-induced prostate, breast and skin tumors detected tissue-specific and shared data sets of known and candidate genes involved in cancer...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28317223/cancer-with-low-cathepsin-d-levels-is-susceptible-to-v-atpase-inhibition
#9
Satoshi Kitazawa, Satoru Nishizawa, Hideyuki Nakagawa, Masaaki Funata, Kazuho Nishimura, Tomoyoshi Soga, Takahito Hara
Vacuolar (H(+) )-ATPases (V-ATPases) have important roles in the supply of nutrients to tumors by mediating autophagy and the endocytic uptake of extracellular fluids. Accordingly, V-ATPases are attractive therapeutic targets for cancer. However, the clinical use of V-ATPase inhibitors as anti-cancer drugs has not been realized, possibly owing to their high toxicity in humans. V-ATPase inhibition may be an appropriate strategy in highly susceptible cancers. In this study, we explored markers of V-ATPase inhibitor sensitivity...
March 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/28316954/molecular-pathways-controlling-autophagy-in-pancreatic-cancer
#10
REVIEW
Maria New, Tim Van Acker, Jaclyn S Long, Jun-Ichi Sakamaki, Kevin M Ryan, Sharon A Tooze
Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancer types where the 5-year survival rate shows no improvement. Despite conflicting evidence, the majority of data points to an essential role for autophagy in PDAC growth and survival, in particular constitutively activated autophagy, can provide crucial fuel to PDAC tumor cells in their nutrient-deprived environment. Autophagy, which is required for cell homeostasis, can both suppress and promote tumorigenesis and tumor survival in a context-dependent manner...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28316888/quantitative-and-correlation-analysis-of-the-dna-methylation-and-expression-of-dapk-in-breast-cancer
#11
Youzhi Zhu, Shuiqin Li, Qingshui Wang, Ling Chen, Kunlin Wu, Yide Huang, Xiangjin Chen, Yao Lin
BACKGROUND: Death-associated protein kinase 1 (DAPK) is an important tumor suppressor kinase involved in the regulation of multiple cellular activities such as apoptosis and autophagy. DNA methylation of DAPK gene was found in various types of cancers and often correlated with the clinicopathological characteristics. However, the mRNA and protein expression of DAPK in the same sample was rarely measured. Thus, it was unclear if the correlation between DAPK gene methylation and clinicopathological parameters was due to the loss of DAPK expression...
2017: PeerJ
https://www.readbyqxmd.com/read/28302910/new-insights-into-autophagosome-lysosome-fusion
#12
REVIEW
Shuhei Nakamura, Tamotsu Yoshimori
Macroautophagy (autophagy) is a highly conserved intracellular degradation system that is essential for homeostasis in eukaryotic cells. Due to the wide variety of the cytoplasmic targets of autophagy, its dysregulation is associated with many diseases in humans, such as neurodegenerative diseases, heart disease and cancer. During autophagy, cytoplasmic materials are sequestered by the autophagosome - a double-membraned structure - and transported to the lysosome for digestion. The specific stages of autophagy are induction, formation of the isolation membrane (phagophore), formation and maturation of the autophagosome and, finally, fusion with a late endosome or lysosome...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28302225/-advances-in-research-of-antitumor-mechanisms-of-isothiocyanates
#13
Huimin Wang, Ke Xu
Isothiocyanates (ITCs) are naturally occurring small molecules that are generated by the enzymic hydrolysis of glucosinolate in cruciferous vegetables. Numerous studies showed that ITCs inhibit the growth of tumors by the mechanisms including inducing cell cycle arrest, promoting apoptosis and producing reactive oxygen species in vitro and in vivo. Recent studies showed that ITCs also inhibit metastasis of cancer cells, induce endoplasmic reticulum stress and autophagy. This review summarizes the antitumor mechanisms of ITCs...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28302224/-advances-in-the-research-of-the-regulation-of-chinese-traditional-medicine-monomer-and-its-derivatives-on-autophagy-in-non-small-cell-lung-cancer
#14
Meiyi Xiang, Ruilei Li, Zhiwei Zhang, Xin Song
The high morbidity and mortality of non-small cell lung cancer (NSCLC) did influence the quality of life of tumor patients world-wide. There is an urgent need to develop new therapies that have high anti-tumor activity and low toxicity side effects. It is widely accepted that autophagy can play diverse roles in carcinogenesis, such as induces pro-death of lung cancer cells or helps the escape from cell death, making it become a proper anticancer target. It's believed that various monomers of Chinese traditional medicine closely correlates to anti-NSCLC activities, and that even could affect the acquired multiple drug resistance (MDR)...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28300829/cystatin-sn-inhibits-auranofin-induced-cell-death-by-autophagic-induction-and-ros-regulation-via-glutathione-reductase-activity-in-colorectal-cancer
#15
Byung Moo Oh, Seon-Jin Lee, Hee Jun Cho, Yun Sun Park, Jong-Tae Kim, Suk Ran Yoon, Sang Chul Lee, Jong-Seok Lim, Bo-Yeon Kim, Yong-Kyung Choe, Hee Gu Lee
Cystatin SN (CST1) is a specific inhibitor belonging to the cystatin superfamily that controls the proteolytic activities of cysteine proteases such as cathepsins. Our previous study showed that high CST1 expression enhances tumor metastasis and invasiveness in colorectal cancer. Recently, auranofin (AF), a gold(I)-containing thioredoxin reductase 1 (TrxR1) inhibitor, has been used clinically to treat rheumatoid arthritis. AF is a proteasome-associated deubiquitinase inhibitor and can act as an anti-tumor agent...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28298203/methylene-blue-photodynamic-therapy-induces-selective-and-massive-cell-death-in-human-breast-cancer-cells
#16
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/28298074/evaluation-of-growth-inhibitory-response-of-resveratrol-and-salinomycin-combinations-against-triple-negative-breast-cancer-cells
#17
Girish Rai, Shankar Suman, Sanjay Mishra, Yogeshwer Shukla
Resveratrol (RSVL) a dietary phytochemical showed to enhance the efficacy of chemotherapeutic drugs. Recently, Salinomycin (SAL) has gained importance as cancer therapeutic value for breast cancer (BC), however, its superfluxious toxicity delimits the utility. Taking the advantage of RSVL, the therapeutic efficacy of RSVL and SAL combination was studied in vitro and in vivo system. Firstly, the synergistic combination dose of RSVL and SAL was calculated and further, the efficacy was examined by wound healing, and Western blots analysis...
March 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28297606/a-novel-cellular-spheroid-based-autophagy-screen-applying-live-fluorescence-microscopy-identifies-nonactin-as-a-strong-inducer-of-autophagosomal-turnover
#18
Francesco Pampaloni, Benjamin Mayer, Konstantin Kabat Vel-Job, Nariman Ansari, Katharina Hötte, Donat Kögel, Ernst H K Stelzer
Dysregulation of the basal autophagic flux has been linked to several pathological conditions, including neurodegenerative diseases and cancer. In addition, autophagy has profound effects on the response of tumor cells to therapy. Hence, the search for pharmacological modulators of autophagy is of great clinical relevance. We established a drug screening assay in which the autophagic flux is measured by recording the fluorescence emission of the tandem fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28296597/acetylation-targets-hsd17b4-for-degradation-via-the-cma-pathway-in-response-to-estrone
#19
Ye Zhang, Ying-Ying Xu, Chuan-Bo Yao, Jin-Tao Li, Xiang-Ning Zhao, Hong-Bin Yang, Min Zhang, Miao Yin, Jing Chen, Qun-Ying Lei
Dysregulation of hormone metabolism is implicated in human breast cancer. 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) catalyzes the conversion of estradiol (E2) to estrone (E1), and is associated with the pathogenesis and development of various cancers. Here we show that E1 upregulates HSD17B4 acetylation at lysine 669 (K669) and thereby promotes HSD17B4 degradation via chaperone-mediated autophagy (CMA), while a single mutation at K669 reverses the degradation and confers migratory and invasive properties to MCF7 cells upon E1 treatment...
March 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28296542/the-autophagy-machinery-restrains-inkt-cell-activation-through-cd1d1-internalization
#20
Christian W Keller, Monica Loi, Svenja Ewert, Isaak Quast, Romina Theiler, Monique Gannagé, Christian Münz, Gennaro De Libero, Stefan Freigang, Jan D Lünemann
Invariant natural killer T (iNKT) cells are innate T cells with powerful immune regulatory functions that recognize glycolipid antigens presented by the CD1D protein. While iNKT-cell-activating glycolipids are currently being explored for their efficacy to improve immunotherapy against infectious diseases and cancer, little is known about the mechanisms that control CD1D antigen presentation and iNKT cell activation in vivo. CD1D molecules survey endocytic pathways to bind lipid antigens in MHC class II containing compartments (MIICs) before recycling to the plasma membrane...
March 15, 2017: Autophagy
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