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Dna repair and autophagy

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https://www.readbyqxmd.com/read/29775010/-molecular-mechanisms-of-chemoresistance-in-head-and-neck-squamous-cell-carcinoma
#1
REVIEW
Y X Zhao, Z F Sun
Head and neck squamous cell carcinoma (HNSCC) is an aggressive neoplasm with the properties of local recurrence and distant metastasis. Currently, cisplatin-based chemotherapy or concurrent radiochemotherapy is still the first choice or the treatment of advanced HNSCC. However, chemoresistance greatly limited the effectiveness of chemotherapy. Therefore, illustrating the mechanisms of chemoresistance is very important for the treatment of HNSCC. In this article, we summarize the molecular mechanisms of chemoresitance in HNSCC from the perspective of drug efflux, apoptosis, DNA damage and repair, epithelial mesenchymal transition and autophagy...
June 5, 2017: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/29701108/acute-kidney-injury-as-a-condition-of-renal-senescence
#2
Lucia Andrade, Camila E Rodrigues, Samirah A Gomes, Irene L Noronha
Acute kidney injury (AKI), characterized by a sharp drop in glomerular filtration, continues to be a significant health burden because it is associated with high initial mortality, morbidity, and substantial health-care costs. There is a strong connection between AKI and mechanisms of senescence activation. After ischemic or nephrotoxic insults, a wide range of pathophysiological events occur. Renal tubular cell injury is characterized by cell membrane damage, cytoskeleton disruption, and DNA degradation, leading to tubular cell death by necrosis and apoptosis...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29670369/inhibition-of-nipbl-enhances-the-chemosensitivity-of-non-small-cell-lung-cancer-cells-via-the-dna-damage-response-and-autophagy-pathway
#3
Lei Zheng, Huanhuan Zhou, Liwei Guo, Xiaoling Xu, Shengjie Zhang, Weizhen Xu, Weimin Mao
Background: Previously, we reported that high expression of nipped-B-like protein (NIPBL) was strongly correlated with poor prognosis, tumor differentiation, and lymph node metastasis. Survival analysis indicated that NIPBL expression was a potential prognostic factor for non-small cell lung cancer (NSCLC). Moreover, loss of NIPBL decreased lung cancer cells proliferation, migration, invasion and promoted apoptosis as well as sensitivity to chemotherapeutic agents. However, the deep mechanisms were not explored...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29658588/autophagy-inhibition-potentiates-saha%C3%A2-mediated-apoptosis-in-glioblastoma-cells-by-accumulation-of-damaged-mitochondria
#4
Kovooru Lohitesh, Heena Saini, Abhilasha Srivastava, Sudeshna Mukherjee, Aniruddha Roy, Rajdeep Chowdhury
Glioblastoma multiforme (GBM), often referred to as a grade IV astrocytoma, is the most invasive type of tumor arising from glial cells. The main treatment options for GBM include surgery, radiation and chemotherapy. However, these treatments tend to be only palliative rather than curative. Poor prognosis of GBM is due to its marked resistance to standard therapy. Currently, temozolomide (TMZ), an alkylating agent is used for treatment of GBM. However, GBM cells can repair TMZ‑induced DNA damage and therefore diminish the therapeutic efficacy of TMZ...
April 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29626215/the-coming-of-age-of-chaperone-mediated-autophagy
#5
REVIEW
Susmita Kaushik, Ana Maria Cuervo
Chaperone-mediated autophagy (CMA) was the first studied process that indicated that degradation of intracellular components by the lysosome can be selective - a concept that is now well accepted for other forms of autophagy. Lysosomes can degrade cellular cytosol in a nonspecific manner but can also discriminate what to target for degradation with the involvement of a degradation tag, a chaperone and a sophisticated mechanism to make the selected proteins cross the lysosomal membrane through a dedicated translocation complex...
April 6, 2018: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29602950/arsenic-containing-hydrocarbons-effects-on-gene-expression-epigenetics-and-biotransformation-in-hepg2-cells
#6
S M Müller, H Finke, F Ebert, J F Kopp, F Schumacher, B Kleuser, K A Francesconi, G Raber, T Schwerdtle
Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents...
March 30, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29584802/perturbed-autophagy-and-dna-repair-converge-to-promote-neurodegeneration-in-amyotrophic-lateral-sclerosis-and-dementia
#7
Callum Walker, Sherif F El-Khamisy
Maintaining genomic stability constitutes a major challenge facing cells. DNA breaks can arise from direct oxidative damage to the DNA backbone, the inappropriate activities of endogenous enzymes such as DNA topoisomerases, or due to transcriptionally-derived RNA/DNA hybrids (R-loops). The progressive accumulation of DNA breaks has been linked to several neurological disorders. Recently, however, several independent studies have implicated nuclear and mitochondrial genomic instability, perturbed co-transcriptional processing, and impaired cellular clearance pathways as causal and intertwined mechanisms underpinning neurodegeneration...
March 23, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29545557/autophagy-maintains-stem-cells-and-intestinal-homeostasis-in-drosophila
#8
Péter Nagy, Gyöngyvér O Sándor, Gábor Juhász
Intestinal homeostasis is maintained by tightly controlled proliferation and differentiation of tissue-resident multipotent stem cells during aging and regeneration, which ensures organismal adaptation. Here we show that autophagy is required in Drosophila intestinal stem cells to sustain proliferation, and preserves the stem cell pool. Autophagy-deficient stem cells show elevated DNA damage and cell cycle arrest during aging, and are frequently eliminated via JNK-mediated apoptosis. Interestingly, loss of Chk2, a DNA damage-activated kinase that arrests the cell cycle and promotes DNA repair and apoptosis, leads to uncontrolled proliferation of intestinal stem cells regardless of their autophagy status...
March 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29486795/the-first-in-class-alkylating-deacetylase-inhibitor-molecule-tinostamustine-shows-antitumor-effects-and-is-synergistic-with-radiotherapy-in-preclinical-models-of-glioblastoma
#9
Claudio Festuccia, Andrea Mancini, Alessandro Colapietro, Giovanni Luca Gravina, Flora Vitale, Francesco Marampon, Simona Delle Monache, Simona Pompili, Loredana Cristiano, Antonella Vetuschi, Vincenzo Tombolini, Yi Chen, Thomas Mehrling
BACKGROUND: The use of alkylating agents such as temozolomide in association with radiotherapy (RT) is the therapeutic standard of glioblastoma (GBM). This regimen modestly prolongs overall survival, also if, in light of the still dismal prognosis, further improvements are desperately needed, especially in the patients with O6-methylguanine-DNA-methyltransferase (MGMT) unmethylated tumors, in which the benefit of standard treatment is less. Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor (AK-DACi) molecule that fuses the DNA damaging effect of bendamustine with the fully functional pan-histone deacetylase (HDAC) inhibitor, vorinostat, in a completely new chemical entity...
February 27, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29480462/role-of-p62-in-the-regulation-of-cell-death-induction
#10
REVIEW
Lihong Fan, Shutao Yin, Enxiang Zhang, Hongbo Hu
p62 is a multifunctional adaptor protein implicated in various cellular processes. It has been found to regulate selective autophagy, cell survival, cell death, oxidative stress, DNA repair and inflammation, and to play a role in a number of diseases, such as tumourigenesis, Paget's disease of bone, neurodegenerative disease, diabetes, and obesity. Cell death induction is an important cellular process. The dysregulation of cell death induction is involved in the pathogenesis of various diseases, such as cancer, neurodegeneration diseases, and diabetes...
April 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29458719/culture-degeneration-in-conidia-of-beauveria-bassiana-and-virulence-determinants-by-proteomics
#11
Jiraporn Jirakkakul, Sittiruk Roytrakul, Chettida Srisuksam, Pratchya Swangmaneecharern, Suthathip Kittisenachai, Janthima Jaresitthikunchai, Juntira Punya, Peerada Prommeenate, Jittisak Senachak, Laihong So, Anuwat Tachaleat, Morakot Tanticharoen, Supapon Cheevadhanarak, Songsak Wattanachaisaereekul, Alongkorn Amnuaykanjanasin
The quality of Beauveria bassiana conidia directly affects the virulence against insects. In this study, continuous subculturing of B. bassiana on both rice grains and potato dextrose agar (PDA) resulted in 55 and 49 % conidial yield reduction after 12 passages and 68 and 60 % virulence reduction after 20 and 12 passages at four d post-inoculation, respectively. The passage through Tenebrio molitor and Spodoptera exigua restored the virulence of rice and PDA subcultures, respectively. To explore the molecular mechanisms underlying the conidial quality and the decline of virulence after multiple subculturing, we investigated the conidial proteomic changes...
February 2018: Fungal Biology
https://www.readbyqxmd.com/read/29419407/hyperoxia-causes-mitochondrial-fragmentation-in-pulmonary-endothelial-cells-by-increasing-expression-of-pro-fission-proteins
#12
Cui Ma, Andreas M Beyer, Matthew Durand, Anne V Clough, Daling Zhu, Laura Norwood Toro, Maia Terashvili, Johnathan D Ebben, R Blake Hill, Said H Audi, Meetha Medhora, Elizabeth R Jacobs
OBJECTIVE: We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia. APPROACH AND RESULTS: Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups...
March 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29374563/does-the-use-of-melatonin-overcome-drug-resistance-in-cancer-chemotherapy
#13
REVIEW
Mohammad Hossein Asghari, Emad Ghobadi, Milad Moloudizargari, Marjan Fallah, Mohammad Abdollahi
Our knowledge regarding the implications of melatonin in the therapy of numerous medical conditions, including cancer is constantly expanding. Melatonin can variably affect cancer pathology via targeting several key aspects of any neoplastic condition, including the very onset of carcinogenesis as well as tumor growth, differentiation, and dissemination. Numerous studies have examined the effects of melatonin in the context of various cancers reporting the enhanced efficacy of chemo/radiotherapy in combination with this compound...
March 1, 2018: Life Sciences
https://www.readbyqxmd.com/read/29354495/genetic-determinants-for-chemo-and-radiotherapy-resistance-in-bladder-cancer
#14
REVIEW
Andrea Mari, David D'Andrea, Mohammad Abufaraj, Beat Foerster, Shoji Kimura, Shahrokh F Shariat
Bladder cancer (BCa) is burdened by high rates of chemo- and radio-resistance. We reviewed and summarized the current evidence regarding the genetic determinants of resistance in patients treated with chemotherapy and/or radiotherapy (RT) for BCa. Genetic heterogeneity may preexist to treatment arising with tumorigenesis or increasing progressively during the treatment. Several biological pathways seem to be involved in the cellular response to treatment. These pathways comprehend mechanisms leading to modify the intracellular concentration of the drug, mechanisms leading to increase the repair of DNA damage caused by the treatment, mechanisms leading to increase cell survival, despite DNA damage, acting on the signaling pathways affecting apoptosis, mechanisms promoting autophagy...
December 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/29336782/loss-of-gpnmb-causes-autosomal-recessive-amyloidosis-cutis-dyschromica-in-humans
#15
Chi-Fan Yang, Shuan-Pei Lin, Chien-Ping Chiang, Yu-Hung Wu, Weng Siong H'ng, Chun-Ping Chang, Yuan-Tsong Chen, Jer-Yuarn Wu
Amyloidosis cutis dyschromica (ACD) is a distinct form of primary cutaneous amyloidosis characterized by generalized hyperpigmentation mottled with small hypopigmented macules on the trunks and limbs. Affected families and sporadic case subjects have been reported predominantly in East and Southeast Asian ethnicities; however, the genetic cause has not been elucidated. We report here that the compound heterozygosity or homozygosity of GPNMB truncating alleles is the cause of autosomal-recessive ACD. Six nonsense or frameshift mutations were identified in nine individuals diagnosed with ACD...
February 1, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29329412/lhx8-ablation-leads-to-massive-autophagy-of-mouse-oocytes-associated-with-dna-damage%C3%A2
#16
Laura D'Ignazio, Marc Michel, Melissa Beyer, Kassimier Thompson, Antonino Forabosco, David Schlessinger, Emanuele Pelosi
Following proliferation of oogonia in mammals, great numbers of germ cells are discarded, primarily by apoptosis, while the remainder form primordial follicles (the ovarian reserve) that determine fertility and reproductive lifespan. More massive, rapid, and essentially total loss of oocytes, however, occurs when the transcription factor Lhx8 is ablated-though the cause and mechanism of germ cell loss from the Lhx8-/- ovaries has been unknown. We found that Lhx8-/- ovaries maintain the same number of germ cells throughout embryonic development; rapid decrease in the pool of oocytes starts shortly before birth...
January 10, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29316551/chloroquine-enhances-the-radiosensitivity-of-bladder-cancer-cells-by-inhibiting-autophagy-and-activating-apoptosis
#17
Feng Wang, Jinyuan Tang, Pengchao Li, Shuhui Si, Hao Yu, Xiao Yang, Jun Tao, Qiang Lv, Min Gu, Haiwei Yang, Zengjun Wang
BACKGROUND/AIMS: Chloroquine was formerly used as an anti-malarial agent drug but has now been proven to be useful for various diseases. This study aimed to investigate the radiosensitizing effect of chloroquine in bladder cancer, with an emphasis on autophagy inhibition and apoptosis induction. METHODS: Bladder cancer cell lines were irradiated with or without chloroquine. Cell proliferation was determined by a Cell Counting Kit 8 assay. The radiosensitization effect of chloroquine was evaluated by clonogenic survival and progression of xenograft tumors...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#18
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
December 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29277783/up-regulation-of-uvrag-by-hdac1-inhibition-attenuates-5fu-induced-cell-death-in-hct116-colorectal-cancer-cells
#19
Yoon Kyung Jo, Na Yeon Park, Ji Hyun Shin, Doo Sin Jo, Ji-Eun Bae, Eun Sun Choi, Sungho Maeng, Hong Bae Jeon, Seon Ae Roh, Jong Wook Chang, Jin Cheon Kim, Dong-Hyung Cho
The ultraviolent irradiation resistance-associated gene (UVRAG), a component of the Beclin 1/autophagy-related 6 complex, regulates the autophagy initiation step and functions in the DNA-damage response. UVRAG is frequently mutated in various cancer types, and mutations of UVRAG increase sensitivity to chemotherapy by impairing DNA-damage repair. In this study, we addressed the epigenetic regulation of UVRAG in colorectal cancer cells. UVRAG expression was increased in cells treated with histone deacetylase (HDAC) inhibitors, such as valproic acid and suberoylanilide hydroxamic acid...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29277777/amifostine-protects-mouse-liver-against-radiation-induced-autophagy-blockage
#20
Michael I Koukourakis, Alexandra Giatromanolaki, Konstantina Fylaktakidou, Maria Kouroupi, Efthimios Sivridis, Christos E Zois, Dimitra Kalamida, Achilleas Mitrakas, Stamatia Pouliliou, Ilias V Karagounis, Konstantinos Simopoulos, David J P Ferguson, Adrian L Harris
BACKGROUND/AIM: Amifostine is the only selective normal tissue cytoprotector, approved for the protection against platinum toxicities and radiotherapy-induced xerostomia. Free radical scavenger and DNA repair activities have been attributed to the drug. MATERIALS AND METHODS: We investigated the effect of amifostine on autophagy, lysosomal biogenesis and lipophagy of normal mouse liver exposed to clinically relevant doses of radiation. RESULTS: The study provides evidence that ionizing radiation blocks autophagy activity and lysosomal biogenesis in normal mouse liver...
January 2018: Anticancer Research
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