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Autophagy and radiation resistance

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https://www.readbyqxmd.com/read/29710477/mir-125b-is-downregulated-in-systemic-lupus-erythematosus-patients-and-inhibits-autophagy-by-targeting-uvrag
#1
Wenting Cao, Ge Qian, Wen Luo, Xin Liu, Yunjing Pu, Guilan Hu, Lulu Han, Limei Yuan, Xiao A, Danqi Deng
Systemic lupus erythematosus (SLE) is a severe autoimmune disease and the pathogenesis remains incompletely understood. This study aimed to investigate the role of miR-125b in the pathogenesis of SLE and explore the underlying mechanism. Compared to healthy controls, the expression of miR-125b decreased in peripheral blood mononuclear cells (PBMCs) of SLE patients. In addition, PBMCs exposed to ultraviolet B had lower miR-125b level compared to those unexposed to radiation. We identified UV radiation resistance associated gene (UVRAG) as a target of miR-125b...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29658588/autophagy-inhibition-potentiates-saha%C3%A2-mediated-apoptosis-in-glioblastoma-cells-by-accumulation-of-damaged-mitochondria
#2
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/29644941/role-of-micrornas-in-treatment-response-in-prostate-cancer
#3
Anshuli Razdan, Paul de Souza, Tara Laurie Roberts
Prostate cancer (PCa) is the most common non-skin cancer in men worldwide, resulting in significant mortality and morbidity. Depending on the grade and stage of the cancer, patients may be given radiation therapy, hormonal therapy, or chemotherapy. However, more than half these patients develop resistance to treatment, leading to disease progression and metastases, often with lethal consequences. MicroRNAs (miRNAs) are short, non-coding RNAs, which regulate numerous physiological as well as pathological processes, including cancer...
March 15, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29609505/radiosensitivity-enhancement-of-fe-3-o-4-ag-nanoparticles-on-human-glioblastoma-cells
#4
Xiaohong Zhang, Zhujun Liu, Zhichao Lou, Feng Chen, Shuquan Chang, Yuji Miao, Zhuo Zhou, Xiaodan Hu, Jundong Feng, Qi Ding, Peidang Liu, Ning Gu, Haiqian Zhang
Radiotherapy is one of the main therapeutic methods for cancers, but radiation resistance of cancer cells still remains a serious concern. Searching for radiosensitizers to overcome such resistance is therefore urgently required. The goal of this study is to evaluate and compare the radiosensitizing efficacy of Fe3 O4 -OA, Ag and Fe3 O4 @Ag nanoparticles on U251 cells. The results show that Fe3 O4 @Ag nanoparticles have the highest ability of radiosensitization among the three nanoparticles. The underlying mechanism of Fe3 O4 @Ag nanoparticles' radiosensitivity enhancement is through decrease of the cytoprotective autophagy at the early stage, and increase of the calcium-dependent apoptosis at the later stage...
April 3, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29602802/smad4-gene-mutation-renders-pancreatic-cancer-resistance-to-radiotherapy-through-promotion-of-autophagy
#5
Feng Wang, Xiaojun Xia, Chunying Yang, Jianliang Shen, Junhua Mai, Han-Cheon Kim, Dickson Kirui, Ya'an Kang, Jason B Fleming, Eugene J Koay, Sankar Mitra, Mauro Ferrari, Haifa Shen
PURPOSE: Understanding the mechanism of radioresistance could help develop strategies to improve therapeutic response of patients with PDAC. The SMAD4 gene is frequently mutated in pancreatic cancer. In this study, we investigated the role of SMAD4 deficiency in pancreatic cancer cells' response to radiotherapy. EXPERIMENTAL DESIGN: We downregulated SMAD4 expression with SMAD4 siRNA or SMAD4 shRNA and overexpressed SMAD4 in SMAD4 mutant pancreatic cancer cells followed by clonogenic survival assay to evaluate their effects on cell radioresistance...
March 30, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29470638/long-term-effects-of-low-dose-mouse-liver-irradiation-involve-ultrastructural-and-biochemical-changes-in-hepatocytes-that-depend-on-lipid-metabolism
#6
Malgorzata Lysek-Gladysinska, Anna Wieczorek, Anna Walaszczyk, Karol Jelonek, Artur Jozwik, Monika Pietrowska, Wolfgang Dörr, Dorota Gabrys, Piotr Widlak
The aim of the study was to investigate long-term effects of radiation on the (ultra)structure and function of the liver in mice. The experiments were conducted on wild-type C57BL/6J and apolipoprotein E knock-out (ApoE-/- ) male mice which received a single dose (2 or 8 Gy) of X-rays to the heart with simultaneous exposure of liver to low doses (no more than 30 and 120 mGy, respectively). Livers were collected for analysis 60 weeks after irradiation and used for morphological, ultrastructural, and biochemical studies...
May 2018: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/29313410/ulk1-phosphorylates-ser30-of-becn1-in-association-with-atg14-to-stimulate-autophagy-induction
#7
Ji-Man Park, Minchul Seo, Chang Hwa Jung, Douglas Grunwald, Matthew Stone, Neil Michael Otto, Erik Toso, Yeseul Ahn, Michael Kyba, Timothy J Griffin, LeeAnn Higgins, Do-Hyung Kim
ULK1 (unc51-like autophagy activating kinase 1) is a serine/threonine kinase that plays a key role in regulating macroautophagy/autophagy induction in response to amino acid starvation. Despite the recent progress in understanding ULK1 functions, the molecular mechanism by which ULK1 regulates the induction of autophagy remains elusive. In this study, we determined that ULK1 phosphorylates Ser30 of BECN1 (Beclin 1) in association with ATG14 (autophagy-related 14) but not with UVRAG (UV radiation resistance associated)...
February 21, 2018: Autophagy
https://www.readbyqxmd.com/read/29232380/inhibition-of-grp78-abrogates-radioresistance-in-oropharyngeal-carcinoma-cells-after-egfr-inhibition-by-cetuximab
#8
Chaonan Sun, Chuyang Han, Yuanjun Jiang, Ning Han, Miao Zhang, Guang Li, Qiao Qiao
The EGFR-specific mAb cetuximab is one of the most effective treatments for oropharyngeal carcinoma, while patient responses to EGFR inhibitors given alone are modest. Combination treatment with radiation can improve the efficacy of treatment through increasing radiosensitivity, while resistance to radiation after administration of cetuximab limits its efficiency. Radiation and drugs can damage the endoplasmic reticulum (ER) homeostatic state and result in ER stress (ERS), subsequently causing resistance to radiation and drugs...
2017: PloS One
https://www.readbyqxmd.com/read/29184027/vacuolar-trafficking-protein-vps38-is-dispensable-for-autophagy
#9
Han Nim Lee, Xavier Zarza, Jeong Hun Kim, Min Ji Yoon, Sang-Hoon Kim, Jae-Hoon Lee, Nadine Paris, Teun Munnik, Marisa S Otegui, Taijoon Chung
Phosphatidylinositol 3-P (PI3P) is a signaling molecule that controls a variety of processes in endosomal, autophagic, and vacuolar/lysosomal trafficking in yeasts and mammals. Vacuolar protein sorting 34 (Vps34) is a conserved PI3K present in multiple complexes with specific functions and regulation. In yeast, the PI3K complex II consists of Vps34p, Vps15p, Vps30p/Atg6p, and Vps38p, and is essential for vacuolar protein sorting. Here, we describe the Arabidopsis ( Arabidopsis thaliana ) homolog of yeast Vps38p and human UV radiation resistance-associated gene protein...
February 2018: Plant Physiology
https://www.readbyqxmd.com/read/29180045/unraveling-the-human-protein-atlas-of-metastatic-melanoma-in-the-course-of-ultraviolet-radiation-derived-photo-therapy
#10
Eumorphia G Konstantakou, Athanassios D Velentzas, Athanasios K Anagnostopoulos, Aikaterini F Giannopoulou, Ema Anastasiadou, Issidora S Papassideri, Gerassimos E Voutsinas, George Th Tsangaris, Dimitrios J Stravopodis
To explore the photo-therapeutic capacity of UV radiation in solid tumors, we herein employed an nLC-MS/MS technology to profile the proteomic landscape of irradiated WM-266-4 human metastatic-melanoma cells. Obtained data resulted in proteomic catalogues of 5982 and 7280 proteins for UVB- and UVC-radiation conditions, respectively, and indicated the ability of UVB/C-radiation forms to eliminate metastatic-melanoma cells through induction of synergistically operating programs of apoptosis and necroptosis. However, it seems that one or more WM-266-4 cell sub-populations may escape from UV-radiation's photo-damaging activity, acquiring, besides apoptosis tolerance, an EMT phenotype that likely offers them the advantage of developing resistance to certain chemotherapeutic drugs...
November 24, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29104459/effects-of-oral-glutamine-on-inflammatory-and-autophagy-responses-in-cancer-patients-treated-with-abdominal-radiotherapy-a-pilot-randomized-trial
#11
Juan J Ortiz de Urbina, Beatriz San-Miguel, Alfonso Vidal-Casariego, Irene Crespo, Diana I Sánchez, José L Mauriz, Jesús M Culebras, Javier González-Gallego, María J Tuñón
Background and Aims: Abdominal radiotherapy (RT) causes harm to the mid gastrointestinal mucosa by release of pro-inflammatory cytokines and promotes autophagic changes in tumor cells. This study was aimed to measure the effect of glutamine administration on markers of inflammation and autophagy in cancer patients treated with RT. Methods: In this double-blind, randomized, controlled pilot trial 43 patients under abdominal RT diagnosed of pelvic or abdominal malignancies receiving glutamine (30 g/d) or placebo (casein, 30 g/d)...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29098039/similarity-in-the-functions-of-hif-1%C3%AE-and-hif-2%C3%AE-proteins-in-cervical-cancer-cells
#12
Lixia Jiang, Shaohua Shi, Qiaofa Shi, Huijuan Zhang, Rong Hu, Meizhen Wang
Hypoxia is a common feature of many solid tumours, including cervical cancer. Aggressive tumour progression is mostly associated with hypoxia. Furthermore, hypoxic conditions in tumours are also associated with resistance to chemotherapy and radiation, and with poor prognosis. Hypoxia inducible factor (HIF)-1, composed of a constitutively expressed β-subunit (HIF-β/ARNT) and one of the three known oxygen-regulated α-subunits, HIF-1α, HIF-2α, or HIF-3α, mediates the tumour cell response to hypoxia. The distinction between the roles of HIF-1α and HIF-2α in tumorigenesis is not clearly delineated...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/28947954/bh3-mimetic-obatoclax-gx15-070-mediates-mitochondrial-stress-predominantly-via-mcl-1-inhibition-and-induces-autophagy-dependent-necroptosis-in-human-oral-cancer-cells
#13
Prasad Sulkshane, Tanuja Teni
We have previously reported overexpression of antiapoptotic MCL-1 protein in human oral cancers and its association with therapy resistance and poor prognosis, implying it to be a potential therapeutic target. Hence, we investigated the efficacy and mechanism of action of Obatoclax, a BH3 mimetic pan BCL-2 inhibitor in human oral cancer cell lines. All cell lines exhibited high sensitivity to Obatoclax with complete clonogenic inhibition at 200-400 nM concentration which correlated with their MCL-1 expression...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900507/targeting-micrornas-in-prostate-cancer-radiotherapy
#14
REVIEW
Jie Ni, Joseph Bucci, Lei Chang, David Malouf, Peter Graham, Yong Li
Radiotherapy is one of the most important treatment options for localized early-stage or advanced-stage prostate cancer (CaP). Radioresistance (relapse after radiotherapy) is a major challenge for the current radiotherapy. There is great interest in investigating mechanisms of radioresistance and developing novel treatment strategies to overcome radioresistance. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression at the post-transcriptional level, participating in numerous physiological and pathological processes including cancer invasion, progression, metastasis and therapeutic resistance...
2017: Theranostics
https://www.readbyqxmd.com/read/28872463/mtorc1-hyperactivation-arrests-bone-growth-in-lysosomal-storage-disorders-by-suppressing-autophagy
#15
Rosa Bartolomeo, Laura Cinque, Chiara De Leonibus, Alison Forrester, Anna Chiara Salzano, Jlenia Monfregola, Emanuela De Gennaro, Edoardo Nusco, Isabella Azario, Carmela Lanzara, Marta Serafini, Beth Levine, Andrea Ballabio, Carmine Settembre
The mammalian target of rapamycin complex 1 (mTORC1) kinase promotes cell growth by activating biosynthetic pathways and suppressing catabolic pathways, particularly that of macroautophagy. A prerequisite for mTORC1 activation is its translocation to the lysosomal surface. Deregulation of mTORC1 has been associated with the pathogenesis of several diseases, but its role in skeletal disorders is largely unknown. Here, we show that enhanced mTORC1 signaling arrests bone growth in lysosomal storage disorders (LSDs)...
October 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28870998/histone-deacetylases-as-new-therapeutic-targets-in-triple-negative-breast-cancer-progress-and-promises
#16
REVIEW
Nikolaos Garmpis, Christos Damaskos, Anna Garmpi, Emmanouil Kalampokas, Theodoros Kalampokas, Eleftherios Spartalis, Afrodite Daskalopoulou, Serena Valsami, Michael Kontos, Afroditi Nonni, Konstantinos Kontzoglou, Despina Perrea, Nikolaos Nikiteas, Dimitrios Dimitroulis
Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR) and HER2 gene. It comprises approximately 15-20% of breast cancers (BCs). Unfortunately, TNBC's treatment continues to be a clinical problem because of its relatively poor prognosis, its aggressiveness and the lack of targeted therapies, leaving chemotherapy as the mainstay of treatment. It is essential to find new therapies against TNBC, in order to surpass the resistance and the invasiveness of already existing therapies...
September 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28870216/trifluoperazine-a-novel-autophagy-inhibitor-increases-radiosensitivity-in-glioblastoma-by-impairing-homologous-recombination
#17
Xin Zhang, Ran Xu, Chao Zhang, Yangyang Xu, Mingzhi Han, Bin Huang, Anjing Chen, Chen Qiu, Frits Thorsen, Lars Prestegarden, Rolf Bjerkvig, Jian Wang, Xingang Li
BACKGROUND: Resistance to adjuvant radiotherapy is a major cause of treatment failure in patients with glioblastoma (GBM). Autophagy inhibitors have been shown to enhance the efficacy of radiotherapy for certain solid tumors. However, current inhibitors do not penetrate the blood-brain-barrier (BBB). Here, we assessed the radiosensitivity effects of the antipsychotic drug trifluoperazine (TFP) on GBM in vitro and in vivo. METHODS: U251 and U87 GBM cell lines as well as GBM cells from a primary human biopsy (P3), were used in vitro and in vivo to evaluate the efficacy of TFP treatment...
September 5, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28857256/autophagy-dependent-crosstalk-between-gilt-and-pax-3-influences-radiation-sensitivity-of-human-melanoma-cells
#18
Jessica D Hathaway-Schrader, Bently P Doonan, Azim Hossain, Faisal F Y Radwan, Lixia Zhang, Azizul Haque
Melanoma represents an ever-increasing problem in the western world as incidence rates continue to climb. Though manageable during early stages, late stage metastatic disease is highly resistant to current intervention. We have previously shown that gamma-interferon-inducible lysosomal thiol-reductase (GILT) enhances HLA class II antigen processing and immune detection of human melanoma cells. Here we report that GILT expression inhibits a potential target, paired box-3 (PAX-3) protein, in late stage human metastatic melanoma...
February 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28726776/autophagosome-maturation-mediated-by-rab7-contributes-to-neuroprotection-of-hypoxic-preconditioning-against-global-cerebral-ischemia-in-rats
#19
Lixuan Zhan, Siyuan Chen, Kongping Li, Donghai Liang, Xinyong Zhu, Liu Liu, Zhiwei Lu, Weiwen Sun, En Xu
Autophagy disruption leads to neuronal damage in hypoxic-ischemic brain injury. Rab7, a member of the Rab GTPase superfamily, has a unique role in the regulation of autophagy. Hypoxic preconditioning (HPC) provides neuroprotection against transient global cerebral ischemia (tGCI). However, the underlying mechanisms remain poorly understood. Thus, the current study explored the potential molecular mechanism of the neuroprotective effect of HPC by investigating how Rab7 mediates autophagosome (AP) maturation after tGCI in adult rats...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28627629/reducing-autophagy-and-inducing-g1-phase-arrest-by-aloperine-enhances-radio-sensitivity-in-lung-cancer-cells
#20
Zhijie Xu, Yuanliang Yan, Shuangshuang Zeng, Long Qian, Shuang Dai, Lingfang Xiao, Lin Wang, Xue Yang, Yi Xiao, Zhicheng Gong
Aloperine (ALO), an isolated alkaloid from the leaves of Sophora alopecuroides (S. alopecuroides), has been suggested to exhibit anti-inflammatory and antitumor properties, and has been traditionally used to treat various diseases, including cancers. However, little is known about the effects of ALO on the radio-sensitivity of lung cancer cells. In the present study, we confirmed that agent ALO inhibits cell growth, promotes cell aopotosis and induces G1 phase arrest and consequently enhanced the radio-sensitivity in radio-resistant lung cancer cells A549/IR...
June 19, 2017: Oncology Reports
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