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https://www.readbyqxmd.com/read/28225015/identification-of-protein-biomarkers-and-signaling-pathways-associated-with-prostate-cancer-radioresistance-using-label-free-lc-ms-ms-proteomic-approach
#1
Lei Chang, Jie Ni, Julia Beretov, Valerie C Wasinger, Jingli Hao, Joseph Bucci, David Malouf, David Gillatt, Peter H Graham, Yong Li
Identifying biomarkers and signaling pathways are important for the management of prostate cancer (CaP) radioresistance. In this study, we identified differential proteins and signaling pathways from parental CaP cell lines and CaP radioresistant (RR) sublines using a label-free LC-MS/MS proteomics approach. A total of 309 signaling pathway proteins were identified to be significantly altered between CaP and CaP-RR cells (p ≤ 0.05, fold differences >1.5, ≥80% power). Among these proteins, nineteen are common among three paired CaP cell lines and associated with metastasis, progression and radioresistance...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28221700/multikinase-inhibitors-sorafenib-and-sunitinib-as-radiosensitizers-in-head-and-neck-cancer-cell-lines
#2
Annette Affolter, Gerson Samosny, Anne-Sophie Heimes, Johanna Schneider, Wilko Weichert, Albrecht Stenzinger, Katharina Sommer, Alexandra Jensen, Arnulf Mayer, Walburgis Brenner, Wolf J Mann, Jürgen Brieger
BACKGROUND: Radioresistance is a common feature of head and neck squamous cell carcinoma (HNSCC). We previously showed that the irradiation- activated vascular endothelial growth factor (VEGF)-extracellular signal-regulated kinase (ERK)-axis is fundamental for the survival of resistant tumors. In this study, we examined if treatment with potent multikinase (MK) inhibitors, sorafenib and sunitinib, could radiosensitize tumor cells. METHODS: Cultured HNSCC cell lines were treated with inhibitors and subsequently irradiated...
February 21, 2017: Head & Neck
https://www.readbyqxmd.com/read/28216370/targeting-autophagy-in-cancer-stem-cells-as-an-anticancer-therapy
#3
Yuanyuan Lei, Dan Zhang, Jin Yu, Hui Dong, Jianwei Zhang, Shiming Yang
Cancer stem cells (CSCs), which comprise a small proportion of total cancer cells, have special capacities for self-renewal, differentiation and tumor formation. Currently, CSCs are regarded as the major cause of the failure in anticancer therapy, such as chemoresistance and/or radioresistance, tumor recurrence and metastasis. Autophagy, a process of cellular self-digestion and response to stress, has a role in tumor formation and progression, and it may play a dual role in CSCs-related resistance to anticancer therapy...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28211872/rictor-mtorc2-deficiency-enhances-keratinocyte-stress-tolerance-via-mitohormesis
#4
Beatrice Tassone, Stefania Saoncella, Francesco Neri, Ugo Ala, Davide Brusa, Mark A Magnuson, Paolo Provero, Salvatore Oliviero, Chiara Riganti, Enzo Calautti
How metabolic pathways required for epidermal tissue growth and remodeling influence the ability of keratinocytes to survive stressful conditions is still largely unknown. The mechanistic target of rapamycin complex 2 (mTORC2) regulates growth and metabolism of several tissues, but its functions in epidermal cells are poorly defined. Rictor is an adaptor protein essential for mTORC2 activity. To explore the roles of mTORC2 in the epidermis, we have conditionally deleted rictor in mice via K14-Cre-mediated homologous recombination and found that its deficiency causes moderate tissue hypoplasia, reduced keratinocyte proliferation and attenuated hyperplastic response to TPA...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28209968/activating-akt1-mutations-alter-dna-double-strand-break-repair-and-radiosensitivity
#5
S Oeck, K Al-Refae, H Riffkin, G Wiel, R Handrick, D Klein, G Iliakis, V Jendrossek
The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with prominent nuclear access, the phospho-mimicking Akt1-TDSD and the clinically relevant PH-domain mutation Akt1-E17K, accelerated DSB repair and improved survival of irradiated Tramp-C1 murine prostate cancer cells and Akt1-knockout murine embryonic fibroblasts in vitro, the classical constitutively active membrane-targeted myrAkt1 mutant had the opposite effects...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208648/n-butylidenephthalide-regulated-tumor-stem-cell-genes-ezh2-axl-and-reduced-its-migration-and-invasion-in-glioblastoma
#6
Ssu-Yin Yen, Hong-Meng Chuang, Mao-Hsuan Huang, Shinn-Zong Lin, Tzyy-Wen Chiou, Horng-Jyh Harn
Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20-21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28205588/hypoxia-induced-angiotensin-ii-by-the-lactate-chymase-dependent-mechanism-mediates-radioresistance-of-hypoxic-tumor-cells
#7
Guozhu Xie, Ying Liu, Qiwei Yao, Rong Zheng, Lanfang Zhang, Jie Lin, Zhaoze Guo, Shasha Du, Chen Ren, Quan Yuan, Yawei Yuan
The renin-angiotensin system (RAS) is a principal determinant of arterial blood pressure and fluid and electrolyte balance. RAS component dysregulation was recently found in some malignancies and correlated with poor patient outcomes. However, the exact mechanism of local RAS activation in tumors is still unclear. Here, we find that the local angiotensin II predominantly exists in the hypoxic regions of tumor formed by nasopharyngeal carcinoma CNE2 cells and breast cancer MDA-MB-231 cells, where these tumor cells autocrinely produce angiotensin II by a chymase-dependent rather than an angiotensin converting enzyme-dependent mechanism...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203236/the-deubiquitinating-enzyme-cylindromatosis-dampens-cd8-t-cell-responses-and-is-a-critical-factor-for-experimental-cerebral-malaria-and-blood-brain-barrier-damage
#8
Ursula Schmid, Werner Stenzel, Josephin Koschel, Maria Raptaki, Xu Wang, Michael Naumann, Kai Matuschewski, Dirk Schlüter, Gopala Nishanth
Cerebral malaria is a severe complication of human malaria and may lead to death of Plasmodium falciparum-infected individuals. Cerebral malaria is associated with sequestration of parasitized red blood cells within the cerebral microvasculature resulting in damage of the blood-brain barrier and brain pathology. Although CD8(+) T cells have been implicated in the development of murine experimental cerebral malaria (ECM), several other studies have shown that CD8(+) T cells confer protection against blood-stage infections...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28202528/distinct-levels-of-radioresistance-in-lgr5-colonic-epithelial-stem-cells-versus-lgr5-small-intestinal-stem-cells
#9
Guoqiang Hua, Chu Wang, Yan Pan, Zhaoshi Zeng, Sang Gyu Lee, Maria Laura Martin, Adriana Haimovitz-Friedman, Zvi Fuks, Philip B Paty, Richard N Kolesnick
While small and large intestines possess seemingly similar Wnt-driven Leucine-rich repeat-containing G protein coupled receptor 5 (Lgr5)+ adult epithelial stem cells, we report here that the two organs exhibit distinct mechanisms of tissue response to ionizing radiation. Employing Lgr5-lacZ transgenic mice and Lgr5 in situ hybridization, we found colonic epithelial stem cells (CESC) markedly more radioresistant in vivo than small intestinal crypt base columnar stem cells (CBC) (D0 6.0±0.3 Gy vs. 1.3±0.1, respectively; p0...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28199717/acquisition-of-radioresistance-by-il-6-treatment-is-caused-by-suppression-of-oxidative-stress-derived-from-mitochondria-after-%C3%AE-irradiation
#10
Yuki Tamari, Genro Kashino, Hiromu Mori
No abstract text is available yet for this article.
February 13, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28180110/assessing-tumor-oxygenation-for-predicting-outcome-in-radiation-oncology-a-review-of-studies-correlating-tumor-hypoxic-status-and-outcome-in-the-preclinical-and-clinical-settings
#11
REVIEW
Florence Colliez, Bernard Gallez, Bénédicte F Jordan
Tumor hypoxia is recognized as a limiting factor for the efficacy of radiotherapy, because it enhances tumor radioresistance. It is strongly suggested that assessing tumor oxygenation could help to predict the outcome of cancer patients undergoing radiation therapy. Strategies have also been developed to alleviate tumor hypoxia in order to radiosensitize tumors. In addition, oxygen mapping is critically needed for intensity modulated radiation therapy (IMRT), in which the most hypoxic regions require higher radiation doses and the most oxygenated regions require lower radiation doses...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28175572/334%C3%A2-a-functional-screen-identifies-mirnas-that-induce-radioresistance-in-glioblastomas
#12
Clark C Chen, Patryk Moskwa, Pascal O Zinn, Brian R Hirshman, Young Eun Choi, Sachet A Shukla, Wojciech Fendler, Jun Lu, Todd R Golub, Anita Hjelmeland, Dipanjan Chowdhury
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28166815/regulation-of-submaxillary-gland-androgen-regulated-protein-3a-via-estrogen-receptor-2-in-radioresistant-head-and-neck-squamous-cell-carcinoma-cells
#13
Jennifer Grünow, Chao Rong, Jan Hischmann, Karim Zaoui, Christa Flechtenmacher, Klaus-Josef Weber, Peter Plinkert, Jochen Hess
BACKGROUND: Molecular mechanisms of intrinsic or acquired radioresistance serve as critical barrier for curative therapy of head and neck squamous cell carcinoma (HNSCC) and remain a major obstacle for progression-free and disease-specific survival. METHODS: HNSCC cell lines were treated with a protocol of fractionated irradiation (IR, 4× 2Gy) alone or in combination with antagonists of estrogen receptor signaling and viability was determined by a colony-forming assay (CFA)...
February 6, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28151689/evaluation-of-the-resistance-of-chroococcidiopsis-spp-to-sparsely-and-densely-ionizing-irradiation
#14
Cyprien Verseux, Mickael Baqué, Riccardo Cifariello, Claudia Fagliarone, Marina Raguse, Ralf Moeller, Daniela Billi
Studying the resistance of cyanobacteria to ionizing radiation provides relevant information regarding astrobiology-related topics including the search for life on Mars, lithopanspermia, and biological life-support systems. Here, we report on the resistance of desert cyanobacteria of the genus Chroococcidiopsis, which were exposed (as part of the STARLIFE series of experiments) in both hydrated and dried states to ionizing radiation with different linear energy transfer values (0.2 to 200 keV/μm). Irradiation with up to 1 kGy of He or Si ions, 2 kGy of Fe ions, 5 kGy of X-rays, or 11...
February 2, 2017: Astrobiology
https://www.readbyqxmd.com/read/28151479/increase-in-the-radioresistance-of-normal-skin-fibroblasts-but-not-tumor-cells-by-mechanical-injury
#15
Zelin Chen, Xin Wang, Taotao Jin, Yu Wang, Christopher S Hong, Li Tan, Tingyu Dai, Liao Wu, Zhengping Zhuang, Chunmeng Shi
The timing of radiation after mechanical injury such as in the case of surgery is considered a clinical challenge because radiation is assumed to impair wound healing. However, the physiological responses and underlying mechanisms of this healing impairment are still unclear. Here, we show that mechanical injury occurring before ionizing radiation decreases radiation-induced cell damage and increases cell repair in normal fibroblasts but not tumor cells in vitro and in vivo. At the molecular level, mechanical injury interrupts focal adhesion complexes and cell-cell cadherin interactions, transducing mechanical signals into intracellular chemical signals via activation of the phosphatidylinositol 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 beta (GSK-3β) pathways...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28147323/the-dna-repair-function-of-cux1-contributes-to-radioresistance
#16
Zubaidah M Ramdzan, Vasudeva Ginjala, Jordan B Pinder, Dudley Chung, Caroline M Donovan, Simran Kaur, Lam Leduy, Graham Dellaire, Shridar Ganesan, Alain Nepveu
Ionizing radiation generates a broad spectrum of oxidative DNA lesions, including oxidized base products, abasic sites, single-strand breaks and double-strand breaks. The CUX1 protein was recently shown to function as an auxiliary factor that stimulates enzymatic activities of OGG1 through its CUT domains. In the present study, we investigated the requirement for CUX1 and OGG1 in the resistance to radiation. Cancer cell survival following ionizing radiation is reduced by CUX1 knockdown and increased by higher CUX1 expression...
January 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28143717/the-bet-bromodomain-inhibitor-jq1-radiosensitizes-non-small-cell-lung-cancer-cells-by-upregulating-p21
#17
Jian Wang, Ye Wang, Hong Mei, Zhongyuan Yin, Yuanyuan Geng, Tao Zhang, Gang Wu, Zhenyu Lin
Radiotherapy is an important treatment modality in the management of locally advanced non-small cell lung cancer (NSCLC). However, radioresistance markedly impairs its efficacy in clinic. Bromodomain and extra-terminal (BET) bromodomain inhibitors have demonstrated dramatic antitumor activity in several preclinical human cancer models. In this study, we investigated for the first time the effect of JQ1, a novel BET bromodomain inhibitor, on tumor cell radiosensitivity of NSCLC in vitro and in vivo. Our results demonstrated that JQ1 significantly enhanced the effect of irradiation in NSCLC cell lines through a c-myc-independent mechanism...
January 29, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28138801/mir-668-enhances-the-radioresistance-of-human-breast-cancer-cell-by-targeting-i%C3%AE%C2%BAb%C3%AE
#18
Ming Luo, Ling Ding, Qingjian Li, Herui Yao
BACKGROUND: A large proportion of breast cancer patients are resistant to radiotherapy, which is a mainstay treatment for this malignancy, but the mechanisms of radioresistance remain unclear. METHODS AND MATERIALS: To evaluate the role of miRNAs in radioresistance, we established two radioresistant breast cancer cell lines MCF-7R and T-47DR derived from parental MCF-7 and T-47D. Moreover, miRNA microarray, quantitative RT-PCR analysis, luciferase reporter assay and western blotting were used...
January 30, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28138553/influenza-a-induces-dysfunctional-immunity-and-death-in-mecp2-overexpressing-mice
#19
James C Cronk, Jasmin Herz, Taeg S Kim, Antoine Louveau, Emily K Moser, Ashish K Sharma, Igor Smirnov, Kenneth S Tung, Thomas J Braciale, Jonathan Kipnis
Loss of function or overexpression of methyl-CpG-binding protein 2 (MeCP2) results in the severe neurodevelopmental disorders Rett syndrome and MeCP2 duplication syndrome, respectively. MeCP2 plays a critical role in neuronal function and the function of cells throughout the body. It has been previously demonstrated that MeCP2 regulates T cell function and macrophage response to multiple stimuli, and that immune-mediated rescue imparts significant benefit in Mecp2-null mice. Unlike Rett syndrome, MeCP2 duplication syndrome results in chronic, severe respiratory infections, which represent a significant cause of patient morbidity and mortality...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28137320/irradiation-influence-on-the-phenoloxidase-pathway-and-an-anti-oxidant-defense-mechanism-in-spodoptera-litura-lepidoptera-noctuidae-and-its-implication-in-radio-genetic-f-1-sterility-and-biorational-pest-suppression-tactics
#20
B Sachdev, Z Khan, M Zarin, P Malhotra, R K Seth, R K Bhatnagar
The present study was conducted to appraise the ontogenic radio-sensitivity of a serious tropical pest, Spodoptera litura (Fabr.). The molecular responses pertaining to the phenoloxidase (PO) pathway and an anti-oxidant defense mechanism were evaluated in order to understand its implication in pest control at pre-harvest and post-harvest intervals. Irradiation exhibited an inverse relationship with age with respect to impact on developmental and transcriptional responses. Transcript abundance of PO cascade enzymes, prophenoloxidase (slppo-2), its activating enzyme (slppae-1) and free-radical scavenging enzymes, superoxide dismutase (slsod) and catalase (slcat) was evaluated upon gamma irradiation alone and the dual-stress of radiation plus microbial challenge...
January 31, 2017: Bulletin of Entomological Research
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