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Cancer and radioresistance

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https://www.readbyqxmd.com/read/29222038/hdac6-inhibition-induces-glioma-stem-cells-differentiation-and-enhances-cellular-radiation-sensitivity-through-the-shh-gli1-signaling-pathway
#1
Wei Yang, Yingying Liu, Ruoling Gao, Hongquan Yu, Ting Sun
The existence of small numbers of stem-like cells, called glioma stem cells (GSCs), in human glioblastoma multiforme (GBM) is responsible for recurrence due to resistance to radiotherapy and chemotherapy. Inhibition of histone deacetylase 6 (HDAC6) enhanced radiosensitivity of cancer cells. However, the effect of inhibiting HDAC6 on stemness and radioresistance of GSCs and its molecular mechanism are largely unknown. In the present study, we found that HDAC6 was upregulated in GSCs comparing to non-stem tumor cells...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29218592/mathematical-modeling-of-the-effects-of-tumor-heterogeneity-on-the-efficiency-of-radiation-treatment-schedule
#2
Farinaz Forouzannia, Heiko Enderling, Mohammad Kohandel
Radiotherapy uses high doses of energy to eradicate cancer cells and control tumors. Various treatment schedules have been developed and tried in clinical trials, yet significant obstacles remain to improving the radiotherapy fractionation. Genetic and non-genetic cellular diversity within tumors can lead to different radiosensitivity among cancer cells that can affect radiation treatment outcome. We propose a minimal mathematical model to study the effect of tumor heterogeneity and repair in different radiation treatment schedules...
December 7, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/29208461/simvastatin-inhibits-the-development-of-radioresistant-esophageal-cancer-cells-by-increasing-the-radiosensitivity-and-reversing-emt-process-via-the-pten-pi3k-akt-pathway
#3
Yingying Jin, Kun Xu, Qingjuan Chen, Baofeng Wang, Jiyuan Pan, Shan Huang, Yang Wei, Hongbing Ma
Acquired radioresistance compromises the efficacy of radiotherapy for carcinomas including esophageal cancer (EC), thus resulting in recurrence and poor survival. Recent research corroborated radiosensitive function of simvastatin in stem-like breast cancer cells. However, its role in EC radioresistance remains poorly elucidated. Here, we developed a radioresistant EC cell line Ec9706-R with higher resistance to irradiation relative to control Ec9706 cells. Intriguingly, Ec9706-R cells exhibited epithelial-mesenchymal transition (EMT) characteristics with high invasion and migration ability...
December 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29207178/mir%C3%A2-328%C3%A2-3p-enhances-the-radiosensitivity-of-osteosarcoma-and-regulates-apoptosis-and-cell-viability-via-h2ax
#4
Zhen Yang, Qing-De Wa, Chao Lu, Wei Pan, Zi-Μo Lu, Jun Ao
Osteosarcoma is a kind of high-risk sarcoma of the skeleton typically observed in people under 25 years old. Currently, radiotherapy is widely applied in cancer treatment. However, osteosarcoma is radioresistant and accordingly new, more effective radiosensitizers are needed. miRNAs have been reported to play an important role in osteosarcoma radiosensitivity. We examined the modulating effect of miR‑328‑3p in vivo and in vitro. miR‑328‑3p was downregulated in HOS‑2R cells. The overexpression of miR‑328‑3p enhanced the radiosensitivity of osteosarcoma cells...
November 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29207170/bmi-1-suppression-increases-the-radiosensitivity-of-oesophageal-carcinoma-via-the-pi3k-akt-signaling-pathway
#5
Xing-Xiao Yang, Ming Ma, Mei-Xiang Sang, Xue-Yuan Zhang, Zhi-Kun Liu, Heng Song, Shu-Chai Zhu
B-cell‑specific Moloney murine leukaemia virus integration site-1 (BMI-1) contributes to the growth of tumour cells post-irradiation (IR). The aim of the present study was to characterize the effects of BMI-1 on cell viability, radiosensitivity and its mechanisms of action in oesophageal squamous cell cancer (ESCC). Western blotting and immunohistochemistry were employed to evaluate the protein expression of BMI-1 in ESCC cells and specimens, respectively. Additionally, the protein expression levels of BMI-1, H2AK119ub and γH2AX in ESCC cells were detected following different doses of IR and at different times after IR...
December 5, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29200875/rkip-reduction-enhances-radioresistance-by-activating-the-shh-signaling-pathway-in-non-small-cell-lung-cancer
#6
Shi-Yang Xie, Guang Li, Chong Han, Yang-Yang Yu, Nan Li
Non-small-cell lung cancer (NSCLC) is exceptionally deadly because the tumors lack sensitive early-stage diagnostic biomarkers and are resistant to radiation and chemotherapy. Here, we investigated the role and mechanism of Raf kinase inhibitory protein (RKIP) in NSCLC radioresistance. The clinical data showed that the RKIP expression level was generally lower in radioresistant NSCLC tissues than in radiosensitive tissues. Reduced RKIP expression was related to NSCLC radioresistance and poor prognosis. In vitro experiments showed that RKIP knockdown increased radioresistance and metastatic ability in NSCLC cell lines...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29194401/drug-resistance-driven-by-cancer-stem-cells-and-their-niche
#7
REVIEW
Marta Prieto-Vila, Ryou-U Takahashi, Wataru Usuba, Isaku Kohama, Takahiro Ochiya
Drug resistance represents one of the greatest challenges in cancer treatment. Cancer stem cells (CSCs), a subset of cells within the tumor with the potential for self-renewal, differentiation and tumorigenicity, are thought to be the major cause of cancer therapy failure due to their considerable chemo- and radioresistance, resulting in tumor recurrence and eventually metastasis. CSCs are situated in a specialized microenvironment termed the niche, mainly composed of fibroblasts and endothelial, mesenchymal and immune cells, which also play pivotal roles in drug resistance...
December 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29189105/characterization-of-diffuse-intrinsic-pontine-glioma-radiosensitivity-using-synchrotron-microbeam-radiotherapy-and-conventional-radiation-therapy-in-vitro
#8
L M Smyth, P A W Rogers, J C Crosbie, J F Donoghue
Synchrotron microbeam radiation therapy is a promising preclinical radiotherapy modality that has been proposed as an alternative to conventional radiation therapy for diseases such as diffuse intrinsic pontine glioma (DIPG), a devastating pediatric tumor of the brainstem. The primary goal of this study was to characterize and compare the radiosensitivity of two DIPG cell lines (SF7761 and JHH-DIPG-1) to microbeam and conventional radiation. We hypothesized that these DIPG cell lines would exhibit differential responses to each radiation modality...
November 30, 2017: Radiation Research
https://www.readbyqxmd.com/read/29180477/mir-139-5p-modulates-radiotherapy-resistance-in-breast-cancer-by-repressing-multiple-gene-networks-of-dna-repair-and-ros-defense
#9
Marina Pajic, Danielle Froio, Sheridan Daly, Louise Doculara, Ewan Millar, Peter H Graham, Alison Drury, Angela Steinmann, Charles E de Bock, Alice Boulghourjian, Anaiis Zaratzian, Susan Carroll, Joanne Toohey, Sandra A O'Toole, Adrian L Harris, Francesca M Buffa, Harriet E Gee, Georgina E Hollway, Timothy J Molloy
Radiotherapy (RT) is essential to the treatment of most solid tumors and acquired or innate resistance to this therapeutic modality is a major clinical problem. Here we show that miR-139-5p is a potent modulator of radiotherapy response in breast cancer (BC) via its regulation of genes involved in multiple DNA repair and reactive oxygen species defense pathways. Treatment of breast cancer cells with a miR-139-5p mimic strongly synergized with radiation both in vitro and in vivo, resulting in significantly increased oxidative stress, accumulation of unrepaired DNA damage and induction of apoptosis...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29179977/altered-o-glycosylation-is-associated-with-inherent-radioresistance-and-malignancy-of-human-laryngeal-carcinoma
#10
Xiaoxia Dong, Zhiguo Luo, Yingying Wang, Lu Meng, Qiwen Duan, Li Qiu, Feng Peng, Li Shen
Radioresistance (inherent or acquired) remains a major obstacle affecting the clinical outcome of radiotherapy for laryngeal carcinoma. Results from our laboratory and other groups suggest that aberrant glycosylation contributes to cancer acquired radioresistance. However, the role of glycosylation in inherent radioresistance of laryngeal carcinoma has not been fully uncovered. In this study, we investigated the glycan profiling of the inherent radioresistant (Hep-2max) and radiosensitive (Hep-2min) cell lines using lectin microarray analysis...
November 26, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29167558/recurring-amplification-at-11q22-1-q22-2-locus-plays-an-important-role-in-lymph-node-metastasis-and-radioresistance-in-oscc
#11
Priyanka G Bhosale, Manishkumar Pandey, Simona Cristea, Mickey Shah, Asawari Patil, Niko Beerenwinkel, Alejandro A Schäffer, Manoj B Mahimkar
A key feature in the pathogenesis of OSCC is genetic instability, which results in altered expression of genes located in amplified/deleted chromosomal regions. In a previous study we have shown that the amplification of the 11q22.1-q22.2 region, encoding cIAP1 and cIAP2, is associated with lymph node metastasis and poor clinical outcome in OSCC. Here, we validate the aCGH results by nuc ish and detect a weak amplification at the 11q22.1-q22.2 locus in 37% of the 182 samples tested. We find positive correlation of 11q22...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29166609/gpr56-adgrg1-inhibits-mesenchymal-differentiation-and-radioresistance-in-glioblastoma
#12
Marta Moreno, Leire Pedrosa, Laia Paré, Estela Pineda, Leire Bejarano, Josefina Martínez, Veerakumar Balasubramaniyan, Ravesanker Ezhilarasan, Naveen Kallarackal, Sung-Hak Kim, Jia Wang, Alessandra Audia, Siobhan Conroy, Mercedes Marin, Teresa Ribalta, Teresa Pujol, Antoni Herreros, Avelina Tortosa, Helena Mira, Marta M Alonso, Candelaria Gómez-Manzano, Francesc Graus, Erik P Sulman, Xianhua Piao, Ichiro Nakano, Aleix Prat, Krishna P Bhat, Núria de la Iglesia
A mesenchymal transition occurs both during the natural evolution of glioblastoma (GBM) and in response to therapy. Here, we report that the adhesion G-protein-coupled receptor, GPR56/ADGRG1, inhibits GBM mesenchymal differentiation and radioresistance. GPR56 is enriched in proneural and classical GBMs and is lost during their transition toward a mesenchymal subtype. GPR56 loss of function promotes mesenchymal differentiation and radioresistance of glioma initiating cells both in vitro and in vivo. Accordingly, a low GPR56-associated signature is prognostic of a poor outcome in GBM patients even within non-G-CIMP GBMs...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29164272/signaling-pathways-and-mesenchymal-transition-in-pediatric-high-grade-glioma
#13
REVIEW
Michaël H Meel, Sophie A Schaper, Gertjan J L Kaspers, Esther Hulleman
Pediatric high-grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPG), are the most lethal types of cancer in children. In recent years, it has become evident that these tumors are driven by epigenetic events, mainly mutations involving genes encoding Histone 3, setting them apart from their adult counterparts. These tumors are exceptionally resistant to chemotherapy and respond only temporarily to radiotherapy. Moreover, their delicate location and diffuse growth pattern make complete surgical resection impossible...
November 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29160417/radiotherapy-modulates-expression-of-egfr-ercc1-and-p53-in-cervical-cancer
#14
V H de Almeida, A C de Melo, D D Meira, A C Pires, A Nogueira-Rodrigues, H K Pimenta-Inada, F G Alves, G Moralez, L S Thiago, C G Ferreira, C Sternberg
Cervical cancer is a public health problem and the molecular mechanisms underlying radioresistance are still poorly understood. Here, we evaluated the modulation of key molecules involved in cell proliferation, cell cycle and DNA repair in cervical cancer cell lines (CASKI and C33A) and in malignant tissues biopsied from 10 patients before and after radiotherapy. The expression patterns of epidermal growth factor receptor (EGFR), excision repair cross-complementation group 1 (ERCC1) and p53 were evaluated in cancer cell lines by quantitative PCR and western blotting, and in human malignant tissues by immunohistochemistry...
November 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29152122/cisplatin-radiosensitizes-radioresistant-human-mesenchymal-stem-cells
#15
Alexander Rühle, Ramon Lopez Perez, Christin Glowa, Klaus-Josef Weber, Anthony D Ho, Jürgen Debus, Rainer Saffrich, Peter E Huber, Nils H Nicolay
Cisplatin-based chemo-radiotherapy is widely used to treat cancers with often severe therapy-associated late toxicities. While mesenchymal stem cells (MSCs) were shown to aid regeneration of cisplatin- or radiation-induced tissue lesions, the effect of the combined treatment on the stem cells remains unknown. Here we demonstrate that cisplatin treatment radiosensitized human bone marrow-derived MSCs in a dose-dependent manner and increased levels of radiation-induced apoptosis. However, the defining stem cell properties of MSCs remained largely intact after cisplatin-based chemo-radiation, and stem cell motility, adhesion, surface marker expression and the characteristic differentiation potential were not significantly influenced...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29143133/association-of-dna-repair-genes-polymorphisms-and-mutations-with-increased-risk-of-head-and-neck-cancer-a-review
#16
REVIEW
Agata Dylawerska, Wojciech Barczak, Anna Wegner, Wojciech Golusinski, Wiktoria Maria Suchorska
DNA repair mechanisms allow maintain genomic stability and proper functioning within the cells. Any aberrations may cause an increased risk of many diseases such as cancer. The most crucial risk factors for head and neck squamous cell carcinoma are behavioral factors, predominantly chronic exposure to tobacco, alcohol addiction, and infection with human papillomavirus or Epstein-Barr virus. These agents can induce DNA damage; therefore, cells must activate appropriate mechanisms in order to function correctly...
November 15, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29141489/non-linear-conversion-of-hx4-uptake-for-automatic-segmentation-of-hypoxic-volumes-and-dose-prescription
#17
Ana Ureba, Emely Lindblom, Alexandru Dasu, Johan Uhrdin, Aniek J G Even, Wouter van Elmpt, Philippe Lambin, Peter Wersäll, Iuliana Toma-Dasu
BACKGROUND: Tumour hypoxia is associated with increased radioresistance and poor response to radiotherapy. Pre-treatment assessment of tumour oxygenation could therefore give the possibility to tailor the treatment by calculating the required boost dose needed to overcome the increased radioresistance in hypoxic tumours. This study concerned the derivation of a non-linear conversion function between the uptake of the hypoxia-PET tracer (18)F-HX4 and oxygen partial pressure (pO2). MATERIAL AND METHODS: Building on previous experience with FMISO including experimental data on tracer uptake and pO2, tracer-specific model parameters were derived for converting the normalised HX4-uptake at the optimal imaging time point to pO2...
November 16, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29126793/inhibition-of-notch1-hes1-signaling-pathway-improves-radiosensitivity-of-colorectal-cancer-cells
#18
Hongzhi Zhang, Huijuan Jiang, Lei Chen, Juncai Liu, Xigang Hu, Huixiang Zhang
Notch signaling pathway has been demonstrated to mediate radioresistance of several tumors. Our study aims to explore the function of Notch1/HES1 pathway in the radioresistance of colorectal cancer (CRC). The results demonstrated that expressions of Notch1 and Hes1 were up-regulated with the increasing irradiation dose. DAPT (N-[(3,5-difluorophenacetyl)acety1]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester) or si-Notch1 reduced expressions of Notch1 and Hes1, exacerbated irradiation-induced cell proliferation inhibition, and improved radiosensitivity of CRC cells...
November 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29115557/hypoxia-induces-differential-expression-patterns-of-osteopontin-and-cd44-in-colorectal-carcinoma
#19
Gisela Wohlleben, Konstantin Hauff, Martin Gasser, Ana Maria Waaga-Gasser, Tanja Grimmig, Michael Flentje, Bülent Polat
The plasma protein osteopontin (OPN) is considered to be a tumor biomarker, where elevated plasma levels are associated with poor prognosis. Additionally, OPN is expressed in the presence of tumor hypoxia, which is an adverse prognostic factor in radiation oncology. One of its receptors, the proposed tumor stem cell marker CD44, is also associated with aggressive tumors, shown for example in colon cancer. The expression of CD44 and its splice variants (particularly CD44v6) can be upregulated by OPN itself. In the present study, we aimed to investigate the influence of hypoxia on the expression of OPN and its binding partners CD44 and CD44v6 in colon carcinoma cell lines in vitro, using SW480, SW620, HT29 and HCT116 cells...
November 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29115478/torin2-enhances-the-radiosensitivity-of-mcf%C3%A2-7-breast-cancer-cells-by-downregulating-the-mtor-signaling-pathway-and-atm-phosphorylation
#20
Jia Luo, Guocheng Pi, He Xiao, Yunfei Ye, Qing Li, Lianhua Zhao, Huan Huang, Hong Luo, Qin Zhang, Dong Wang, Ge Wang
Radiotherapy has an important role in the comprehensive treatment of breast cancer. However, the clinical outcome of adjuvant radiotherapy may be limited due to intrinsic radioresistance, it is necessary to explore efficient radiosensitization methods that improve the clinical outcome of patients undergoing radiotherapy. The present study aimed to investigate whether the novel mechanistic target of rapamycin (mTOR) inhibitor Torin2 enhances the radiosensitivity of MCF‑7 breast cancer cells. A Cell Counting Kit‑8 (CCK‑8) assay was performed to measure the effect of Torin2 on cell proliferation, while clonogenic assays were employed to determine the effect of Torin2 in combination with radiation on the proliferation of MCF‑7 cells...
October 20, 2017: Molecular Medicine Reports
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