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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
#1
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
#2
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
#3
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
#4
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/29152427/dramatic-response-of-a-large-sacral-chordoma-to-intensity-modulated-proton-beam-therapy
#5
Craig Schneider, Melissa Vyfhuis, Emily Morse, Tejan Diwanji, James W Snider, Sina Mossahebi, Katarina Steacy, Robert Malyapa
Sacral chordomas are slow-growing, indolent, and locally invasive tumors that typically present with pain and neurologic dysfunction. Wide en-bloc surgical excision is the primary treatment, but achieving adequate margins is difficult and surgery is often associated with significant morbidity. Adjuvant radiation therapy (RT) is utilized to decrease the risk of local recurrence or as definitive treatment for nonsurgical candidates. Although chordomas are considered to be relatively radioresistant tumors, several studies have demonstrated tumor response to high-dose proton therapy...
September 10, 2017: Curēus
https://www.readbyqxmd.com/read/29152141/notch1-ablation-radiosensitizes-glioblastoma-cells
#6
Na Han, Guangyuan Hu, Lei Shi, Guoxian Long, Lin Yang, Qingsong Xi, Qiuyun Guo, Jianhua Wang, Zhen Dong, Mengxian Zhang
Broad specific Notch1 inhibitors suppress glioblastoma multiforme (GBM) growth but have significant gastrointestinal toxicities. Here, we examined Notch1 expression in GBM tissue specimens and its correlation with the overall survival (OS) of GBM patients. Furthermore, using the CRISPR/Cas9 system, we investigated the effects of Notch1 downregulation on clonogenic growth and angiogenesis of GBM cells and xenografts. Immunohistochemistry showed positive Notch1 expression in 71% (49/69) of GBM tissues. Our multivariate Cox regression analysis further revealed that Notch1 expression was an independent adverse prognostic factor for OS...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152122/cisplatin-radiosensitizes-radioresistant-human-mesenchymal-stem-cells
#7
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
#8
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
#9
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/29137372/microrna-33a-5p-increases-radiosensitivity-by-inhibiting-glycolysis-in-melanoma
#10
Ke Cao, Jingjing Li, Jia Chen, Li Qian, Aijun Wang, Xiang Chen, Wei Xiong, Jintian Tang, Shijie Tang, Yong Chen, Yao Chen, Yan Cheng, Jianda Zhou
Glycolysis was reported to have a positive correlation with radioresistance. Our previous study found that the miR-33a functioned as a tumor suppressor in malignant melanoma by targeting hypoxia-inducible factor1-alpha (HIF-1α), a gene known to promote glycolysis. However, the role of miR-33a-5p in radiosensitivity remains to be elucidated. We found that miR-33a-5p was downregulated in melanoma tissues and cells. Cell proliferation was downregulated after overexpression of miR-33a-5p in WM451 cells, accompanied by a decreased level of glycolysis...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132682/-biomarkers-of-radiation-induced-dna-repair-processes
#11
REVIEW
Alexis Vallard, Chloé Rancoule, Jean-Baptiste Guy, Sophie Espenel, Sylvie Sauvaigo, Claire Rodriguez-Lafrasse, Nicolas Magné
The identification of DNA repair biomarkers is of paramount importance. Indeed, it is the first step in the process of modulating radiosensitivity and radioresistance. Unlike tools of detection and measurement of DNA damage, DNA repair biomarkers highlight the variations of DNA damage responses, depending on the dose and the dose rate. The aim of the present review is to describe the main biomarkers of radiation-induced DNA repair. We will focus on double strand breaks (DSB), because of their major role in radiation-induced cell death...
November 10, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29126793/inhibition-of-notch1-hes1-signaling-pathway-improves-radiosensitivity-of-colorectal-cancer-cells
#12
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/29125832/minibeam-radiotherapy-with-small-animal-irradiators-in-vitro-and-in-vivo-feasibility-studies
#13
Soha Bazyar, Christina R Inscoe, E Timothy O'Brian, Otto Zhou, Yueh Z Lee
Minibeam radiation therapy (MBRT) delivers an ultrahigh dose of x-ray (⩾100 Gy) in 200-1000 µm beams (peaks), separated by wider non-irradiated regions (valleys) usually as a single temporal fraction. Preclinical studies performed at synchrotron facilities revealed that MBRT is able to ablate tumors while maintaining normal tissue integrity. The main purpose of the present study was to develop an efficient and accessible method to perform MBRT using a conventional x-ray irradiator. We then tested this new method both in vitro and in vivo...
November 10, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29121984/carbon-ion-radiotherapy-impact-of-tumor-differentiation-on-local-control-in-experimental-prostate-carcinomas
#14
Christin Glowa, Peter Peschke, Stephan Brons, Oliver C Neels, Klaus Kopka, Jürgen Debus, Christian P Karger
BACKGROUND: To summarize the research activities of the "clinical research group heavy ion therapy", funded by the German Research Foundation (DFG, KFO 214), on the impact of intrinsic tumor characteristics (grading, hypoxia) on local tumor control after carbon ((12)C-) ion- and photon irradiations. METHODS: Three sublines of syngeneic rat prostate tumors (R3327) with various differentiation levels (highly (-H), moderately (-HI) or anaplastic (-AT1), (diameter 10 mm) were irradiated with 1, 2 and 6 fractions of either (12)C-ions or 6 MV photons using increasing dose levels...
November 9, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/29118323/valproic-acid-sensitizes-hepatocellular-carcinoma-cells-to-proton-therapy-by-suppressing-nrf2-activation
#15
Jeong Il Yu, Changhoon Choi, Sung-Won Shin, Arang Son, Ga-Haeng Lee, Shin-Yeong Kim, Hee Chul Park
Although efficacy of combined histone deacetylase (HDAC) inhibitors and conventional photon radiotherapy is being tested in clinical trials, their combined effect with proton beam radiotherapy has yet to be determined. Here, we compared combined effect of valproic acid (VPA), a class I and II HDAC inhibitor and antiepileptic drug with proton and photon irradiation in hepatocellular carcinoma (HCC) cells in vitro and in vivo. We found that VPA sensitized more Hep3B cells to proton than to photon irradiation...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115557/hypoxia-induces-differential-expression-patterns-of-osteopontin-and-cd44-in-colorectal-carcinoma
#16
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
#17
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
https://www.readbyqxmd.com/read/29115464/microrna-222-promotes-tumor-growth-and-confers-radioresistance-in-nasopharyngeal-carcinoma-by-targeting-pten
#18
Wei Wu, Xi Chen, Shilong Yu, Rui Wang, Ruikun Zhao, Chao Du
MicroRNA-222 (miR‑222) has been reported to be involved in the initiation, development and metastasis of tumors, as well as conferring resistance to chemotherapeutic drugs or radiotherapy in various types of cancer. However, the role and the underlying molecular mechanism of miR‑222 specifically in nasopharyngeal carcinoma (NPC) remains unclear. Thus, the biological function and underlying mechanism of in miR‑222 was investigated in NPC tissue specimens and cell lines. miR‑222 was upregulated in NPC tissues and malignant cell lines compared with adjacent normal samples and cell lines...
October 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115437/simvastatin-enhances-the-radiosensitivity-of-p53%C3%A2-deficient-cells-via-inhibition-of-mouse-double-minute-2-homolog
#19
Ji Young Lee, Mi-Sook Kim, Jae Eun Ju, Mi So Lee, Namhyun Chung, Youn Kyoung Jeong
Simvastatin exhibits anticancer activities, but its molecular mechanisms and radiosensitizing effects relative to p53 status remain unclear. In this study, we investigated whether the combination of simvastatin and ionizing radiation (IR) would enhance the antitumor effects of IR alone in HCT116 p53+/+ and p53‑/- colon cancer cells. Using colony formation assays and a xenograft mouse model, we found that simvastatin potently stimulated radiosensitization of HCT116 p53‑/- cells and xenograft tumors. The combination of simvastatin with IR decreased G2/M arrest and delayed the repair of IR-induced DNA damage; however, no differences between the HCT116 p53+/+ and p53‑/- cells were evident...
November 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29113987/bap1-is-a-novel-target-in-hpv-negative-head-and-neck-cancer
#20
Xiyou Liu, Liangpeng Yang, David P Molkentine, David Valdacanas, Shiying Yu, Manish Kumar, Raymond E Meyn, John Heymach, Heath D Skinner
PURPOSE: This study examined the potential role of the nuclear deubiquitinating enzyme BRCA1-associated protein-1 (BAP1) in radioresistance in head and neck squamous cell cancer (HNSCC). EXPERIMENTAL DESIGN: We overexpressed, knocked down, and rescued BAP1 expression in six HNSCC cell lines, three human papillomavirus (HPV) -negative and HPV-positive, and examined the effects on radiosensitivity in vitro and in HNSCC mouse xenograft models. Radiosensitivity was assessed by clonogenic cell survival and tumor growth delay assays; changes in protein expression were analyzed by immunofluorescence staining and western blotting...
November 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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