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https://www.readbyqxmd.com/read/27913065/hpv-status-cancer-stem-cell-marker-expression-hypoxia-gene-signatures-and-tumour-volume-identify-good-prognosis-subgroups-in-patients-with-hnscc-after-primary-radiochemotherapy-a-multicentre-retrospective-study-of-the-german-cancer-consortium-radiation-oncology
#1
Annett Linge, Fabian Lohaus, Steffen Löck, Alexander Nowak, Volker Gudziol, Chiara Valentini, Cläre von Neubeck, Martin Jütz, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E Combs, David Mönnich, Daniel Zips, Frank Buchholz, Daniela E Aust, Gustavo B Baretton, Howard D Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Mechthild Krause, Michael Baumann
OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received primary radiochemotherapy (RCTx). MATERIALS AND METHODS: For 158 patients with locally advanced HNSCC of the oral cavity, oropharynx or hypopharynx who were treated at six DKTK partner sites, the impact of tumour volume, HPV DNA, p16 overexpression, p53 expression, CSC marker expression and hypoxia-associated gene signatures on outcome of primary RCTx was retrospectively analyzed...
November 29, 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27910734/targeting-the-akt-cyclin-d1-pathway-to-overcome-intrinsic-and-acquired-radioresistance-of-tumors-for-effective-radiotherapy
#2
Tsutomu Shimura
PURPOSE: Radiotherapy (RT) is a powerful tool in the treatment of cancer, having the advantage of preserving normal tissues. Clinical outcomes of RT are significantly improved by technological advances, enabling increased radiation doses directed very specifically to a tumor. However, tumor radioresistance remains a major impediment to effective RT. We have shown that human tumor cells surviving after repeated exposure to fractionated radiation (FR) of X-rays for 1 month have acquired radioresistance through constitutive activation of AKT and downstream cyclin D1 nuclear retention...
December 2, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27903972/gdf15-contributes-to-radioresistance-and-cancer-stemness-of-head-and-neck-cancer-by-regulating-cellular-reactive-oxygen-species-via-a-smad-associated-signaling-pathway
#3
Yan-Liang Li, Joseph T Chang, Li-Yu Lee, Kang-Hsing Fan, Ya-Ching Lu, Yi-Chen Li, Chang-Hsu Chiang, Guo-Rung You, Hsin-Ying Chen, Ann-Joy Cheng
Radiotherapy is an integral part for the treatment of head and neck cancer (HNC), while radioresistance is a major cause leads to treatment failure. GDF15, a member of the TGF-β superfamily, is hypothesized to participate in various types of homeostasis. However, the potential role of this molecule in regulation of radiosensitivity remains unclear. In this study, we demonstrated that GDF15 contributed to radioresistance of HNC, as determined by both gain- and lost-of-functional experiments. These results were achieved by the induction of mitochondrial membrane potential and suppression of intracellular reactive oxygen species (ROS)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903181/prognostic-factors-for-melanoma-brain-metastases-treated-with-stereotactic-radiosurgery
#4
Shelly X Bian, David Routman, Jonathan Liu, Dongyun Yang, Susan Groshen, Gabriel Zada, Nicholas Trakul, Michael K Wong, Cheng Yu, Eric L Chang
OBJECTIVE Stereotactic radiosurgery (SRS) is routinely used to treat brain metastases from melanoma due to their radioresistant nature. The median survival for these patients is 4-6 months, according to earlier studies. The aim of this study was to evaluate prognostic factors that influence survival in patients with metastatic melanoma to the brain treated with SRS. METHODS This retrospective analysis included all patients with melanoma brain metastases treated with SRS at the University of Southern California between 1994 and 2015...
December 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27903123/drug-priming-enhances-radiosensitivity-of-adamantinomatous-craniopharyngioma-via-downregulation-of-survivin
#5
Christina Stache, Christiane Bils, Rudolf Fahlbusch, Jörg Flitsch, Michael Buchfelder, Harald Stefanits, Thomas Czech, Udo Gaipl, Benjamin Frey, Rolf Buslei, Annett Hölsken
OBJECTIVE In this study, the authors investigated the underlying mechanisms responsible for high tumor recurrence rates of adamantinomatous craniopharyngioma (ACP) after radiotherapy and developed new targeted treatment protocols to minimize recurrence. ACPs are characterized by the activation of the receptor tyrosine kinase epidermal growth factor receptor (EGFR), known to mediate radioresistance in various tumor entities. The impact of tyrosine kinase inhibitors (TKIs) gefitinib or CUDC-101 on radiation-induced cell death and associated regulation of survivin gene expression was evaluated...
December 2016: Neurosurgical Focus
https://www.readbyqxmd.com/read/27902466/long-non-coding-rna-urothelial-carcinoma-associated-1-uca1-mediates-radiation-response-in-prostate-cancer
#6
Alireza Fotouhi Ghiam, Samira Taeb, Xiaoyong Huang, Vincent Huang, Jessica Ray, Seville Scarcello, Christianne Hoey, Sahar Jahangiri, Emmanouil Fokas, Andrew Loblaw, Robert G Bristow, Danny Vesprini, Paul Boutros, Stanley K Liu
Radioresistance remains a significant obstacle in the treatment of Prostate Cancer (PCa). To simulate the clinical scenario of irradiation resistance (IRR), we created DU145-IRR PCa cell lines by treatment with 2 Gy daily IR for 59 fractions. DU145-IRR cells acquired an aggressive phenotype as evidenced by increased clonogenic survival, tumorigenic potential and invasiveness. We performed transcriptome profiling to discover dysregulated genes in DU145-IRR cells and identified the long non-coding RNA (lncRNA), Urothelial carcinoma-associated 1 (UCA1)...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899964/radiation-induces-the-generation-of-cancer-stem-cells-a-novel-mechanism-for-cancer-radioresistance
#7
Fengsheng Li, Kunming Zhou, Ling Gao, Bin Zhang, Wei Li, Weijuan Yan, Xiujun Song, Huijie Yu, Sinian Wang, Nan Yu, Qisheng Jiang
Radioresistance remains a major obstacle for the radiotherapy treatment of cancer. Previous studies have demonstrated that the radioresistance of cancer is due to the existence of intrinsic cancer stem cells (CSCs), which represent a small, but radioresistant cell subpopulation that exist in heterogeneous tumors. By contrast, non-stem cancer cells are considered to be radiosensitive and thus, easy to kill. However, recent studies have revealed that under conditions of radiation-induced stress, theoretically radiosensitive non-stem cancer cells may undergo dedifferentiation subsequently obtaining the phenotypes and functions of CSCs, including high resistance to radiotherapy, which indicates that radiation may directly result in the generation of novel CSCs from non-stem cancer cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27898411/radioprotective-effects-of-heat-killed-mycobacterium-tuberculosis-in-cultured-cells-and-radiosensitive-tissues
#8
Yuanyuan Chen, Yang Xu, Jicong Du, Jiaming Guo, Xiao Lei, Jianguo Cui, Cong Liu, Ying Cheng, Bailong Li, Fu Gao, Jintao Ju, Jianming Cai, Yanyong Yang
BACKGROUND: Exposure to ionizing radiation (IR) often causes severe damage to radiosensitive tissues, which limits the use of radiotherapy in cancer patients. Novel safe and effective radioprotectant is urgently required. It has been reported toll like receptor 2 (TLR2) plays a critical role in radioresistance. In this study, we demonstrated the protective effects of Heat-Killed Mycobacterium tuberculosis (HKMT), a potent TLR2 agonist, against IR. METHODS: Cell survival and apoptosis were determined by CCK-8 assay and Annexin V assay, respectively...
November 30, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27877235/x-ray-induced-photodynamic-therapy-a-combination-of-radiotherapy-and-photodynamic-therapy
#9
Geoffrey D Wang, Ha T Nguyen, Hongmin Chen, Phillip B Cox, Lianchun Wang, Koichi Nagata, Zhonglin Hao, Andrew Wang, Zibo Li, Jin Xie
Conventional photodynamic therapy (PDT)'s clinical application is limited by depth of penetration by light. To address the issue, we have recently developed X-ray induced photodynamic therapy (X-PDT) which utilizes X-ray as an energy source to activate a PDT process. In addition to breaking the shallow tissue penetration dogma, our studies found more efficient tumor cell killing with X-PDT than with radiotherapy (RT) alone. The mechanisms behind the cytotoxicity, however, have not been elucidated. In the present study, we investigate the mechanisms of action of X-PDT on cancer cells...
2016: Theranostics
https://www.readbyqxmd.com/read/27871924/mir-335-regulates-the-chemo-radioresistance-of-small-cell-lung-cancer-cells-by-targeting-parp-1
#10
Yingshan Luo, Lihua Tong, Hui Meng, Weiliang Zhu, Linlang Guo, Ting Wei, Jian Zhang
The role of miR-335 in the regulation of chemosensitivity and radiosensitivity of small cell lung cancer (SCLC) was investigated. miR-335 was significantly downregulated in multi-drug-resistant SCLC H69AR and H446DDP cells compared with parental cells as detected by qRT-PCR. Then, we demonstrated the negative correlation between miR-335 expression and the chemo-radiosensitivity of SCLC cells, including cell proliferation, cell clonality and cell apoptosis. In addition, miR-335 overexpression inhibited cell migration in vitro and tumor growth in vivo, whereas inhibition of miR-335 promoted cell migration and tumor growth...
November 18, 2016: Gene
https://www.readbyqxmd.com/read/27867017/genomic-amplification-of-fanconi-anemia-complementation-group-a-fanca-in-head-and-neck-squamous-cell-carcinoma-hnscc-cellular-mechanisms-of-radioresistance-and-clinical-relevance
#11
Julia Hess, Kristian Unger, Michael Orth, Ulrike Schötz, Lars Schüttrumpf, Verena Zangen, Igor Gimenez-Aznar, Agata Michna, Ludmila Schneider, Ramona Stamp, Martin Selmansberger, Herbert Braselmann, Ludwig Hieber, Guido A Drexler, Sebastian Kuger, Diana Klein, Verena Jendrossek, Anna A Friedl, Claus Belka, Horst Zitzelsberger, Kirsten Lauber
Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance...
November 17, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27861529/oxygen-distributions-evaluation-of-computational-methods-using-a-stochastic-model-for-large-tumour-vasculature-to-elucidate-the-importance-of-considering-a-complete-vascular-network
#12
Jakob H Lagerlöf, Peter Bernhardt
PURPOSE: To develop a general model that utilises a stochastic method to generate a vessel tree based on experimental data, and an associated irregular, macroscopic tumour. These will be used to evaluate two different methods for computing oxygen distribution. METHODS: A vessel tree structure, and an associated tumour of 127 cm3, were generated, using a stochastic method and Bresenham's line algorithm to develop trees on two different scales and fusing them together...
2016: PloS One
https://www.readbyqxmd.com/read/27847320/inhibition-of-cdk9-induces-apoptosis-and-potentiates-the-effect-of-cisplatin-in-hypopharyngeal-carcinoma-cells
#13
Shengda Cao, Yingyi Yu, Shangren Chen, Dapeng Lei, Shudong Wang, Xinliang Pan, Jun Peng
Myeloid cell leukemia-1 (Mcl-1) plays an important role in survival, chemo- and radioresistance of head and neck squamous cell carcinoma (HNSCC). Cyclin-dependent kinase 9/cyclin T (CDK9) promotes excessive production of multiple pro-survival proteins including Mcl-1, leading to impaired apoptosis of cancer cells. As such, CDK9 is an emerging therapeutic target in cancer therapy. We herein report the first study of targeting CDK9 as a treatment strategy for hypopharyngeal squamous cell carcinoma (HSCC), an aggressive malignancy associated with one of the worst prognoses within HNSCC...
November 12, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27837456/cycling-cd34-expression-in-subpopulations-of-head-and-neck-squamous-cell-carcinoma-cell-lines-is-involved-in-radioresistance-and-change-in-cytokeratin-expression-profile
#14
Tobias Ettl, Matthias Hautmann, Torsten E Reichert, Richard Bauer
The expression of the hair follicle stem cell marker CD34 was analyzed in five different head and neck squamous cell carcinoma (HNSCC) cell lines with different antibodies. All HNSCC cell lines expressed CD34 on their cell surface. After cell cycle synchronization via serum starvation, we observed cyclic CD34 expression in HNSCC cells dependent on cell cycle progression via immunofluorescent staining and flow cytometric analysis. Investigation of the CD34(+) and CD34(-) HNSCC populations revealed most of the cells in S-phase and G2/M-Phase in CD34(+) cells in contrast to CD34(-) cells...
November 11, 2016: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/27834628/consensus-guidelines-for-postoperative-stereotactic-body-radiation-therapy-for-spinal-metastases-results-of-an-international-survey
#15
Kristin J Redmond, Simon S Lo, Scott G Soltys, Yoshiya Yamada, Igor J Barani, Paul D Brown, Eric L Chang, Peter C Gerszten, Samuel T Chao, Robert J Amdur, Antonio A F De Salles, Matthias Guckenberger, Bin S Teh, Jason Sheehan, Charles R Kersh, Michael G Fehlings, Moon-Jun Sohn, Ung-Kyu Chang, Samuel Ryu, Iris C Gibbs, Arjun Sahgal
OBJECTIVE Although postoperative stereotactic body radiation therapy (SBRT) for spinal metastases is increasingly performed, few guidelines exist for this application. The purpose of this study is to develop consensus guidelines to promote safe and effective treatment for patients with spinal metastases. METHODS Fifteen radiation oncologists and 5 neurosurgeons, representing 19 centers in 4 countries and having a collective experience of more than 1300 postoperative spine SBRT cases, completed a 19-question survey about postoperative spine SBRT practice...
November 11, 2016: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/27834104/upregulating-dab2ip-expression-via-egr-1-inhibition-a-new-approach-for-overcoming-fractionated-irradiation-induced-cross-tolerance-to-ionizing-radiation-and-mitomycin-c-in-tumor-cells
#16
Rulve Chang, Hui He, Guangmin Mao, Zhaolu Kong
PURPOSE: In this study, we evaluated the effect of fractionated irradiation (FI) on tumor cells sensitivity to ionizing radiation (IR) and antineoplastic drugs, and examined the potential of early growth response-1 (EGR-1) inhibition to sensitize tumor cells to IR. MATERIALS AND METHODS: PC3 and HepG2 cells were subjected to γ-rays at 2 Gy for ten times. Survived cells were named PC3/R and HepG2/R, respectively. Cells sensitivity to irradiation and chemotherapeutic drugs, including cisplatin (PT), doxorubicin (DOX), mitomycin C (MMC) and 5-fluorouracil (5-FU) were identified by colony formation assay and MMT method, respectively...
November 11, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27824512/hypoxia-a-double-edged-sword-in-cancer-therapy
#17
Hamed Manoochehri Khoshinani, Saeid Afshar, Rezvan Najafi
Hypoxia is a common feature of malignant tumors. There is an interactive connection between hypoxia and chemoresistance, radioresistance, invasiveness, and angiogenesis. Therefore, tumor hypoxia has been considered as a validated target for treating cancer. This review focuses on the role of hypoxia on chemoresistance and radioresistance. In addition, we address several approaches targeting tumor hypoxia, known as hypoxia-targeted therapy.
November 8, 2016: Cancer Investigation
https://www.readbyqxmd.com/read/27823965/warburg-effect-hexokinase-ii-and-radioresistance-of-laryngeal-carcinoma
#18
REVIEW
Jiang-Tao Zhong, Shui-Hong Zhou
Radiotherapy is now widely used as a part of multidisciplinary treatment approaches for advanced laryngeal carcinoma and preservation of laryngeal function. However, the mechanism of the radioresistance is still unclear. Some studies have revealed that the Warburg effect promotes the radioresistance of various malignant tumors, including laryngeal carcinoma. Among the regulators involved in the Warburg effect, hexokinase-II (HK-II) is a crucial glycolytic enzyme that catalyzes the first essential step of glucose metabolism...
November 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27815359/antibody-targeting-grp78-enhances-the-efficacy-of-radiation-therapy-in-human-glioblastoma-and-non-small-cell-lung-cancer-cell-lines-and-tumor-models
#19
David Ya Dadey, Vaishali Kapoor, Kelly Hoye, Arpine Khudanyan, Andrea Collins, Dinesh Thotala, Dennis E Hallahan
PURPOSE: Non-small-cell lung cancer (NSCLC) and glioblastoma multiforme (GBM) have poor median survival. NSCLC and GBM overexpress glucose regulated protein 78 (GRP78), which has a role in radioresistance and recurrence. In this study, we determined the effect of anti-GRP78 antibody and the combined effect of the anti-GRP78 antibody with ionizing radiation (XRT) on NSCLC and GBM cell lines both in vitro and in vivo. EXPERIMENTAL DESIGN: NSCLC and GBM cancer cell lines were treated with anti-GRP78 antibodies and evaluated for proliferation, colony formation, cell death and PI3K/Akt/mTOR signaling...
November 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27807620/genetic-background-of-enhanced-radioresistance-in-an-anhydrobiotic-insect-transcriptional-response-to-ionizing-radiations-and-desiccation
#20
Alina Ryabova, Kyosuke Mukae, Alexander Cherkasov, Richard Cornette, Elena Shagimardanova, Tetsuya Sakashita, Takashi Okuda, Takahiro Kikawada, Oleg Gusev
It is assumed that resistance to ionizing radiation, as well as cross-resistance to other abiotic stresses, is a side effect of the evolutionary-based adaptation of anhydrobiotic animals to dehydration stress. Larvae of Polypedilum vanderplanki can withstand prolonged desiccation as well as high doses of ionizing radiation exposure. For a further understanding of the mechanisms of cross-tolerance to both types of stress exposure, we profiled genome-wide mRNA expression patterns using microarray techniques on the chironomid larvae collected at different stages of desiccation and after exposure to two types of ionizing radiation-70 Gy of high-linear energy transfer (LET) ions ((4)He) and the same dose of low-LET radiation (gamma rays)...
November 2, 2016: Extremophiles: Life Under Extreme Conditions
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