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https://www.readbyqxmd.com/read/29775397/receptor-tyrosine-kinase-signaling-in-cancer-radiotherapy-and-its-targeting-for-tumor-radiosensitization
#1
Poushali Bhattacharya, Neena G Shetake, Badri N Pandey, Amit Kumar
PURPOSE: One of the most important implications of 'Radiation Biology' research is to improve cancer radiotherapy with minimum side effects. In this regard, combination of chemotherapy with radiation has significantly improved tumor control as well as overall survival in a variety of cancers. However, this has been achieved at the cost of significant normal tissue toxicity, due to the lack of specificity of chemotherapy. Membrane-localized receptor tyrosine kinases (RTKs) have been found to play a driving role in various hallmarks of cancer...
May 18, 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29774792/hypofractionated-radiotherapy-is-superior-to-conventional-fractionation-in-an-orthotopic-model-of-anaplastic-thyroid-cancer
#2
Ayman J Oweida, Andy Phan, Benjamin Vancourt, Tyler Robin, Mohammad K Hararah, Shilpa Bhatia, Dallin Milner, Shelby Lennon, Laura Pike, David Raben, Bryan R Haugen, Nikita Pozdeyev, Rebecca E Schweppe, Sana D Karam
Anaplastic thyroid cancer is an aggressive and highly lethal disease with poor outcomes and resistance to therapy. Despite multimodality treatment including radiation therapy and chemotherapy, response rates remain below 15% with a median time to progression of less than 3 months. Recent advances in radiotherapy delivery and gene-expression profiling may help guide patient selection for personalized therapy. The purpose of this study was to characterize the response to radiation in a panel of ATC cell lines and to test alternative radiotherapy fractionation schedules for overcoming radioresistance...
May 18, 2018: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29773816/experimental-investigation-of-radiobiology-in-head-and-neck-cancer-cell-lines-as-a-function-of-hpv-status-by-mtt-assay
#3
Paul Reid, Puthenparampil Wilson, Yanrui Li, Loredana G Marcu, Alexander H Staudacher, Michael P Brown, Eva Bezak
Head and neck cancers (HNCs) are aggressive epithelial tumours frequently treated using radiation. HNC biology shows distinctions dependent on the oncologic involvement of the human papilloma virus (HPV). Clinically, HPV positive HNCs respond better to radiotherapy but few in vitro data demonstrate radiobiological differences explaining differences in clinical outcomes. This pilot study examined radiobiological responses to irradiation and subsequent regeneration in two HNC cell lines (HPV positive and negative)...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773344/lncrna-oip5-as1-regulates-radioresistance-by-targeting-dyrk1a-through-mir-369-3p-in-colorectal-cancer-cells
#4
Yanmei Zou, Shuo Yao, Xiuqiong Chen, Dian Liu, Jianhua Wang, Xun Yuan, Jie Rao, Huihua Xiong, Shiying Yu, Xianglin Yuan, Feng Zhu, Guohong Hu, Yihua Wang, Hua Xiong
OBJECT: This study aimed to investigate the role of lncRNA OIP5-AS1 in regulating radioresistance of colorectal cancer (CRC) cells. METHODS: Microarray analysis was used to screen out lncRNAs differentially expressed in radio-resistant CRC cell lines. Expression levels of OIP5-AS1, miR-369-3p and DYRK1A in CRC cell lines were measured by qRT-PCR. Protein expression of DYRK1A was determined by western blot. The target relationships among OIP5-AS1, miR-369-3p and DYRK1A were validated by dual luciferase reporter assay...
April 14, 2018: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29771500/rational-design-of-cancer-targeted-selenadiazole-derivative-as-efficient-radiosensitizer-for-precise-cancer-therapy
#5
Delong Zeng, Shulin Deng, Chengcheng Sang, Jianfu Zhao Zhao, Tianfeng Chen
Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovery of targeted therapies for personalized cancer medicine. Herein, cancer targeting RGD peptide has been covalently conjugated to selenadiazole derivative (RGD-SeD) to improve its cancer selectivity. The RGD decoration significantly enhances the anticancer efficacy of RGD-SeD in αVβ3 integrin-overexpressing HepG2 liver cancer cells, but not in normal liver cells. Cellular uptake assay and fluorescent imaging confirmed the selectivity of RGD-SeD to integrin overexpressing cancer cells...
May 17, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29770473/icotinib-enhances-lung-cancer-cell-radiosensitivity-in-vitro-and-in-vivo-by-inhibiting-mapk-erk-and-akt-activation
#6
Yonghong Fu, Sen Zhang, Dongjie Wang, Jing Wang
Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing radiosensitivity. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell radiosensitivity and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29769307/orally-bioavailable-and-blood-brain-barrier-penetrating-atm-inhibitor-az32-radiosensitizes-intracranial-gliomas-in-mice
#7
Jeremy Karlin, Jasmine Allen, Syed F Ahmad, Gareth Hughes, Victoria Sheridan, Rajesh Odedra, Paul Farrington, Elaine B Cadogan, Lucy C Riches, Antonio Garcia-Trinidad, Andrew G Thomason, Bhavika Patel, Jennifer Vincent, Alan Lau, Kurt G Pike, Thomas A Hunt, Amrita Sule, Nicholas C K Valerie, Laura Biddlestone-Thorpe, Jenna Kahn, Jason M Beckta, Nitai Mukhopadhyay, Bernard Barlaam, Sebastien L Degorce, Jason Kettle, Nicola Colclough, Joanne Wilson, Aaron Smith, Ian P Barrett, Li Zheng, Tianwei Zhang, Yingchun Wang, Kan Chen, Martin Pass, Stephen T Durant, Kristoffer Valerie
Inhibition of ataxia-telangiectasia mutated (ATM) during radiotherapy of glioblastoma multiforme (GBM) may improve tumor control by short-circuiting the response to radiation-induced DNA damage. A major impediment for clinical implementation is that current inhibitors have limited CNS bioavailability, thus, the goal was to identify ATM inhibitors (ATMi) with improved CNS penetration. Drug screens and refinement of lead compounds identified AZ31 and AZ32. The compounds were then tested in vivo for efficacy and impact on tumor and healthy brain...
May 16, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29765534/bi2536-induces-mitotic-catastrophe-and-radiosensitization-in-human-oral-cancer-cells
#8
Chieh-Yuan Cheng, Chung-Ji Liu, Yu-Chuen Huang, Shu-Hua Wu, Hsu-Wei Fang, Yu-Jen Chen
BI2536 has been developed as a potential therapeutic agent for various cancers but not in oral cancer cells. Since BI2536 exhibits mitosis-regulating activity which are the most radiosensitive, we hypothesized that BI2536 might modulate the radiosensitivity of oral cancer cells. Human normal fibroblasts, oral cancer SAS, and OECM1 cells were treated with BI2536 (0-50 nM) and/or radiation (0-4 Gy). MTT assay, Liu's staining, flow cytometry, clonogenic assay, Annexin V/propidium iodide (PI) staining, western blot analysis, and small interfering RNA knockdown experiments were used to assess cell viability, morphology, cell cycle progression, radiation survival, and expression of regulatory proteins in vitro ...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29763377/influence-of-polg-on-radiosensitivity-of-nasopharyngeal-carcinoma-cells
#9
Ruiqing Chen, Zeng Wang, Ruilong Lan, Fei Huang, Jinrong Chen, Yuanteng Xu, Hengshan Zhang, Lurong Zhang
BACKGROUND AND OBJECTIVE: There is a high incidence of nasopharyngeal carcinoma (NPC), malignant head and neck tumors, in southern China. Radioresistance is the main cause affecting the efficacy of NPC treatments. The POLG gene particularly plays an important role in radiation-induced damage repair. In this study, the authors established RNAi CNE-1 and CNE-2 knockdown in two NPC cell lines to observe whether this gene affects the radiosensitivity of NPC cells. MATERIALS AND METHODS: Four short hairpin RNA (shRNA) expression plasmids targeting POLG gene were constructed and transfected into the NPC cell lines CNE-1 and CNE-2...
May 2018: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29762138/theranostic-gold-magnetite-hybrid-nanoparticles-for-mri-guided-radiosensitization
#10
Devid Maniglio, Filippo Benetti, Luca Minati, Jorge Jovicich, Aldo Valentini, G Speranza, Claudio Migliaresi
The main limitation of drug-enhanced radiotherapy concerns the difficulty to evaluate the effectiveness of cancer targeting after drug administration hindering the standardization of therapies based on current radiosensitizing compounds. The challenge regards the development of systems able to combine imaging and radiotherapy enhancement in order to perform highly reliable cancer theragnosis. For these reasons, gold-magnetite hybrid nanoparticles are proposed as innovative theranostic nanotools for imaging-guided radiosensitization in cancer treatment...
May 15, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29760601/tumor-cell-accelerated-senescence-is-associated-with-dna-pkcs-status-and-telomere-dysfunction-induced-by-radiation
#11
Miaomiao Zhang, Xiaopeng Guo, Yue Gao, Dong Lu, Wenjian Li
Whether telomere structure integrity is related to radiosensitivity is not well investigated thus far. In this study, we investigated the relation between telomere instability and radiation-induced accelerated senescence. Partial knockdown of DNA-dependent catalytic subunit of protein kinase (DNA-PKcs) in human breast cancer cell line MCF-7 was established by small interfering RNA. Radiosensitivity of control and DNA-PKcs knockdown MCF-7 cells was analyzed by clonogenetic assay. Cell growth was measured by real-time cell electronic sensing...
April 2018: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/29760046/dual-hdac-and-pi3k-inhibition-abrogates-nf%C3%AE%C2%BAb-and-foxm1-mediated-dna-damage-response-to-radiosensitize-pediatric-high-grade-gliomas
#12
Sharmistha Pal, David Kozono, Xiaodong Yang, Wojciech Fendler, Whitney Fitts, Jing Ni, John A Alberta, Jean Zhao, Kevin X Liu, Jie Bian, Nathalene Truffaux, William A Weiss, Adam C Resnick, Pratiti Bandopadhayay, Keith L Ligon, Steven G Dubois, Sabine Mueller, Dipanjan Chowdhury, Daphne A Haas-Kogan
Aberrant chromatin remodeling and activation of the phosphatidylinositol 3-kinase (PI3K) pathway have been identified as important mediators of pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) pathogenesis. As inhibition of these pathways are promising therapeutic avenues and radiation is the only modality to prolong survival of DIPG patients, we sought to explore radiosensitizing functions of such inhibition and explore mechanisms of action of such agents. Here we demonstrate that combined treatment with radiotherapy and CUDC-907, a novel first-in-class dual inhibitor of histone deacetylases (HDAC) and PI3K, evokes a potent cytotoxic response in pHGG and DIPG models...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29758120/concomitant-administration-of-radiation-with-eribulin-improves-the-survival-of-mice-harboring-intracerebral-glioblastoma
#13
Shunichiro Miki, Shoji Imamichi, Hiroaki Fujimori, Arata Tomiyama, Kenji Fujimoto, Kaishi Satomi, Yuko Matsushita, Sanae Matsuzaki, Masamichi Takahashi, Eiichi Ishikawa, Tetsuya Yamamoto, Akira Matsumura, Akitake Mukasa, Ryo Nishikawa, Kenkichi Masutomi, Yoshitaka Narita, Mitsuko Masutani, Koichi Ichimura
Glioblastoma is the most common and devastating type of malignant brain tumor. We recently found that eribulin suppresses glioma growth in vitro and in vivo and that eribulin is efficiently transferred into mouse brain tumors at a high concentration. Eribulin is a non-taxane microtubule inhibitor approved for breast cancer and liposarcoma. Cells arrested in M-phase by chemotherapeutic agents such as microtubule inhibitors are highly sensitive to radiation-induced DNA damage. Several recent case reports demonstrated the clinical benefits of eribulin combined with radiation therapy for metastatic brain tumors...
May 14, 2018: Cancer Science
https://www.readbyqxmd.com/read/29753417/persistent-depletion-of-plasma-gelsolin-pgsn-after-exposure-of-mice-to-heavy-silicon-ions
#14
Kanokporn Noy Rithidech, Paiboon Reungpatthanaphong, Montree Tungjai, Witawat Jangiam, Louise Honikel, Elbert B Whorton
Little is known about plasma proteins that can be used as biomarkers for early and late responses to radiation. The purpose of this study was to determine a link between depletion of plasma gelsolin (pGSN) and cell-death as well as inflammatory responses in the lung (one of the tissues known to be radiosensitive) of the same exposed CBA/CaJ mice after exposure to heavy silicon (28 Si) ions. To prevent the development of multiple organ dysfunctions, pGSN (an important component of the extracellular actin-scavenging system) is responsible for the removal of actin that is released into the circulation during inflammation and from dying cells...
May 2018: Life Sciences in Space Research
https://www.readbyqxmd.com/read/29749804/radiosensitizing-effects-of-different-size-bovine-serum-albumin-templated-gold-nanoparticles-on-h22-hepatoma-bearing-mice
#15
ShuLiang Liu, JinMei Piao, YunCai Liu, JingLong Tang, Peng Liu, DaPeng Yang, Li Zhang, Nan Ge, Zhezhen Jin, QiXiao Jiang, LianHua Cui
AIM: To evaluate intravenously injected bovine serum albumin-templated gold nanoparticles (BSA-GNPs) for radiosensitization effects on H22 hepatoma-bearing mice. MATERIALS & METHODS: BSA-GNPs in different size were injected intravenously with a dose of 4 mg Au/kg. After 30 min injection, the tumor-bearing mice were irradiated with 5 Gy x-ray. RESULTS: BSA-GNPs in 8, 50 and 187 nm were synthesized and have no obvious cytotoxicity to HeLa, HepG2 and HeCat cells when the concentration was up to 32 μM...
May 11, 2018: Nanomedicine
https://www.readbyqxmd.com/read/29749270/the-effect-of-time-interval-between-radiotherapy-and-hyperthermia-on-planned-equivalent-radiation-dose
#16
C M van Leeuwen, J Crezee, A L Oei, N A P Franken, L J A Stalpers, A Bel, H P Kok
PURPOSE: Thermoradiotherapy is an effective treatment for locally advanced cervical cancer. However, the optimal time interval between radiotherapy and hyperthermia, resulting in the highest therapeutic gain, remains unclear. This study aims to evaluate the effect of time interval on the therapeutic gain using biological treatment planning. METHODS: Radiotherapy and hyperthermia treatment plans were created for 15 cervical cancer patients. Biological modeling was used to calculate the equivalent radiation dose, that is, the radiation dose that results in the same biological effect as the thermoradiotherapy treatment, for different time intervals ranging from 0-4 h...
May 11, 2018: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/29748236/modeling-and-predicting-tumor-response-in-radioligand-therapy
#17
Peter Kletting, Anne Thieme, Nina Eberhardt, Andreas Rinscheid, Calogero D'Alessandria, Jakob Allmann, Hans-Jürgen Wester, Robert Tauber, Ambros J Beer, Gerhard Glatting, Matthias Eiber
The aim of this work was to develop a theranostic method that allows predicting PSMA-positive tumor volume after radioligand therapy (RLT) based on a pre-therapeutic PET/CT measurement and physiologically based pharmacokinetic/dynamic (PBPK/PD) modeling at the example of RLT using 177 Lu-labeled PSMA for imaging and therapy (PSMA I&T). Methods: A recently developed PBPK model for 177 Lu PSMA I&T RLT was extended to account for tumor (exponential) growth and reduction due to irradiation (linear quadratic model)...
May 10, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29747544/deep-hyperthermia-with-the-hypercollar-system-combined-with-irradiation-for-advanced-head-and-neck-carcinoma-a-feasibility-study
#18
G M Verduijn, E M de Wee, Z Rijnen, P Togni, J A U Hardillo, I Ten Hove, M Franckena, G C van Rhoon, M M Paulides
PURPOSE: Radiotherapy (RT) treatment of locally-advanced and recurrent head and neck carcinoma (HNC) results in disappointing outcomes. Combination of RT with cisplatin or cetuximab improves survival but the increased toxicity and patient's comorbidity warrant the need for a less-toxic radiosensitizer. Stimulated by several randomized studies demonstrating the radio-sensitizing effect of hyperthermia, we developed the HYPERcollar. Here, we report early experience and toxicity in patients with advanced HNC...
May 11, 2018: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/29746213/gene-expression-in-parp1-deficient-mice-exposed-to-a-median-lethal-dose-of-gamma-rays
#19
M A Suresh Kumar, Evagelia C Laiakis, Shanaz A Ghandhi, Shad R Morton, Albert J Fornace, Sally A Amundson
There is a current interest in the development of biodosimetric methods for rapidly assessing radiation exposure in the wake of a large-scale radiological event. This work was initially focused on determining the exposure dose to an individual using biological indicators. Gene expression signatures show promise for biodosimetric application, but little is known about how these signatures might translate for the assessment of radiological injury in radiosensitive individuals, who comprise a significant proportion of the general population, and who would likely require treatment after exposure to lower doses...
May 10, 2018: Radiation Research
https://www.readbyqxmd.com/read/29745724/radiosensitivity-and-transgenerational-effects-in-non-human-species
#20
C Adam-Guillermin, T Hertal-Aas, D Oughton, L Blanchard, F Alonzo, O Armant, N Horemans
The ALLIANCE working group on effects of ionising radiation on wildlife brings together European researchers to work on the topics of radiosensitivity and transgenerational effects in non-human biota. Differences in radiation sensitivity across species and phyla are poorly understood, but have important implications for understanding the overall effects of radiation and for radiation protection; for example, sensitive species may require special attention in monitoring and radiation protection, and differences in sensitivity between species also lead to overall effects at higher levels (community, ecosystem), since interactions between species can be altered...
January 1, 2018: Annals of the ICRP
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