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https://www.readbyqxmd.com/read/27910734/targeting-the-akt-cyclin-d1-pathway-to-overcome-intrinsic-and-acquired-radioresistance-of-tumors-for-effective-radiotherapy
#1
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/27909463/synthetic-nanoparticles-for-delivery-of-radioisotopes-and-radiosensitizers-in-cancer-therapy
#2
REVIEW
Jun Zhao, Min Zhou, Chun Li
Radiotherapy has been, and will continue to be, a critical modality to treat cancer. Since the discovery of radiation-induced cytotoxicity in the late 19th century, both external and internal radiation sources have provided tremendous benefits to extend the life of cancer patients. Despite the dramatic improvement of radiation techniques, however, one challenge persists to limit the anti-tumor efficacy of radiotherapy, which is to maximize the deposited dose in tumor while sparing the rest of the healthy vital organs...
2016: Cancer Nanotechnology
https://www.readbyqxmd.com/read/27908167/computer-aided-prognosis-for-cell-death-categorization-and-prediction-in-vivo-using-quantitative-ultrasound-and-machine-learning-techniques
#3
M J Gangeh, A Hashim, A Giles, L Sannachi, G J Czarnota
PURPOSE: At present, a one-size-fits-all approach is typically used for cancer therapy in patients. This is mainly because there is no current imaging-based clinical standard for the early assessment and monitoring of cancer treatment response. Here, the authors have developed, for the first time, a complete computer-aided-prognosis (CAP) system based on multiparametric quantitative ultrasound (QUS) spectroscopy methods in association with texture descriptors and advanced machine learning techniques...
December 2016: Medical Physics
https://www.readbyqxmd.com/read/27906620/the-radiosensitizing-effect-of-fluorocyclopentenyl-cytosine-rx-3117-in-ovarian-and-lung-cancer-cell-lines
#4
Dzjemma Sarkisjan, Jaap van den Berg, Evelyn Smit, Young B Lee, Deog J Kim, Godefridus J Peters
RX-3117 (fluorocyclopentenyl-cytosine) is a novel cytidine analog currently being evaluated in a Phase Ib clinical trial in cancer patients with solid tumors. The radiosensitizing effect of RX-3117 was studied in A2780 ovarian cancer cells and non-small cell lung cancer cell lines and related to cell survival and the effect on cell cycle and cell cycle proteins. RX-3117 has a schedule-dependent radiosensitizing effect, but only at pre-incubation (dose modifying factors: 1.4-1.8), observed at pulse and fractionated irradiation...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27903980/identification-of-biomarker-micrornas-for-predicting-the-response-of-colorectal-cancer-to-neoadjuvant-chemoradiotherapy-based-on-microrna-regulatory-network
#5
Yaqun Zhu, Qiliang Peng, Yuxin Lin, Li Zou, Peipei Shen, Feifei Chen, Ming Min, Li Shen, Jiajia Chen, Bairong Shen
Preoperative radiotherapy or chemoradiotherapy has become a standard procedure for treatment of patients with locally advanced colorectal cancer (CRC). However, patients' responses to treatment are different and personalized. MicroRNAs (miRNAs) are promising biomarkers for predicting personalized responses. In this study, we collected 30 publicly reported miRNAs associated with chemoradiotherapy of CRC. We extracted 46 differentially expressed miRNAs from samples of responders and non-responders to preoperative radiotherapy from the Gene Expression Omnibus dataset (Student's t test, p-value < 0...
November 26, 2016: Oncotarget
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
#6
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/27903196/the-impact-of-cobalt-60-source-age-on-biologically-effective-dose-in-high-dose-functional-gamma-knife-radiosurgery
#7
Benjamin H Kann, James B Yu, John M Stahl, James E Bond, Christopher Loiselle, Veronica L Chiang, Ranjit S Bindra, Jason L Gerrard, David J Carlson
OBJECTIVE Functional Gamma Knife radiosurgery (GKRS) procedures have been increasingly used for treating patients with tremor, trigeminal neuralgia (TN), and refractory obsessive-compulsive disorder. Although its rates of toxicity are low, GKRS has been associated with some, if low, risks for serious sequelae, including hemiparesis and even death. Anecdotal reports have suggested that even with a standardized prescription dose, rates of functional GKRS toxicity increase after replacement of an old cobalt-60 source with a new source...
December 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27903123/drug-priming-enhances-radiosensitivity-of-adamantinomatous-craniopharyngioma-via-downregulation-of-survivin
#8
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
#9
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/27901292/differential-in-radiosensitizing-potency-of-enantiomers-of-the-fatty-acid-synthase-inhibitor-c75
#10
Colin Rae, John W Babich, Robert J Mairs
The elevated activity of fatty acid synthase has been reported in a number of cancer types. Inhibition of this enzyme has been demonstrated to induce cancer cell death and reduce tumor growth. In addition, the fatty acid synthase inhibitor drug C75 has been reported to synergistically enhance the cancer-killing ability of ionizing radiation. However, clinical use of C75 has been limited due to its producing weight loss, believed to be caused by alterations in the activity of carnitine palmitoyltransferase-1...
November 30, 2016: Chirality
https://www.readbyqxmd.com/read/27900012/ubenimex-enhances-the-radiosensitivity-of-renal-cell-carcinoma-cells-by-inducing-autophagic-cell-death
#11
Shuai Liu, Xiaoqing Wang, Jiaju Lu, Liping Han, Yongfei Zhang, Zheng Liu, Sentai Ding, Zhao Liu, Dongbin Bi, Zhihong Niu
Renal cell carcinoma (RCC) is resistant to standard radiotherapy. Ubenimex, an aminopeptidase N inhibitor, is widely used as an adjunct therapy after surgery to enhance the function of immunocompetent cells and confer antitumor effects. Our previous study demonstrated that ubenimex induces autophagic cell death in RCC cells. Recently, the molecular mechanism of autophagy induction has been associated with radiosensitivity in RCC cells. In the present study, the ability of ubenimex to enhance RCC cell sensitivity to radiation via the induction of autophagic cell death was determined, and the mechanism of action of this effect was investigated...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899964/radiation-induces-the-generation-of-cancer-stem-cells-a-novel-mechanism-for-cancer-radioresistance
#12
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/27899034/ionizing-radiation-sensitivity-of-the-ocular-lens-and-its-dose-rate-dependence
#13
Nobuyuki Hamada
PURPOSE: In 2011, the International Commission on Radiological Protection reduced the threshold for the lens effects of low linear energy transfer (LET) radiation. On one hand, the revised threshold of 0.5 Gy is much lower than previously recommended thresholds, but mechanisms behind high radiosensitivity remain incompletely understood. On the other hand, such threshold is independent of dose rate, in contrast to previously recommended separate thresholds each for single and fractionated/protracted exposures...
November 30, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27898411/radioprotective-effects-of-heat-killed-mycobacterium-tuberculosis-in-cultured-cells-and-radiosensitive-tissues
#14
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/27895920/pd1-pd-l1-inhibition-as-a-potential-radiosensitizer-in-head-and-neck-squamous-cell-carcinoma-a-case-report
#15
Misako Nagasaka, Mark Zaki, Harold Kim, S Naweed Raza, George Yoo, Ho-Sheng Lin, Ammar Sukari
BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION: We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27893451/rotating-and-translating-anthropomorphic-head-voxel-models-to-establish-an-horizontal-frankfort-plane-for-dental-cbct-monte-carlo-simulations-a-dose-comparison-study
#16
A Stratis, G Zhang, R Jacobs, R Bogaerts, H Bosmans
In order to carry out Monte Carlo (MC) dosimetry studies, voxel phantoms, modeling human anatomy, and organ-based segmentation of CT image data sets are applied to simulation frameworks. The resulting voxel phantoms preserve patient CT acquisition geometry; in the case of head voxel models built upon head CT images, the head support with which CT scanners are equipped introduces an inclination to the head, and hence to the head voxel model. In dental cone beam CT (CBCT) imaging, patients are always positioned in such a way that the Frankfort line is horizontal, implying that there is no head inclination...
December 21, 2016: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/27893445/a-method-for-high-energy-low-dose-mammography-using-edge-illumination-x-ray-phase-contrast-imaging
#17
Paul C Diemoz, Alberto Bravin, Anikó Sztrókay-Gaul, Marie Ruat, Susanne Grandl, Doris Mayr, Sigrid Auweter, Alberto Mittone, Emmanuel Brun, Cyril Ponchut, Maximilian F Reiser, Paola Coan, Alessandro Olivo
Since the breast is one of the most radiosensitive organs, mammography is arguably the area where lowering radiation dose is of the uttermost importance. Phase-based x-ray imaging methods can provide opportunities in this sense, since they do not require x-rays to be stopped in tissue for image contrast to be generated. Therefore, x-ray energy can be considerably increased compared to those usually exploited by conventional mammography. In this article we show how a novel, optimized approach can lead to considerable dose reductions...
December 21, 2016: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/27890801/eus-guided-paclitaxel-injection-as-an-adjunctive-therapy-to-systemic-chemotherapy-and-concurrent-external-beam-radiation-before-surgery-for-localized-or-locoregional-esophageal-cancer-a-multicenter-prospective-randomized-trial
#18
John M DeWitt, S Krishna Murthy, Ramesh Ardhanari, G Aaron DuVall, Grzegorz Wallner, Paul Litka, Claire Daugherty, Kirk Fowers
BACKGROUND AND AIMS: OncoGel is paclitaxel (PTX) formulated in a thermosensitive, biodegradable copolymer for focused cytotoxicity and radiosensitization. A phase IIa study suggested EUS-guided PTX injection into esophageal tumors subsequently receiving radiation therapy (RT) was safe. METHODS: In an international multicenter, prospective randomized phase IIb study, patients with local or locoregional adenocarcinoma or squamous cell carcinoma (SCCA) of the esophagus/GE junction and eligible for neoadjuvant chemoradiotherapy (CRT) before surgery were randomized to standard of care (SOC) plus EUS-guided PTX injection or SOC alone...
November 24, 2016: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/27882128/microrna-145-sensitizes-cervical-cancer-cells-to-low-dose-irradiation-by-downregulating-oct4-expression
#19
Siqi Yan, Xiangjun Li, Qiao Jin, Jun Yuan
Poor elucidation of the mechanisms involved in regulating the radiosensitivity of cancers prevents the extensive application of low-dose radiotherapy in clinical settings. The present study was conducted to investigate the role of microRNA-145 (miR-145) in the modulation of cervical cancer cell radiosensitivity, as well as to identify the underlying target of miR-145 during this process. Cervical cancer tera cells were initially exposed to doses of radiation between 1 and 6 Gy before the assessments of the cell viability and apoptosis rate...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27881872/in-vitro-and-in-vivo-assessment-of-direct-effects-of-simulated-solar-and-galactic-cosmic-radiation-on-human-hematopoietic-stem-progenitor-cells
#20
C Rodman, G Almeida-Porada, S George, J Moon, S Soker, T Pardee, M Beaty, P Guida, S P Sajuthi, C D Langefeld, S J Walker, P F Wilson, C D Porada
Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation, and likely one or more solar particle events (SPEs). Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions. We show that exposing human hematopoietic stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated high-energy protons and iron ions: 1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; 2) dramatically reduces in vitro colony-formation; 3) markedly alters engraftment and lineage commitment in vivo; and 4) leads to the development, in vivo, of what appears to be T-ALL...
November 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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