The group analyzed the effects of IL-6 on radiosensitivity and DNA damage following X-ray irradiation on two OSCC cell lines and OSCC tissue samples with radioresistant cells. They demonstrated that increased levels of IL-6 resulted in suppressed radiation induced cell death and that blocking IL-6 signalling sensitized tumor cells to radiation.. Overall, the radio-resistant effects of IL-6 were associated with decreased DNA damage following radiation exposure. In addition, the team investigated the role of the Nrf2-antioxidant pathway and highlighted that IL-6 interacts with the Nrf2-antioxidant pathway in order to provide protection from radiation therapy to cancer cells.. One of research group leaders Hideki Nakayama (Kumamoto University) commented: "This interaction and the resulting protection from oxidative damage that we have discovered here is very interesting. We hope new therapies that target IL-6 will give us an advantage over many types of radiation-resistant cancers.". Although they ...
Reasons for an increased radiocurability of HPV-positive tumors are not defined yet. Disruption of the viral E2-gene has been shown to be associated with poor outcome in patients with cervical cancer[4, 7, 8]. Not only in cervical cancer, but also in HPV-positive head and neck cancer E2-protein may be relevant for treatment success[15]. There is still a debate about direct influence of HPV on radiosensitivity. Because for these clinical reports and the referred interference of E2-protein with regulation of apoptosis and cell cycle control[6, 16] we established the W12/S12 cell system to analyze influence of E2-gene status on radiosensitivity. This cell model mimics the natural way of integration of virus leading to disruption of the E2-gene[11, 12]. We could demonstrate that a disrupted E2-gene leads to radioresistance, because W12/S12 cells differ only in E2-gene status, molecular tumor background is identical. Inactivation of normal function of tumor suppressor proteins pRb and p53 are ...
The effectiveness of radiotherapy treatment could be significantly improved if tumor cells could be rendered more sensitive to ionizing radiation (IR) without altering the sensitivity of normal tissues. However, many of the key therapeutically exploitable mechanisms that determine intrinsic tumor radiosensitivity are largely unknown. We have conducted a small interfering RNA (siRNA) screen of 200 genes involved in DNA damage repair aimed at identifying genes whose knockdown increased tumor radiosensitivity. Parallel siRNA screens were conducted in irradiated and unirradiated tumor cells (SQ20B) and irradiated normal tissue cells (MRC5). Using gammaH2AX foci at 24 hours after IR, we identified several genes, such as BRCA2, Lig IV, and XRCC5, whose knockdown is known to cause increased cell radiosensitivity, thereby validating the primary screening end point. In addition, we identified POLQ (DNA polymerase ) as a potential tumor-specific target. Subsequent investigations showed that POLQ knockdown
Purpose: The clinical radiation responses of different organs vary widely and likely depend on the intrinsic radiosensitivities of their different cell populations. Double-strand breaks (DSBs) are the most deleterious form of DNA damage induced by ionizing radiation, and the cells capacity to rejoin radiation-induced DSBs is known to affect their intrinsic radiosensitivity. To date, only little is known about the induction and processing of radiation-induced DSBs in complex normal tissues. Using an in vivo model with repair-proficient mice, the highly sensitive {gamma}H2AX immunofluorescence was established to investigate whether differences in DSB rejoining could account for the substantial differences in clinical radiosensitivity observed among normal tissues. Methods and Materials: After whole body irradiation of C57BL/6 mice (0.1, 0.5, 1.0, and 2.0 Gy), the formation and rejoining of DSBs was analyzed by enumerating {gamma}H2AX foci in various organs representative of both early-responding ...
Successful cancer treatment with radiation depends heavily on whether a therapeutic gain can be achieved. Sophisticated radiation delivery instrumentation can minimize the normal tissue included in the radiation field; however, invariably normal tissues are included, necessitating a need to identify agents that might differentially radiosensitize tumor as opposed to normal tissues. Cytotoxic chemotherapy combined with radiation is currently used to enhance local tumor control at the expense of increasing normal tissue toxicity (17). Ideally, what is needed are approaches that result in selective tumor radiosensitization.. The current findings suggest that AZD7762-mediated Chk1/2 inhibition may offer considerable selective tumor radiosensitization. AZD7762 did not exert appreciable cytotoxicity alone both in vitro and in vivo. In addition, the normal human fibroblast cell line 1522 was not radiosensitized by AZD7762, suggesting that other normal tissues would not be radiosensitized by AZD7762. In ...
Ive been reading Nick Lanes excellent book Oxygen. He points out that respiration (i.e., oxygen) causes damage thats biochemically the same thing as radiation poisoning, though most air-breathing creatures have evolved mechanisms for coping with oxygen damage that fall apart when subjected to too much of the same kind of damage, too quickly, from radiation. But critters that readily withstand radiation didnt develop their defensive tools out of nowhere after the dawn of the Atomic Age: they built on the exactly the same kind of mechanisms theyd been using for eons to repair damage from oxygen. ...
Mechanically, lncRNA could work as a ceRNA sponging with its target miRNA and exert different functions. It has been demonstrated that lncRNA HOTAIR binds with many miRNA including miR-130a, miR-218, miR-7, miR-203, etc. in gallbladder cancer, hepatocellular carcinoma, or renal cancer cells [33-35]. Binding sites of these miRNAs have been identified within the sequence of HOTAIR. And after binding, HOTAIR reduced the level of miRNA through a ceRNA sponging mechanism, which results in a up-regulation of miRNA targets and changes in signaling transduction. In our study, we found that miR-218 might be a potential target of lncRNA HOTAIR. Moreover, miR-218 was found to inhibit tumor suppressing genes and regulate chemoresistance in breast cancer cells [36,37]. Surprisingly, miR-218 was also reported to increase radiosensitivity in human cervical cancer [38]. Thus in this study, we investigated the role of HOTAIR-miR-218 axis on radiosensitivity of breast cancer cells. And we found that miR-218 was ...
Through Phase I and II SBIR NCI support, Omniox has developed a breakthrough oxygen carrying protein, OMX-4.80, that delivers oxygen to tumors and greatly reduc...
The Wnt/β-catenin pathway regulates the cell growth and survival following radiation in various types of cancer cells. Our previous report show that activation of the Wnt/β-catenin signaling pathway is a key radioprotective mechanism in irradiated head and neck cancer (HNC) cells. However, the molecular mechanisms by which β-catenin regulates radiation sensitivity are not clear. Here we attempted to elucidate the mechanism of cell death following radiation by studying how β-catenin silencing controls the radiation sensitivity of radioresistant HNC cells.. Of nine cell lines examined, the most radioresistant cell line (AMC-HN-9) were selected for this experiments. β-catenin silencing using small interfering RNA(siRNA) down-regulated β-catenin expression up to 72 h, which was confirmed by western blot analysis. The sensitivity to radiation was anlayzed by clonogenic analysis and MTT assay. As a result, β-catenin silencing remarkably decreased the survival of irradiated AMC-HN-9 cells and ...
In the age of personalized cancer medicine, individual measurements of in vitro radiosensitivity and proliferation parameters have great potential for predicting treatment outcome. However, cellular radiosensitivity is quite heterogeneous and therefore concerns exist towards its impact on treatment predictions. It was therefore the purpose of this study to investigate this aspect. Individually-determined radiosensitivities and potential doubling times, as well as tumor volumes from 46 head-and-neck carcinomas treated with radiotherapy, were used to predict tumor control probabilities (TCP) under various biologically-relevant assumptions for heterogeneity in radiosensitivity. TCP predictions were then compared to clinical local control using a ROC curve analysis. The analysis showed that TCP calculated under the assumption of heterogeneous radiosensitivity have the same power of distinguishing between patients with or without local control as from single values for the radiobiological parameters ...
Ni J; Cozzi P; Beretov J; Deng J; Bucci J; Graham P; Li Y, 2017, Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer progression and chemo/radio-resistance in vitro and in vivo, in CANCER RESEARCH, AMER ASSOC CANCER RESEARCH, Washington, DC, presented at Annual Meeting of the American-Association-for-Cancer-Research (AACR), Washington, DC, 01 April 2017 - 05 April 2017, http://dx.doi.org/10.1158/1538-7445.AM2017-2833. Ni J; Cozzi P; Hao J; Beretov J; Chang L; Duan W; Delprado W; Graham P; Bucci J; Kearsley J; Li Y, 2014, CD44 isoform variant 6 is associated with prostate cancer progression, metastasis and chemo-/radio-resistance via PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways in vitro, in CANCER RESEARCH, AMER ASSOC CANCER RESEARCH, San Diego, CA, presented at 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR), San Diego, CA, 05 April 2014 - 09 April 2014, http://dx.doi.org/10.1158/1538-7445.AM2014-4005 ...
We have also found that the let-7 family-of-miRNAs was over-represented in a class of miRNAs that are down-regulated post-irradiation by miRNA microarray in lung cancer cell lines. We were able to show that let-7 family manipulation significantly impacts the radiation response in vitro in mammalian cells as well as in vivo in a C. elegans model of cell death called Radelegans. Specifically, let-7 loss leads to radioresistance and its overexpression leads to radiosensitivity. We have shown in Radelegans and in mammalian cells that these effects are partly regulated by let-7 targets including the RAS oncogene as well as other DNA damage response pathway genes. We hypothesize that low let-7 levels, as seen in lung cancer, result in tumor radioresistance in vivo. ...
E-cadherin is the major adhesion protein associated with epithelial cells loss of its expression is diagnostic of the epithelial to mesenchymal transition (EMT). Our preliminary data suggest that EMT, detected as the loss of E-cadherin expression, may regulate tumor cell radiosensitivity, i.e. cells that have undergone EMT are relatively radioresistant compared to the lines that have retained the epithelial phenotype, which typically are relatively radiosensitive. To definitively test this hypothesis we compared expression levels of E-cadherin and other EMT related markers in ER-a negative (MDA-MB-231 and Hs578t) and ER-a positive (MCF-7) human breast cancer cells. Clonogenic cell survival assays showed that the cell lines expressing estrogen receptor (MCF-7) were more sensitive to increasing doses of radiation and had high expression of E-cadherin. Treatment of MCF-7 cells with 100nM siRNA to E-cadherin for 72 hrs made the cells more resistant to radiation with the surviving fraction changing ...
HDAC inhibitors have been shown to sensitize tumor cell lines and rodent tumors to ionizing radiation, so it is not surprising to find that PCI-24781 also acts as a radiosensitizer in two human tumor cell lines. Although several potential mechanisms of radiosensitization by HDAC inhibitors have been proposed, the mechanism for sensitization by PCI-24781 has not been examined and is relevant to its optimal combination with radiation in the clinic. Results shown here point to misrepair of radiation damage, but this will require further substantiation. Our results also rule out two potential mechanisms of sensitization: redistribution to a more radiosensitive cell cycle phase and inhibition of initial rejoining of radiation-induced double-strand breaks.. Initial experiments examined the toxicity of PCI-24781 in exponentially growing SiHa and WiDr cell lines. Histone acetylation was near maximum after the lowest dose (0.1 μmol/L) and treatment time (4 h; Fig. 1) in line with previous results (2). ...
The Engineered Metallic Nanostructures Laboratory (EMNL) focuses on understanding the design, synthesis, stability, and mechanical behavior of metallic nanostructures including monolithic nanocrystalline alloys, crystalline-amorphous nanolaminates, metallic glass matrix composites, and other unique hierarchical metallic structures. These novel materials are synthesized through electroforming, sputter and pulsed laser deposition, and additive spray manufacturing techniques. Experiments are used in concert with atomistic simulations to study thermal stability, radiation tolerance, and deformation behavior that results from competing mechanisms at the nanoscale. EMNL group members conduct research at the Center for Functional Nanomaterials and NSLS-II at Brookhaven National Laboratory, the Advanced Energy Center at Stony Brook University, and collaborate with the Institute for Advanced Computational Science. EMNL is supported by the National Science Foundation through the Division of Materials Research and
Newborn mice of several inbred strains develop few or no tumors following inoculation with highly tumorigenic strains of polyomavirus. Here we show that such resistant strains can be divided into two groups based on the responses of adult mice to radiation followed by virus inoculation. Most strains show a radiation-sensitive form of resistance (Rr-s) and develop tumors following radiation and virus challenge. This type of resistance has previously been recognized as immunological, based on T-cell responses against virus-encoded neoantigen(s) expressed in tumor cells. Other strains exhibit a radiation-resistant form of resistance (Rr-r) and fail to develop tumors when treated in the same manner. Three additional properties of Rr-r mice distinguish them from Rr-s mice: (i) survival of newborns following inoculation with a highly virulent and usually lethal strain of virus, (ii) resistance to virus spread in newborns inoculated with either tumorigenic or virulent virus strains, and (iii)
We report on the performance of an analog application-specified integrated circuit (ASIC) developed for the front-end electronics of the X-ray CCD camera system (SXI: Soft X-ray Imager) onboard the ASTRO-H satellite. The ASIC consists of four identical channels and they simultaneously process the CCD signals at the pixel rate of 68kHz. Delta-Sigma modulator is adopted to achieve effective noise shaping and obtain a high resolution decimal values with relatively simple circuits. We will implement 16 ASIC chips in total in the focal plane assembly. The results of the unit test shows that it works properly with moderately low input noise of ,30μV at the pixel rate of 80kHz. Power consumption is sufficiently low of 150mW. Dynamic range of input signals is +-20mV that covers effective energy range of the CCD chips of SXI (0.2-20keV). The integrated non-linearity of 0.2% satisfies the same performance as the conventional CCD detectors in orbit. The radiation tolerance against total ionizing dose ...
Although radiotherapy is considered an effective treatment choice in patients with OSCC, the outcome is not favorable in certain cases. The difference in the outcome mainly depends on the radiosensitivity of tumor cells. Although a set of human genes related to radiosensitivity has been identified (23-29), the detailed mechanism of radioresistance remains unknown. Thus, the present study aimed to identify molecules that control the response to radiotherapy in OSCC. We identified 167 genes that were upregulated by X-ray irradiation (8 Gy) in Ca9-22 cells by using DNA microarray analysis. We used the IPA tool to analyze the functional networks and gene ontology of these genes, and we detected six genetic networks that were each characterized by different representative functions (Table II). Among the genes, LCN2, which mapped to network 2, had the greatest increase in expression after X-ray irradiation (Table I). A variety of functions of the LCN2 protein has been reported. These functions include ...
We present a novel Process Algebra designed for multi-scale integration modelling: Process Algebra with Layers (PAL). The unique feature of PAL is the modularisation of scale into integrated layers: Object and Population. An Object can represent a molecule, organelle, cell, tissue, organ or any organism. Populations hold specific types of Object, for example, life stages, cell phases and infectious states. The syntax and semantics of this novel language are presented. A PAL model of the multi-scale system of cell growth and damage from cancer treatment is given. This model allows the analysis of different scales of the system. The Object and Population levels give insight into the length of a cell cycle and cell population growth respectively. The PAL model results are compared to wet laboratory survival fractions of cells given different doses of radiation treatment [1]. This comparison shows how PAL can be used to aid in investigations of cancer treatment in systems biology.. Keywords ...
Article Radiation response modification: novel approaches. Current limitations in the application of radiomodifiers refer to significant acute toxicity, intravenous administration for most of them and loss of most antiradiation properties when radiat...
TY - JOUR. T1 - Evidence that unrejoined DNA double-strand breaks are not predominantly responsible for chromosomal radiosensitivity of AT fibroblasts. AU - Loucas, Bradford. AU - Cornforth, Michael. PY - 2004/11. Y1 - 2004/11. N2 - To examine more fully the nature of chromosomal radiosensitivity in ataxia telangiectasia (AT) cells, we employed 24-color combinatorial painting to visualize 137CS γ-ray-induced chromosome-type aberrations in cells of two AT and one normal primary human fibroblast strains irradiated in log-phase growth. As a measure of misrejoined radiation-induced DSBs, we quantified exchange breakpoints associated with both simple and complex exchanges. As a measure of unrejoined DSBs, we quantified breakpoints from terminal deletions as well as deletions associated with incomplete exchange. For each of these end points, the frequency of damage per unit dose was markedly higher in AT cells compared to normal cells, although the proportion of total breaks that remained unrejoined ...
Telomerase is a ribonucleoprotein complex that elongates telomeres by adding hexameric (TTAGGG) repeats to the telomeric ends of the chromosomes, thus compensating for the continued erosion of telomeres. Telomerase activity is present in unicellular organisms and germ cells, both places where it is expected to play a role in indefinite cycling and protection from shortening of the telomeres. One phenotypic manifestation that is virtually pathognomonic of several cancer cells is the telomerase activity. Telomerase activity is enhanced in several cell types after treatment with ionizing radiation (IR). Whether there is a direct correlation between the levels of telomerase activity and IR response for tumor cell kill is yet to be addressed in detail. In this review, information is summarized on telomerase activity as a measure for monitoring the radiocurability of tumors. As tumor growth is partly due to deregulated cell cycling, insights into telomerase activity through the cell cycle may prove ...
Radiotherapy has played a limited role for the treatment of human esophageal cancer owing to the risk of tumor radioresistance. Core 1 β1, 3-galactosyltransferase (C1GalT1), which catalyzes the formation of core 1 O-glycan structures, is frequently overexpressed during tumorigenesis. However, the exact effects and mechanisms of C1GalT1 in the radioresistance of esophageal cancer remain unclear. In this study, Public databases and our data revealed that C1GalT1 expression was up-regulated in esophageal cancer tissues and was associated with poor survival. Upon irradiation, we found that esophageal cancer cells with high levels of C1GalT1 could tolerate cell death and had increased resistance to radiotherapy. Irradiation also promoted the expression of C1GalT1 and core 1 O-glycan structures. C1GalT1 knockdown increased the radiosensitivity of esophageal cancer cells, and attenuated irradiation-enhanced migration and invasion. Mechanistic investigations showed that C1GalT1 modified O-glycan ...
In the present study, we explored function and underlying mechanisms of lncRNA TUG1 in the radiosensitivity of bladder cancer. Our study declared that TUG1 expression was markedly upregulated in bladder cancer tissues and cell lines. Moreover, TUG1 knockdown enhanced the radiosensitivity of bladder cancer cell lines, evidenced by the reduced cell viability, the increased cell apoptosis and the inhibited colony survival fractions. Furthermore, our findings suggest that TUG1 knockdown enhances radiosensitivity of bladder cancer cells in vivo and in vitro by suppressing the expression of HMGB1.. LncRNA TUG1 was overexpressed in several kinds of cancer tissues such as esophageal carcinoma [20], osteosarcoma [22] and hepatocellular carcinoma [26]. However, TUG1 was downregulated in non-small cell lung cancer and glioma [21, 27]. All these studies revealed that TUG1 could function as an oncogene or tumor suppressor in different cancers. In the present study, we found that TUG1 expression was increased ...
1. Torre LA, Bray F, Siegel RL. et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87-108 2. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67:7-30 3. Chen W, Zheng R, Baade PD. et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115-32 4. Wong TS, Gao W, Li ZH. et al. Epigenetic dysregulation in laryngeal squamous cell carcinoma. J Oncol. 2012;2012:739461 5. Shimura T, Kakuda S, Ochiai Y. et al. Targeting the AKT/GSK3beta/cyclin D1/Cdk4 survival signaling pathway for eradication of tumor radioresistance acquired by fractionated radiotherapy. Int J Radiat Oncol Biol Phys. 2011;80:540-8 6. Li Z, Yang X, Xia N. et al. PTOP and TRF1 help enhance the radio resistance in breast cancer cell. Cancer Cell Int. 2014;14:7 7. Zhou FX, Xiong J, Luo ZG. et al. cDNA expression analysis of a human radiosensitive-radioresistant cell line model identifies telomere function as a hallmark of radioresistance. Radiat Res. 2010;174:550-7 8. Kim JS, Chang ...
Electronic components, based on current semiconductor technologies and operating in radiation rich environments, suffer degradation of their performance as a result of radiation exposure. Silicon carbide (SiC) provides an alternate solution as a radiation hard material, because of its wide bandgap and higher atomic displacement energies, for devices intended for radiation environment applications. However, the radiation tolerance and reliability of SiC-based devices needs to be understood by testing devices under controlled radiation environments. These kinds of studies have been previously performed on diodes and MESFETs, but multilayer devices such as bipolar junction transistors (BJT) have not yet been studied.. In this thesis, SiC material, BJTs fabricated from SiC, and various dielectrics for SiC passivation are studied by exposure to high energy ion beams with selected energies and fluences. The studies reveal that the implantation induced crystal damage in SiC material can be partly ...
We present a purely digital infrastructure for measuring SET pulsewidths in logic gates. Such a facility is crucial for experimentally studying radiation sensitivity and SET propagation of a circuit. Our digital-only implementation facilitates measurement within a standard-cell CMOS chip, without the need of any analog or customized circuitry on-chip. Besides high resolution and area efficiency, a fundamental requirement guiding the development of our solution was radiation tolerance, as it shall be employed on a test chip that is fully exposed to radiation in an experimental study. We validate our architecture, for various primary radiation target circuits, by analog simulation, injecting SETs of varying strength using the standard double-exponential current model. ...
Tumor radioresistance leading to local therapy failure remains a major obstacle for successful treatment of high-grade glioma. We hypothesized that distinct radiobiological features of particle therapy with carbon ions may circumvent glioma radioresistance. We demonstrate that carbon irradiation (CIR) efficiently eradicates radioresistant patient-derived glioma stem cells (GSCs), leading to growth inhibition and prolonged survival. The impact of CIR at the tumor-stroma interface was further investigated in 2 syngeneic mouse and 2 orthotopic GSC xenograft models. Intriguingly, tumor regressions and long-term local controls were observed at doses greater than or equal to 15-Gy CIR. Fractionated CIR further prolonged survival. The enhanced relative biological effectiveness of CIR in vivo was attributed to its potent antiangiogenic effects and eradication of radioresistant hypoxic tumor cells. Blockade of the HIF1-α/stromal cell-derived factor 1/CXCR4 axis by CIR reduced the recruitment of ...
The mechanisms involved in radiation-induced cellular injury and death remain incompletely understood. In addition to the direct formation of highly reactive hydroxyl radicals (HO.) by radiolysis of water, oxidative stress events in the cytoplasm due to formation of H2O2 may also be important. Since the major pool of low-mass redox-active intracellular iron seems to reside within lysosomes, arising from the continuous intralysosomal autophagocytotic degradation of ferruginous materials, formation of H2O2 inside and outside these organelles may cause lysosomal labilization with release to the cytosol of lytic enzymes and low-mass iron. If of limited magnitude, such release may induce reparative autophagocytosis, causing additional accumulation of redox-active iron within the lysosomal compartment. We have used radio-resistant histiocytic lymphoma (J774) cells to assess the importance of intralysosomal iron and lysosomal rupture in radiation-induced cellular injury. We found that a 40 Gy ...
Electronic components, based on current semiconductor technologies and operating in radiation rich environments, suffer degradation of their performance as a result of radiation exposure. Silicon carbide (SiC) provides an alternate solution as a radiation hard material, because of its wide bandgap and higher atomic displacement energies, for devices intended for radiation environment applications. However, the radiation tolerance and reliability of SiC-based devices needs to be understood by testing devices under controlled radiation environments. These kinds of studies have been previously performed on diodes and MESFETs, but multilayer devices such as bipolar junction transistors (BJT) have not yet been studied.. In this thesis, SiC material, BJTs fabricated from SiC, and various dielectrics for SiC passivation are studied by exposure to high energy ion beams with selected energies and fluences. The studies reveal that the implantation induced crystal damage in SiC material can be partly ...
The effect of ataxia-telangiectasia mutated kinase-dependent hyperphosphorylation of checkpoint kinase-2 on oligodeoxynucleotide 7909 containing CpG motifs-enhanced sensitivity to X-rays in human lung adenocarcinoma A549 cells Xiaoqun Liu,1,* Xiangdong Liu,2,* Tiankui Qiao,1 Wei Chen,1 Sujuan Yuan1 1Department of Oncology, 2Department of Ophthalmology, Affiliated Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Objective: The aim of the study reported here was to further investigate the potential effect of ataxia-telangiectasia mutated (ATM) kinase-dependent hyperphosphorylation of checkpoint kinase-2 (Chk2) on radiosensitivity enhanced by oligodeoxynucleotide 7909 containing CpG motifs (CpG ODN7909) in human lung adenocarcinoma A549 cells. Methods: In vitro A549 cells were randomly separated into control, CpG, X-ray, CpG+X-ray, ATM kinase-small interfering RNA (siRNA)+CpG+X-ray (ATM-siRNA), and Chk2-siRNA+CpG+X-ray
TY - JOUR. T1 - Differentiation of normal and radioresistant prostate cancer xenografts using magnetization transfer-prepared MRI. AU - Lam, Wilfred W.. AU - Oakden, Wendy. AU - Murray, Leedan. AU - Klein, Jonathan. AU - Iorio, Caterina. AU - Screaton, Robert A.. AU - Koletar, Margaret M.. AU - Chu, William. AU - Liu, Stanley K.. AU - Stanisz, Greg J.. PY - 2018/12/1. Y1 - 2018/12/1. N2 - The ability of MRI to differentiate between normal and radioresistant cancer was investigated in prostate tumour xenografts in mice. Specifically, the process of magnetization exchange between water and other molecules was studied. It was found that magnetization transfer from semisolid macromolecules (MT) and chemical exchange saturation transfer (CEST) combined were significantly different between groups (p , 0.01). Further, the T 2 relaxation of the semisolid macromolecular pool (T 2,B), a parameter specific to MT, was found to be significantly different (p , 0.01). Also significantly different were the rNOE ...
The study is aimed to understand atomic scale details of defect-boundary interactions, which are critical to develop radiation tolerant fuel cladding materials for harsher neutron environments. By means of molecular dynamics simulations, we addressed the key questions of (1) how defects are trapped by a grain boundary, (2) how defect are annihilated at a grain boundary, and (3) what are upper limits of radiation tolerance of boundary-engineered metals. The modeling is performed by using large-scale atomic/molecular massively parallel simulator (LAMMPS) code and pure Fe is selected as the model material. For mechanism of defect tapping towards a grain boundary, we find that, instead of the general consensus that the trapping is caused by biased defect diffusions due to relatively lower defect formation energies at a grain boundary, long range defect migration is realized by creation of chain like defects. A chain is induced by the stress field around a defect, and is formed by pushing its ...
The report summarizes the ZnSexTe(1-x) light-emitting diode work carried out under the present contract. It includes recent investigations of the thermodynamics of ZnSexTe(1-x) crystal growth which are concerned with the effects of varying the partial pressure of the chalcogen and the donor or acceptor doping. The report also reviews the status of the thin-film GaAs storage diode. The experimental procedures and results are described in some detail. Reproducibility and compatibility with integrated circuitry are satisfactory and make this device attractive for use in memory arrays. Preliminary results on radiation tolerance are also given. (Author)(*SEMICONDUCTOR DIODES
Hazkani I, Motiei M, Betzer O, Sadan T, Bragilovski D, Lubimov L, Mizrachi A, Hadar T, Levi M, Ben-Aharon I, Haviv I, Popovtzer R, Popovtzer A. Can molecular profiling enhance radiotherapy? Impact of personalized targeted gold nanoparticles on radiosensitivity and imaging of adenoid cystic carcinoma. Theranostics 2017; 7(16):3962-3971. doi:10.7150/thno.19615 ...
We presented a planning approach with physician navigation as a defining part of the process. While making planning more patient independent by creating standardized databases, our approach makes it more individualized for each patient by not following the same standard prescription for everyone but finding the best trade-offs for every individual. This study sought to determine if standardized MCO templates plus physician navigation of the resulting Pareto surfaces could offer a viable alternative to the standard planning process, where tradeoffs are explored by the treatment planners and the physicians are only involved in the final YES/NO decision.. Our retrospective planning study is subject to limitations given by inherent differences between clinical and physician driven planning. Although clinical plans were generated by different dosimetrists, they were regarded as comparable. Different qualities within plans may have resulted due to individual planning strategies and personal ...
NVP-BEZ235 is a recently developed combined PI3K/mTOR inhibitor being used clinically that has been shown to be a radiosensitizer (Konstantinidou et al., 2009; Fokas et al., 2012a,b; Mukherjee et al., 2012). We found that the compound radiosensitizes a variety of cancer cell lines with varying genetic changes, including EGFR amplification (SQ20B), p53 mutation (HT29), PTEN deletion (U251), and K-ras mutation (A549). We tested the drug in three different noncancer cell lines (WTFB, C10, and wild-type MEFs) and found that there was minimal radiosensitization.. The primary purpose of our study was to understand mechanistically how NVP-BEZ235 radiosensitizes cancer cells. Our findings indicate that the effect of the drug on the PI3K/mTOR pathway does not completely explain its radiosensitizing effect. In both SQ20B and U251 cells, knockdown of p110α, an isoform associated with radiation resistance (Kim et al., 2005), mTOR, or the two together led to modest radiosensitization, but not as great as ...
Radiotherapy is one of the most common therapeutic methods for treatment of many types of cancer. Despite many decades of development and experience there is much to improve, both in efficacy of treatment and to decrease the incidences of adverse healthy tissue reactions. Around 20 % of the radiotherapy patients show a broad range in the severity of normal tissue reactions to radiotherapy, and dose limits are governed by severe reactions in the most radiosensitive patients (, 5 %). Identification of patients with low, moderate or high clinical radiosensitivity before commencing of radiotherapy would allow individual adaptation of the maximum dose with an overall increase in the cure rate. Characterization of factors that may modify the biological effects of ionizing radiation has been a subject of intense research efforts. Still, there is no assay currently available that can reliably predict the clinical radiosensitivity. The aim of this work has been to investigate the role of oxidative stress ...
Parry J.M.; Parry E.M.; Davies P.J.; Evans W.E., 1976: Cell division and the effects of cell age upon radiation sensitivity in yeast
The [email protected] Centre provides a platform for research students to deposit their Ph.D. theses and make it available to the entire scholarly community in open access ...
The modern founding concept of radiation biology that deals with X-rays and ?-rays is that ionizing radiation is dangerous because of its damaging effects on DNA. Mounting experimental evidence does not fit into this theoretical framework, instead supporting that radiation resistance is governed by protein damage. Recent studies from several independent labs implicate protein damage as the major probable cause of death in irradiated cells. Whereas DNA lesion-yields in cells exposed to a given dose of radiation appear to be fixed, protein-lesion yields are variable and closely related to survival. There are profound practical implications to this new view of radiation toxicity. Basically, if you want to survive radiation, protect your proteins! D. radiodurans has shown us how to protect proteins from radiation and other sources of reactive oxygen species (ROS). For the latest review see Michael J Daly (2012) Death by protein damage in irradiated cells.. One original goal of radiobiology was to ...
Directly inhibiting the activity of a key protein mediator of inflammation reduced radiation toxicity in zebrafish embryos, and may ultimately be of help to patients receiving radiation therapy, according to researchers from ...
40%, 76%, and 44%, respectively.8 Not unexpectedly, Although this was a small study, the local control was 5-year overall survival was significantly improved for 54% in the once-a-day arm versus 73% in the altered frac- patients who completed all therapy, 51% versus 24% tionation arm.3 In 1974, the introduction of doxorubicin (P ¼ .0001), and the local/regional control rate was 84% chemotherapy yielded another significant gain in IBC for patients who completed all therapy. This rate of local/ outcome. Although the addition of chemotherapy had no regional control was higher than historical rates. Examina- effect on local control (73% vs 74%3), the 5-year survival tion of the factors that predicted for local recurrence after improved from ,5% to 30%-50% because of the reduc- radiation among patients in Group 1 revealed that age tion in distant metastasis. Importantly, the addition of ,45 years, less than partial response to chemotherapy, !4 chemotherapy rendered more patients operable, and ...
CSTs simulation software provides accurate 3D electromagnetic EDA solutions for the numerical solution of Maxwells Equations, from statics up to highest frequencies.
Normal B cells responsive to thymus independent-type 1 Ags (TI-1) are resistant to low doses of ionizing radiation in vivo (200-300 cGy), compared with TI-1 responsive B cells of mice with the CBA/N X-linked immunodeficiency (xid). This difference in radiosensitivity is an intrinsic B cell property; normal B cells adoptively transferred into xid mice remain TI-1-responsive after irradiation in situ. Because irradiation induces programmed cell death (PCD) in lymphocytes, we determined whether PCD were regulated differently in normal and xid B cells. B cells isolated immediately after irradiation from normal or xid donors when cultured without stimulators became apoptotic with the same kinetics and to the same extent, showing that apoptosis was induced equally in both populations. Apoptosis could be suppressed and mitogenesis could be induced frequently, however, if irradiated B cells were cultured with B cell activators. When activators using separate signal transduction pathways were compared, a
In cells, the damage caused by ionizing radiation is mainly due to free-radical-induced alterations of their DNA. The reactions involved have been studied on a model level: DNA and DNA components in...
A new test could help to explain why some tumours are more resistant to therapy than others. the probe, developed in Briatin, could one day help cancer pat
... is ultraviolet radiation resistant and can be applied to any poured foundation wall, cinder blocks, stucco, steel, wood and galvanized metal.
The way organisms respond to radiation exposure is important since induced DNA lesions can lead to mutation, genomic instability, and death, cancer or other del...
Hypoxia is a feature of most tumours, albeit with variable incidence and severity within a given patient population. It is a negative prognostic and predictive factor owing to its multiple contributions to chemoresistance, radioresistance, angiogenesis, vasculogenesis, invasiveness, metastasis, resi …