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Anne Vral - One of the best experts on this subject based on the ideXlab platform.
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Radiosensitivity analysis in patients with a primary immunodeficiency disease.
2020Co-Authors: Anne Vral, Kathleen Claes, Ans Baeyens, Carolien Bonroy, Victoria Bordon, Elien Beyls, Evi Duthoo, Lynn Backers, Stephanie Vermeulen, Filomeen HaerynckAbstract:Primary Immune Deficiency Diseases (PIDs) are life-threatening genetic disorders of the immune system. A subset of PIDs is caused by mutations in genes involved in the repair of DNA double-strand breaks, by which affected patients may also be radiosensitive. For many reasons PID patients can be exposed to radiation (bone marrow transplantation, radiotherapy, diagnostic imaging), but this may pose serious risks to radiosensitive subjects. Surprisingly, Radiosensitivity testing is currently not included in the workup of PIDs in most European countries. The main goal of our study is to translate Radiosensitivity analysis in the diagnostic workup for PIDs in Belgium. To this aim, two cell-cycle specific in vitro Radiosensitivity assays will be included in the standard diagnostic procedures in patients with suspected PID at the Ghent University Hospital (reference center for Belgium): (1) the G0 cytokinesis-block micronucleus assay (CBMN) which is about to be translated into the clinical practice, (2) the S/G2 CBMN which has been developed in our labs with positive proof-of-concept but which must be further optimized before translation. Both assays will be performed on peripheral blood lymphocytes of the patients. Furthermore, Radiosensitivity assays will also be optimized for fibroblasts, obtained from skin biopsies of patients. In our study design, Radiosensitivity analysis will be the central core of two innovative diagnostic and therapeutic algorithms, which will include immunophentyping, direct subsequent genetic analysis and guide optimal patient care. Micronucleus analysis in lymphocytes of patients is currently ongoing and first results will be presented. We believe that inclusion of Radiosensitivity testing will represent a major improvement in the timely diagnosis and management of patients affected by these life-threatening, heterogeneous and difficult-to-diagnose diseases.
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Comparison of the colony formation and crystal violet cell proliferation assays to determine cellular Radiosensitivity in a repair-deficient MCF10A cell line
Radiation Measurements, 2020Co-Authors: Veerle Vandersickel, Jacobus Slabbert, Hubert Thierens, Anne VralAbstract:Abstract Colony formation as measured by the in vitro clonogenic assay is a very important endpoint to determine cellular Radiosensitivity and tumor response to radiotherapy. In the framework of assessing in vitro cellular Radiosensitivity, proliferation assays could represent an attractive alternative to the clonogenic assay for cell lines that do not form proper colonies. In the present study, we compared cellular Radiosensitivity measurements obtained by the crystal violet (CV) cell proliferation assay and the standard colony formation assay in repair-deficient and-proficient human MCF10A cell lines. Compared to the clonogenic assay, the CV cell proliferation assay yielded higher surviving fractions for the same radiation dose. This is reflected in larger mean inactivation dose values – a parameter that reflects the area under the survival curve. However, as the dose modifying factors obtained by both assays are comparable, the CV cell proliferation assay can be used to compare the in vitro cellular Radiosensitivity of cell lines that lack the ability to form well-defined colonies.
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Chromosomal Radiosensitivity of HIV positive individuals.
International journal of radiation biology, 2010Co-Authors: A Baeyens, Sibusiso Jozela, Debby Van Der Merwe, Pascale Willem, Jacobus P Slabbert, Anne VralAbstract:Radiosensitivity in relation to the human immunodeficiency virus (HIV) status is important in South Africa as the prevalence of HIV infections is high. In this study the in vitro chromosomal Radiosensitivity of HIV positive individuals was investigated and compared with that of HIV negative individuals.
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radiation induced damage to normal tissues after radiotherapy in patients treated for gynecologic tumors association with single nucleotide polymorphisms in xrcc1 xrcc3 and ogg1 genes and in vitro chromosomal Radiosensitivity in lymphocytes
International Journal of Radiation Oncology Biology Physics, 2005Co-Authors: Kim De Ruyck, Marc Van Eijkeren, Rudy Morthier, Leo De Ridder, Kathleen Claes, Anne De Paepe, Anne Vral, Hubert ThierensAbstract:Purpose: To examine the association of polymorphisms in XRCC1 (194Arg/Trp, 280Arg/His, 399Arg/Gln, 632Gln/Gln), XRCC3 (5′ UTR 4.541A>G, IVS5-14 17.893A>G, 241Thr/Met), and OGG1 (326Ser/Cys) with the development of late radiotherapy (RT) reactions and to assess the correlation between in vitro chromosomal Radiosensitivity and clinical Radiosensitivity. Methods and Materials: Sixty-two women with cervical or endometrial cancer treated with RT were included in the study. According to the Common Terminology Criteria for Adverse Events, version 3.0, scale, 22 patients showed late adverse RT reactions. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays were performed to examine polymorphic sites, the G2 assay was used to measure chromosomal Radiosensitivity, and patient groups were compared using actuarial methods. Results: The XRCC3 IVS5-14 polymorphic allele was significantly associated with the risk of developing late RT reactions (odds ratio 3.98, p = 0.025), and the XRCC1 codon 194 variant showed a significant protective effect ( p = 0.028). Patients with three or more risk alleles in XRCC1 and XRCC3 had a significantly increased risk of developing normal tissue reactions (odds ratio 10.10, p = 0.001). The mean number of chromatid breaks per cell was significantly greater in patients with normal tissue reactions than in patients with no reactions (1.16 and 1.34, respectively; p = 0.002). Patients with high chromosomal Radiosensitivity showed a 9.2-fold greater annual risk of complications than patients with intermediate chromosomal Radiosensitivity. Combining the G2 analysis with the risk allele model allowed us to identify 23% of the patients with late normal tissue reactions, without false-positive results. Conclusion: The results of the present study showed that clinical Radiosensitivity is associated with an enhanced G2 chromosomal Radiosensitivity and is significantly associated with a combination of different polymorphisms in DNA repair genes.
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Chromosomal aberrations and in vitro Radiosensitivity: intra-individual versus inter-individual variability.
Toxicology letters, 2004Co-Authors: Anne Vral, A Baeyens, Hubert Thierens, Leo De RidderAbstract:In order to assess the applicability of the micronucleus (MN) and G2 assays as biomarkers of in vitro Radiosensitivity and cancer susceptibility, we investigated the inter- and intra-individual variation of these endpoints. For the MN assay unstimulated blood cultures from 57 healthy donors were exposed in vitro to 3.5 Gy Co gamma-rays and for the G2 assay PHA stimulated cultures were irradiated with a dose of 0.4 Gy Co gamma-rays in the G2 phase of the cell cycle. For 14 donors, 2-15 repeat samples were tested over a period of 3 years. The repeat experiments revealed that the intra-individual variability was not significantly different from the inter-individual variability for both G2 and MN assays. As the intra-individual variability determines the reproducibility of the assay, our results highlight the limitations of these endpoints in detecting reproducible differences in radiation sensitivity between individuals within a normal population. Due to the high intra-individual variability and no significant difference with the inter-individual variability found in our study we conclude that care has to be taken when results obtained with chromosomal aberration assays based on one blood sample are used to assess the individual Radiosensitivity. Multiple blood sampling may be necessary to draw reliable conclusions. Although more validation studies on the reliability of the G2 and MN assay will be required before they can be used in a confident way as biomarkers of individual Radiosensitivity or cancer susceptibility the assays are very valuable to examine population Radiosensitivity and the relationship between Radiosensitivity, cancer predisposition and genotype.
Hubert Thierens - One of the best experts on this subject based on the ideXlab platform.
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Comparison of the colony formation and crystal violet cell proliferation assays to determine cellular Radiosensitivity in a repair-deficient MCF10A cell line
Radiation Measurements, 2020Co-Authors: Veerle Vandersickel, Jacobus Slabbert, Hubert Thierens, Anne VralAbstract:Abstract Colony formation as measured by the in vitro clonogenic assay is a very important endpoint to determine cellular Radiosensitivity and tumor response to radiotherapy. In the framework of assessing in vitro cellular Radiosensitivity, proliferation assays could represent an attractive alternative to the clonogenic assay for cell lines that do not form proper colonies. In the present study, we compared cellular Radiosensitivity measurements obtained by the crystal violet (CV) cell proliferation assay and the standard colony formation assay in repair-deficient and-proficient human MCF10A cell lines. Compared to the clonogenic assay, the CV cell proliferation assay yielded higher surviving fractions for the same radiation dose. This is reflected in larger mean inactivation dose values – a parameter that reflects the area under the survival curve. However, as the dose modifying factors obtained by both assays are comparable, the CV cell proliferation assay can be used to compare the in vitro cellular Radiosensitivity of cell lines that lack the ability to form well-defined colonies.
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radiation induced damage to normal tissues after radiotherapy in patients treated for gynecologic tumors association with single nucleotide polymorphisms in xrcc1 xrcc3 and ogg1 genes and in vitro chromosomal Radiosensitivity in lymphocytes
International Journal of Radiation Oncology Biology Physics, 2005Co-Authors: Kim De Ruyck, Marc Van Eijkeren, Rudy Morthier, Leo De Ridder, Kathleen Claes, Anne De Paepe, Anne Vral, Hubert ThierensAbstract:Purpose: To examine the association of polymorphisms in XRCC1 (194Arg/Trp, 280Arg/His, 399Arg/Gln, 632Gln/Gln), XRCC3 (5′ UTR 4.541A>G, IVS5-14 17.893A>G, 241Thr/Met), and OGG1 (326Ser/Cys) with the development of late radiotherapy (RT) reactions and to assess the correlation between in vitro chromosomal Radiosensitivity and clinical Radiosensitivity. Methods and Materials: Sixty-two women with cervical or endometrial cancer treated with RT were included in the study. According to the Common Terminology Criteria for Adverse Events, version 3.0, scale, 22 patients showed late adverse RT reactions. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays were performed to examine polymorphic sites, the G2 assay was used to measure chromosomal Radiosensitivity, and patient groups were compared using actuarial methods. Results: The XRCC3 IVS5-14 polymorphic allele was significantly associated with the risk of developing late RT reactions (odds ratio 3.98, p = 0.025), and the XRCC1 codon 194 variant showed a significant protective effect ( p = 0.028). Patients with three or more risk alleles in XRCC1 and XRCC3 had a significantly increased risk of developing normal tissue reactions (odds ratio 10.10, p = 0.001). The mean number of chromatid breaks per cell was significantly greater in patients with normal tissue reactions than in patients with no reactions (1.16 and 1.34, respectively; p = 0.002). Patients with high chromosomal Radiosensitivity showed a 9.2-fold greater annual risk of complications than patients with intermediate chromosomal Radiosensitivity. Combining the G2 analysis with the risk allele model allowed us to identify 23% of the patients with late normal tissue reactions, without false-positive results. Conclusion: The results of the present study showed that clinical Radiosensitivity is associated with an enhanced G2 chromosomal Radiosensitivity and is significantly associated with a combination of different polymorphisms in DNA repair genes.
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Chromosomal aberrations and in vitro Radiosensitivity: intra-individual versus inter-individual variability.
Toxicology letters, 2004Co-Authors: Anne Vral, A Baeyens, Hubert Thierens, Leo De RidderAbstract:In order to assess the applicability of the micronucleus (MN) and G2 assays as biomarkers of in vitro Radiosensitivity and cancer susceptibility, we investigated the inter- and intra-individual variation of these endpoints. For the MN assay unstimulated blood cultures from 57 healthy donors were exposed in vitro to 3.5 Gy Co gamma-rays and for the G2 assay PHA stimulated cultures were irradiated with a dose of 0.4 Gy Co gamma-rays in the G2 phase of the cell cycle. For 14 donors, 2-15 repeat samples were tested over a period of 3 years. The repeat experiments revealed that the intra-individual variability was not significantly different from the inter-individual variability for both G2 and MN assays. As the intra-individual variability determines the reproducibility of the assay, our results highlight the limitations of these endpoints in detecting reproducible differences in radiation sensitivity between individuals within a normal population. Due to the high intra-individual variability and no significant difference with the inter-individual variability found in our study we conclude that care has to be taken when results obtained with chromosomal aberration assays based on one blood sample are used to assess the individual Radiosensitivity. Multiple blood sampling may be necessary to draw reliable conclusions. Although more validation studies on the reliability of the G2 and MN assay will be required before they can be used in a confident way as biomarkers of individual Radiosensitivity or cancer susceptibility the assays are very valuable to examine population Radiosensitivity and the relationship between Radiosensitivity, cancer predisposition and genotype.
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chromosomal Radiosensitivity in breast cancer patients with a known or putative genetic predisposition
British Journal of Cancer, 2002Co-Authors: Ans Baeyens, Hubert Thierens, Kathleen Claes, Bruce Poppe, Ludwine Messiaen, L De Ridder, Anne VralAbstract:Chromosomal Radiosensitivity in breast cancer patients with a known or putative genetic predisposition
John B Little - One of the best experts on this subject based on the ideXlab platform.
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differential role of dna pkcs phosphorylations and kinase activity in Radiosensitivity and chromosomal instability
Radiation Research, 2011Co-Authors: Hatsumi Nagasawa, John B Little, Akihiro Kurimasa, David J Chen, Sairei So, Yuanlin Peng, John R Brogan, Joel S Bedford, Benjamin P C ChenAbstract:Abstract The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is the key functional element in the DNA-PK complex that drives nonhomologous end joining (NHEJ), the predominant DNA double-strand break (DSB) repair mechanism operating to rejoin such breaks in mammalian cells after exposure to ionizing radiation. It has been reported that DNA-PKcs phosphorylation and kinase activity are critical determinants of Radiosensitivity, based on responses reported after irradiation of asynchronously dividing populations of various mutant cell lines. In the present study, the relative Radiosensitivity to cell killing as well as chromosomal instability of 13 DNA-PKcs site-directed mutant cell lines (defective at phosphorylation sites or kinase activity) were examined after exposure of synchronized G1 cells to 137Cs γ rays. DNA-PKcs mutant cells defective in phosphorylation at multiple sites within the T2609 cluster or within the PI3K domain displayed extreme Radiosensitivity. Cells defective at the S2056 c...
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overview of Radiosensitivity of human tumor cells to low dose rate irradiation
International Journal of Radiation Oncology Biology Physics, 2008Co-Authors: James M. Slater, Jerry R. Williams, Daila S Gridley, Yonggang Zhang, Cameron J Koch, Haoming Zhou, John B LittleAbstract:Purpose We compared clonogenic survival in 27 human tumor cell lines that vary in genotype after low-dose-rate (LDR) or high-dose rate (HDR) irradiation. We measured susceptibility to LDR-induced redistribution in the cell cycle in eight of these cell lines. Methods and Materials We measured clonogenic survival after up to 96 hours of LDR (0.25 Gy/h) irradiation. We compared these with clonogenic survival after HDR irradiation (50 Gy/h). Using flow cytometry, we measured LDR-induced redistribution as a function of time during LDR irradiation in eight of these cell lines. Results Coefficients that describe clonogenic survival after both LDR and HDR irradiation segregate into four Radiosensitivity groups that associate with cell genotype: mutant (mut)ATM, wild-type TP53, mutTP53, and an unidentified gene in radioresistant glioma cells. The LDR and HDR Radiosensitivity correlates at lower doses (∼2 Gy HDR, ∼6 Gy LDR), but not at higher doses (HDR > 4 Gy; LDR > 6 Gy). The rate of LDR-induced loss of clonogenic survival changes at approximately 24 hours; wild-type TP53 cells become more resistant and mutTP53 cells become more sensitive. Redistribution induced by LDR irradiation also changes at approximately 24 hours. Conclusions Radiosensitivity of human tumor cells to both LDR and HDR irradiation is genotype dependent. Analysis of coefficients that describe cellular Radiosensitivity segregates 27 cell lines into four statistically distinct groups, each associating with specific genotypes. Changes in cellular Radiosensitivity and redistribution in the cell cycle are strongly time dependent. Our data establish a genotype-dependent time-dependent model that predicts clonogenic survival, explains the inverse dose-rate effect, and suggests possible clinical applications.
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a quantitative overview of Radiosensitivity of human tumor cells across histological type and tp53 status
International Journal of Radiation Biology, 2008Co-Authors: Jerry R. Williams, Daila S Gridley, Yonggang Zhang, James A Russell, Cameron J Koch, Haoming Zhou, James S Slater, John B LittleAbstract:Purpose: We have previously shown in a limited number of tumor cell lines derived from only two histological types that clonogenic survival patterns fall into Radiosensitivity groups, each group associating with a specific genotype. We now establish a global, quantitative description of human tumor cells based on genotype-dependent Radiosensitivity across histological types.Methods: We measure clonogenic Radiosensitivity in 39 human tumor cell lines that vary in histological type (colorectal, glioblastoma, prostate, bladder, teratoma, breast, melanoma and liver) and expression of several genes purported to influence Radiosensitivity: ATM (ataxia telangiectasia mutated), TP53 (tumor protein 53), CDKN1A (cyclin-dependent kinase N1A), 14-3-3σ (an isoform of the 14-3-3 gene) and DNA mismatch repair genes. For each survival curve we use the linear-quadratic model and a linear-linear model to extract multiple coefficients and seek correlation across histological types.Results: Under one-parameter analysis, surv...
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human tumor cells segregate into Radiosensitivity groups that associate with atm and tp53 status
Acta Oncologica, 2007Co-Authors: Jerry R. Williams, Yonggang Zhang, James A Russell, Cameron J Koch, John B LittleAbstract:We seek to determine whether cellular Radiosensitivity in nineteen human colorectal tumor cell lines and three human glioblastoma tumor cell lines segregate into statistically distinct groups and whether such groups correlate with gene expression. We measure clonogenic survival in 22 cell lines that vary in Radiosensitivity and in expression of selected genes: ATM, TP53, CDKN1A, 14-3-3σ, Ki-ras and DNA mismatch repair genes. We describe and compare Radiosensitivity in these cell lines by one-parameter or two parameter analysis. Radiosensitivity varies among and between colorectal tumor cell lines and glioblastoma cell lines. When compared directly using survival, or using two-parameter analysis of Radiosensitivity, cell lines distribute into four statistically-significant Radiosensitivity groups. These groups associate strongly with the status of two genes, ATM and TP53, but do not associate with CDKN1A, 14-3-3σ, Ki-ras and DNA mismatch repair genes. Intrinsic cellular Radiosensitivity of 22 colorectal an...
Jerry R. Williams - One of the best experts on this subject based on the ideXlab platform.
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Radiobiology of Radioresistant Glioblastoma
Advances in the Biology Imaging and Therapies for Glioblastoma, 2011Co-Authors: Jerry R. Williams, Daila S Gridley, James M. SlaterAbstract:Therapy of glioblastoma has been very problematic with disappointing results using multiple therapeutic approaches. In general, glioblastomas are considered radioresistant tumors with different radiation modalities failing to control them in the clinic. However a comprehensive and detailed analysis of the Radiosensitivity of glioblastoma cells has not been performed. We now present such an analysis in this chapter seeking a better definition of patterns of Radiosensitivity in glioblastomas compared to other tumor cells. These data show that some glioblastomas have unusual responses to radiation that may render them more resistant to some forms of radiotherapy but also render them amenable to exploitation by other forms of radiotherapy. Multiple mechanisms have been proposed to be associated with radioresistance in human glioblastoma cells: Bao et al (1) have suggested increased DNA damage response. Karim et al (2) have proposed differential cyclo-oxygenase response in radioresistant glios. Brandani et al (3) have suggested HSP 70 elevation. Akuguka et al (4) have suggested increased rates in DNA double strand break rejoining association with micronuclei. Scmidberger et al (5) observed variation interferon-induced ┚ associates with increased Radiosensitivity in four out of five glioblastomas. Yao et al (6) suggest variation in cell cycle arrest, modulation of the expression of cyclin-dependent kinase inhibitors, and autophagy. Streffer et al (7) showed BCLfamily proteins modulate Radiosensitivity in human malignant glioma cells. Kraus et al (8) showed aberrant p21 regulation in radioresistant primary glioblastoma multiforme cells bearing wild-type p53. Haas-Kogan (9) et al showed p53 function influences the effect of fractionated radiotherapy on glioblastoma tumors. Hsiao et al (10) showed functional expression of human p21(WAF1/CIP1) gene in rat glioma cells suppresses tumor growth in vivo and induces Radiosensitivity. Yount et al (11) showed cell cycle synchrony unmasks the influence of p53 function on Radiosensitivity of human glioblastoma cells. Britten et al (12) showed differential level of DSB repair fidelity effected by nuclear protein extracts derived from radiosensitive and radioresistant human tumour cells. Guichard et al (13) suggest potentially lethal damage repair as a possible determinant of human tumour Radiosensitivity including glioblastoma. Kal et al (14) have suggested rhabdomyosarcomas, similar to glioblastomas are sensitive to low dose-rate irradiation.
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overview of Radiosensitivity of human tumor cells to low dose rate irradiation
International Journal of Radiation Oncology Biology Physics, 2008Co-Authors: James M. Slater, Jerry R. Williams, Daila S Gridley, Yonggang Zhang, Cameron J Koch, Haoming Zhou, John B LittleAbstract:Purpose We compared clonogenic survival in 27 human tumor cell lines that vary in genotype after low-dose-rate (LDR) or high-dose rate (HDR) irradiation. We measured susceptibility to LDR-induced redistribution in the cell cycle in eight of these cell lines. Methods and Materials We measured clonogenic survival after up to 96 hours of LDR (0.25 Gy/h) irradiation. We compared these with clonogenic survival after HDR irradiation (50 Gy/h). Using flow cytometry, we measured LDR-induced redistribution as a function of time during LDR irradiation in eight of these cell lines. Results Coefficients that describe clonogenic survival after both LDR and HDR irradiation segregate into four Radiosensitivity groups that associate with cell genotype: mutant (mut)ATM, wild-type TP53, mutTP53, and an unidentified gene in radioresistant glioma cells. The LDR and HDR Radiosensitivity correlates at lower doses (∼2 Gy HDR, ∼6 Gy LDR), but not at higher doses (HDR > 4 Gy; LDR > 6 Gy). The rate of LDR-induced loss of clonogenic survival changes at approximately 24 hours; wild-type TP53 cells become more resistant and mutTP53 cells become more sensitive. Redistribution induced by LDR irradiation also changes at approximately 24 hours. Conclusions Radiosensitivity of human tumor cells to both LDR and HDR irradiation is genotype dependent. Analysis of coefficients that describe cellular Radiosensitivity segregates 27 cell lines into four statistically distinct groups, each associating with specific genotypes. Changes in cellular Radiosensitivity and redistribution in the cell cycle are strongly time dependent. Our data establish a genotype-dependent time-dependent model that predicts clonogenic survival, explains the inverse dose-rate effect, and suggests possible clinical applications.
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a quantitative overview of Radiosensitivity of human tumor cells across histological type and tp53 status
International Journal of Radiation Biology, 2008Co-Authors: Jerry R. Williams, Daila S Gridley, Yonggang Zhang, James A Russell, Cameron J Koch, Haoming Zhou, James S Slater, John B LittleAbstract:Purpose: We have previously shown in a limited number of tumor cell lines derived from only two histological types that clonogenic survival patterns fall into Radiosensitivity groups, each group associating with a specific genotype. We now establish a global, quantitative description of human tumor cells based on genotype-dependent Radiosensitivity across histological types.Methods: We measure clonogenic Radiosensitivity in 39 human tumor cell lines that vary in histological type (colorectal, glioblastoma, prostate, bladder, teratoma, breast, melanoma and liver) and expression of several genes purported to influence Radiosensitivity: ATM (ataxia telangiectasia mutated), TP53 (tumor protein 53), CDKN1A (cyclin-dependent kinase N1A), 14-3-3σ (an isoform of the 14-3-3 gene) and DNA mismatch repair genes. For each survival curve we use the linear-quadratic model and a linear-linear model to extract multiple coefficients and seek correlation across histological types.Results: Under one-parameter analysis, surv...
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human tumor cells segregate into Radiosensitivity groups that associate with atm and tp53 status
Acta Oncologica, 2007Co-Authors: Jerry R. Williams, Yonggang Zhang, James A Russell, Cameron J Koch, John B LittleAbstract:We seek to determine whether cellular Radiosensitivity in nineteen human colorectal tumor cell lines and three human glioblastoma tumor cell lines segregate into statistically distinct groups and whether such groups correlate with gene expression. We measure clonogenic survival in 22 cell lines that vary in Radiosensitivity and in expression of selected genes: ATM, TP53, CDKN1A, 14-3-3σ, Ki-ras and DNA mismatch repair genes. We describe and compare Radiosensitivity in these cell lines by one-parameter or two parameter analysis. Radiosensitivity varies among and between colorectal tumor cell lines and glioblastoma cell lines. When compared directly using survival, or using two-parameter analysis of Radiosensitivity, cell lines distribute into four statistically-significant Radiosensitivity groups. These groups associate strongly with the status of two genes, ATM and TP53, but do not associate with CDKN1A, 14-3-3σ, Ki-ras and DNA mismatch repair genes. Intrinsic cellular Radiosensitivity of 22 colorectal an...
Xigang Hu - One of the best experts on this subject based on the ideXlab platform.
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knockdown of lncrna pvt1 enhances Radiosensitivity in non small cell lung cancer by sponging mir 195
Cellular Physiology and Biochemistry, 2017Co-Authors: Dapeng Wu, Yong Li, Huixiang Zhang, Xigang HuAbstract:BACKGROUND/AIMS: Plasmacytoma variant translocation 1 (PVT1) exerts an oncogenic role in many tumors, including lung cancer. However, the roles of PVT1 in regulating Radiosensitivity of NSCLC and its underlying mechanism are still unclear. METHODS: Expression levels of PVT1 and miR-195 in NSCLC tissues and cells were examined by qRT-PCR. Effects of PVT1 and miR-195 on cell proliferation, apoptosis and colony formation abilities were assessed by MTT assay, flow cytometry and colony formation assay. Luciferase reporter assay was performed to confirm the relationship between PVT1 and miR-195. Tumor xenograft experiments were conducted to observe the effect of PVT1 on Radiosensitivity of NSCLC in vivo. RESULTS: PVT1 was negatively correlated with miR-195 expression in NSCLC tissues and associated with poor prognosis of NSCLC patients. Expression of PVT1 and miR-195 varied inversely after irradiation in NSCLC cells. PVT1 knockdown or miR-195 overexpression enhanced Radiosensitivity of NSCLC in vitro by inhibiting proliferation and inducing apoptosis. PVT1 directly interacted with miR-195 and regulated its expression. Moreover, PVT1 knockdown improved Radiosensitivity of NSCLC cells in vitro and in vivo by sponging miR-195. CONCLUSION: Knockdown of PVT1 enhances Radiosensitivity of NSCLC by sponging miR-195, providing a novel therapeutic target to improve radiotherapy efficiency in NSCLC.