Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    German Medical Science; Düsseldorf, Köln
    In:  77. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.; 20060524-20060528; Mannheim; DOC06hnod382 /20060424/
    Publication Date: 2006-04-25
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
  • 3
    Keywords: CANCER ; IRRADIATION ; radiotherapy ; Germany ; TOXICITY ; LUNG-CANCER ; RISK ; RISKS ; GENE ; GENES ; HYBRIDIZATION ; SURGERY ; radiation ; PATIENT ; DNA ; GENETIC POLYMORPHISMS ; SKIN ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; VARIANTS ; BREAST ; breast cancer ; BREAST-CANCER ; DESIGN ; DNA-REPAIR ; REPAIR ; DAMAGE ; PROBES ; CARRIERS ; CANCER PATIENTS ; body mass index ; NUCLEOTIDE EXCISION-REPAIR ; DNA repair ; radiation sensitivity ; ACID SUBSTITUTION VARIANTS ; radiosensitivity ; MASSES ; RE ; VARIANT ; CAPACITY ; CANCER SUSCEPTIBILITY ; XPD ; ALLELES ; INTERVAL ; DNA repair gene ; DNA repair genes ; GENETIC-POLYMORPHISM ; CARRIER ; GENOTYPE ; HAPLOTYPE
    Abstract: Purpose: Several DNA repair gene polymorphisms have been described, which affect DNA repair capacity and modulate cancer susceptibility. We evaluated the association of six polymorphisms in the DNA repair genes: XRCC1 (Arg(194) Trp, Arg(280)His, and Arg(399)GIn), APE1 (Asp(148)Glu), and XPD (Lys(751)Gln and Asp(312)Asn), with the risk of acute skin reactions following radiotherapy. Design: We conducted a prospective study of 446 female patients with breast cancer who received radiotherapy after breast-conserving surgery. Individual genetic polymorphisms were determined using melting point analysis of sequence-specific hybridization probes. The development of acute skin reactions (moist desquamation) associated with DNA repair gene polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Results: Overall, the development of acute toxicity, which presented in 77 patients, was not associated with the genetic variants studied, although the hazard ratios (HR) were generally below 1. Risks were however differential by body mass index. Among normal-weight patients only, both carriers of theAPE1 (148)Glu and the XRCC1 (399)Gln alleles had decreased risk of acute skin reactions after radiotherapy (HR, 0.49 and 0.51, respectively). The results for XRCC1 were confirmed by haplotype analysis. When considering joint effects, we observed that compared with homozygote carriers of the wild-type allele in both genes, the risk was most strongly reduced in carriers of both APE1 (148)Glu and XRCC1 (399)GIn alleles with normal weight [HR, 0.19; 95% confidence interval (95% CI), 0.06-0.56] but not in those with overweight (HR, 1.39; 95% CI, 0.56-3.45; P-interaction = 0-009). Conclusion: The XRCC1 (399)Gln or APE1 (148)Glu alleles may be protective against the development of acute side effects after radiotherapy in patients with normal weight
    Type of Publication: Journal article published
    PubMed ID: 16000577
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: CANCER ; CELLS ; EXPRESSION ; IRRADIATION ; radiotherapy ; CELL ; Germany ; THERAPY ; TOXICITY ; COHORT ; RISK ; SURGERY ; radiation ; PATIENT ; DNA ; INDEX ; QUALITY ; SKIN ; treatment ; BREAST ; breast cancer ; BREAST-CANCER ; LESIONS ; RADIATION-THERAPY ; ASSAY ; WOMEN ; DNA-REPAIR ; REPAIR ; COMET ASSAY ; DAMAGE ; LYMPHOCYTES ; BEAM ; DNA-DAMAGE ; PARAMETERS ; CANCER-PATIENTS ; KINETICS ; body mass index ; DNA repair ; DNA repair capacity ; PERIPHERAL-BLOOD LYMPHOCYTES ; ATAXIA-TELANGIECTASIA ; HETEROZYGOTES ; INTRINSIC RADIOSENSITIVITY ; radiation tolerance,DNA repair capacity,breast neoplasms,body mass index
    Abstract: Background and purpose: Intrinsic and extrinsic factors can affect the occurrence of side effects of radiotherapy. The influence of therapy modalities, personal characteristics and individual DNA repair capacity on the risk of acute skin toxicity was thus evaluated.Materials and methods: In a prospective study of 478 female breast cancer patients receiving adjuvant radiotherapy of the breast after breast-conserving surgery, acute skin toxicity was documented systematically using a modified version of the common toxicity criteria. Prognostic personal and treatment characteristics were identified for the entire cohort. Individual DNA repair capacity was determined in a subgroup of 113 patients with alkaline comet assay using phytohemagglutinin stimulated lymphocytes. Using proportional hazards analysis to account for cumulative biologically effective radiation dose, the hazard for the development of acute skin reactions (moist desquamation) associated with DNA repair capacity was modeled.Results: Of the 478 participants, 84 presented with acute reactions by the end of treatment. Higher body mass index was significantly associated with an increased risk for acute reactions (hazard ratio = 1.09 per 1 kg/m(2)), adjusted for treating hospital and photon beam quality. The comet assay parameters examined, including background DNA damage in non-irradiated cells, DNA damage induced by 5 Gy, and DNA repair capacity, were not significantly associated with risk of acute skin toxicity.Conclusions: Higher BMI is predictive of acute skin toxicity, however, individual repair parameters as determined by the alkaline comet assay are not informative enough. More comprehensive analyses including late effects of radiotherapy and repair kinetics optimized for different radiation-induced DNA lesions are warranted. (C) 2003 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 14643951
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: APOPTOSIS ; CANCER ; IONIZING-RADIATION ; radiotherapy ; Germany ; IN-VIVO ; TOXICITY ; RISK ; RISKS ; GENE ; GENES ; HYBRIDIZATION ; SURGERY ; radiation ; PATIENT ; GENETIC POLYMORPHISMS ; SKIN ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; VARIANTS ; BREAST ; breast cancer ; BREAST-CANCER ; AGE ; WOMEN ; REPAIR ; p53 ; PCR ; DNA-DAMAGE ; Jun ; CANCER-PATIENTS ; BODY ; p21 ; CANCER PATIENTS ; TP53 ; MASS INDEX ; RE ; VARIANT ; WEIGHT ; OVERWEIGHT ; prospective ; prospective study ; INCREASED RISK ; acute toxicity ; female breast cancer ; CODON-31 ; REPOPULATION
    Abstract: p53 and p21 play an important role in G1/S checkpoint control in response to ionizing radiation. Yet the genetic polymorphisms in these genes have not been investigated with respect to radiation toxicity in patients. We therefore assessed the association between TP53 Arg72Pro, p53PIN3 and p21 Ser31Arg polymorphisms and the risk of acute skin toxicity after radiotherapy in a prospective study of 446 female breast cancer patients (average age 60.3 +/- 9.0 years) receiving radiotherapy after breast conserving surgery. The p53PIN3 polymorphism was determined by standard PCR, and TP53 Arg72Pro and p21 Ser31Arg polymorphisms using melting point analysis of sequence-specific hybridization probes. The development of acute skin toxicity (moist desquamation) was modelled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Overall, the development of acute skin toxicity, which presented in 77 patients, was not significantly associated with the polymorphisms studied. Risks were however differential by body mass index. Compared to non-carriers, TP53 72Pro carriers had a non-significantly decreased risk of acute skin toxicity in normal weight women (hazard ratio 0.46, 95% CI, 0.18-1.18) but not in overweight patients (hazard ratio 1.07, 95% CI, 0.61-1.89) (p(interaction) =0.14). Haplotype analysis for the TP53 polymorphisms suggested that effect modification by TP53 72Pro may differ according to the p53PIN3 allele (p(interaction)=0.06). Furthermore, in TP53 72Pro carriers with p21 Ser/Ser genotype, the occurrence of acute toxicity was reduced in normal weight but not overweight patients. In conclusion, the TP53 72Pro variant may be associated with the development of acute skin toxicity after radiotherapy in patients with normal weight. Large clinical studies are needed to clearly confirm this association
    Type of Publication: Journal article published
    PubMed ID: 16331344
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: CANCER ; IRRADIATION ; radiotherapy ; Germany ; TOXICITY ; FOLLOW-UP ; INFORMATION ; COHORT ; LONG-TERM ; NEW-YORK ; RISK ; TISSUE ; SURGERY ; radiation ; TIME ; PATIENT ; RISK-FACTORS ; SKIN ; treatment ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; DIFFERENCE ; AGE ; risk factors ; smoking ; RECURRENCE ; PROGNOSTIC-FACTORS ; MULTIVARIATE ; CANCER-PATIENTS ; PROGNOSTIC FACTORS ; NORMAL TISSUE ; side effects ; CANCER PATIENTS ; PROGNOSTIC FACTOR ; COMPLICATIONS ; TELANGIECTASIA ; fibrosis ; ONCOLOGY ; REGRESSION ; RE ; INCREASE ; prospective studies ; CARCINOGEN-DNA ADDUCTS ; PROGNOSTIC-FACTOR ; development ; INTERVAL ; analysis ; USA ; prospective ; prospective study ; odds ratio ; RISK-FACTOR ; LOGISTIC-REGRESSION ; nonsmokers ; REPAIR GENES ; CLINICAL RADIOSENSITIVITY ; CONSERVATION THERAPY ; CONSERVING THERAPY ; cosmesis ; EORTC BOOST ; late side effects ; NO BOOST TRIAL ; POSTMASTECTOMY RADIOTHERAPY ; RADIATION-INJURY
    Abstract: Radiotherapy after breast-conserving surgery is commonly applied to reduce recurrence of breast cancer but may cause acute and late side effects. To identify prognostic factors for the development of late toxicity after radiotherapy, we conducted a prospective study of breast cancer patients. We assessed late complications of radiotherapy and collected information on epidemiologic factors in a cohort of breast cancer patients who had received radiotherapy after breast-conserving surgery. Among 416 patients with complete follow-up data, the association between possible risk factors and development of late complications was evaluated using multivariate logistic regression analysis. After a median follow-up time of 51 months, 131 (31.4%) patients presented with telangiectasia and 28 (6.7%) patients with fibrosis. We observed a strong association between development of telangiectasia and fibrosis (p 〈 0.01). Increasing age of the patient was a risk factor for both telangiectasia and fibrosis (p-value for trend 〈 0.01 and 0.03, respectively). Patients with acute skin toxicity (odds ratio (OR) 1.8, 95% confidence interval (CI) 1.0-3.1) were at higher risk to develop telangiectasia. Long-term smoking was associated with a significant increase in risk of telangiectasia compared to non-smokers (OR 2.3, 95% CI 1.2-4.6). Our study revealed several factors other than radiation dose that may predispose to late complications following radiotherapy. Further understanding of differences in response to irradiation may advance individualized treatment and improve cosmetic outcome
    Type of Publication: Journal article published
    PubMed ID: 17221151
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: CANCER ; CELLS ; EXPRESSION ; IN-VITRO ; IRRADIATION ; radiotherapy ; Germany ; THERAPY ; NEW-YORK ; RISK ; SURGERY ; radiation ; PATIENT ; DNA ; DONOR ; RISK-FACTORS ; INDUCTION ; SKIN ; fibroblasts ; SUSCEPTIBILITY ; BREAST ; breast cancer ; BREAST-CANCER ; RADIATION-THERAPY ; ASSAY ; DNA-REPAIR ; REPAIR ; REPRODUCIBILITY ; risk factors ; cancer risk ; COMET ASSAY ; DAMAGE ; LYMPHOCYTES ; DNA repair ; radiation sensitivity ; alkaline single-cell microgel electrophoresis assay ; CELLULAR RADIOSENSITIVITY ; CHROMOSOMAL RADIOSENSITIVITY ; DNA repair capacity ; DOUBLE-STRAND BREAKS ; IN-VITRO RADIOSENSITIVITY ; NORMAL-TISSUE RADIOSENSITIVITY ; PERIPHERAL-BLOOD LYMPHOCYTES ; radiation effects ; radiosensitivity ; TELANGIECTASIA
    Abstract: Purpose: Repair of radiation-induced DNA damage plays a critical role for both the susceptibility of patients to side effects after radiotherapy and their subsequent cancer risk. The study objective was to evaluate whether DNA repair data determined in vitro are correlated with the occurrence of acute side effects during radiotherapy. Methods and Materials: Breast cancer patients receiving radiation therapy after a breast- conserving surgery were recruited in a prospective epidemiologic study. As an indicator for clinical radiosensitivity, adverse reactions of the skin were recorded. Cryo-preserved lymphocytes from 113 study participants were gamma-irradiated with 5 Gy in vitro and analyzed using the alkaline comet assay. Reproducibility of the assay was determined by repeated analysis (n = 26) of cells from a healthy donor. A coefficient of variation of 0.3 was calculated. Results: The various parameters determined to characterize the individual DNA repair capacity showed large differences between patients. Eleven patients were identified with considerably enhanced DNA damage induction, and 7 patients exhibited severely reduced DNA repair capacity after 15 and 30 min. Six patients were considered as clinically radiosensitive, indicated by moist desquamation of the skin after a total radiation dose of about 50 Gy. Conclusions: Using the alkaline comet assay as described here, breast cancer patients were identified showing abnormal cellular radiation effects, but this repair deficiency corresponded only at a very limited extent to the acute radiation sensitivity of the skin. Because impaired DNA repair could be involved in the development of late irradiation effects, individuals exhibiting severely reduced DNA repair capacity should be followed for the development of late clinical symptoms. (C) 2003 Elsevier Science Inc
    Type of Publication: Journal article published
    PubMed ID: 12654430
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: CANCER ; EXPRESSION ; radiotherapy ; MODEL ; THERAPY ; TOXICITY ; CLASSIFICATION ; GENERATION ; RISK ; GENE ; GENES ; METABOLISM ; radiation ; NITRIC-OXIDE SYNTHASE ; NITRIC-OXIDE ; treatment ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; BREAST ; breast cancer ; BREAST-CANCER ; RADIATION-THERAPY ; DESIGN ; NUMBER ; STRESS ; WOMEN ; REPAIR ; GENOTYPES ; OUTCOMES ; FUTURE ; OXIDATIVE STRESS ; OXYGEN ; reactive oxygen species ; MASS INDEX ; ONCOLOGY ; REGRESSION ; ASSOCIATIONS ; RE ; OXIDATIVE-STRESS ; INCREASE ; SYNTHASE ; MYELOPEROXIDASE ; SUPEROXIDE-DISMUTASE ; REACTIVE OXYGEN ; LEVEL ; INTERVAL ; analysis ; GENOTYPE ; acute toxicity ; BMI ; cancer research ; CANCER-TREATMENT ; manganese ; manganese superoxide dismutase ; MNSOD ; nitric oxide ; RISK-FACTOR ; ROS ; SKIN TOXICITY ; VEGETABLE CONSUMPTION
    Abstract: Purpose: Because radiotherapy exerts cytotoxic effects via generation of massive oxidative stress, we hypothesized that catalase, manganese superoxide dismutase, myeloperoxidase (MPO), and endothelial nitric oxide synthase (eNOS) genotypes might result in greater risk of radiotoxicity. Experimental Design: Cases (n = 446) were Caucasian women with breast cancer who received radiotherapy following lumpectomy. Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight. The development of acute reactions (moist desquamation) associated with genotypes was modeled using the Cox proportional hazards model, accounting for cumulative biologically effective radiation dose. Results: Genotypes associated with higher levels of reactive oxygen species (ROS) were not associated with risk of radiotoxicity. However, relationships between overweight/obesity [body mass index (BMI), 〉25] and radiotoxicity risk seemed to be modified by eNOS and MPO genotypes associated with higher generation of nitric oxide and ROS, respectively. Women with high BMI (〉25) and eNOS GG genotypes were at more than a 6-fold increase in risk (hazard ratio, 6.39; 95% confidence interval, 2.53-16.15) compared with those with BMI 〈25, and for MPO, those with high BMI ()25) and GG genotypes also had greater risk of radiotoxicity (hazard ratio, 3.61; 95% confidence interval, 1.78-7.35) compared with those with BMI 〈25. Overweight/obesity was not a strong risk factor among women with other eNOS and MPO genotypes. Exploratory analysis using classification and regression trees indicated that total number of risk alleles contributed, in part, to acute toxicity outcomes among a subgroup of women. Conclusions: Associations between BMI and radiotoxicity risk may be most apparent among women with genotypes related to higher levels of oxidative stress. Regression trees may be useful in future studies to examine the contributions of multiple factors to individual susceptibility to adverse effects of cancer treatment
    Type of Publication: Journal article published
    PubMed ID: 17145829
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
  • 10
    Keywords: CANCER ; CANCER CELLS ; CELLS ; radiotherapy ; BLOOD ; CELL ; MODEL ; MODELS ; THERAPY ; FOLLOW-UP ; LONG-TERM ; RISK ; GENE ; GENES ; SAMPLE ; SAMPLES ; TISSUE ; radiation ; TIME ; PATIENT ; MECHANISM ; GENETIC POLYMORPHISMS ; mechanisms ; SKIN ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; BREAST ; breast cancer ; BREAST-CANCER ; RADIATION-THERAPY ; WOMEN ; CANCER-CELLS ; MULTIVARIATE ; NORMAL TISSUE ; PREDICTORS ; OXIDATIVE STRESS ; RANDOMIZED TRIAL ; OXYGEN ; COMPLICATIONS ; DNA-REPAIR GENES ; reactive oxygen species ; fibrosis ; ONCOLOGY ; THERAPIES ; radiation therapy ; analysis ; USA ; POSTMASTECTOMY RADIOTHERAPY ; INDUCED SUBCUTANEOUS FIBROSIS ; long-term toxicities ; LUMPECTOMY ; NORMAL TISSUE COMPLICATIONS
    Abstract: Telangiectasia and subcutaneous fibrosis are the most common late dermatologic side effects observed in response to radiation treatment. Radiotherapy acts on cancer cells largely due to the generation of reactive oxygen species (ROS). ROS also induce normal tissue toxicities. Therefore, we investigated if genetic variation in oxidative stress-related enzymes confers increased susceptibility to late skin complications. Women who received radiotherapy following lumpectomy for breast cancer were followed prospectively for late tissue side effects after initial treatment. Final analysis included 390 patients. Polymorphisms in genes involved in oxidative stress-related mechanisms (GSTA1, GSTM1, GSTT1, GSTP1, MPO, MnSOD, eNOS, CAD were determined from blood samples by MALDI-TOF. The associations between telangiectasia and genotypes were evaluated by multivariate unconditional logistic regression models. Patients with variant GSTA1 genotypes were at significantly increased risk of telangiectasia (OR 1.86, 95% CI 1.11-3.11). Reduced odds ratios of telangiectasia were noted for women with lower-activity eNOS genotype (OR 0.58, 95% CI 0.36-0.93). Genotype effects were modified by follow-up time, with the highest risk observed after 4 years of radiotherapy for gene polymorphisms in ROS-neutralizing enzymes. Decreased risk with eNOS polymorphisms was significant only among women with less than 4 years of follow-up. All other risk estimates were nonsignificant. Late effects of radiation therapy on skin appear to be modified by variants in genes related to protection from oxidative stress. The application of genomics to outcomes following radiation therapy holds the promise of radiation dose adjustment to improve both cosmetic outcomes and quality of life for breast cancer patients. (C) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 18027873
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...