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Sökning: WFRF:(Turesson Ingela)

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1.
  • Hopewell, J W, et al. (författare)
  • Time factor for acute tissue reactions following fractionated irradiation: a balance between repopulation and enhanced radiosensitivity.
  • 2003
  • Ingår i: International journal of radiation biology. - 0955-3002. ; 79:7, s. 513-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Experimental data for acute radiation-induced skin reactions are reviewed. These show that for dose fractionation schedules with gaps, repopulation is initiated after a lag period. After this lag period, the isoeffective dose for a given level of skin reaction first increases rapidly, but then slows. The timing of the lag period is related to the total turnover time of the tissue under investigation and, for example, is shorter in rodent skin than in pig or human skin. At the point when accelerated repopulation is initiated, there is a major shortening of the turnover time of the target cell population. At this time, there is evidence, for a short period, for an increase in radiosensitivity of the surviving stem cells in a number of acutely responding normal tissues. This effect is clearly illustrated by the results of experiments using sequential dose fractionation schedules. Prolongation of the schedule from 'short' to schedules that include irradiation over the period when the cell turnover is accelerated is associated with a marked increase in tissue radiosensitivity. Clinically, this is best illustrated by a comparison of the effects of accelerated fractionation schedules, involving multiple fractions/day, with daily fractionation schedules. The increase in radiosensitivity produced by the prolongation of the treatment from 2 to 4-5 weeks was equivalent to > or =1 Gy day(-1). Comparable findings were obtained from animal studies. In the oral mucosa of mice, the initiation of accelerated cell proliferation in surviving cells is associated with the loss of dose sparing by subsequent dose fractionation due to the loss of the capacity to repair sublethal damage. Studies in pig and human skin have indicated that increased radiosensitivity is associated with a loss of cells in the G1 phase of the cell cycle. A collation of these two sets of findings suggests that the repair of sublethal damage takes place over this phase of the cell cycle. One clinical implication of these findings is that the alpha/beta ratio for acute skin reaction changes with the length of the overall treatment time; it is approximately 4.0 Gy for 'short' fractionation schedules that avoid any shortening of the cell cycle time. This increases to 11.2-13.3 Gy for schedules given in 3-4 weeks and to approximately 35 Gy for schedules given in 5-6 weeks. Results for pig skin were in total agreement with those for human skin.
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2.
  • Jebsen, Nina L., et al. (författare)
  • Five-year Results From A Scandinavian Sarcoma Group Study (SSG XIII) Of Adjuvant Chemotherapy Combined With Accelerated Radiotherapy In High-Risk Soft Tissue Sarcoma Of Extremities And Trunk Wall
  • 2011
  • Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 81:5, s. 1359-1366
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To evaluate adjuvant chemotherapy and interpolated accelerated radiotherapy (RT) for adult patients with high-risk soft tissue sarcoma in the extremities or trunk wall. Methods and Materials: High-risk soft tissue sarcoma was defined as high-grade malignancy and at least two of the following criteria: size >= 8 cm, vascular invasion, or necrosis. Six cycles of doxorubicin and ifosfamide were prescribed for all patients. RT to a total dose of 36 Gy (1.8 Gy twice daily) was inserted between two chemotherapy cycles after marginal margin resection regardless of tumor depth or after wide-margin resection for deep-seated tumors. RT was boosted to 45 Gy in a split-course design in the case of intralesional margin resection. Results: A total of 119 patients were eligible, with a median follow-up of 5 years. The 5-year estimate of the local recurrence, metastasis-free survival, and overall survival rate was 12%, 59%, and 68%, respectively. The group receiving RT to 36 Gy had a local recurrence rate of 10%. In contrast, the local recurrence rate was 29% in the group treated with RT to 45 Gy. The presence of vascular invasion and low chemotherapy dose intensity had a negative effect on metastasis-free and overall survival. Toxicity was moderate after both the chemotherapy and the RT. Conclusions: Accelerated RT interposed between chemotherapy cycles in a selected population of patients with high-risk soft tissue sarcoma resulted in good local and distant disease control, with acceptable treatment-related morbidity. The greater radiation dose administered after intralesional surgery was not sufficient to compensate for the poorer surgical margin. Vascular invasion was the most important prognostic factor for metastasis-free and overall survival. (C) 2011 Elsevier Inc.
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3.
  • Laytragoon-Lewin, Nongnit, et al. (författare)
  • DNA Content and Methylation of p16, DAPK and RASSF1A Gene in Tumour and Distant, Normal Mucosal Tissue of Head and Neck Squamous Cell Carcinoma Patients
  • 2010
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:11, s. 4643-4648
  • Tidskriftsartikel (refereegranskat)abstract
    • Long-term survival of head and neck squamous cell carcinoma (HNSCC) patients has not improved significantly during the last 20 years and recurrent disease is frequently observed. In this study, the potential presence of pre-malignant cells or rare malignant cells at the time of diagnosis in HNSCC was investigated. Patients and Methods: Fifty-nine biopsies obtained from 41 HNSCC patients were analysed. Eighteen of these biopsies were normal mucosal tissue, located at least 5 cm from the tumour margin. DNA content and DNA methylation of p16, DAPK and RASSF1A was examined. Results: Thirty-nine out of 41 (95%) tumour biopsies showed p16 methylation and 21 (51%) of them displayed aneuploidy. Of 18 distant normal mucosal biopsies, 6 (33%) of these showed evidence of aneuploidy and 15(83%) of them showed methylated p16 genes. Among paired samples, the highest frequencies of DNA methylation were found in tumours with aneuploidy. Regardless of DNA content, methylation at DAPK, RASSF1A or p16 were found in the corresponding distant mucosal biopsies. Conclusion: The cells with abnormal DNA content or DNA methylation in mucosal tissue were not detected clinically or by pathological macroscopic and microscopic examination. Thus, distant mucosal tissue DNA content and DNA methylation analyses in combination with histopathology will provide a better prognostic base for the evaluation and treatment of HNSCC patients.
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4.
  • Laytragoon-Lewin, Nongnit, et al. (författare)
  • Human papillomavirus (HPV), DNA aberrations and cell cycle progression in anal squamous cell carcinoma patients
  • 2007
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:6C, s. 4473-4479
  • Tidskriftsartikel (refereegranskat)abstract
    • Human papillomavirus (HP) infections of the genital tract are sexually transmitted and prevalent worldwide. In this study, the role of HPV in 72 patients with anal squamous cell carcinoma was investigated. Patients and Methods: Polymerase chain reaction (PCR) in combination with in situ hybridization was used to identify HPV-DNA in the patients biopsies. The HPV typing was conducted by pyrosequencing. Cell cycle and DNA content were analysed by cytometry. Results: Ninety percent of the carcinoma biopsies carried high-risk oncogenic HPV in their malignant cells. Eighty-one percent of these demonstrated a single infection with HPV16, 18 or 33 and 19% were double infected with HPV16 and HPV18 Accumulations of viral genes were seen at the necrotic area of the tumours. The HPV genome in the tumour cell influenced significant the host cell cycle progression, but not DNA aberrations. Within these patients, HPV status in the malignant cells was not found to be associated with patient survival time. Conclusion: High-risk oncogenic HPV may play an important role in the initiation of host cell proliferation in anal squamous cell carcinoma. However, infection with HPV may not have any direct influence itself on the clinical outcome of these patients considering the treatments currently available.
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5.
  • Laytragoon-Lewin, Nongnit, et al. (författare)
  • In vitro effect of radiation, antibody to epidermal growth factor receptor and Docetaxel in human head and neck squamous carcinoma cells with mutant P53 and over-expressed EGFR
  • 2009
  • Ingår i: Journal of Cancer Research and Clinical Oncology. - 0171-5216 .- 1432-1335. ; 135:2, s. 203-9
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Radiotherapy is the most frequently used and cheapest treatment both for curative and palliative purposes in HNSCC. Despite advances in technology and intensive treatments with radiation, only half of the patients are cured. New therapeutic approaches focusing on the molecular mechanism that mediate tumour cell growth or cell death in combination with radiotherapy have been suggested. The effects of radiation, antibody to EGFR and Docetaxel as single treatment or in combinations on HNSCC cells were investigated. METHODS: The established HNSCC cells with mutant (mt) P53 and over-expressed normal EGFR was used as the in vitro model. Gene expression profile, cell cycle progression and cell death were used as the indication of treatment outcome. RESULTS: With c-DNA microarray of well-characterised functional genes, massive changes in the genes expression of HNSCC were detected. The alterations of gene expression profiles do not have any correlation neither on tumour cell growth nor cell death. HNSCC cells with mt P53 and over-expressed normal EGFR did not response to radiation, anti-EGFR monoclonal antibody and their combination therapy. Effective treatment could be obtained from single therapy with Docetaxel. No additive effects on cell cycle arrest or cell death were seen in the combination of Docetaxel to anti-EGFR antibody, radiation or anti-EGFR antibody + radiation. CONCLUSIONS: The c-DNA microarray analysis does not indicate any specific target or treatment effects of HNSCC with mt P53 and over-expressed normal EGFR. Single therapy, target at microtubules might be the most suitable treatment modulation in this tumour type.
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6.
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7.
  • Pettersson, Anna, et al. (författare)
  • Effects of a dietary intervention on acute gastrointestinal side effects and other aspects of health-related quality of life : A randomized controlled trial in prostate cancer patients undergoing radiotherapy
  • 2012
  • Ingår i: Radiotherapy and Oncology. - 0167-8140 .- 1879-0887. ; 103:3, s. 333-340
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose:To study the effect of a dietary intervention on acute gastrointestinal side effects and other aspects of health-related quality of life (HRQOL) in prostate cancer patients referred to radiotherapy.Materials and methods:A total of 130 patients were randomly assigned to one of two groups: an intervention group (IG, n = 64), instructed to reduce their intake of insoluble dietary fibres and lactose, a standard care group (SC, n = 66), instructed to continue their normal diet. Gastrointestinal side effects and other aspects of HRQOL were evaluated from baseline up to 2 months after completed radiotherapy, using the EORTC QLQ-C30 and QLQ-PR25 and the study-specific Gastrointestinal Side Effects Questionnaire (GISEQ). A scale indicating adherence to dietary instructions was developed from a Food Frequency Questionnaire (FFQ), with lower scores representing better compliance. Descriptive and inferential statistical analyses were conducted.Results:There was an interaction effect between randomization and time in the FFQ Scores (p < 0.001), indicating that both groups followed their assigned dietary instructions. The dietary intervention had no effect on gastrointestinal side effects or other aspects of HRQOL. During radiotherapy, the percentage of patients with bowel symptoms and bloated abdomen was lower in IG compared to SC, but the between-group differences were not statistically significant. During radiotherapy, the percentage of patients with bowel symptoms, urinary symptoms, pain, fatigue and diminished physical and role functioning increased in both groups.Conclusions: The dietary intervention had no effect on gastrointestinal side effects or other aspects of HRQOL. The tendency towards lower prevalence of bowel symptoms in IG may indicate some positive effect of the dietary intervention, but methodological refinements, clearer results and longer follow-up are needed before the value of diet change can be established with certainty.
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8.
  • Qvarnström, F., et al. (författare)
  • Double strand break induction and kinetics indicate preserved hypersensitivity in keratinocytes to subtherapeutic doses for 7 weeks of radiotherapy
  • 2017
  • Ingår i: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 122:1, s. 163-169
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose Previously we reported that hyper-radiosensitivity (HRS) was evidenced by quantifying DNA double strand break (DSB) foci in epidermis biopsies collected after delivering radiotherapeutic one and five dose fractions. The aim of this study was to determine whether HRS was preserved throughout a 7-week radiotherapy treatment, and also to examine the rate of foci decline and foci persistence between dose fractions. Materials and methods 42 patients with prostate cancer received 7-week fractionated radiotherapy treatment (RT) with daily dose fractions of 0.05–1.10 Gy to the skin. Before RT, and at several times throughout treatment, skin biopsies (n = 452) were collected at 30 min, and 2, 3, 24, and 72 h after dose fractions. DSB-foci markers, γH2AX and 53BP1, were labelled in epidermal keratinocytes with immunofluorescence and immunohistochemical staining. Foci were counted both with digital image analysis and manually. Results HRS in keratinocytes was evidenced by the dose–response relationships of DSB foci, observed throughout the treatment course, independent of sampling time and quantification method. Foci observed at 24 h after dose fractions indicated considerable DSB persistence. Accordingly, foci significantly accumulated after 5 consecutive dose fractions. For doses below 0.3 Gy, persistent foci could be observed even at 72 h after damage induction. A comparison of γH2AX and 53BP1 quantifications in double-stained biopsies showed similar HRS dose–response relationships. Conclusions These results represented the first evidence of preserved HRS, assessed by γH2AX- and 53BP1-labelled DSB foci, throughout a 7-week treatment course with daily repeated subtherapeutic dose fractions. © 2016 Elsevier Ireland Ltd
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9.
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10.
  • Turesson, I., et al. (författare)
  • Epidermal Keratinocyte Depletion during Five Weeks of Radiotherapy is Associated with DNA Double-Strand Break Foci, Cell Growth Arrest and Apoptosis: Evidence of Increasing Radioresponsiveness and Lack of Repopulation; The Number of Melanocytes Remains Unchanged
  • 2020
  • Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 193:5, s. 481-496
  • Tidskriftsartikel (refereegranskat)abstract
    • During fractionated radiotherapy, epithelial cell populations are thought to decrease initially, followed by accelerated repopulation to compensate cell loss. However, previous findings in skin with daily 1.1 Gy dose fractions indicate continued and increasing cell depletion. Here we investigated epidermal keratinocyte response with daily 2 Gy fractions as well as accelerated and hypofractionation. Epidermal interfollicular melanocytes were also assessed. Skin-punch biopsies were collected from breast cancer patients before, during and after mastectomy radiotherapy to the thoracic wall with daily 2 Gy fractions for 5 weeks. In addition, 2.4 Gy radiotherapy four times per week and 4 Gy fractions twice per week for 5 weeks, and two times 2 Gy daily for 2.5 weeks, were used. Basal keratinocyte density of the interfollicular epidermis was determined and immunostainings of keratinocytes for DNA double-strand break (DSB) foci, growth arrest, apoptosis and mitosis were quantified. In addition, interfollicular melanocytes were counted. Initially minimal keratinocyte loss was observed followed by pronounced depletion during the second half of treatment and full recovery at 2 weeks post treatment. DSB foci per cell peaked towards the end of treatment. p21-stained cell counts increased during radiotherapy, especially the second half. Apoptotic frequency was low throughout radiotherapy but increased at treatment end. Mitotic cell count was significantly suppressed throughout radiotherapy and did not recover during weekend treatment gaps, but increased more than threefold compared to unexposed skin 2 weeks post-radiotherapy. The number of melanocytes remained constant over the study period. Germinal keratinocyte loss rate increased gradually during daily 2 Gy fractions for 5 weeks, and similarly for hypofractionation. DSB foci number after 2 Gy irradiation revealed an initial radioresistance followed by increasing radiosensitivity. Growth arrest mediated by p21 strongly suggests that cells within or recruited into the cell cycle during treatment are at high risk of loss and do not contribute significantly to repopulation. It is possible that quiescent (G0) cells at treatment completion accounted for the accelerated post-treatment repopulation. Recent knowledge of epidermal tissue regeneration and cell cycle progression during genotoxic and mitogen stress allows for a credible explanation of the current finding. Melanocytes were radioresistant regarding cell depletion. © 2020 by Radiation Research Society. All rights of reproduction in any form reserved.
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