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Sample records for growth factor radiotherapie

  1. Radiotherapy and receptor of epidermal growth factor; Radiotherapie et recepteur de l'Epidermal Growth Factor

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    Deberne, M. [Institut Gustave-Roussy, 94 - Villejuif (France)

    2009-10-15

    The expression level of the receptor of the epidermal growth factor is in correlation with the tumor cells radiosensitivity. An overexpression of the E.G.F.R. is often present in the bronchi cancer, epidermoid carcinomas of the O.R.L. sphere, esophagus, uterine cervix, and anal duct but also in the rectum cancers and glioblastomas. At the clinical level, the E.G.F.R. expression is in correlation with an unfavourable prognosis after radiotherapy in numerous tumoral localizations. In the rectum cancers it is an independent prognosis factor found in multifactorial analysis: increase of the rate of nodes and local recurrence when the E.G.F.R. is over expressed. In the uterine cervix cancers, the survival is is negatively affected in multifactorial analysis by the E.G.F.R. membranes expression level. At the therapy level, the development of anti E.G.F.R. targeted therapies (tyrosine kinase inhibitors and monoclonal antibodies) opens a new therapy field at radio-sensitivity potentiality. The irradiation makes an activation of the E.G.F.R. way that would be partially responsible of the post irradiation tumoral repopulation. This activation leads the phosphorylation of the PI3 kinase ways and M.A.P. kinase ones, then the Akt protein one that acts an apoptotic modulator part. It has been shown that blocking the E.G.F.R. way acts on three levels: accumulation of ells in phase G1, reduction of the cell repair and increasing of apoptosis. he inhibition of post irradiation action of the E.G.F.R. signal way is a factor explaining the ionizing radiation - anti E.G.F.R. synergy. The preclinical data suggest that the E.G.F.R. blocking by the monoclonal antibodies is more important than the use of tyrosine kinase inhibitors. A first positive randomized study with the cetuximab, published in 2006 in the epidermoid carcinomas of the O.R.L. sphere lead to its authorization on the market with the radiotherapy for this localization. The use of cetuximab in other indication with or in

  2. Radiotherapy and receptor of epidermal growth factor

    International Nuclear Information System (INIS)

    Deberne, M.

    2009-01-01

    The expression level of the receptor of the epidermal growth factor is in correlation with the tumor cells radiosensitivity. An overexpression of the E.G.F.R. is often present in the bronchi cancer, epidermoid carcinomas of the O.R.L. sphere, esophagus, uterine cervix, and anal duct but also in the rectum cancers and glioblastomas. At the clinical level, the E.G.F.R. expression is in correlation with an unfavourable prognosis after radiotherapy in numerous tumoral localizations. In the rectum cancers it is an independent prognosis factor found in multifactorial analysis: increase of the rate of nodes and local recurrence when the E.G.F.R. is over expressed. In the uterine cervix cancers, the survival is is negatively affected in multifactorial analysis by the E.G.F.R. membranes expression level. At the therapy level, the development of anti E.G.F.R. targeted therapies (tyrosine kinase inhibitors and monoclonal antibodies) opens a new therapy field at radio-sensitivity potentiality. The irradiation makes an activation of the E.G.F.R. way that would be partially responsible of the post irradiation tumoral repopulation. This activation leads the phosphorylation of the PI3 kinase ways and M.A.P. kinase ones, then the Akt protein one that acts an apoptotic modulator part. It has been shown that blocking the E.G.F.R. way acts on three levels: accumulation of ells in phase G1, reduction of the cell repair and increasing of apoptosis. he inhibition of post irradiation action of the E.G.F.R. signal way is a factor explaining the ionizing radiation - anti E.G.F.R. synergy. The preclinical data suggest that the E.G.F.R. blocking by the monoclonal antibodies is more important than the use of tyrosine kinase inhibitors. A first positive randomized study with the cetuximab, published in 2006 in the epidermoid carcinomas of the O.R.L. sphere lead to its authorization on the market with the radiotherapy for this localization. The use of cetuximab in other indication with or in

  3. Antivascular Endothelial Growth Factor Bevacizumab for Radiation Optic Neuropathy: Secondary to Plaque Radiotherapy

    International Nuclear Information System (INIS)

    Finger, Paul T.; Chin, Kimberly J.

    2012-01-01

    Purpose: To evaluate the intravitreal antivascular endothelial growth factor, bevacizumab, for treatment of radiation optic neuropathy (RON). Methods and Materials: A prospective interventional clinical case series was performed of 14 patients with RON related to plaque radiotherapy for choroidal melanoma. The RON was characterized by optic disc edema, hemorrhages, microangiopathy, and neovascularization. The entry criteria included a subjective or objective loss of vision, coupled with findings of RON. The study subjects received a minimum of two initial injections of intravitreal bevacizumab (1.25 mg in 0.05 mL) every 6–8 weeks. The primary objectives included safety and tolerability. The secondary objectives included the efficacy as measured using the Early Treatment Diabetic Retinopathy Study chart for visual acuity, fundus photography, angiography, and optical coherence tomography/scanning laser ophthalmoscopy. Results: Reductions in optic disc hemorrhage and edema were noted in all patients. The visual acuity was stable or improved in 9 (64%) of the 14 patients. Of the 5 patients who had lost vision, 2 had relatively large posterior tumors, 1 had had the vision decrease because of intraocular hemorrhage, and 1 had developed optic atrophy. The fifth patient who lost vision was noncompliant. No treatment-related ocular or systemic side effects were observed. Conclusions: Intravitreal antivascular endothelial growth factor bevacizumab was tolerated and generally associated with improved vision, reduced papillary hemorrhage, and resolution of optic disc edema. Persistent optic disc neovascularization and fluorescein angiographic leakage were invariably noted. The results of the present study support additional evaluation of antivascular endothelial growth factor medications as treatment of RON.

  4. Antivascular Endothelial Growth Factor Bevacizumab for Radiation Optic Neuropathy: Secondary to Plaque Radiotherapy

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    Finger, Paul T., E-mail: pfinger@eyecancer.com [New York Eye Cancer Center, New York, NY (United States); Chin, Kimberly J. [New York Eye Cancer Center, New York, NY (United States)

    2012-02-01

    Purpose: To evaluate the intravitreal antivascular endothelial growth factor, bevacizumab, for treatment of radiation optic neuropathy (RON). Methods and Materials: A prospective interventional clinical case series was performed of 14 patients with RON related to plaque radiotherapy for choroidal melanoma. The RON was characterized by optic disc edema, hemorrhages, microangiopathy, and neovascularization. The entry criteria included a subjective or objective loss of vision, coupled with findings of RON. The study subjects received a minimum of two initial injections of intravitreal bevacizumab (1.25 mg in 0.05 mL) every 6-8 weeks. The primary objectives included safety and tolerability. The secondary objectives included the efficacy as measured using the Early Treatment Diabetic Retinopathy Study chart for visual acuity, fundus photography, angiography, and optical coherence tomography/scanning laser ophthalmoscopy. Results: Reductions in optic disc hemorrhage and edema were noted in all patients. The visual acuity was stable or improved in 9 (64%) of the 14 patients. Of the 5 patients who had lost vision, 2 had relatively large posterior tumors, 1 had had the vision decrease because of intraocular hemorrhage, and 1 had developed optic atrophy. The fifth patient who lost vision was noncompliant. No treatment-related ocular or systemic side effects were observed. Conclusions: Intravitreal antivascular endothelial growth factor bevacizumab was tolerated and generally associated with improved vision, reduced papillary hemorrhage, and resolution of optic disc edema. Persistent optic disc neovascularization and fluorescein angiographic leakage were invariably noted. The results of the present study support additional evaluation of antivascular endothelial growth factor medications as treatment of RON.

  5. Mathematical modeling of liver metastases tumour growth and control with radiotherapy

    International Nuclear Information System (INIS)

    Campbell, Adrienne; Sivakumaran, Thiru; Wong, Eugene; Davidson, Melanie; Lock, Michael

    2008-01-01

    Generating an optimized radiation treatment plan requires understanding the factors affecting tumour control. Mathematical models of tumour dynamics may help in future studies of factors predicting tumour sensitivity to radiotherapy. In this study, a time-dependent differential model, incorporating biological cancer markers, is presented to describe pre-treatment tumour growth, response to radiation, and recurrence. The model uses Gompertzian-Exponential growth to model pre-treatment tumour growth. The effect of radiotherapy is handled by a realistic cell-kill term that includes a volume-dependent change in tumour sensitivity. Post-treatment, a Gompertzian, accelerated, delayed repopulation is employed. As proof of concept, we examined the fit of the model's prediction using various liver enzyme levels as markers of metastatic liver tumour growth in a liver cancer patient. A tumour clonogen population model was formulated. Each enzyme was coupled to the same tumour population, and served as surrogates of the tumour. This dynamical model was solved numerically and compared to the measured enzyme levels. By minimizing the mean-squared error of the model enzyme predictions, we determined the following tumour model parameters: growth rate prior to treatment was 0.52% per day; the fractional radiation cell kill for the prescribed dose (60 Gy in 15 fractions) was 42% per day, and the tumour repopulation rate was 2.9% per day. These preliminary results provided the basis to test the model in a larger series of patients, to apply biological markers for improving the efficacy of radiotherapy by determining the underlying tumour dynamics.

  6. Clinical significance of changes of serum vascular endothelial growth factor level before and after radiotherapy in patients with esophageal carcinoma

    International Nuclear Information System (INIS)

    Yu Jingping; Sun Zhiqiang; Ni Xinchu; Wang Jian; Li Yi; Hu Lijun; Li Dongqing; Sun Suping

    2011-01-01

    Objective: To investigate the changes and clinical value of serum vascular endothelial growth factor (VEGF) level before, during and after radiotherapy in patients with esophageal carcinoma. Methods: The sera of 67 esophageal carcinoma patients and 30 healthy control cases were collected. The VEGF level in serum samples were measured with enzyme-linked immunosorbent assay (ELISA) method. The relations among VEGF level changes,clinical stages and radiotherapy effect were analyzed. Results: The VEGF levels of patients with esophagus cancer before, during and after radiotherapy were significantly higher than those in control group (F=11.65, P<0.01). The VEGF level after radiotherapy was significant lower than that before radiotherapy (F=10.72, P<0.01). The average VEGF level of patients with T 3 and T 4 was significantly higher than that of control group (F=14.10, P<0.01). The average VEGF level of patients with N 1 and N 2 was significantly higher than that of control group (F=8.64, P<0.01). In 62 patients,the serum VEGF level increased in 21 cases but decreased in 41 cases after radiotherapy. With difference in radiotherapy efficiency of 61.90% and 90.24%, respectively (χ 2 =6.08, P<0.05). The average VEGF level during and after radiotherapy for 50 cases of CR + PR were significantly lower than that before radiotherapy (F=7.98, P<0.01). Conclusions: Monitoring the serum VEGF level of patients with esophagus cancer can help evaluate the radiosensitivity, which has a significance in predicting the prognosis of radiotherapy. (authors)

  7. Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results

    International Nuclear Information System (INIS)

    Baumann, Michael; Krause, Mechthild

    2004-01-01

    Background and purpose: Inhibition of the epidermal growth factor receptor (EGFR) is a fastly developing field in preclinical and clinical cancer research. This review presents the current status of knowledge and discusses radiobiological mechanisms which may underly the efficacy of EGFR inhibitors combined with irradiation. Materials and methods: Preclinical and clinical results on combined targeting of the EGFR and irradiation from the literature and from this laboratory are reviewed. Focus is given to the radiobiological rationale of this approach and to endpoints of experimental radiotherapy. Results: Overexpression of the EGFR is associated with decreased local tumour control after radiotherapy, especially when the overall treatment time is long. Inhibition of the EGFR either alone or in combination with irradiation decreases the growth rate of tumours expressing this receptor. Preclinical data provide proof-of-principle that local tumour control may be improved by combining irradiation with C225 mAb. In a randomised phase III clinical trial, simultaneous irradiation and treatment with the EGFR antibody Cetuximab (Erbitux[reg]; C225) in head and neck cancer patients resulted in significantly improved locoregional tumour control and survival compared to curative irradiation alone. Acute skin reactions increased in the experimental arm. The underlying mechanisms of enhanced radiation effects of combined EGFR inhibition with irradiation and of the partly conflicting results in different studies are poorly understood. There is increasing evidence, that important intertumoral heterogeneity in the response to EGFR inhibition alone and combined with irradiation exists, which appears to be at least partly dependent on specific mutations of the receptor as well as of molecules that are involved in the intracellular signal transduction pathway. Conclusions and outlook: Further investigations at all levels of the translational research chain exploring the mechanisms of

  8. The curative effects of radiotherapy-based therapies for human epidermal growth factor receptor 2-positive breast cancer: A meta-analysis.

    Science.gov (United States)

    Shao, Minghai; Zhang, Chi; Qin, Qin; Zhang, Zhaoyue; Zhu, Hongcheng; Di, Xiaoke; Sun, Xinchen

    2017-09-01

    This meta-analysis was designed to fully assess the curative effects of radiotherapy-based therapies for human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). English articles were retrieved through searching Cochrane library, PubMed, and Embase databases updated to February 2017. Studies were selected based on the inclusion and exclusion criteria. The curative effects of radiotherapy-based therapies forHER2+ BC patients were assessed using hazard rates (HRs) or odds ratios (ORs), as well as their 95% confidence intervals (CIs). In addition, Egger test was used to assess publication bias, followed by sensitivity analysis. All statistic methods were conducted using R 3.12 software. A total of 9 eligible studies were included into this meta-analysis, which involved 2236 HER2+ BC patients. Egger test showed that the eligible studies had no publication bias (t = 2.198, P = .05918). Sensitivity analysis demonstrated that the results were stable. HER2+ BC patients in radiotherapy group had lower locoregional recurrences than those in other groups. Moreover, meta-analysis showed that no significant difference was found between HER2+ BC patients in radiotherapy group and other groups on the 1-year overall survival (P = 0.5263, I = 65.4%), 3-year overall survival (P = 0.4591, I = 0), and 5-year overall survival (P = 0.06277, I = 0). Radiotherapy-based therapies might have certain advantages in treating HER2+ BC patients.

  9. Modulation of radiosensitivity by growth factors

    International Nuclear Information System (INIS)

    Paris, F.

    2013-01-01

    The full text of the publication follows. For the past 70 years, radiotherapy protocols were defined to target and kill cancer cells. New research developments showed that the tissue or tumor radiosensitivities might be directly modulated by its own microenvironment. Between all the micro-environmental cells, endothelial cells are playing a unique role due to the need of angio-genesis for tumor genesis and to the microvascular endothelial cell apoptosis involved in acute normal tissue and tumor radiosensitivities. Both endothelial behaviours may be controlled by specific growth factors secreted by tumor cells. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two cytokines involved in angio genesis and endothelial cell survival. Because radiation exposure develops opposite molecular and cellular responses by inhibiting proliferation and by enhancing apoptosis, inhibiting these cytokines has been proposed as a relevant strategy to improve radiotherapy efficiency. Drugs or antibody against VEGF, or other growth factors have been used with success to limit endothelial cell resistance, but also to transiently normalize of blood vessels to improve oxygen distribution into the tumor. However, better characterisation of the role of the cytokines will help to better improve the strategy of the use of their antagonists. We demonstrate that bFGF or sphingosin 1 phosphate (S1P), a lipid endothelial growth factor, protects endothelial cells from radiation stress by inhibiting the pre-mitotic apoptosis through enhancement of pro-survival molecular cascade, such as the Pi3K/AKT pathway, but not post-mitotic death. This discrepancy allowed a specific use of S1P as pharmacological drug protecting quiescent endothelial cells, present in normal tissue blood vessels, but not in proliferating angiogenic blood vessels, majority present in tumor blood vessel. In vivo studies are underway. (author)

  10. The expression of epidermal growth factor receptor results in a worse prognosis for patients with rectal cancer treated with preoperative radiotherapy: a multicenter, retrospective analysis

    International Nuclear Information System (INIS)

    Giralt, Jordi; Heras, Manuel de las; Cerezo, Laura; Eraso, Aranzazu; Hermosilla, Edurado; Velez, Dolores; Lujan, Juan; Espin, Eloi; Rossello, Jose; Majo, Joaquin; Benavente, Sergi; Armengol, Manel; Torres, I. de

    2005-01-01

    Background and purpose: Expression of epidermal growth factor receptor (EGFR) is observed in 50-70% of colorectal carcinoma and is associated with poor prognosis. The aim of this study was to determine the prognostic value of EGFR status before radiotherapy in a group of patients with locally advanced rectal cancer treated with preoperative radiotherapy. Patients and methods: Eighty-seven patients were studied retrospectively. Treatment consisted of pelvic radiotherapy, in 50 patients with concomitant chemotherapy and surgical resection. Immunohistochemistry for EGFR was determined at the preradiation biopsy and in the resected specimens. Immunohistochemical analysis for EGFR expression was evaluated according to extension and staining intensity. We defined positive staining (EGFR positive), when extension was 5% or more. Results: A total of 52 of 87 tumors showed EGFR positive status at biopsy (60%) and EGFR expression was associated neither with clinical tumor stage nor with clinical nodal stage. EGFR positive expression was linked to a lack of pathologic complete response to preoperative radiotherapy (P=0.006). Disease-free survival was lower among patients with EGFR positive status before radiotherapy (P=0.003). In a multivariate analysis EGFR expression at biopsy was a statistically significant predictor of disease-free survival, RR=2.88 (1.1-7.8), P=0.036. Conclusions: EGFR is expressed in a significant number of rectal tumors. EGFR-positive expression before radiotherapy is an indicator for poor response and low disease-free survival

  11. Combination of vascular endothelial growth factor antisense oligonucleotide therapy and radiotherapy increases the curative effects against maxillofacial VX2 tumors in rabbits

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    Zheng Linfeng, E-mail: zhenglinfeng04@yahoo.com.cn [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Li Yujie, E-mail: yujieli01@yahoo.com.cn [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Wang Han, E-mail: bingowh@hotmail.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Zhao Jinglong, E-mail: jinglongz@yahoo.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Wang Xifu, E-mail: wangxiechen001@163.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Hu Yunsheng, E-mail: springmorninghu@163.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Zhang Guixiang, E-mail: guixiangzhang@sina.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China)

    2011-05-15

    Purpose: To study the effects of combination of vascular endothelial growth factor (VEGF) antisense oligonucleotide therapy and radiotherapy on maxillofacial VX2 tumors in rabbits. Methods: We used 24 New Zealand white rabbits as a model to induce maxillofacial VX2 tumor. The rabbits were randomly divided into the following 4 groups: radiotherapy group (group A), treated with 16 Gy of radiotherapy; VEGF antisense oligonucleotide treatment group (group B), treated with an injection of 150 {mu}g of VEGF antisense oligonucleotide into the local tumor; VEGF antisense oligonucleotide combined with radiotherapy group (group C), treated with an injection of 150 {mu}g of VEGF antisense oligonucleotide into the local tumor immediately after 16 Gy of radiotherapy; and control group (group D), treated with an injection of 300 {mu}l 5% aqueous glucose solution into the local tumor. On days 3 and 14 after treatment, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed to calculate maximal enhancement ratio (MER), slope of enhancement (SLE), and tumor volume change. Rabbits were killed on day 14 to obtain samples for pathological examination and immunohistochemical staining for VEGF. Results: In group C, tumor volume was significantly reduced on day 14 after treatment, and the difference was statistically different as compared to that before treatment, on day 3 after treatment and other groups (P < 0.01). Values of both MER and SLE after treatment were significantly lower than the values before treatment (P < 0.05). Pathological specimen revealed tumor cell edema, bleeding, necrosis, vascular wall thickening and occlusion, and decreased VEGF expression. The immunohistochemical score (IHS) of group C was significantly different from groups A and D respectively (P < 0.05). Conclusion: Injecting the tumor with VEGF antisense oligonucleotide immediately after radiotherapy can enhance the curative effect on rabbit maxillofacial VX2 tumor, and DCE-MRI can serve

  12. Prognostic factors and therapeutic options of radiotherapy in pediatric brain stem gliomas

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    Liu, Yu-Ming; Shiau, Cheng-Ying; Wong, Tai-Tong; Wang, Ling-Wei; Wu, Le-Jung; Chi, Kwan-Hwa; Chen, Kuang Y.; Yen, Sang-Hue [Veterans General Hospital-Taipei, Taipei, Taiwan (China)

    1998-08-01

    A retrospective analysis was made to clarify the relationship between prognosis, radiation dose and survival of brain stem gliomas. From 1983 to 1995, 22 children with brain stem tumors were treated by radiotherapy in the Veterans General Hospital-Taipei. Twelve patients had pathology proof and the remainder were diagnosed by computerized tomography and/or magnetic resonance imaging. Seven patients had postoperative radiotherapy. Fifteen patients had radiotherapy as primary management, five of whom had adjuvant chemotherapy. All patients received 4000-7060 cGy, either in conventional daily or hyperfractionated twice daily radiotherapy. Survival from date of diagnosis was calculated by the Kaplan-Meier method. Univariate analyses and multivariate analyses were calculated by the log rank test and the Cox proportional hazard model, respectively. Most patients showed improvement following treatment. The overall 2-year survival rate was 55.5% with a median survival of 27.1 months. Two-year survival for patients with primary management of operation and radiotherapy (n=7), radiotherapy alone (n=10) and radiotherapy with adjuvant chemotherapy (n=5) were 66.7, 50 and 53.3%, respectively. In univariate analysis, the study revealed that the growth pattern of tumors and the simultaneous presence of cranial neuropathy and long tract sign were significant prognostic factors (P=0.017 and 0.036). A trend of better outcome with radiation dose >6600 cGy and the hyperfractionation scheme was also noted in our study (P=0.0573 and 0.0615). However, only the hyperfractionation scheme showed significance in multivariate analyses (P=0.0355). Survival was not significantly affected by age, gender or method of diagnosis. Radiotherapy appears to be an effective treatment modality of brain stem tumors. Patients with both cranial neuropathy and long tract signs had a poorer outcome. Hyperfractionated radiotherapy may give better local control and lead to better survival. (author)

  13. Prognostic factors and therapeutic options of radiotherapy in pediatric brain stem gliomas

    International Nuclear Information System (INIS)

    Liu, Yu-Ming; Shiau, Cheng-Ying; Wong, Tai-Tong; Wang, Ling-Wei; Wu, Le-Jung; Chi, Kwan-Hwa; Chen, Kuang Y.; Yen, Sang-Hue

    1998-01-01

    A retrospective analysis was made to clarify the relationship between prognosis, radiation dose and survival of brain stem gliomas. From 1983 to 1995, 22 children with brain stem tumors were treated by radiotherapy in the Veterans General Hospital-Taipei. Twelve patients had pathology proof and the remainder were diagnosed by computerized tomography and/or magnetic resonance imaging. Seven patients had postoperative radiotherapy. Fifteen patients had radiotherapy as primary management, five of whom had adjuvant chemotherapy. All patients received 4000-7060 cGy, either in conventional daily or hyperfractionated twice daily radiotherapy. Survival from date of diagnosis was calculated by the Kaplan-Meier method. Univariate analyses and multivariate analyses were calculated by the log rank test and the Cox proportional hazard model, respectively. Most patients showed improvement following treatment. The overall 2-year survival rate was 55.5% with a median survival of 27.1 months. Two-year survival for patients with primary management of operation and radiotherapy (n=7), radiotherapy alone (n=10) and radiotherapy with adjuvant chemotherapy (n=5) were 66.7, 50 and 53.3%, respectively. In univariate analysis, the study revealed that the growth pattern of tumors and the simultaneous presence of cranial neuropathy and long tract sign were significant prognostic factors (P=0.017 and 0.036). A trend of better outcome with radiation dose >6600 cGy and the hyperfractionation scheme was also noted in our study (P=0.0573 and 0.0615). However, only the hyperfractionation scheme showed significance in multivariate analyses (P=0.0355). Survival was not significantly affected by age, gender or method of diagnosis. Radiotherapy appears to be an effective treatment modality of brain stem tumors. Patients with both cranial neuropathy and long tract signs had a poorer outcome. Hyperfractionated radiotherapy may give better local control and lead to better survival. (author)

  14. Volume Changes After Stereotactic LINAC Radiotherapy in Vestibular Schwannoma: Control Rate and Growth Patterns

    International Nuclear Information System (INIS)

    Langenberg, Rick van de; Dohmen, Amy J.C.; Bondt, Bert J. de; Nelemans, Patty J.; Baumert, Brigitta G.; Stokroos, Robert J.

    2012-01-01

    Purpose: The purpose of this study was to evaluate the control rate of vestibular schwannomas (VS) after treatment with linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) or radiotherapy (SRT) by using a validated volumetric measuring tool. Volume-based studies on prognosis after LINAC-based SRS or SRT for VS are reported scarcely. In addition, growth patterns and risk factors predicting treatment failure were analyzed. Materials and Methods: Retrospectively, 37 VS patients treated with LINAC based SRS or SRT were analyzed. Baseline and follow-up magnetic resonance imaging scans were analyzed with volume measurements on contrast enhanced T1-weighted magnetic resonance imaging. Absence of intervention after radiotherapy was defined as “no additional intervention group, ” absence of radiological growth was defined as “radiological control group. ” Significant growth was defined as a volume change of 19.7% or more, as calculated in a previous study. Results: The cumulative 4-year probability of no additional intervention was 96.4% ± 0.03; the 4-year radiological control probability was 85.4% ± 0.1). The median follow-up was 40 months. Overall, shrinkage was seen in 65%, stable VS in 22%, and growth in 13%. In 54% of all patients, transient swelling was observed. No prognostic factors were found regarding VS growth. Previous treatment and SRS were associated with transient swelling significantly. Conclusions: Good control rates are reported for LINAC based SRS or SRT in VS, in which the lower rate of radiological growth control is attributed to the use of the more sensitive volume measurements. Transient swelling after radiosurgery is a common phenomenon and should not be mistaken for treatment failure. Previous treatment and SRS were significantly associated with transient swelling.

  15. Experimental radiotherapy and clinical radiobiology. Vol. 20. Proceedings

    International Nuclear Information System (INIS)

    Baumann, Michael; Dahm-Daphi, Jochen; Dikomey, Ekkehard; Petersen, Cordula; Rodemannn, Hans-Peter; Zips, Daniel

    2011-01-01

    The proceedings include contributions on the following issues: laser driven proton accelerators on the way for radiotherapy, radiobiological evaluation of new radiations; molecular factors of radiation response; biological targeting; EGFR epidermal growth factor receptor/targeting - combined internal and external irradiation, radiobiology of normal tissues; dose-volume histograms for the radiotherapy: curves without radiobiological relevance or important information for the therapy planning; HPV (human papilloma virus) and radiation sensitivity of HNSCC (head and neck squamous cell carcinomas): evidence, radiobiological mechanism, clinical consequences and perspectives; mechanisms of action and intertumoral heterogeneity of response to EGFR inhibition in radiotherapy of solid tumors; evaluation of biomarkers for radiotherapy.

  16. Analysis for prognostic factors of radiotherapy for esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Nakano, Takashi; Ito, Jun; Ito, Ichiro; Yamanaka, Mikio; Suto, Hisao; Mitsuhashi, Norio; Niibe, Hideo

    1984-01-01

    Two hundred and fifty patients with squamous cell carcinoma of the esophagus were treated at our department from 1969 to 1981 with radiotherapy involving radiation alone and pre-and/or post-operative radiotherapy. For 167 patients receiving radiotherapy alone, 144 were inoperable cases and only 60 patients could be radically treated. The others were palliative treated patients because of the locally advanced state or distant metastases or severe complications. For 83 patients receiving pre-and/or post-operative radiotherapy, 62 were radically treated. Results of radiotherapy were analyzed to elucidate factors responsible for these prognosis. Relative 5 years survival rates for radically treated patients were 26% in radiotherapy alone and 20% in pre-and/or post-operative radiotherapy respectively. In radiotherapy alone, quite a good prognoses could be obtained in the patients with tumors less than 5cm at radiografical finding (42% for 5 yrs), with tumors located in Ei, Ea esophagus (40%), with tumors of serrative and tumorous X-P types (48%, 43%, respectively) and with good radiation response at the end of radiotherapy (54%). From the analysis of 12 patients surviving more than 5 years from onset of treatment, not only tumor size less than 5cm but also radiation response was major factor responsible for the prognosis. It might be important to treat patients precisely according to their own clinical characteristics and considering tumor host relationship. (author)

  17. Personalized Radiation Oncology: Epidermal Growth Factor Receptor and Other Receptor Tyrosine Kinase Inhibitors.

    Science.gov (United States)

    Higgins, Geoff S; Krause, Mechthild; McKenna, W Gillies; Baumann, Michael

    Molecular biomarkers are currently evaluated in preclinical and clinical studies in order to establish predictors for treatment decisions in radiation oncology. The receptor tyrosine kinases (RTK) are described in the following text. Among them, the most data are available for the epidermal growth factor receptor (EGFR) that plays a major role for prognosis of patients after radiotherapy, but seems also to be involved in mechanisms of radioresistance, specifically in repopulation of tumour cells between radiotherapy fractions. Monoclonal antibodies against the EGFR improve locoregional tumour control and survival when applied during radiotherapy, however, the effects are heterogeneous and biomarkers for patient selection are warranted. Also other RTK´s such as c-Met and IGF-1R seem to play important roles in tumour radioresistance. Beside the potential to select patients for molecular targeting approaches combined with radiotherapy, studies are also needed to evluate radiotherapy adaptation approaches for selected patients, i.e. adaptation of radiation dose, or, more sophisticated, of target volumes.

  18. A human factor analysis of a radiotherapy accident

    International Nuclear Information System (INIS)

    Thellier, S.

    2009-01-01

    Since September 2005, I.R.S.N. studies activities of radiotherapy treatment from the angle of the human and organizational factors to improve the reliability of treatment in radiotherapy. Experienced in nuclear industry incidents analysis, I.R.S.N. analysed and diffused in March 2008, for the first time in France, the detailed study of a radiotherapy accident from the angle of the human and organizational factors. The method used for analysis is based on interviews and documents kept by the hospital. This analysis aimed at identifying the causes of the difference recorded between the dose prescribed by the radiotherapist and the dose effectively received by the patient. Neither verbal nor written communication (intra-service meetings and protocols of treatment) allowed information to be transmitted correctly in order to permit radiographers to adjust the irradiation zones correctly. This analysis highlighted the fact that during the preparation and the carrying out of the treatment, various factors led planned controls to not be performed. Finally, this analysis highlighted the fact that unsolved areas persist in the report over this accident. This is due to a lack of traceability of a certain number of key actions. The article concluded that there must be improvement in three areas: cooperation between the practitioners, control of the actions and traceability of the actions. (author)

  19. Loss of insulin-like growth factor II imprinting is a hallmark associated with enhanced chemo/radiotherapy resistance in cancer stem cells.

    Science.gov (United States)

    Zhao, Xin; Liu, Xiaoliang; Wang, Guanjun; Wen, Xue; Zhang, Xiaoying; Hoffman, Andrew R; Li, Wei; Hu, Ji-Fan; Cui, Jiuwei

    2016-08-09

    Insulin-like growth factor II (IGF2) is maternally imprinted in most tissues, but the epigenetic regulation of the gene in cancer stem cells (CSCs) has not been defined. To study the epigenetic mechanisms underlying self-renewal, we isolated CSCs and non-CSCs from colon cancer (HT29, HRT18, HCT116), hepatoma (Hep3B), breast cancer (MCF7) and prostate cancer (ASPC) cell lines. In HT29 and HRT18 cells that show loss of IGF2 imprinting (LOI), IGF2 was biallelically expressed in the isolated CSCs. Surprisingly, we also found loss of IGF2 imprinting in CSCs derived from cell lines HCT116 and ASPC that overall demonstrate maintenance of IGF2 imprinting. Using chromatin conformation capture (3C), we found that intrachromosomal looping between the IGF2 promoters and the imprinting control region (ICR) was abrogated in CSCs, in parallel with loss of IGF2 imprinting in these CSCs. Loss of imprinting led to increased IGF2 expression in CSCs, which have a higher rate of colony formation and greater resistance to chemotherapy and radiotherapy in vitro. These studies demonstrate that IGF2 LOI is a common feature in CSCs, even when the stem cells are derived from a cell line in which the general population of cells maintain IGF2 imprinting. This finding suggests that aberrant IGF2 imprinting may be an intrinsic epigenetic control mechanism that enhances stemness, self-renewal and chemo/radiotherapy resistance in cancer stem cells.

  20. Imaging of Epidermal Growth Factor Receptor Expression in Head and Neck Cancer with SPECT/CT and 111In-Labeled Cetuximab-F(ab')2

    NARCIS (Netherlands)

    Dijk, L.K. van; Hoeben, B.A.W.; Kaanders, J.H.A.M.; Franssen, G.M.; Boerman, O.C.; Bussink, J.

    2013-01-01

    Combined treatment of advanced head and neck squamous cell carcinomas (HNSCC) with radiotherapy and the epidermal growth factor receptor (EGFR) inhibitor cetuximab improves clinical outcome in comparison to radiotherapy alone but is effective only in a few cases. To select those patients most likely

  1. Radiotherapy plus cetuximab for the squamous cells carcinoma of head and neck

    International Nuclear Information System (INIS)

    Bonner, James A.; Harari, Paul M.; Giralt, Jordi; Azarnia, Nozar; Shin, Dong M.; Cohen, Roger B.; Jones, Cristopher U.; Sur, Ranjan; Raben, David; Jassem, Jacek; Ove, Roger; Kies, Merrill S.; Baselga, Jose; Youssoufian, Hagop; Amellal, Nadia; Rowinsky, Eric K.; Ang, K. Kian

    2006-01-01

    A multinational randomized study was realized, to compare radiotherapy alone with radiotherapy combined with cetuximab, a monoclonal antibody against the receiver epidermal growth factor in the treatment of squamous cell carcinoma of head and neck locally advanced [es

  2. Late Toxicities after Conventional Radiotherapy for Nasopharyngeal Carcinoma: Incidence and Risk Factors

    International Nuclear Information System (INIS)

    Siala, W.; Mnejja, W.; Elloumi, F.; Daoud, J.; Ghorbel, A.; Mnif, J.; Frikha, M.

    2014-01-01

    Background. To determine the incidence and analyze the factors affecting late toxicity for nasopharyngeal carcinoma patients treated with conventional radiotherapy. Patients and Methods. Retrospective analysis was performed on 239 NPC patients treated between 1993 and 2004 in our institution. One hundred and fifty-seven patients were treated with conventional fractionation (2 Gy per fraction, 5 fractions per week) and eighty-two patients with hyperfractionated radiotherapy (1.6 Gy per fraction twice a day, 5 days per week). One hundred fifty nine patients underwent neoadjuvant cisplatin based chemotherapy. Late toxicity was evaluated according to the RTOG/EORTC score. Results. Xerostomia was the most common related complication (98.7%). Neoadjuvant chemotherapy and hyperfractionated radiotherapy did not increase late toxicities. Multivariate analyses showed that radiation dose was a significant factor for hearing impairment, younger age for trismus, initial node status for neck fibrosis, and initial dental hygiene for dental complications. Female gender was associated with significantly higher incidence of trismus and hearing impairment. Conclusion. Conventional radiotherapy was associated with a high rate of late toxicities which affect patients’ quality of life. With the development of three-dimensional conformal radiotherapy and intensity modulated radiotherapy, a reduced incidence of radiation related complications could be expected.

  3. Factors influencing the parotid function in nasopharyngeal carcinoma treated with parotid-sparing radiotherapy

    International Nuclear Information System (INIS)

    Liu Wenshan; Lee Jongkang; Su Maochang; Lee, S.P.; Chen Ginden; Lee Hongshen; Lee Huei

    2006-01-01

    The background of this study was to evaluate the factors influencing post-irradiation parotid gland function in nasopharyngeal cancer treated with parotid-sparing radiotherapy. This study consisted of 45 patients with nasopharyngeal cancer treated with radiotherapy including 3D conformal radiotherapy, intensity-modulated radiotherapy and high-dose-rate brachytherapy. The mean follow-up time was 37.5 months (range: 15-50 months). Objective parotid gland function was assessed by series sialoscintigraphy pre-irradiation and post-irradiation at 1, 6, 12 and 18 months. Subjective salivary function was recorded by the LENT/SOMA system. Wilcoxon signed-rank test was used to compare the secretion ratio (SR) of parotid gland before and after treatment. Mann-Whitney rank-sum test was used to determine the factors influencing the post-irradiated SR. Chi-square test was used to compare the correlation between subjective grading of xerostomia and objective grading of parotid glands. There was a significant difference between the pre-irradiation and post-irradiation parotid gland's SR at 1 (0.30 versus 0.01, P 0.05) and 18 months (0.30 versus 0.18, P>0.05). There was significant correlation between subjective and objective salivary function (P=0.024) at 12 months after radiotherapy. The factor that impacted the preservation of parotid function was mean dose to the parotid gland >38.0 Gy (P<0.05). Our results demonstrated that parotid function could recover 1 year after treatment with parotid-sparing radiotherapy in patients with nasopharyngeal cancer. The most important factor that influenced parotid function was the mean dose to the parotid gland. (author)

  4. Erythropoietin and radiotherapy; Erythropoietine et radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Le Fur, E.; Albarghach, M.N.; Pradier, O. [CHU de Morvan, Dept. de radiotherapie, 29 - Brest (France)

    2010-01-15

    Erythropoietin (E.P.O.) is a glycoprotein hormone. This hormone is a growth factor for red blood cells precursors in the bone marrow. The decrease of oxygen partial pressure, a reduced number of erythrocytes caused by bleeding or excessive destruction, or increased tissues oxygen requirements lead to increased secretion of E.P.O.. Its action takes place on bone marrow erythroblastic cells through specific receptors. E.P.O. stimulates the proliferation of red cell precursors stem cells in the bone marrow, thus increasing their production in one to two weeks. The effectiveness of E.P.O. at increasing haemoglobin and improving patients quality of life has been demonstrated by several studies. However, its use in radiotherapy remains controversial. While tumour hypoxia caused by anaemia is a factor of radio resistance and thus a source of local failure, tumour expression of E.P.O. receptors presents a significant risk for tumour progression and neo-angiogenesis, which would be increased during the administration of E.P.O.. The purpose of this article is to answer the question: is there a place for E.P.O. in combination with radiotherapy in the management of cancer?

  5. Severe skin reaction secondary to concomitant radiotherapy plus cetuximab

    International Nuclear Information System (INIS)

    Berger, Bernhard; Belka, Claus

    2008-01-01

    The therapeutic use of monoclonal antibodies against the epidermal growth factor receptor (EGFR) is specifically associated with dermatologic reactions of variable severity. Recent evidence suggests superiority of the EGFR inhibitor (EGFRI) cetuximab plus radiotherapy compared to radiotherapy alone in patients with squamous cell carcinoma of the head and neck. Although not documented in a study population, several reports indicate a possible overlap between radiation dermatitis and the EGFRI-induced skin rash. We here present a case of severe skin reaction secondary to the addition of cetuximab to radiotherapy

  6. Factors influencing time between surgery and radiotherapy : A population based study of breast cancer patients

    NARCIS (Netherlands)

    Katik, S.; Gort, M.; Jobsen, Jan J.; Maduro, John H.; Struikmans, H.; Siesling, S.

    2015-01-01

    This study describes variation in the time interval between surgery and radiotherapy in breast cancer (BC) patients and assesses factors at patient, hospital and radiotherapy centre (RTC) level influencing this variation. To do so, the factors were investigated in BC patients using multilevel

  7. An investigation of anxiety about radiotherapy deploying the radiotherapy categorical anxiety scale

    International Nuclear Information System (INIS)

    Shimotsu, Sakie; Karasawa, Kumiko; Ito, Kana; Saito, Anneyuko I.; Izawa, Hiromi; Kawase, Eri; Horikawa, Naoshi

    2010-01-01

    Radiotherapy is one of the major methods for treating cancer, but many patients undergoing radiotherapy have deep concerns about receiving radiation treatment. This problem is not generally appreciated and has not been adequately studied. The objective of this investigation was to empirically investigate the anxieties that cancer patients feel towards radiotherapy by using questionnaires to classify and quantitatively measure their concerns. A preliminary interview to develop a questionnaire was carried out with 48 patients receiving radiotherapy to discover their anxieties about on-going treatments. Subsequently, a main study was performed using a questionnaire with 185 patients to classify their types of anxiety and to ascertain the reliability and validity of the responses. Confirmatory factor analysis was then carried out with a 17-item Radiotherapy Categorical Anxiety Scale. Three anxiety factors were abstracted by factor analysis: adverse effects of radiotherapy, environment of radiotherapy, and treatment effects of radiotherapy. Reliability, content validity, and concurrent validity were obtained. The adequacy of the three-factor model of anxiety concerning radiotherapy was confirmed. A 17-item Radiotherapy Categorical Anxiety Scale was formulated to quantitatively measure the specific types of anxiety among cancer patients receiving radiotherapy. (author)

  8. Transforming growth factor alpha, Shope fibroma growth factor, and vaccinia growth factor can replace myxoma growth factor in the induction of myxomatosis in rabbits.

    Science.gov (United States)

    Opgenorth, A; Nation, N; Graham, K; McFadden, G

    1993-02-01

    The epidermal growth factor (EGF) homologues encoded by vaccinia virus, myxoma virus, and malignant rabbit fibroma virus have been shown to contribute to the pathogenicity of virus infection upon inoculation of susceptible hosts. However, since the primary structures of these growth factors and the disease profiles induced by different poxvirus genera vary substantially, the degree to which the various EGF homologues perform similar roles in viral pathogenesis remains unclear. In order to determine whether different EGF-like growth factors can perform qualitatively similar functions in the induction of myxomatosis in rabbits, we created recombinant myxoma virus variants in which the native growth factor, myxoma growth factor (MGF), was disrupted and replaced with either vaccinia virus growth factor, Shope fibroma growth factor, or rat transforming growth factor alpha. Unlike the control virus containing an inactivated MGF gene, which caused marked attenuation of the disease syndrome and substantially less proliferation of the epithelial cell layers in the conjunctiva and respiratory tract, the recombinant myxoma virus strains expressing heterologous growth factors produced infections which were both clinically and histopathologically indistinguishable from wild-type myxomatosis. We conclude that these poxviral and cellular EGF-like growth factors, which are diverse with respect to primary structure and origin, have similar biological functions in the context of myxoma virus pathogenesis and are mitogenic for the same target cells.

  9. Risk factors for radiotherapy incidents and impact of an online electronic reporting system

    International Nuclear Information System (INIS)

    Chang, David W.; Cheetham, Lynn; Marvelde, Luc te; Bressel, Mathias; Kron, Tomas; Gill, Suki; Tai, Keen Hun; Ball, David; Rose, William; Silva, Linas; Foroudi, Farshad

    2014-01-01

    Background and purpose: To ascertain the rate, type, significance, trends and the potential risk factors associated with radiotherapy incidents in a large academic department. Materials and methods: Data for all radiotherapy activities from July 2001 to January 2011 were reviewed from radiotherapy incident reporting forms. Patient and treatment data were obtained from the radiotherapy record and verification database (MOSAIQ) and the patient database (HOSPRO). Logistic regression analyses were performed to determine variables associated with radiotherapy incidents. Results: In that time, 65,376 courses of radiotherapy were delivered with a reported incident rate of 2.64 per 100 courses. The rate of incidents per course increased (1.96 per 100 courses to 3.52 per 100 courses, p < 0.001) whereas the proportion of reported incidents resulting in >5% deviation in dose (10.50 to 2.75%, p < 0.001) had decreased after the introduction of an online electronic reporting system. The following variables were associated with an increased rate of incidents: afternoon treatment time, paediatric patients, males, inpatients, palliative plans, head-and-neck, skin, sarcoma and haematological malignancies. In general, complex plans were associated with higher incidence rates. Conclusion: Radiotherapy incidents were infrequent and most did not result in significant dose deviation. A number of risk factors were identified and these could be used to highlight high-risk cases in the future. Introduction of an online electronic reporting system resulted in a significant increase in the number of incidents being reported

  10. A protective role for keratinocyte growth factor in a murine model of chemotherapy and radiotherapy-induced mucositis

    International Nuclear Information System (INIS)

    Borges, Luis; Rex, Karen L.; Chen, Jennifer N.; Wei, Ping; Kaufman, Stephen; Scully, Sheila; Pretorius, James K.; Farrell, Catherine L.

    2006-01-01

    Purpose: To evaluate the activity of palifermin (rHuKGF) in a murine model of mucosal damage induced by a radiotherapy/chemotherapy (RT/CT) regimen mimicking treatment protocols used in head-and-neck cancer patients. Methods and Materials: A model of mucosal damage induced by RT/CT was established by injecting female BDF1 mice with cisplatin (10 mg/kg) on Day 1; 5-fluorouracil (40 mg/kg/day) on Days 1-4, and irradiation (5 Gy/day) to the head and neck on Days 1-5. Palifermin was administered subcutaneously on Days -2 to 0 (5 mg/kg/day) and on Day 5 (5 mg/kg). Evaluations included body weight, organ weight, keratinocyte growth factor receptor expression, epithelial thickness, and cellular proliferation. Results: Initiation of the radiochemotherapeutic regimen resulted in a reduction in body weight in control animals. Palifermin administration suppressed weight loss and resulted in increased organ weight (salivary glands and small intestine), epithelial thickness (esophagus and tongue), and cellular proliferation (tongue and salivary glands). Conclusions: Administration of palifermin before RT/CT promotes cell proliferation and increases in epithelial thickness in the oral mucosa, salivary glands, and digestive tract. Palifermin administration before and after RT/CT mitigates weight loss and a trophic effect on the intestinal mucosa and salivary glands, suggesting that palifermin use should be investigated further in the RT/CT settings, in which intestinal mucositis and salivary gland dysfunction are predominant side effects of cytotoxic therapy

  11. Epidermal growth factor and insulin-like growth factor I upregulate the expression of the epidermal growth factor system in rat liver

    DEFF Research Database (Denmark)

    Bor, M V; Sørensen, B S; Vinter-Jensen, L

    2000-01-01

    BACKGROUND/AIM: Both epidermal growth factor and insulin-like growth factor I play a role in connection with the liver. In the present study, the possible interaction of these two growth factor systems was studied by investigating the effect of epidermal growth factor or insulin-like growth factor...... I treatment on the expression of the epidermal growth factor receptor, and its activating ligands, transforming growth factor-alpha and epidermal growth factor. METHODS: Fifty-five male rats received no treatment, human recombinant epidermal growth factor or human recombinant insulin-like growth.......8+/-1.6 fmol/mg protein epidermal growth factor and 144+/-22 fmol/mg protein transforming growth factor-alpha. Both epidermal growth factor and insulin-like growth factor I treatment increased the expression of mRNA for transforming growth factor-alpha and epidermal growth factor receptor, as well...

  12. Factors that affect the accuracy in the precise radiotherapy for abdomen tumors

    International Nuclear Information System (INIS)

    Yang Tieming; Ju Yongjian

    2008-01-01

    The precise radiotherapy has been widely used in the clinics. But there are many factors that affect the accuracy in the course of implementation. Finally the effect of radiotherapy is affected. These factors are reviewed. And the previous research data about the abdomen tumors is summed up. Also how the accuracy was affected by the respiratory movement, positioning, position fixed technology, weight, retraction and motion of the tumor and the situation of surrounding organs will be analyzed. At last, how to avoid these errors in clinics will be discussed. (authors)

  13. Dosimetry, clinical factors and medication intake influencing urinary symptoms after prostate radiotherapy: An analysis of data from the RADAR prostate radiotherapy trial

    International Nuclear Information System (INIS)

    Yahya, Noorazrul; Ebert, Martin A.; Bulsara, Max; Haworth, Annette; Kennedy, Angel; Joseph, David J.; Denham, Jim W.

    2015-01-01

    Purpose/objective: To identify dosimetry, clinical factors and medication intake impacting urinary symptoms after prostate radiotherapy. Material and methods: Data describing clinical factors and bladder dosimetry (reduced with principal component (PC) analysis) for 754 patients treated with external beam radiotherapy accrued by TROG 03.04 RADAR prostate radiotherapy trial were available for analysis. Urinary symptoms (frequency, incontinence, dysuria and haematuria) were prospectively assessed using LENT-SOMA to a median of 72 months. The endpoints assessed were prevalence (grade ⩾1) at the end of radiotherapy (representing acute symptoms), at 18-, 36- and 54-month follow-ups (representing late symptoms) and peak late incidence including only grade ⩾2. Impact of factors was assessed using multivariate logistic regression models with correction for over-optimism. Results: Baseline symptoms, non-insulin dependent diabetes mellitus, age and PC1 (correlated to the mean dose) impact symptoms at >1 timepoints. Associations at a single timepoint were found for cerebrovascular condition, ECOG status and non-steroidal anti-inflammatory drug intake. Peak incidence analysis shows the impact of baseline, bowel and cerebrovascular condition and smoking status. Conclusions: The prevalence and incidence analysis provide a complementary view for urinary symptom prediction. Sustained impacts across time points were found for several factors while some associations were not repeated at different time points suggesting poorer or transient impact

  14. Factors influencing conformity index in radiotherapy for non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Brennan, Sinead M

    2010-01-01

    The radiotherapy conformity index (CI) is a useful tool to quantitatively assess the quality of radiotherapy treatment plans, and represents the relationship between isodose distributions and target volume. A conformity index of unity implies high planning target volume (PTV) coverage and minimal unnecessary irradiation of surrounding tissues. We performed this analysis to describe the CI for lung cancer 3-dimensional conformal radiotherapy (3DCRT) and to identify clinical and technical determinants of CI, as it is not known which factors are associated with good quality 3D conformal radiotherapy treatment planning. Radiotherapy treatment plans from a database of 52 patients with inoperable Stage 1 to 3b lung cancer, on a hypofractionated 3DCRT trial were evaluated. A CI was calculated for all plans using the definition of the ICRU 62:CI = (TV\\/PTV), which is the quotient of the treated volume (TV) and the PTV. Data on patient, tumor, and planning variables, which could influence CI, were recorded and analyzed. Mean CI was 2.01 (range = 1.06-3.8). On univariate analysis, PTV (p = 0.023), number of beams (p = 0.036), medial vs. lateral tumor location (p = 0.016), and increasing tumor stage (p = 0.041) were associated with improved conformity. On multiple regression analysis, factors found to be associated with CI included central vs. peripheral tumor location (p = 0.041) and PTV size (p = 0.058). The term 3DCRT is used routinely in the literature, without any indication of the degree of conformality. We recommend routine reporting of conformity indices. Conformity indices may be affected by both planning variables and tumor factors.

  15. The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Hua; Yang, Ying-Hua [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Binmadi, Nada O. [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Department of Oral Basic and Clinical Sciences, King Abdulaziz University, Jeddah 21589 (Saudi Arabia); Proia, Patrizia [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Department of Sports Science (DISMOT), University of Palermo, Via Eleonora Duse 2 90146, Palermo (Italy); Basile, John R., E-mail: jbasile@umaryland.edu [Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650W. Baltimore Street, 7-North, Baltimore, MD 21201 (United States); Greenebaum Cancer Center, 22S. Greene Street, Baltimore, MD 21201 (United States)

    2012-08-15

    Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors. -- Highlights: Black-Right-Pointing-Pointer Similar to VEGF, SEMA4D promotes angiogenesis in vitro and in vivo. Black-Right-Pointing-Pointer Both VEGF and SEMA4D are produced by OSCC cells in a HIF-dependent manner. Black-Right-Pointing-Pointer These factors combine to elicit a robust pro-angiogenic phenotype in OSCC. Black-Right-Pointing-Pointer Anti-SEMA4D

  16. The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Zhou, Hua; Yang, Ying-Hua; Binmadi, Nada O.; Proia, Patrizia; Basile, John R.

    2012-01-01

    Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors. -- Highlights: ► Similar to VEGF, SEMA4D promotes angiogenesis in vitro and in vivo. ► Both VEGF and SEMA4D are produced by OSCC cells in a HIF-dependent manner. ► These factors combine to elicit a robust pro-angiogenic phenotype in OSCC. ► Anti-SEMA4D blocking antibody inhibits Plexin-B1 activation. ► SEMA4D is a valid anti-angiogenic target in the

  17. Experimental radiotherapy and clinical radiobiology. Vol. 20. Proceedings; Experimentelle Strahlentherapie und Klinische Strahlenbiologie. Bd. 20. Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, Michael; Dahm-Daphi, Jochen; Dikomey, Ekkehard; Petersen, Cordula; Rodemannn, Hans-Peter; Zips, Daniel (eds.)

    2011-07-01

    The proceedings include contributions on the following issues: laser driven proton accelerators on the way for radiotherapy, radiobiological evaluation of new radiations; molecular factors of radiation response; biological targeting; EGFR epidermal growth factor receptor/targeting - combined internal and external irradiation, radiobiology of normal tissues; dose-volume histograms for the radiotherapy: curves without radiobiological relevance or important information for the therapy planning; HPV (human papilloma virus) and radiation sensitivity of HNSCC (head and neck squamous cell carcinomas): evidence, radiobiological mechanism, clinical consequences and perspectives; mechanisms of action and intertumoral heterogeneity of response to EGFR inhibition in radiotherapy of solid tumors; evaluation of biomarkers for radiotherapy.

  18. Radioactive EGFR Antibody Cetuximab in Multimodal Cancer Treatment: Stability and Synergistic Effects With Radiotherapy

    International Nuclear Information System (INIS)

    Rades, Dirk; Wolff, Christian; Nadrowitz, Roger; Breunig, Christian; Schild, Steven E.; Baehre, Manfred; Meller, Birgit

    2009-01-01

    Purpose: Systemic therapies when added to whole brain radiotherapy have failed to improve the survival of patients with multiple brain metastases. The epidermal growth factor receptor antibody cetuximab is an attractive option, if it is able to cross the blood-brain barrier. This might be proven with molecular imaging if the radiolabeled antibody is stable long enough to be effective. This study investigated the stability of radiolabeled cetuximab (Erbitux) ( 131 I-Erbi) and potential synergistic effects with radiotherapy in vitro. Methods and Materials: Two cell lines were investigated, A431 with numerous epidermal growth factor receptors, and JIMT without epidermal growth factor receptors. We labeled 0.4 mg cetuximab with 50 MBq of [ 131 I] iodide. Stability was determined for 72 h. The cell cultures were incubated with 131 I-Erbi or cold cetuximab for 72 h. Uptake and cell proliferation were measured every 24 h after no radiotherapy or irradiation with 2, 4, or 10 Gy. Results: The radiolabeling yield of 131 I-Erbi was always >80%. The radiochemical purity was still 93.6% after 72 h. A431 cells showed a 131 I-Erbi uptake about 100-fold greater than the JIMT controls. After 48 h, the A431 cultures showed significantly decreased proliferation. At 72 h after irradiation, 131 I-Erbi resulted in more pronounced inhibition of cell proliferation than the cold antibody in all radiation dose groups. Conclusion: 131 I-Erbi was stable for ≤72 h. Radiotherapy led to increased tumor cell uptake of 131 I-Erbi. Radiotherapy and 131 I-Erbi synergistically inhibited tumor cell proliferation. These results provide the prerequisite data for a planned in vivo study of whole brain radiotherapy plus cetuximab for brain metastases.

  19. Transforming growth factor-β1/Smad/connective tissue growth factor axis: The main pathway in radiation-induced fibrosis of osteoradionecrosis?

    Directory of Open Access Journals (Sweden)

    Qian Wei Zhuang

    2013-01-01

    Full Text Available Introduction: Osteoradionecrosis (ORN of the mandible is a serious complication following radiation therapy for malignancies of the head and neck. Radiation-induced fibrosis (RIF is a new theory that accounts for the damage to normal tissues after radiotherapy, and the radiation-induced fibroatrophic mechanism includes the free-radical formation, endothelial dysfunction, inflammation, microvascular thrombosis, fibrosis and remodeling, and finally bone and tissue necrosis. The Hypothesis: Previous studies revealed that transforming growth factor-β1 (TGF-β1 is the master switch cytokine responsible for the regulation of fibroblast proliferation and differentiation that result in RIF. Among the targets of TGF-β1, connective tissue growth factor (CTGF is a downstream mediator through the Smad3/4 pathway and plays an important role in connective tissue homeostasis and fibroblast proliferation. Studies have proved that the TGF-β1/Smad/CTGF signaling pathway is involved in the RIF of soft tissues, so the authors put forward a hypothesis that the TGF-β1/Smad/CTGF axis is also the main pathway in RIF of ORN. Evaluation of the Hypothesis: The validation of our hypothesis may provide new insights for better understanding the pathogenesis of ORN and open new perspectives for anti-fibrotic therapies, and pioneer novel approaches to treat ORN.

  20. Factors implicated to radioresistance of breast cancer and their possible roles

    International Nuclear Information System (INIS)

    Yan Weili; Huang Gang

    2006-01-01

    Radiotherapy plays an important role in the management of breast cancer. The recurrence of breast cancer after radiotherapy is considered to be related with radioresistance in breast cancer cells. Various factors, extranuclear and intranuclear, such as insulin-like growth factor-1 receptor, phosphatidylinositol 3-kinase pathway, epidermal growth factor, human epidermal growth factor receptors, p53, c-erb B2, Bcl-2, BRCA1, BRCA2, telomeres and gene expression signature, that have been implicated to influence the radiation response. (authors)

  1. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    International Nuclear Information System (INIS)

    Hua Chiaho; Wu Shengjie; Chemaitilly, Wassim; Lukose, Renin C.; Merchant, Thomas E.

    2012-01-01

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test ≥7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  2. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu Shengjie [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Chemaitilly, Wassim [Division of Endocrinology, Department of Pediatric Medicine, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Lukose, Renin C.; Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  3. Clinical Studies on conformal radiotherapy combined with epidermal ...

    African Journals Online (AJOL)

    Purpose: To study the effect of conformal radiotherapy combined with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in the second-line treatment of non-small cell lung cancer (NSCLC). Methods: A total of 316 patients attending Shanghai Pulmonary Hospital affiliated to Tongji University, were divided ...

  4. Prognostic factors, patterns of recurrence and toxicity for patients with esophageal cancer undergoing definitive radiotherapy or chemo-radiotherapy

    International Nuclear Information System (INIS)

    Haefner, Matthias F.; Lang, Kristin; Krug, David; Koerber, Stefan A.; Debus, Juergen; Sterzing, Florian; Uhlmann, Lorenz; Kieser, Meinhard

    2015-01-01

    The aim of this study was to evaluate the effectiveness and tolerability of definitive chemo-radiation or radiotherapy alone in patients with esophageal cancer. We retrospectively analyzed the medical records of n = 238 patients with squamous cell carcinoma or adenocarcinoma of the esophagus treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2000 and 2012. Patients of all stages were included to represent actual clinical routine. We performed univariate and multivariate analysis to identify prognostic factors for overall survival (OS) and progression-free survival (PFS). Moreover, treatment-related toxicity and patterns of recurrence were assessed. Patients received either chemo-radiation (64%), radiotherapy plus cetuximab (10%) or radiotherapy alone (26%). In 69%, a boost was applied, resulting in a median cumulative dose of 55.8 Gy; the remaining 31% received a median total dose of 50 Gy. For the entire cohort, the median OS and PFS were 15.0 and 11.0 months, respectively. In multivariate analysis, important prognostic factors for OS and PFS were T stage (OS: P = 0.005; PFS: P = 0.006), M stage (OS: P = 0.015; PFS: P = 0.003), concomitant chemotherapy (P < 0.001) and radiation doses of >55 Gy (OS: P = 0.019; PFS: P = 0.022). Recurrences occurred predominantly as local in-field relapse or distant metastases. Toxicity was dominated by nutritional impairment (12.6% with G3/4 dysphagia) and chemo-associated side effects. Definitive chemo-radiation in patients with esophageal cancer results in survival rates comparable with surgical treatment approaches. However, local and distant recurrence considerably restrict prognosis. Further advances in radio-oncological treatment strategies are necessary for improving outcome. (author)

  5. Classical prognostic factors in patients with non-advanced endometrial cancer treated with postoperative radiotherapy

    International Nuclear Information System (INIS)

    Karolewski, K.; Kojs, Z.; Jakubowicz, J.; Urbanski, K.; Michalak, A.

    2006-01-01

    Aim: Analysis of classical prognostic factors in patients with non-advanced endometrial cancer treated with postoperative radiotherapy. Materials/Methods: In the years 1985 - 1999, 705 patients underwent postoperative radiotherapy due to endometrial cancer: 529 patients with FIGO stage I and 176 with FIGO stage II cancer. Mean age was 58 years. In 96% of patients endometrioid adenocarcinoma was found. In 49.9% the cancer had a high, in 27.9% a medium, and in 22.2% a low degree of differentiation. Results: 82% of patients had 5-year disease-free survival. In univariate analysis a significantly higher rate of disease-free survival was observed in: patients younger than 60, with moderately and well differentiated cancers, with stage I endometrioid adenocarcinoma with less than 50% myometrial invasion. In multivariate analysis degree of cancer differentiation was the only independent prognostic factor. Conclusions: In a group of patients with non-advanced endometrial cancer treated with postoperative radiotherapy, degree of cancer differentiation is the primary prognostic factor. (authors)

  6. Radiotherapy

    Directory of Open Access Journals (Sweden)

    Rema Jyothirmayi

    1999-01-01

    Full Text Available Purpose. Conservative treatment in the form of limited surgery and post-operative radiotherapy is controversial in hand and foot sarcomas, both due to poor radiation tolerance of the palm and sole, and due to technical difficulties in achieving adequate margins.This paper describes the local control and survival of 41 patients with soft tissue sarcoma of the hand or foot treated with conservative surgery and radiotherapy. The acute and late toxicity of megavoltage radiotherapy to the hand and foot are described. The technical issues and details of treatment delivery are discussed. The factors influencing local control after radiotherapy are analysed.

  7. Erythropoietin and radiotherapy

    International Nuclear Information System (INIS)

    Le Fur, E.; Albarghach, M.N.; Pradier, O.

    2010-01-01

    Erythropoietin (E.P.O.) is a glycoprotein hormone. This hormone is a growth factor for red blood cells precursors in the bone marrow. The decrease of oxygen partial pressure, a reduced number of erythrocytes caused by bleeding or excessive destruction, or increased tissues oxygen requirements lead to increased secretion of E.P.O.. Its action takes place on bone marrow erythroblastic cells through specific receptors. E.P.O. stimulates the proliferation of red cell precursors stem cells in the bone marrow, thus increasing their production in one to two weeks. The effectiveness of E.P.O. at increasing haemoglobin and improving patients quality of life has been demonstrated by several studies. However, its use in radiotherapy remains controversial. While tumour hypoxia caused by anaemia is a factor of radio resistance and thus a source of local failure, tumour expression of E.P.O. receptors presents a significant risk for tumour progression and neo-angiogenesis, which would be increased during the administration of E.P.O.. The purpose of this article is to answer the question: is there a place for E.P.O. in combination with radiotherapy in the management of cancer?

  8. Correlation factor analysis between radiation pneumonitis and chemo-radiotherapy in breast cancer patients

    International Nuclear Information System (INIS)

    Li Huiping; Wang Junjie; Ma Liwen; Zhang Shulan; Deng Huijing; Jia Tingzhen

    2004-01-01

    Objective: To investigate the relationship between radiotherapy-induced lung injury and chemotherapy agents as well as other factors. Methods: A total of 85 breast cancer patients received radiotherapy with sequential or concurrent chemotherapy after surgery were analysed for radiation dose, chemotherapy schedule, age, and lung disease history. Results: Five patients had clinical symptoms of radiation pneumonitis, one of them was necessary to treat and 16 patients developed radiological changes (18.8%). Close relationship was noted between incidence of radiation pneumonitis and radiation dose, timing and drugs used in chemotherapy and lung disease history. Conclusion: High irradiation dose, concurrent chemotherapy, and lung disease history can increase the rate of radiotherapy-induced pulmonary injury in breast cancer patients. (authors)

  9. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

    Science.gov (United States)

    Gaviglio, Angela L; Knelson, Erik H; Blobe, Gerard C

    2017-05-01

    High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.-Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. © FASEB.

  10. The role of radiotherapy in the management of POEMS syndrome.

    Science.gov (United States)

    Suh, Yang-Gun; Kim, Young-Suk; Suh, Chang-Ok; Kim, Yu Ri; Cheong, June-Won; Kim, Jin Seok; Cho, Jaeho

    2014-11-28

    POEMS syndrome is a paraneoplastic syndrome caused by an underlying plasma cell proliferative disease. In this study, we examined the treatment outcomes and role of radiotherapy in the management of POEMS syndrome. In total, 33 patients diagnosed with POEMS syndrome were analyzed. These patients presented with osteosclerotic myeloma (OSM, n = 13), Castleman's disease (CD, n = 4), OSM with CD (n = 10), and vascular endothelial growth factor elevation without gross lesions (VEGFe, n = 6), respectively. The patients were treated by radiotherapy alone (n = 4), chemotherapy alone (n = 16), or a combination thereof (n = 9). The clinical response rates of radiotherapy, chemotherapy, and radiotherapy plus chemotherapy were 75%, 69%, and 89%, respectively. In addition, the hematologic response rates were 50%, 69%, and 71%, respectively. Among the six patients with limited multiple lesions who underwent radiotherapy, the clinical symptoms were improved in five patients after radiotherapy. The median progression-free survival (PFS) was 51 months, and the median overall survival (OS) was 65 months. In univariate analysis, the administration of chemotherapy was significantly associated with better PFS (p = 0.007) and OS (p = 0.020). In contrast, underlying VEGFe was a significant factor worsening PFS (p = 0.035) and OS (p = 0.008). Radiotherapy produces a reliable clinical response and is effective in improving POEMS-associated symptoms that are refractory to chemotherapy in selected patients with clustered or limited multiple lesions that can be covered by single radiation field.

  11. The role of radiotherapy in the management of POEMS syndrome

    International Nuclear Information System (INIS)

    Suh, Yang-Gun; Kim, Young-Suk; Suh, Chang-Ok; Kim, Yu Ri; Cheong, June-Won; Kim, Jin Seok; Cho, Jaeho

    2014-01-01

    POEMS syndrome is a paraneoplastic syndrome caused by an underlying plasma cell proliferative disease. In this study, we examined the treatment outcomes and role of radiotherapy in the management of POEMS syndrome. In total, 33 patients diagnosed with POEMS syndrome were analyzed. These patients presented with osteosclerotic myeloma (OSM, n = 13), Castleman’s disease (CD, n = 4), OSM with CD (n = 10), and vascular endothelial growth factor elevation without gross lesions (VEGFe, n = 6), respectively. The patients were treated by radiotherapy alone (n = 4), chemotherapy alone (n = 16), or a combination thereof (n = 9). The clinical response rates of radiotherapy, chemotherapy, and radiotherapy plus chemotherapy were 75%, 69%, and 89%, respectively. In addition, the hematologic response rates were 50%, 69%, and 71%, respectively. Among the six patients with limited multiple lesions who underwent radiotherapy, the clinical symptoms were improved in five patients after radiotherapy. The median progression-free survival (PFS) was 51 months, and the median overall survival (OS) was 65 months. In univariate analysis, the administration of chemotherapy was significantly associated with better PFS (p = 0.007) and OS (p = 0.020). In contrast, underlying VEGFe was a significant factor worsening PFS (p = 0.035) and OS (p = 0.008). Radiotherapy produces a reliable clinical response and is effective in improving POEMS-associated symptoms that are refractory to chemotherapy in selected patients with clustered or limited multiple lesions that can be covered by single radiation field

  12. Prognostic factors in the treatment of locally advanced hepatocellular carcinoma with radiotherapy and arterial infusion

    International Nuclear Information System (INIS)

    Wang, Y.; Jin, Y.; Zhang, Z.

    2000-01-01

    Prognostic factors in the treatment of local advanced hepatocellular carcinoma with radiotherapy, transcatheter arterial embolization and arterial infusion. The treatment effects of radiotherapy and combination modality therapy for the local advanced hepatocellular carcinoma (HCC) were retrospectively reviewed. Three hundred and fifty-six patients of HCC (187 recurrent cases after surgical resection) were treated by: radiotherapy only ; bi-therapeutic method: hepatic artery ligation (HAL) and/or hepatic artery embolization (HAE) plus radiotherapy; and tri-therapeutic method (bi-therapeutic method plus hepatic artery infusion) from 1975 to 1996. Kaplan-Meier method has been used to evaluate the survival rates. There were no significant differences among these three treatment groups in the symptom relied rate, but the mean relief time period was much shorter in radiotherapy alone group (2.5 vs 44 months, P 0.05). There were evident differences in five-year survivals among these three treatment groups: 0 % for radiotherapy alone, 22.8 % for bi-therapeutic method and 38.8 % for tri-therapeutic method (P < 0.01). The prognosis was influenced by Okuda classification. Non-resectable local advanced HCC can be treated by the combination modality therapy, including radiotherapy, with a quite high cure rate. Radiotherapy alone can relief the symptoms. (authors)

  13. Risk factors predicting the outcome of salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy

    International Nuclear Information System (INIS)

    Kinoshita, Hidefumi; Shimizu, Yosuke; Mizowaki, Takashi

    2013-01-01

    Salvage radiotherapy is the only curative treatment for patients with prostate cancer showing biochemical progression after radical prostatectomy. In this study, we evaluated the clinicopathological parameters that influence the outcome of salvage radiotherapy. Medical records of 49 patients who underwent salvage radiotherapy after radical prostatectomy from 1997 to 2008 at the Graduate School of Medicine, Kyoto University, were retrospectively reviewed. Radiotherapy was carried out with 66 Gy on the prostatic bed. Biochemical progression-free survival after salvage radiotherapy at 2, 5 and 7 years was 51.0%, 42.2% and 42.2%, respectively. Significant parameters predicting biochemical progression after salvage radiotherapy by Cox regression analysis were prostatectomy Gleason score sum ≥8 (hazard ratio 0.08; 95% confidence interval 0.03-0.22; P=0.001), prostate-specific antigen nadir after radical prostatectomy ≥0.04 ng/mL (hazard ratio 0.30; 95% confidence interval 0.13-0.69; P=0.005) and negative surgical margin (hazard ratio 0.28; 95% confidence interval 0.12-0.70; P=0.006). When the patients were subgrouped by these risk factors, the 5-year progression-free survival rates after salvage radiotherapy were 77.8%, 50.0% and 6.7% in patients with 0, 1 and ≥2 predictors, respectively. In order to discriminate favorable candidates for salvage radiotherapy, Gleason score of prostatectomy, prostate-specific antigen nadir after prostatectomy and positive surgical margin represent independent predictors. Thus, progression-free survival might be more precisely predicted according to the presence/absence of these risk factors. The significance of this risk classification should be confirmed by large prospective studies. (author)

  14. Nuclear medicine imaging to predict response to radiotherapy: a review

    International Nuclear Information System (INIS)

    Wiele, Christophe van de; Lahorte, Christophe; Oyen, Wim; Boerman, Otto; Goethals, Ingeborg; Slegers, Guido; Dierckx, Rudi Andre

    2003-01-01

    Purpose: To review available literature on positron emission tomography (PET) and single photon emission computerized tomography (SPECT) for the measurement of tumor metabolism, hypoxia, growth factor receptor expression, and apoptosis as predictors of response to radiotherapy. Methods and Materials: Medical literature databases (Pubmed, Medline) were screened for available literature and critically analyzed as to their scientific relevance. Results: Studies on 18 F-fluorodeoxyglucose PET as a predictor of response to radiotherapy in head-and-neck carcinoma are promising but need confirmation in larger series. 18 F-fluorothymine is stable in human plasma, and preliminary clinical data obtained with this marker of tumor cell proliferation are promising. For imaging tumor hypoxia, novel, more widely available radiopharmaceuticals with faster pharmacokinetics are mandatory. Imaging of ongoing apoptosis and growth factor expression is at a very early stage, but results obtained in other domains with radiolabeled peptides appear promising. Finally, for most of the tracers discussed, validation against a gold standard is needed. Conclusion: Optimization of the pharmacokinetics of relevant radiopharmaceuticals as well as validation against gold-standard tests in large patient series are mandatory if PET and SPECT are to be implemented in routine clinical practice for the purpose of predicting response to radiotherapy

  15. Risk Factors of Developing Long-Lasting Breast Pain After Breast Cancer Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lundstedt, Dan, E-mail: dan.lundstedt@vgregion.se [Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg (Sweden); Department of Oncology, Sahlgrenska University Hospital, Gothenburg (Sweden); Gustafsson, Magnus [Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg (Sweden); Department of Therapeutic Radiation Physics, Sahlgrenska University Hospital, Gothenburg (Sweden); Steineck, Gunnar [Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg (Sweden); Division of Clinical Cancer Epidemiology, Department of Oncology-Pathology, the Karolinska Institute, Stockholm (Sweden); Malmstroem, Per [Skane Department of Oncology, Skane University Hospital, Lund (Sweden); Alsadius, David [Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg (Sweden); Department of Oncology, Sahlgrenska University Hospital, Gothenburg (Sweden); Sundberg, Agnetha [Department of Therapeutic Radiation Physics, Sahlgrenska University Hospital, Gothenburg (Sweden); Wilderaeng, Ulrica [Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg (Sweden); Holmberg, Erik [Oncologic Centre, Sahlgrenska University Hospital, Gothenburg (Sweden); Johansson, Karl-Axel [Department of Therapeutic Radiation Physics, Sahlgrenska University Hospital, Gothenburg (Sweden); Karlsson, Per [Department of Oncology, Sahlgrenska University Hospital, Gothenburg (Sweden)

    2012-05-01

    Purpose: Postoperative radiotherapy decreases breast cancer mortality. However, studies have revealed a long-lasting breast pain among some women after radiotherapy. The purpose of this study was to identify risk factors that contribute to breast pain after breast cancer radiotherapy. Methods and Materials: We identified 1,027 recurrence-free women in two cohorts of Swedish women treated for breast cancer. The women had breast-conserving surgery and postoperative radiotherapy, the breast was treated to 48 Gy in 2.4-Gy fractions or to 50 Gy in 2.0-Gy fractions. Young women received a boost of up to 16 Gy. Women with more than three lymph node metastases had locoregional radiotherapy. Systemic treatments were given according to health-care guidelines. Three to 17 years after radiotherapy, we collected data using a study-specific questionnaire. We investigated the relation between breast pain and potential risk modifiers: age at treatment, time since treatment, chemotherapy, photon energy, fractionation size, boost, loco-regional radiotherapy, axillary surgery, overweight, and smoking. Results: Eight hundred seventy-seven women (85%) returned the questionnaires. Among women up to 39 years of age at treatment, 23.1% had breast pain, compared with 8.7% among women older than 60 years (RR 2.66; 95% CI 1.33-5.36). Higher age at treatment (RR 0.96; 95% CI 0.94-0.98, annual decrease) and longer time since treatment (RR 0.93; 95% CI 0.88-0.98, annual decrease) were related to a lower occurrence of breast pain. Chemotherapy increased the occurrence of breast pain (RR 1.72; 95% CI 1.19-2.47). In the multivariable model only age and time since treatment were statistically significantly related to the occurrence of breast pain. We found no statistically significant relation between breast pain and the other potential risk modifiers. Conclusions: Younger women having undergone breast-conserving surgery with postoperative radiotherapy report a higher occurrence of long

  16. Risk factors for postoperative complications after total laryngectomy following radiotherapy or chemoradiation

    DEFF Research Database (Denmark)

    Wulff, N B; Kristensen, C.A.; Andersen, E

    2015-01-01

    OBJECTIVES: To determine the rates of and risk factors for postoperative complications following total laryngectomy in patients treated with radiotherapy or chemoradiation. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 143 patients undergoin...

  17. The progress of tumor gene-radiotherapy induced by Egr-1 promoter

    International Nuclear Information System (INIS)

    Guo Rui; Li Biao

    2010-01-01

    The promoter of early growth response gene-1 (Egr-1) is a cis-acting element of Egr-1, and its activity is regulated by inducers such as ionizing radiation, free radical. In designated gene-radiotherapy system, radiation combined with therapeutic gene (such as tumor necrosis factor-α gene, suicide gene) can spatially and temporally regulate therapeutic gene expression in the irradiated field, produced a marked effect, while little systemic toxicities were observed. The combination of radiotherapy and gene therapy is promising in tumor therapy. (authors)

  18. Insulin-like growth factors act synergistically with basic fibroblast growth factor and nerve growth factor to promote chromaffin cell proliferation

    DEFF Research Database (Denmark)

    Frödin, M; Gammeltoft, S

    1994-01-01

    We have investigated the effects of insulin-like growth factors (IGFs), basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) on DNA synthesis in cultured chromaffin cells from fetal, neonatal, and adult rats by using 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling for 24 or 48 h...... implications for improving the survival of chromaffin cell implants in diseased human brain....

  19. Palliative Radiotherapy in the Local Management of Stage IVB Esophageal Cancer: Factors Affecting Swallowing and Survival.

    Science.gov (United States)

    Suzuki, Gen; Yamazaki, Hideya; Aibe, Norihiro; Masui, Koji; Tatekawa, Kotoha; Sasaki, Naomi; Kimoto, Takuya; Nishimura, Takeshi; Nakashima, Akihiro; Takenaka, Tadashi; Fujiwara, Hitoshi; Ishikawa, Takeshi; Yamada, Kei

    2017-06-01

    To clarify the role of external-beam radiotherapy in the local management of state IVB esophageal cancer. We reviewed records of 31 patients with histopathologically-proven squamous cell carcinoma who underwent radiotherapy for their primary lesion. The change in dysphagia score from before to after treatment was assessed. Nutritional support-free survival (NSFS) was also evaluated. The median overall survival was 6 months. The overall rate of improvement in dysphagia score was 73% (23/31). The median NSFS was 5 months. Age at presentation esophageal cancer is an effective treatment option for dysphagia. Factors highly associated with improvement of swallowing are age, tumor location, and tumor length. Response to radiotherapy is the most important factor in improving NSFS. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  20. Hormone levels in radiotherapy treatment related fatigue

    International Nuclear Information System (INIS)

    Biswal, B.M.; Mallik, G.S.

    2003-01-01

    Radiotherapy is known to cause debilitating treatment related fatigue. Fatigue in general is a conglomeration of psychological, physical, hematological and unknown factors influencing the internal milieu of the cancer patient. Radiotherapy can add stress at the cellular and somatic level to aggravate further fatigue in cancer patients undergoing radiotherapy. Stress related hormones might be mediating in the development of fatigue. This is an ongoing prospective study to evaluate if the hormonal profile related to stress is influenced by radiotherapy treatment related fatigue. The study was conducted from September 2002 onwards in the division of Radiotherapy and Oncology of our Medical School. Previously untreated patients with histopathology proof of malignancy requiring external beam radiotherapy were considered for this study. Selection criteria were applied to exclude other causes of fatigue. Initial fatigue score was obtained using Pipers Fatigue Score questionnaire containing 23 questions, subsequently final fatigue score was obtained at the end of radiotherapy. Blood samples were obtained to estimate the levels of ACTH, TSH, HGH, and cortisol on the final assessment. The hormone levels were compared with resultant post radiotherapy fatigue score. At the time of reporting 50 patients were evaluable for the study. The total significant fatigue score was observed among 12 (24%) patients. The individual debilitating fatigue score were behavioral severity 14 (28%), affective meaning 14(28%), Sensory 13 (26%) and cognitive mood 10 (20%) respectively. From the analysis of hormonal profile, growth hormone level > 1 ng/mL and TSH <0.03 appears to be associated with high fatigue score (though statistically not significant); whereas there was no correlation with ACTH and serum cortisol level. In our prospective study severe radiotherapy treatment related fatigue was found among our patient population. Low levels of TSH and high levels of GH appear to be associated

  1. Clinical research of teeth damage from radiotherapy

    International Nuclear Information System (INIS)

    Li Erzhou; Yan Maosheng; Chen Wei; Li Qing

    2003-01-01

    Objective: To analyze various factors inducing teeth damage from radiotherapy and the preventive and treatment methods. Methods: One hundred cases of patients treated by radiotherapy were divided into two groups. In group one there were 60 cases whose teeth were irradiated during treatment; in group two there were 40 cases whose teeth were not irradiated during treatment. Results: The caries incidence was 60% for group one and 15% for group two (P<0.01). By auto-control in 15 patients, the caries incidence on the sick side was obviously higher than that of the healthy side. Hundred percent caries incidence was found in 6 cases who received a dosage of 70 Gy. Conclusion: The authors believe that radiation damage to the teeth is associated with the following factors: 1. The dosage and location of irradiation are closely related to caries incidence; 2. The active dentinoblasts are very sensitive to radiation; 3. Damage to the salivary glands from radiotherapy can result in reduction of salvia and pH value, leading to a high growth rate of Streptococcus mutans. Following preventive measures could be considered in future cases: to apply a caries prevention coating or protective dental crown and TPS, to adjust the dose and time of irradiation, to select conformal radiotherapy technique. The key points for protecting the teeth and salivary gland from caries and damage are protection of the proliferation ability of pulp cells, anti-inflammation, promotion of microcirculation, and strengthening body resistance

  2. Galangin inhibits human osteosarcoma cells growth by inducing transforming growth factor-β1-dependent osteogenic differentiation.

    Science.gov (United States)

    Liu, Chunhong; Ma, Mingming; Zhang, Junde; Gui, Shaoliu; Zhang, Xiaohai; Xue, Shuangtao

    2017-05-01

    Osteosarcoma is the most common primary malignancy of the musculoskeletal system, and is associated with excessive proliferation and poor differentiation of osteoblasts. Currently, despite the use of traditional chemotherapy and radiotherapy, no satisfactory and effective agent has been developed to treat the disease. Herein, we found that a flavonoid natural product, galangin, could significantly attenuate human osteosarcoma cells proliferation, without causing obvious cell apoptosis. Moreover, galangin enhanced the expression of osteoblast differentiation markers (collagen type I, alkaline phosphatase, osteocalcin and osteopontin) remarkably and elevated the alkaline phosphatase activity in human osteosarcoma cells. And galangin could also attenuated osteosarcoma growth in vivo. These bioactivities of galangin resulted from its selective activation of the transforming growth factor (TGF)-β1/Smad2/3 signaling pathway, which was demonstrated by pathway blocking experiments. These findings suggested that galangin could be a promising agent to treat osteosarcoma. In addition, targeting TGF-β1 to induce osteogenic differentiation might represent a novel therapeutic strategy to treat osteosarcoma with minimal side effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Risk analysis factors for local recurrence in Ewing's sarcoma: when should adjuvant radiotherapy be administered?

    Science.gov (United States)

    Albergo, J I; Gaston, C L L; Parry, M C; Laitinen, M K; Jeys, L M; Tillman, R M; Abudu, A T; Grimer, R J

    2018-02-01

    The aim of this study was to analyse a group of patients with non-metastatic Ewing's sarcoma at presentation and identify prognostic factors affecting the development of local recurrence, in order to assess the role of radiotherapy. A retrospective review of all patients with a Ewing's sarcoma treated between 1980 and 2012 was carried out. Only those treated with chemotherapy followed by surgery and/or radiotherapy were included. Patients were grouped according to site (central or limb) for further analysis of the prognostic factors. A total of 388 patients were included in the study. Of these, 60 (15%) developed local recurrence at a mean median of 27 months (sd 24, range 7 to 150) and the five-year local recurrence-free survival (5yrLRFS) was 83%. For central tumours, the size of the tumour and histological response to chemotherapy were found to be significant factors for local recurrence. For limb tumours, local recurrence was affected by intralesional and marginal resections, but not by the histological response to chemotherapy. Radiotherapy in those with a marginal resection reduced the risk of local recurrence (5yrLRFS: 96% versus 81%, p = 0.044). Local recurrence significantly affects the overall survival in patients with a Ewing's sarcoma. For those with a tumour in a limb, radiotherapy reduced the risk of local recurrence, especially in those with a marginal margin of excision, but the effect in central tumours was less clear. Radiotherapy for those who have had a wide margin of resection does not reduce the risk of local recurrence, regardless of the histological response to chemotherapy. Cite this article: Bone Joint J 2018;100-B: 247-55. ©2018 The British Editorial Society of Bone & Joint Surgery.

  4. Immunological factors correlated in radiation effect in cancer patients treated by radiotherapy alone or radiotherapy with combined chemotherapy

    International Nuclear Information System (INIS)

    Kimura, Shuji

    1981-01-01

    Local immunological factors are thought to be parenchymal reaction of normal and tumor tissues. Those were studied by morphological changes of angiographic findings and histological methods which included photomicroscopic, electromicroscopic and enzymic-histochemical studies. It was demonstrated that the effect of radiotherapy depended on not only local blood supply but also parenchymal reaction of the host. Especially, the parenchymal reaction at 2000 or 3000 rad irradiation was regarded as nonspecific tissue repair as well as immunological protective reactions brought about by enhancement of the tumor antigenicity. It was proved that T-cell system played a main role in this parenchymal reaction. Changes of systemic immunological factors were studied in 17 laryngeal cancer and 80 lung cancer patients treated by radiotherapy alone or radiotherapy with combined chemotherapy. Due to the fact that damages of the host before treatment were not so serious and integral dose given to the patients was a little in cases of laryngeal cancer immunological parameters such as absolute lymphocyte counts, PHA and PPD skin test activities, lymphocyte blastoid transformation with PHA, PWM and Con A, did not show significant change. However, as for lung cancer treated by large integral dose irradiation combined with chemotherapy, immunological parameters were depressed in inverse proportion to the dose of irradiation and chemotherapeutic agents. Moreover T-cell subsets (early E-rosette forming cells, IgG Fc-receptor positive cells), lymphocyte sub-populations, ADCC activity, serum immunoglobulins, and serum protein were also investigated in cases of lung cancer. We have evaluated the immunological parameters in relation to the therapeutic effect. As a result, it was suggested that several parameters should be needed to forecast the prognosis. (author)

  5. Barriers to palliative radiotherapy referral: A Canadian perspective

    International Nuclear Information System (INIS)

    Samant, Rajiv S.; Fitzgibbon, Edward; Meng, Joanne; Graham, Ian D.

    2007-01-01

    Radiotherapy is an effective but underutilized treatment modality for cancer patients. We decided to investigate the factors influencing radiotherapy referral among family physicians in our region. A 30-item survey was developed to determine palliative radiotherapy knowledge and factors influencing referral. It was sent to 400 physicians in eastern Ontario (Canada) and the completed surveys were evaluated. The overall response rate was 50% with almost all physicians seeing cancer patients recently (97%) and the majority (80%) providing palliative care. Approximately 56% had referred patients for radiotherapy previously and 59% were aware of the regional community oncology program. Factors influencing radiotherapy referral included the following: waiting times for radiotherapy consultation and treatment, uncertainty about the benefits of radiotherapy, patient age, and perceived patient inconvenience. Physicians who referred patients for radiotherapy were more than likely to provide palliative care, work outside of urban centres, have hospital privileges and had sought advice from a radiation oncologist in the past. A variety of factors influence the referral of cancer patients for radiotherapy by family physicians and addressing issues such as long waiting times, lack of palliative radiotherapy knowledge and awareness of Cancer Centre services could increase the rate of appropriate radiotherapy patient referral

  6. A proliferation saturation index to predict radiation response and personalize radiotherapy fractionation

    International Nuclear Information System (INIS)

    Prokopiou, Sotiris; Moros, Eduardo G.; Poleszczuk, Jan; Caudell, Jimmy; Torres-Roca, Javier F.; Latifi, Kujtim; Lee, Jae K.; Myerson, Robert; Harrison, Louis B.; Enderling, Heiko

    2015-01-01

    Although altered protocols that challenge conventional radiation fractionation have been tested in prospective clinical trials, we still have limited understanding of how to select the most appropriate fractionation schedule for individual patients. Currently, the prescription of definitive radiotherapy is based on the primary site and stage, without regard to patient-specific tumor or host factors that may influence outcome. We hypothesize that the proportion of radiosensitive proliferating cells is dependent on the saturation of the tumor carrying capacity. This may serve as a prognostic factor for personalized radiotherapy (RT) fractionation. We introduce a proliferation saturation index (PSI), which is defined as the ratio of tumor volume to the host-influenced tumor carrying capacity. Carrying capacity is as a conceptual measure of the maximum volume that can be supported by the current tumor environment including oxygen and nutrient availability, immune surveillance and acidity. PSI is estimated from two temporally separated routine pre-radiotherapy computed tomography scans and a deterministic logistic tumor growth model. We introduce the patient-specific pre-treatment PSI into a model of tumor growth and radiotherapy response, and fit the model to retrospective data of four non-small cell lung cancer patients treated exclusively with standard fractionation. We then simulate both a clinical trial hyperfractionation protocol and daily fractionations, with equal biologically effective dose, to compare tumor volume reduction as a function of pretreatment PSI. With tumor doubling time and radiosensitivity assumed constant across patients, a patient-specific pretreatment PSI is sufficient to fit individual patient response data (R 2 = 0.98). PSI varies greatly between patients (coefficient of variation >128 %) and correlates inversely with radiotherapy response. For this study, our simulations suggest that only patients with intermediate PSI (0.45–0.9) are

  7. Assessment of factors connected with radiotherapy influencing the cosmetic effect in breast conserving therapy

    International Nuclear Information System (INIS)

    Blaszczyk, P.; Roszkowski, K.; Blaszczyk, E.; Kowalewski, J.

    2009-01-01

    Aim: To compare cosmetic results of different radiotherapy schedules used in the treatment of breast cancer after breast radiotherapy and to identify factors affecting cosmetic outcomes. Material and methods: Ninety-four patients irradiated. Median follow-up of 29 months (range 18-154 mo.). Patients were treated with standard fractionation 45-50 Gy/20-25 fx/4-5 weeks. Boost up to 10 Gy. Late effects were evaluated using the LENT-SOMA scoring scale. The cosmetic results were assessed on a four-point scale and presence of concomitant chemotherapy. Results: LENT-SOMA grade 3 toxicity was observed only in 8 (8,5%) patients. The factor associated with hyperpigmentation is large breast size. The significant risk factors for teleangiectasia are high dose and use photon energy 1,33 MeV beam. Factors found to impact significantly cosmetics adversely fibrosis was large breast size. Breast fibrosis were more frequent observed in woman after whole dose 50 Gy. There were no differences in breast skin thick between analysed factors. Conclusions: After irradiating large breasts more often than one observes the fibrosis of the breast in the case of small and average breasts and discolour of the skin. Irradiating photons from the cobalt source in the comparison with photons about higher energy at women with large breasts, there is the reason more frequent occurrence of the skin angioma. For the final cosmetic effect of radiotherapy in saving treatment, they do not have the impact: tumor size, boost method, chemical treatment, patients age. (authors)

  8. Prognostic factors in the radiotherapy of Graves' ophthalmopathy

    International Nuclear Information System (INIS)

    Petersen, I.A.; Kriss, J.P.; McDougall, I.R.; Donaldson, S.S.

    1990-01-01

    Between April 1968 and February 1988, 311 patients with symptomatic and progressive Graves' ophthalmopathy were treated with megavoltage orbital radiotherapy. The patients were divided into three groups: I treated with 20 Gy/2 weeks; II treated with 30 Gy/3 weeks, and III received 20 Gy/2 weeks. The degree of eye involvement was evaluated numerically before and after therapy for each of five parameters: soft tissue signs, proptosis, eye muscle impairment, corneal involvement, and sight loss. Pre-treatment and current thyroid diagnosis and status were also noted. To evaluate the effects of radiotherapy alone, follow-up was terminated at the time any eye surgery was done; for those not treated surgically the minimum follow-up was 12 months. Because there were significant demographic differences between the patient groups, the results of each group were analyzed separately. A stepwise linear regression analysis was performed to determine if there were any significant variables affecting outcome. Based on these data formulae were derived which enable outcome to be predicted in any patient. Before therapy more than 90% of patients in all groups had soft tissue and eye muscle involvement, whereas 65-75% had proptosis and about half 50% had some degree of sight loss. Radiotherapy arrested progression of ophthalmic parameters in all but 1-6% of the patients. Objective and symptomatic improvement was noted for all parameters assessed, but there was marked individual variability. The best responses were noted for soft tissue, corneal involvement, and sight loss; however over half the patients had some improvement in eye muscle function and proptosis. Factors which resulted in less favorable outcome included male gender, advanced age, need for concurrent therapy for hyperthyroidism, and no history of hyperthyroidism. No complications have been observed

  9. Transforming growth factor alpha and epidermal growth factor in laryngeal carcinomas demonstrated by immunohistochemistry

    DEFF Research Database (Denmark)

    Christensen, M E; Therkildsen, M H; Poulsen, Steen Seier

    1993-01-01

    the basal cell layer. The present investigation and our previous results confirm the existence of EGF receptors, TGF-alpha and EGF in laryngeal carcinomas. In addition, we conclude that the conditions do exist for growth factors to act through an autocrine system in poorly differentiated tumours and through......Fifteen laryngeal squamous cell carcinomas were investigated for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) using immunohistochemical methods. In a recent study the same material was characterized for epidermal growth factor receptors (EGF...... receptors) which were confined predominantly to the undifferentiated cells. The expression of this growth factor system in malignant cells may play a role in carcinogenesis and/or tumour growth. All carcinomas were positive for TGF-alpha and 12 were positive for EGF. In moderately-to-well differentiated...

  10. Growth Hormone Protects the Intestine Preserving Radiotherapy Efficacy on Tumors: A Short-Term Study.

    Directory of Open Access Journals (Sweden)

    Victor Caz

    Full Text Available The efficacy of radiotherapy on tumors is hampered by its devastating adverse effects on healthy tissue, particularly that of the gastrointestinal tract. These effects cause acute symptoms that are so disruptive to patients that they can lead to interruption of the radiotherapy program. These adverse effects could limit the intensity of radiation received by the patient, resulting in a sublethal dose to the tumor, thus increasing the risk of tumor resistance. The lack of an effective treatment to protect the bowel during radiation therapy to allow higher radiation doses that are lethal to the tumor has become a barrier to implementing effective therapy. In this study, we present a comparative analysis of both intestinal and tumor tissue in regard to the efficacy and the preventive impact of a short-term growth hormone (GH treatment in tumor-bearing rats as a protective agent during radiotherapy. Our data show that the exogenous administration of GH improved intestinal recovery after radiation treatment while preserving the therapeutic effect against the tumor. GH significantly increased proliferation in the irradiated intestine but not in the irradiated tumors, as assessed by Positron Emission Tomography and the proliferative markers Ki67, cyclin D3, and Proliferating Cell Nuclear Antigen. This proliferative effect was consistent with a significant increase in irradiated intestinal villi and crypt length. Furthermore, GH significantly decreased caspase-3 activity in the intestine, whereas GH did not produce this effect in the irradiated tumors. In conclusion, short-term GH treatment protects the bowel, inducing proliferation while reducing apoptosis in healthy intestinal tissue and preserving radiotherapy efficacy on tumors.

  11. Natural history of intracranial meningioma after radiotherapy

    International Nuclear Information System (INIS)

    Monzen, Yoshio

    1999-01-01

    The author examined the natural history of intracranial meningioma after radiotherapy using CT or MR imaging. Twenty patients with intracranial meningioma received radiotherapy from a high-energy linear accelerator (4-10 MV X rays) from 1980 to 1996. The total doses were 50 Gy to the tumor bed in single doses of 2 Gy in 5 weekly fractions. Meningiomas in 10 of 20 patients were reduced within 1 to 38 months after radiotherapy, the average being 11 months. The tumors were controlled for a median of 60 months after radiotherapy (range 19-126 months). Four other patients have shown no change in tumor size after radiotherapy. The tumors were controlled for a median of 70 months after radiotherapy (range 37-127 months). The other six patients have shown tumor growth within 3 to 25 months after radiotherapy, after which the tumors stopped growing for a median of 71 months (range 2-181 months). Neither tumor size nor histological type was related to response. The growth of tumors was controlled by radiotherapy for a median duration of 43 months in the meningothelial type, 52 months in the fibroblastic type, and 61 months in the transitional type. The median duration for all benign tumors was 52 months. A moderate correlation was noted between tumor response and functional outcome after radiotherapy in 9 patients with neurological deficits. The natural histories of intracranial meningiomas after radiotherapy were grouped into three categories. Some tumors showed no change in size over a long period. This was a characteristic response after radiotherapy that differed from that of other brain tumors. The results of this study provide important information for the follow-up of intracranial meningiomas after radiotherapy. (author)

  12. Long-term results of radiotherapy for pituitary adenomas. Evaluation of tumor control and hypopituitarism after radiotherapy

    International Nuclear Information System (INIS)

    Tsuchida, Emiko; Sakai, Kunio; Matsumoto, Yasuo; Sugita, Tadashi; Sasamoto, Ryuta

    1999-01-01

    To evaluate the results of conventional radiotherapy for pituitary adenomas assessed with computed tomography (CT) or magnetic resonance imaging (MRI). Endpoints include tumor control, normalization of hormone levels in functioning adenomas, and hypopituitarism after radiotherapy as an adverse effect. Forty-two patients were treated with radiotherapy from 1982 to 1995 at Niigata University Hospital. Forty patients were irradiated after surgery because of residual adenomas in 33 patients and tumor regrowth in 7 patients. One patient was treated with radiotherapy alone, and the remaining 1 patient was treated with preoperative radiotherapy. Tumor size and extension were evaluated using CT or MRI, and all tumors were macroadenomas. They consisted of 18 non-functioning and 24 functioning adenomas (growth hormone (GH)-secreting: 11, prolactinomas: 7, concomitant GH and prolactin (PRL)-secreting: 5, gonadotropin-secreting: 1). Treatment was given in 200 cGy daily fraction size and a total dose of 50 Gy was given to most patients. Sixteen patients with GH- and/or PRL-secreting adenomas received bromocriptine. Tumor progression was determined by increase in tumor size as shown by CT or MRI. Hypopituitarism after radiotherapy was evaluated using the functions of corticotropin (ACTH), thyrotropin (TSH), and gonadotropin. Median follow-up time from the end of radiotherapy was 103 months. Tumor progression occurred in 2 out of 42 patients and 10-year progression-free rate for all patients was 93.7%. Normalization of GH levels was obtained in 12 of 16 GH-secreting adenomas with a mean time of 27 months after radiotherapy, and 9 of 12 PRL-secreting adenomas achieved normalization of PRL levels with a mean time of 34 months. One gonadotropin-secreting adenoma achieved normalization of gonadotropin level at 21 months after radiotherapy. The incidence of hypopituitarism after radiotherapy increased with time, and cumulative risk of deficiencies of ACTH, TSH, and gonadotropin at 10

  13. Hemoglobin as an independent prognostic factor in the radiotherapy of head and neck tumors

    International Nuclear Information System (INIS)

    Schaefer, U.; Micke, O.; Mueller, S.B.; Schueller, P.; Willich, N.

    2003-01-01

    Purpose: The purpose of this study was to analyze the prognostic value of baseline hemoglobin levels before radiotherapy in patients with head and neck tumors. Patients and Methods: In a retrospective study with a median follow-up of 43 months, we analyzed the results of 214 patients irradiated for head and neck cancer between January 1, 1990 and January 1, 1998 (180 men and 34 women; median age 58 years). The treatment concept consisted in adjuvant radiotherapy in 58 patients, 77 patients received definitive radiochemotherapy, 42 patients definitive radiotherapy, and 37 patients reirradiation for in-field recurrence. Baseline hemoglobin values were divided in four groups of the same patient number (quartiles). Several known prognostic factors like sex, tumor stage, histologic grading, performance status, and treatment scheme were analyzed for their influence on overall and event-free survival and correlated with pretreatment hemoglobin values (Kaplan-Meier method). In addition, univariate und multivariate logistic regression analyses were carried out to evaluate the effect of baseline hemoglobin on response rates. Results: The median survival (event-free survival) of all patients amounted to 15 months (10 months). 25%, 50%, and 75% of patients had hemoglobin values < 11.2 g/dl, < 12.7 g/dl, and < 13.9 g/dl, respectively. In the univariate analysis, the following variables were significant prognostic factors for overall/event-free survival (log-rank test): treatment concept (p < 0.001/ p < 0.001), tumor stage (p < 0.001/p < 0.001), general condition (p < 0.001/p < 0.001), and pretreatment hemoglobin (p = 0.014/p = 0.05). Multivariate analysis (Cox) proved these parameters to be independent of each other. In addition, response rate after radiation showed a strong association between hemoglobin and local control probability (p = 0.02). Conclusion: In this retrospective analysis, baseline hemoglobin level was shown to be an independent significant prognostic factor in

  14. Factors influencing treatment results of definitive radiotherapy following transurethral surgery for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Abe, Tatsuyuki; Kanehira Chihiro

    1999-01-01

    To determine the prognostic factors influencing the outcome of bladder cancer patients treated with definitive radiotherapy following transurethral tumor resection (TURBT). From March 1977 through August 1991, 83 patients with muscle-invasive bladder cancer were treated with TURBT (as thoroughly as possible) and definitive radiotherapy (median total dose: 64 Gy, median fractional dose: 2 Gy). Cystectomy was performed when possible for the residual or recurrent invasive cancer following radiotherapy. The median follow-up period was 76 months. The overall survival (OS) and bladder-preserving survival (BPS) rates at 5 years were 38% and 28%, respectively. Univariate analysis indicated that depth of invasion (T2 vs T3), tumor diameter (<3 cm vs. ≥3 cm), and visible (R1) or not visible (R0) residual tumor after TURBT influenced both OS and BPS. In multivariate analysis, absence of visible residual tumor after TURBT was the only significant prognostic factor related to OS (p<0.001) and BPS (p=0.002). Five-year OS and BPS were 54% and 43% in T2-3R0 and 14% and 7% in T2-3R1, respectively. Absence of visible residual tumor after TURBT was significantly associated with better overall survival and bladder-preserving survival for muscle-invasive bladder cancer patients treated with definitive radiotherapy following TURBT. (author)

  15. Prognostic factors for acute and late skin reactions in radiotherapy patients

    International Nuclear Information System (INIS)

    Turesson, Ingela; Nyman, Jan; Holmberg, Erik; Oden, Anders

    1996-01-01

    Purpose: Patients treated with identical radiotherapy schedules show a substantial variation in the degree of acute and late normal tissue reactions. To identify any possible contributing factors to this phenomenon, we have analyzed the treatments of 402 breast cancer patients. Methods and Materials: The patients received adjuvant postoperative radiotherapy between 1972 and 1985 and have been followed up since then. Multivariate analyses were performed with peak reflectance erythema and peak acute reaction score as endpoints for the acute reactions, and with progression rate of telangiectasia as well as telangiectasia score as endpoints for the late reactions. Twenty patient- and treatment-related factors were tested such as age, menopausal status, hemoglobin level, serum calcium, smoking habits, hypothyroidism, diabetes, hypertension, blood pressure, cardiovascular and autoimmune disease, the influence of hormone therapy and chemotherapy, pretreatment reflectance value, acute skin reactions, radiation quality, individual dose, bilateral fields, and the total effect (TE) for the dose schedule applied. Results: The TE was a strong prognostic factor for all endpoints. In addition to TE, blood pressure was prognostic for the peak erythema measured by reflectance spectrophotometry, and the pretreatment reflectance value was prognostic for the acute score. The only independent prognostic factors found for the progression of skin telangiectasia and telangiectasia score except for TE were the individual dose and the acute skin reactions. Conclusions: These factors explained at most about 30% of the variance describing the total patient-to-patient variability for each endpoint. The remaining variability is still unexplained but may be related to individual differences in cellular radiosensitivity, partly determined by genetic variations and partly by unknown epigenetic factors

  16. [Use of filgrastim, granulocyte colony stimulating factor (G-CSF), in radiotherapy to reduce drop-outs because of radiogenic leukopenia].

    Science.gov (United States)

    Gava, A; Bertossi, L; Ferrarese, F; Coghetto, F; Marazzato, G; Andrulli, A D; Zorat, P L

    1998-03-01

    Radiotherapy patients are at risk of developing leukopenia, which risk depends on the irradiated volume, the rate of irradiated bone marrow and the radiation dose. Radiogenic leukopenia may cause radiotherapy drop-out, with consequent effects, on local tumor control and clinical outcome. The introduction of granulocyte growth factors, such as filgrastim, has permitted to accelerate normal neutrophil count recovery in irradiation-related neutropenia both in vitro and animal models; clinical experience in humans is still lacking, relative to both indications and scheduling. In the Oncologic Radiotherapy Department of Treviso Hospital, 31 patients irradiated for Hodgkin disease, rectal cancer and other malignancies, who presented leukopenia requiring treatment discontinuation, were given filgrastim to assess its actual effect in avoiding further drop-outs and to compare two administration schedules (2 or 3 vials, 30 MIU, weekly). Filgrastim treatment was continued throughout the radiotherapy cycles, for 1 to 5 weeks. Eighteen patients had received previous chemotherapy and 11 were undergoing concurrent 5-fluorouracil chemotherapy-irradiation. A mean 203% increase in leukocyte count was observed (136% in the patients treated with 2 vials/week and 274% in those receiving 3 vials/week); this increase was more apparent in women that in men (256% versus 91%) and slightly higher in patients 50 years old and with target volumes < 5000 ml. Filgrastin treatment was well tolerated by all patients, with no discontinuations due to adverse effects; 9 patients (29%) reported skeletal pain, which was marked in 2 of them only. Eighty percent of patients completed all the radiotherapy cycles with no discontinuation, while 6 patients dropped out because leukopenia persisted. Biweekly filgrastim administration was effective to prevent unscheduled radiotherapy discontinuation in 75% of patients and triweekly administration was effective in 86% of patients. In our experience, filgrastim

  17. Prognostic factors and survival in patients with radiation-related second malignant neoplasms following radiotherapy for nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Mian Xi

    Full Text Available PURPOSE: To analyze the clinicopathological characteristics, treatment modalities, and potential prognostic factors of radiation-related second malignant neoplasms (SMNs in a large group of nasopharyngeal carcinoma (NPC cases. METHODS AND MATERIALS: Institutional electronic medical records of 39,118 patients with NPC treated by definitive radiotherapy between February 1964 and December 2003 were reviewed. A total of 247 patients with confirmed SMN attributable to radiotherapy were included. RESULTS: Median latency between radiotherapy for NPC and the diagnosis of SMN was 9.5 years (range, 3.1-36.8 years. Squamous cell carcinoma was the most common histologic type, followed by fibrosarcoma and adenocarcinoma. Median progression-free survival and overall survival (OS of the 235 patients who underwent treatment were 17.3 months and 28.5 months, respectively. The 5-year OS rates were 42.9%, 23.7%, and 0% for the surgery, radiotherapy, and chemotherapy groups, respectively. The independent prognostic factors associated with survival were sex, histologic type, and treatment modality in both the early stage subgroup and the advanced stage subgroup of SMN. CONCLUSIONS: Sex, histologic type, and treatment modality were the significant prognostic factors for SMN. Complete resection offers the best chance for long-term survival. In select patients with locally advanced and unresectable SMN, reirradiation should be strongly considered as a curative option.

  18. Stereotactic radiotherapy for wet age-related macular degeneration: current perspectives

    Directory of Open Access Journals (Sweden)

    Neffendorf JE

    2015-09-01

    Full Text Available James E Neffendorf, Timothy L Jackson Department of Ophthalmology, School of Medicine, King’s College London, London, United Kingdom Abstract: Neovascular age-related macular degeneration is a leading cause of blindness in the developed world. Currently, the treatment of choice is intravitreal injections of anti-VEGF medications. These require frequent dosing, up to monthly, and impose a substantial burden on patients and the health economy. Ionizing radiation was proposed as a possible treatment for age-related macular degeneration due to its anti-inflammatory and anti-fibrotic properties. Stereotactic radiotherapy is an outpatient-based radiotherapy platform that provides stereotactic application of low energy X-ray to the retina in three highly collimated beams that cross the inferior sclera to overlap at the macula. A randomized, double-masked, sham-controlled trial of 230 patients (INTREPID showed that a single dose of stereotactic radiotherapy significantly reduces the number of intravitreal anti-VEGF injections needed over 2 years. A larger randomized controlled trial (STAR is underway. Keywords: wet age-related macular degeneration, radiation therapy, stereotactic radiotherapy, vascular endothelial growth factor

  19. In Vitro Responsiveness of Glioma Cell Lines to Multimodality Treatment With Radiotherapy, Temozolomide, and Epidermal Growth Factor Receptor Inhibition With Cetuximab

    International Nuclear Information System (INIS)

    Combs, Stephanie E.; Schulz-Ertner, Daniela; Roth, Wilfried; Herold-Mende, Christel; Debus, Juergen; Weber, Klaus-Josef

    2007-01-01

    Background: The majority of glioblastoma multiforme (GBM) cells express the epidermal growth factor receptor (EGFR). The present study evaluates the combination of temozolomide (TMZ), EGFR inhibition, and radiotherapy (RT) in GBM cell lines. Methods and Materials: Human GBM cell lines U87, LN229, LN18, NCH 82, and NCH 89 were treated with various combinations of TMZ, RT, and the monoclonal EGFR antibody cetuximab. Responsiveness of glioma cells to the combination treatment was measured by clonogenic survival. Results: Overall, double and triple combinations of RT, TMZ, and cetuximab lead to additive cytotoxic effects (independent toxicity). A notable exception was observed for U87 and LN 18 cell lines, where the combination of TMZ and cetuximab showed substantial antagonism. Interestingly, in these two cell lines, the combination of RT with cetuximab resulted in a substantial increase in cell killing over that expected for independent toxicity. The triple combination with RT, cetuximab, and TMZ was nearly able to overcome the antagonism for the TMZ/cetuximab combination in U87, however only marginally in LN18, GBM cell lines. Conclusion: It appears that EGFR expression is not correlated with cytotoxic effects exerted by cetuximab. Combination treatment with TMZ, cetuximab and radiation resulted in independent toxicity in three out of five cell lines evaluated, the antagonistic effect of the TMZ/cetuximab combination in two cell lines could indicate that TMZ preferentially kills cetuximab-resistant cells, suggesting for some cross-talk between toxicity mechanisms. Expression of EGFR was no surrogate marker for responsiveness to cetuximab, alone or in combination with RT and TMZ

  20. Growth factor involvement in tension-induced skeletal muscle growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1993-01-01

    Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

  1. Quantitative evaluation of Streptococcus mutans and Candida sp and salivary factors in the oral cavity of patients submitted to radiotherapy

    International Nuclear Information System (INIS)

    Spolidorio, Denise Madalena Palomari; Spolidorio, Luis Carlos; Barbeiro, Roberto Henrique; Bernardo, Wagner Luis Carvalho; Pavan, Sabrina; Hoefling, Jose Francisco

    2001-01-01

    The aim of this study was to quantify the microorganisms Streptococcus mutans and Candida sp in the oral cavity of patients with oropharynx carcinoma, before, during and after radiotherapy, and to correlate the results with salivary factors such as pH, buffer capacity and flow rate. Saliva samples were collected, diluted and inoculated in SB-20 agar and in Sabouraud agar, for Streptococcus mutans and Candida sp, respectively. Previously to dilution, the concentrated saliva was analyzed, and the salivary factors were determined. After the growth of colonies, the number of microorganisms was determined in CFU/ml. The analysis of the results allowed to conclude that the salivary factors are related to the presence of microorganisms, and that the number of CFU/ml increased as salivary flow rate decreased. The effects of radiation compromised salivary homeostasis and favored the increase of infection by yeasts and bacteria. (author)

  2. Potential risk factors for jaw osteoradionecrosis after radiotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Kuhnt, Thomas; Stang, Andreas; Wienke, Andreas; Vordermark, Dirk; Schweyen, Ramona; Hey, Jeremias

    2016-01-01

    To identify potential risk factors for the development of jaw osteoradionecrosis (ORN) after 3D-conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) among patients with newly diagnosed head and neck cancer. This study included 776 patients who underwent 3D-CRT or IMRT for head and neck cancer at the Department of Radiotherapy at the University Hospital Halle-Wittenberg between 2003 and 2013. Sex, dental status prior to radiotherapy, tumor site, bone surgery during tumor resection, concomitant chemotherapy, and the development of advanced ORN were documented for each patient. ORN was classified as grade 3, 4, or 5 according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer classification or grade 3 or 4 according to the late effects in normal tissues/subjective, objective, management, and analytic scale. The cumulative incidence of ORN was estimated. Cox regression analysis was used to identify prognostic risk factors for the development of ORN. Fifty-one patients developed advanced ORN (relative frequency 6.6 %, cumulative incidence 12.4 %). The highest risk was found in patients who had undergone primary bone surgery during tumor resection (hazard ratio [HR] = 5.87; 95 % confidence interval [CI]: 3.09–11.19) and in patients with tumors located in the oral cavity (HR = 4.69; 95 % CI: 1.33–16.52). Sex, dentition (dentulous vs. edentulous), and chemotherapy had no clinically relevant influence. In contrast to most previous studies, we noted a low cumulative incidence of advanced ORN. Patients with tumors located in the oral cavity and those who undergo bone surgery during tumor resection prior to RT may be considered a high-risk group for the development of ORN

  3. Investigation of various growth mechanisms of solid tumour growth within the linear-quadratic model for radiotherapy

    International Nuclear Information System (INIS)

    McAneney, H; O'Rourke, S F C

    2007-01-01

    The standard linear-quadratic survival model for radiotherapy is used to investigate different schedules of radiation treatment planning to study how these may be affected by different tumour repopulation kinetics between treatments. The laws for tumour cell repopulation include the logistic and Gompertz models and this extends the work of Wheldon et al (1977 Br. J. Radiol. 50 681), which was concerned with the case of exponential re-growth between treatments. Here we also consider the restricted exponential model. This has been successfully used by Panetta and Adam (1995 Math. Comput. Modelling 22 67) in the case of chemotherapy treatment planning.Treatment schedules investigated include standard fractionation of daily treatments, weekday treatments, accelerated fractionation, optimized uniform schedules and variation of the dosage and α/β ratio, where α and β are radiobiological parameters for the tumour tissue concerned. Parameters for these treatment strategies are extracted from the literature on advanced head and neck cancer, prostate cancer, as well as radiosensitive parameters. Standardized treatment protocols are also considered. Calculations based on the present analysis indicate that even with growth laws scaled to mimic initial growth, such that growth mechanisms are comparable, variation in survival fraction to orders of magnitude emerged. Calculations show that the logistic and exponential models yield similar results in tumour eradication. By comparison the Gompertz model calculations indicate that tumours described by this law result in a significantly poorer prognosis for tumour eradication than either the exponential or logistic models. The present study also shows that the faster the tumour growth rate and the higher the repair capacity of the cell line, the greater the variation in outcome of the survival fraction. Gaps in treatment, planned or unplanned, also accentuate the differences of the survival fraction given alternative growth

  4. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    Science.gov (United States)

    Unkelbach, Jan; Menze, Bjoern H.; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A.

    2014-02-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  5. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    International Nuclear Information System (INIS)

    Unkelbach, Jan; Dittmann, Florian; Le, Matthieu; Shih, Helen A; Menze, Bjoern H; Ayache, Nicholas; Konukoglu, Ender

    2014-01-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher–Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  6. Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Tae Ryool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2016-03-15

    Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

  7. Growth factors and new periodontology

    Directory of Open Access Journals (Sweden)

    Paknejad M

    1999-06-01

    Full Text Available Growth factors are biological mediators that have a key roll in proliferation, chemotaxy and"ndifferentiation by acting on specific receptors on the surface of cells and regulating events in wound"nhealing.They can be considered hormones that are not released in to the blood stream but have one a"nlocal action. Some of these factors can regulate premature change in GO to Gl phase in cell devesion"ncycle and even may stimulate synthesis of DNA in suitable cells, Growth substances, primarily secreted"nby fibroblasts, endothelia! cells, macrophages and platelet, include platelet derived growth factor"n(PDGF, insulin like growth factor (IGF transforming growth factor (TGFa and (3 and bone"nmorphogenetic proteins BMPs that approximately are the most important of them. (BMPs could be"nused to control events during periodontal, craniofacial and implant wound healing through favoring bone"nformation"nAccording toLynch, combination of PGDF and IGF1 would be effective in promoting growth of all the"ncomponents of the periodontium."nThe aim of this study was to characterize growth factor and review the literature to determine the"nmechanism of their function, classification and application in implant and periodontal treatment.

  8. Immunohistochemical and quantitative changes in salivary EGF, amylase and haptocorrin following radiotherapy for oral cancer

    DEFF Research Database (Denmark)

    Christensen, M E; Hansen, H S; Poulsen, Steen Seier

    1996-01-01

    Epidermal growth factor (EGF), amylase and haptocorrin are molecules produced in the salivary glands. The aim of the present study was to determine immunohistochemical and quantitative alterations in EGF as compared with haptocorrin and amylase following radiotherapy for oral cancer. Changes in t...... a reduction in the mitogenic peptide EGF both immunohistochemically and quantitatively following irradiation for oral cancer, results which may contribute to the understanding of the clinical signs of mucositis.......Epidermal growth factor (EGF), amylase and haptocorrin are molecules produced in the salivary glands. The aim of the present study was to determine immunohistochemical and quantitative alterations in EGF as compared with haptocorrin and amylase following radiotherapy for oral cancer. Changes....... The concentration of EGF in saliva before treatment was significantly higher in patients than in the control group (p oral tumors contribute with EGF to the saliva. In conclusion we have demonstrated...

  9. Status of Radiotherapy around the World: Radiotherapy in China. Chapter 25.6

    International Nuclear Information System (INIS)

    Zhu, Ci; Yin, Wei Bo; Chen, Bo; Zhang, Chun Li; Zhang, Hong Zhi; Li, Ye Xiong

    2017-01-01

    China’s experience of using radiotherapy to treat cancer began with the installation of the first superficial X ray machine at Peking Union Medical College Hospital in early 1920, followed by the first 200 kV deep X ray machine installed at the French Hospital in Shanghai in 1923, and the first Chinese radiotherapy department established at the Affiliated Hospital of Peking University in 1932. However, the field of radiotherapy in China was still in its infancy between the 1930s and 1960s, as all operating machines were imported from foreign countries, making radiotherapy very difficult to access for cancer patients. Progress was slow until the mid-1970s, when the first batch of megavoltage machines (cobalt-60 machines and linacs) was produced by Chinese manufacturers. Owing to the efforts of radiotherapy pioneers such as Wu Huanxing, Gu Xianzhi, Liu Taifu, and Yin Weibo, who brought radiotherapy to China and shaped how Chinese patients would be treated today, radiotherapy was installed as one of the mainstream modalities of cancer treatment. In 1986, the China Society for Radiation Oncology (CSTRO) was founded, indicating that a network advancing radiation oncology practice in China was taking shape. One year later, the first issue of the Chinese Journal of Radiation Oncology was published, offering a platform for the timely exchange and sharing of laboratory and clinical research outcomes among radiation oncology professions across the country. During the past two decades, with the introduction of the gamma knife and stereotactic radiotherapy, 3-D conformal radiotherapy, IMRT, IGRT and other advanced techniques, China experienced not only a big jump in its radiotherapy equipment and facilities, but also a dramatic growth in the excellence of radiation oncology specialist staff nationwide

  10. Gene regulation by growth factors

    International Nuclear Information System (INIS)

    Metz, R.; Gorham, J.; Siegfried, Z.; Leonard, D.; Gizang-Ginsberg, E.; Thompson, M.A.; Lawe, D.; Kouzarides, T.; Vosatka, R.; MacGregor, D.; Jamal, S.; Greenberg, M.E.; Ziff, E.B.

    1988-01-01

    To coordinate the proliferation and differentiation of diverse cell types, cells of higher eukaryotes communicate through the release of growth factors. These peptides interact with specific transmembrane receptors of other cells and thereby generate intracellular messengers. The many changes in cellular physiology and activity that can be induced by growth factors imply that growth factor-induced signals can reach the nucleus and control gene activity. Moreover, current evidence also suggests that unregulated signaling along such pathways can induce aberrant proliferation and the formation of tumors. This paper reviews investigations of growth factor regulation of gene expression conducted by the authors' laboratory

  11. Fast growth associated with aberrant vasculature and hypoxia in fibroblast growth factor 8b (FGF8b) over-expressing PC-3 prostate tumour xenografts

    International Nuclear Information System (INIS)

    Tuomela, Johanna; Solin, Olof; Minn, Heikki; Härkönen, Pirkko L; Grönroos, Tove J; Valta, Maija P; Sandholm, Jouko; Schrey, Aleksi; Seppänen, Jani; Marjamäki, Päivi; Forsback, Sarita; Kinnunen, Ilpo

    2010-01-01

    Prostate tumours are commonly poorly oxygenated which is associated with tumour progression and development of resistance to chemotherapeutic drugs and radiotherapy. Fibroblast growth factor 8b (FGF8b) is a mitogenic and angiogenic factor, which is expressed at an increased level in human prostate tumours and is associated with a poor prognosis. We studied the effect of FGF8b on tumour oxygenation and growth parameters in xenografts in comparison with vascular endothelial growth factor (VEGF)-expressing xenografts, representing another fast growing and angiogenic tumour model. Subcutaneous tumours of PC-3 cells transfected with FGF8b, VEGF or empty (mock) vectors were produced and studied for vascularity, cell proliferation, glucose metabolism and oxygenation. Tumours were evaluated by immunohistochemistry (IHC), flow cytometry, use of radiolabelled markers of energy metabolism ([ 18 F]FDG) and hypoxia ([ 18 F]EF5), and intratumoral polarographic measurements of pO 2 . Both FGF8b and VEGF tumours grew rapidly in nude mice and showed highly vascularised morphology. Perfusion studies, pO 2 measurements, [ 18 F]EF5 and [ 18 F]FDG uptake as well as IHC staining for glucose transport protein (GLUT1) and hypoxia inducible factor (HIF) 1 showed that VEGF xenografts were well-perfused and oxygenised, as expected, whereas FGF8b tumours were as hypoxic as mock tumours. These results suggest that FGF8b-induced tumour capillaries are defective. Nevertheless, the growth rate of hypoxic FGF8b tumours was highly increased, as that of well-oxygenised VEGF tumours, when compared with hypoxic mock tumour controls. FGF8b is able to induce fast growth in strongly hypoxic tumour microenvironment whereas VEGF-stimulated growth advantage is associated with improved perfusion and oxygenation of prostate tumour xenografts

  12. Relative Risks of Contributing Factors to Morbidity and Mortality in Adults With Craniopharyngioma on Growth Hormone Replacement.

    Science.gov (United States)

    Yuen, Kevin C J; Mattsson, Anders F; Burman, Pia; Erfurth, Eva-Marie; Camacho-Hubner, Cecilia; Fox, Janet L; Verhelst, Johan; Geffner, Mitchell E; Abs, Roger

    2018-02-01

    In adults, craniopharyngioma (CP) of either childhood-onset (CO-CP) or adult-onset (AO-CP) is associated with increased morbidity and mortality, but data on the relative risks (RRs) of contributing factors are lacking. To assess the RRs of factors contributing to morbidity and mortality in adults with CO-CP and AO-CP. Data on 1669 patients with CP from KIMS (Pfizer International Metabolic Database) were analyzed using univariate and multiple Poisson and Cox regression methods. When CO-CP and AO-CP groups were combined, history of stroke and hyperlipidemia increased cardiovascular risk, higher body mass index (BMI) and radiotherapy increased cerebrovascular risk, and increased waist circumference increased the risk of developing diabetes mellitus (DM). Compared with patients with CO-CP, patients with AO-CP had a threefold higher risk of tumor recurrence, whereas being female and previous radiotherapy exposure conferred lower risks. Radiotherapy and older age with every 10 years from disease onset conferred a 2.3- to 3.5-fold risk for developing new intracranial tumors, whereas older age, greater and/or increasing BMI, history of stroke, and lower insulinlike growth factor I (IGF-I) standard deviation score measured at last sampling before death were related to increased all-cause mortality. Compared with the general population, adults with CP had 9.3-, 8.1-, and 2.2-fold risks of developing DM, new intracranial tumors, and early death, respectively. Conventional factors that increase the risks of cardio- and cerebrovascular diseases and DM and risks for developing new intracranial tumors contributed to excess morbidity and mortality. In addition, lower serum IGF-I level measured from the last sample before death was inversely associated with mortality risk in patients with CP. Copyright © 2017 Endocrine Society

  13. Radiotherapy for asymptomatic brain metastasis in epidermal growth factor receptor mutant non-small cell lung cancer without prior tyrosine kinase inhibitors treatment: a retrospective clinical study

    International Nuclear Information System (INIS)

    Liu, SongRan; Qiu, Bo; Chen, LiKun; Wang, Fang; Liang, Ying; Cai, PeiQiang; Zhang, Li; Chen, ZhaoLin; Liu, ShiLiang; Liu, MengZhong; Liu, Hui

    2015-01-01

    Non-small cell lung cancer (NSCLC) with brain metastasis (BM) harboring an epidermal growth factor receptor (EGFR) mutation shows good response to tyrosine kinase inhibitors (TKIs). This study is to assess the appropriate timing of brain radiotherapy (RT) for asymptomatic BM in EGFR mutant NSCLC patients. There were 628 patients diagnosed with EGFR mutant NSCLC between October 2005 and December 2011. Treatment outcomes had been retrospectively evaluated in 96 patients with asymptomatic BM without prior TKI treatment. 39 patients received first-line brain RT, 23 patients received delayed brain RT, and 34 patients did not receive brain RT. With a median follow-up of 26 months, the 2-year OS was 40.6 %. Univariate analyses revealed that ECOG performance status (p = 0.006), other distant metastases (p = 0.002) and first line systemic treatment (p = 0.032) were significantly associated with overall survival (OS). Multivariate analyses revealed that other sites of distant metastases (p = 0.030) were prognostic factor. The timing of brain RT was not significantly related to OS (p = 0.246). The 2-year BM progression-free survival (PFS) was 26.9 %. Brain RT as first-line therapy failed to demonstrate a significant association with BM PFS (p = 0.643). First-line brain RT failed to improve long-term survival in TKI-naïve EGFR mutant NSCLC patients with asymptomatic BM. Prospective studies are needed to validate these clinical findings

  14. Neonatal hyperthyroidism impairs epinephrine-provoked secretion of nerve growth factor and epidermal growth factor in mouse saliva.

    Science.gov (United States)

    Lakshmanan, J; Landel, C P

    1986-07-01

    We examined long-term effects of neonatal hyperthyroidism on salivary secretions of nerve growth factor and epidermal growth factor in male and female mice at the age of 31 days. Hyperthyroidism was induced by thyroxine (T4) injections (0.4 microgram/g body weight/day) during days 0-6. Littermate control mice were treated with vehicle. T4 treatment did not alter the amounts of protein secreted into saliva but hormone administration induced alteration in the types of protein secreted. T4 treatment decreased the contents of both nerve growth factor and epidermal growth factor secreted into the saliva. A Sephadex G-200 column chromatographic profile revealed the presence of two distinct nerve growth factor immunoreactive peaks, while epidermal growth factor immunoreactivity predominantly eluted as a single low molecular weight form. T4 treatment did not alter the molecular nature of their secretion, but the treatment decreased their contents. These results indicate an impairment in salivary secretion of nerve growth factor and epidermal growth factor long after T4 treatment has been discontinued.

  15. Fibroblast growth factor receptors in breast cancer.

    Science.gov (United States)

    Wang, Shuwei; Ding, Zhongyang

    2017-05-01

    Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of breast cancer. Recent genetic studies have identified some subtypes of fibroblast growth factor receptors as strong genetic loci associated with breast cancer. In this article, we review the recent epidemiological findings and experiment results of fibroblast growth factor receptors in breast cancer. First, we summarized the structure and physiological function of fibroblast growth factor receptors in humans. Then, we discussed the common genetic variations in fibroblast growth factor receptors that affect breast cancer risk. In addition, we also introduced the potential roles of each fibroblast growth factor receptors isoform in breast cancer. Finally, we explored the potential therapeutics targeting fibroblast growth factor receptors for breast cancer. Based on the biological mechanisms of fibroblast growth factor receptors leading to the pathogenesis in breast cancer, targeting fibroblast growth factor receptors may provide new opportunities for breast cancer therapeutic strategies.

  16. Salivary gland carcinomas: prognostic factors for local control and distant metastasis, the role of radiotherapy

    International Nuclear Information System (INIS)

    Terhaard, C.H.J.; Lubsen, H.; Tweel, I. van der; Hilgers, F.J.M.; Eijkenboom, W.M.H.; Marres, H.A.M.; Tjho-Heslinga, R.E.; Jong, J.M.A. de; Roodenburg, J.L.N.

    1997-01-01

    Purpose: The Dutch Head and Neck Oncology Cooperative Group, in which head and neck groups of all University hospitals and the two cancer institutes are represented, initiated a retrospective study concerning salivary gland carcinomas. A majority of Dutch patients with head and neck carcinomas are treated in the participating centres, and the follow-up is precise. Prognostic factors for local control and survival were studied, with special interest in the role of treatment and the role of histologic type. Methods and materials: Results were obtained of 568 patients with a mean follow-up time of 5 years. The parotid gland was involved in 59%, the submandibular gland in 14%, oral cavity in 24% and 3% was located elsewhere. Mean age was 59 years (range 8-100 yr), 48% was female. T-stage was T 1 in 27%, T 2 in 44%, T 3 in 19% and T 4 in 11%. Positive necknodes were seen in 15%, 3% was initially M 1 . Histologic type was acinic cell carcinoma in 12%, mucoepidermoid ca. in 16%, adenoid cystic ca. in 26%, adenoca. in 24%, carcinoma in pleomorphic adenoma in 8%, squamous cell ca. in 6% and undifferentiated ca. in 7%. Resection margins were radical in 37%, close in 20% and irradical in 40% (3% unknown). Surgery was the primary treatment in 501 patients, combined with postoperative radiotherapy (50-70 Gy, mean dose 62 Gy) in 389 patients. Radiotherapy was the primary treatment in 40 patients (18 M 1 , 30% N+), 20 patients were not treated and 7 patients were treated otherwise. For statistical analysis the Cox PH regression analysis was used (SPSS-PC+). Results: Actuarial local control after 8 years was 80% for surgery alone and 92% for the combined modality (in which more advanced cases prevaled). Independent factors for local control in the surgery±radiotherapy group were: I:T-stage (T 3 vs T 1-2 : RR 3.7; T 4 vs T 1-2 : RR 11.7), II: anatomic site (oral cavity vs parotid and submandibular gland: RR 0.2) and III: treatment modality (surgery alone vs surgery+radiotherapy

  17. Factors that influence the QOL of cancer patients who have undergone radiotherapy as outpatients

    International Nuclear Information System (INIS)

    Senuma, Maiko; Shinoda, Shizuyo; Kitada, Yoko; Takei, Akemi; Kanda, Kiyoko; Seyama, Ruka; Igarashi, Reiko

    2011-01-01

    The purpose of this study was to elucidate the factors that influence the QOL of cancer patients who have undergone radiotherapy in the outpatient setting. The patient's quality of life (QOL) was investigated by using the QOL evaluation standard functional assessment of cancer therapy-general (FACT-G) in 73 cancer patients (mean age 64.2±12.2 yrs standard deviation (SD)) who had undergone radiotherapy as outpatients. The mean QOL score was 74.8±17.1 pointy, and a significant difference was seen in about 25 items as a result of examining the factors that influenced the patient's QOL. In addition, a stepwise multiple regression analysis revealed that the factors which influenced the QOL were the operation due to the original disease, social support (excluding the family), tiredness, relapse and the metastasis, performance status (PS), uneasiness of presence in descending order of influence. The results revealed the strong influence of psychological, mental and social factors on the QOL score. From the patient of view of nursing support for cancer patients, screening for these factors may allow earlier detection of any decrease in the QOL, or identify when the QOL has already decreased. Furthermore, support should be initiated at as early a stage as possible. (author)

  18. Effects of Intrinsic and Extrinsic Factors on the Level of Hope and Psychological Health Status of Patients with Cervical Cancer During Radiotherapy.

    Science.gov (United States)

    Li, Li-Rong; Lin, Mei-Guang; Liang, Juan; Hu, Qiong-Yan; Chen, Dan; Lan, Meng-Ying; Liang, Wu-Qing; Zeng, Yu-Ting; Wang, Ting; Fu, Gui-Fen

    2017-07-19

    BACKGROUND This study aimed to explore the factors affecting the level of hope and psychological health status of patients with cervical cancer (CC) during radiotherapy. MATERIAL AND METHODS A total of 480 CC patients were recruited. Psychological distress scale, Herth hope index, functional assessment cancer therapy-cervix, and Jolowiec coping scale were used to conduct surveys on psychological distress, level of hope, quality of life (QOL), and coping style to analyze the factors affecting the level of hope and psychological health status of CC patients. RESULTS The morbidity of significant psychological distress in 480 CC patients during radiotherapy was 68%, and the main factors causing psychological distress were emotional problems and physical problems. During radiotherapy, most patients had middle and high levels of hope, and the psychological distress index of patients was negatively correlated with the level of hope. The QOL of CC patients during radiotherapy were at middle and high levels, and the QOL was positively correlated with confrontment, optimism, appeasement, and self-reliance, but it was negatively correlated with predestination and emotional expression. CONCLUSIONS For CC patients during radiotherapy, the morbidity of psychological distress was high, but they were at middle and high levels of hope.

  19. Fibroblast growth factor 2 is of prognostic value for patients with locally advanced squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Rades, D.; Seibold, N.D.; Gebhard, M.P.; Noack, F.; Schild, S.E.

    2014-01-01

    Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients treated with surgery followed by radiotherapy. The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95 %-confidence interval (CI): 2.88-19.05; p < 0.001], lower T-category (RR: 2.42; 95 %-CI: 1.47-4.33; p < 0.001), lower N-category (RR: 12.36; 95 %-CI: 3.48-78.91; p < 0.001), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 4.18; 95 %-CI: 1.73-10.53; p = 0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95 %-CI: 0.97-2.82; p = 0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22-11.80; p < 0.001), lower T-category (RR: 2.17; 95 %-CI: 1.38-3.68; p < 0.001), lower N-category (RR: 3.86; 95 %-CI: 1.60-10.85; p = 0.002), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 3.20; 95 %-CI: 1.46-7.30; p = 0.004). HPV-positivity showed a trend (RR: 2.36; 95 %-CI: n.a.; p = 0.054). Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials. (orig.)

  20. Fibroblast growth factor 2 is of prognostic value for patients with locally advanced squamous cell carcinoma of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D.; Seibold, N.D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); Gebhard, M.P.; Noack, F. [University of Luebeck, Institute of Pathology, Luebeck (Germany); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale (United States)

    2014-01-15

    Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients treated with surgery followed by radiotherapy. The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95 %-confidence interval (CI): 2.88-19.05; p < 0.001], lower T-category (RR: 2.42; 95 %-CI: 1.47-4.33; p < 0.001), lower N-category (RR: 12.36; 95 %-CI: 3.48-78.91; p < 0.001), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 4.18; 95 %-CI: 1.73-10.53; p = 0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95 %-CI: 0.97-2.82; p = 0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22-11.80; p < 0.001), lower T-category (RR: 2.17; 95 %-CI: 1.38-3.68; p < 0.001), lower N-category (RR: 3.86; 95 %-CI: 1.60-10.85; p = 0.002), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 3.20; 95 %-CI: 1.46-7.30; p = 0.004). HPV-positivity showed a trend (RR: 2.36; 95 %-CI: n.a.; p = 0.054). Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials. (orig.)

  1. Comparison of radioimmunotherapy and external beam radiotherapy in colon cancer xenografts

    International Nuclear Information System (INIS)

    Buras, R.R.; Wong, J.F.C.; Kuhn, J.A.; Beatty, B.G.; Williams, L.E.; Beatty, J.D.; Wanek, P.M.

    1993-01-01

    Radioimmunotherapy and external beam radiotherapy were compared in a nude mouse human colon cancer model. Radioimmunotherapy was delivered by intraperitoneal injection of 90 Y-labeled anticarcinoembryonic antigen monoclonal antibody (anti-CEA MAB). Single fraction external beam radiotherapy was delivered using a 60 Co teletherapy unit. Control groups received saline, unlabeled anit-CEA monoclonal antibody and labeled nonspecific monoclonal antibody. Tumor growth suppression was expressed as delay to reach 2g compared to saline controls. Unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody had no effect. External beam radiotherapy of 300, 600, 1000 and 2000 cGy produced growth delays of 3, 12, 17, and 22 days, respectively. Radioimmunotherapy with 120 μCi, 175 μCi, and 225 μCi resulted in growth delays of 20, 34, and 36 days. Estimated absorbed tumor dose was 1750 cGy in the 120 μCi group. Similar comparisons were done with the more radioresistant WiDr human colon carcinoma cell line. External beam radiotherapy doses of 400, 800, 1200, and 1600 cGy resulted in growth delays of 6, 21, 36 and 48 days, respectively. Radioimmunotherapy of 120 μCi and 175 μCi resulted in growth delays of 9 and 19 days, respectively. The 120 μCi dose delivered an estimated absorbed tumor dose of 1080 cGy to WiDr tumors. In summary, for the radiosensitive LS174T line, radioimmunotherapy produced biologic effects that were comparable to a similar dose of single fraction external beam radiotherapy. For the more radioresistant WiDr tumor, radioimmunotherapy produced a biologic effect which was less than a similar dose of single fraction external beam radiotherapy. These studies suggest that a tumor's response to radioimmunotherapy relative to that of external beam radiotherapy is, in part, dependent on tumor radiosensitivity and repair capacity. 23 refs., 5 figs. 4 tabs

  2. Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness.

    Science.gov (United States)

    Nakagawa, S; Pawelek, P; Grinnell, F

    1989-06-01

    To learn more about the relationship between extracellular matrix organization, cell shape, and cell growth control, we studied DNA synthesis by fibroblasts in collagen gels that were either attached to culture dishes or floating in culture medium during gel contraction. After 4 days of contraction, the collagen density (initially 1.5 mg/ml) reached 22 mg/ml in attached gels and 55 mg/ml in floating gels. After contraction, attached collagen gels were well organized; collagen fibrils were aligned in the plane of cell spreading; and fibroblasts had an elongated, bipolar morphology. Floating collagen gels, however, were unorganized; collagen fibrils were arranged randomly; and fibroblasts had a stellate morphology. DNA synthesis by fibroblasts in contracted collagen gels was suppressed if the gels were floating in medium but not if the gels were attached, and inhibition was independent of the extent of gel contraction. Therefore, growth of fibroblasts in contracted collagen gels could be regulated by differences in extracellular matrix organization and cell shape independently of extracellular matrix density. We also compared the responses of fibroblasts in contracted collagen gels and monolayer culture to peptide growth factors including fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, and interleukin 1. Cells in floating collagen gels were generally unresponsive to any of the growth factors. Cells in attached collagen gels and monolayer culture were affected similarly by fibroblast growth factor but not by the others. Our results indicate that extracellular matrix organization influenced not only cell growth, but also fibroblast responsiveness to peptide growth factors.

  3. New microbial growth factor

    Science.gov (United States)

    Bok, S. H.; Casida, L. E., Jr.

    1977-01-01

    A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

  4. Postoperative radiotherapy in patients with salivary duct carcinoma. Clinical outcomes and prognostic factors

    International Nuclear Information System (INIS)

    Shinoto, Makoto; Shioyama, Yoshiyuki; Nakamura, Katsumasa

    2013-01-01

    This study sought to investigate the clinical outcome and the role of postoperative radiotherapy for patients with salivary duct carcinoma (SDC) who had undergone surgery and postoperative radiotherapy. We performed a retrospective analysis of 25 SDC patients treated between 1998 and 2011 with surgery and postoperative radiotherapy. The median prescribed dose was 60 Gy (range, 49.5-61.4 Gy). The clinical target volume (CTV) was defined as the tumor bed in four patients, the tumor bed and ipsilateral neck in 14 patients, and the tumor bed and bilateral neck in six patients. Local control (LC), disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The 5-year LC, DFS and OS were 67%, 45% and 47%, respectively. Disease recurrence was found in 12 patients: seven as local, four as regional and eight as distant failure. Perineural and lymphovascular invasion was a significant prognostic factor for LC (P=0.03). Local failure was common, and the presence of local recurrence significantly affected the OS (P<0.05). We conclude that surgery and postoperative radiotherapy is expected to decrease the risk of local failure and contribute to good prognoses for patients with SDC. It might be advisable to have the CTV include the cranial nerves involved and the corresponding parts of the skull base in cases of pathologically positive perineural invasion. (author)

  5. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  6. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    International Nuclear Information System (INIS)

    Nandy, Debashis; Mukhopadhyay, Debabrata

    2011-01-01

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

  7. Distress screening using distress thermometer in head and neck cancer patients undergoing radiotherapy and evaluation of causal factors predicting occurrence of distress

    Directory of Open Access Journals (Sweden)

    Shirley Lewis

    2013-01-01

    Full Text Available Introduction: Distress is commonly seen in head and neck cancer patients undergoing radiotherapy. Causal factors of distress are multifactorial; which encompasses physical, psychological, spiritual, and existential factors with complex interrelationship among the factors. Materials and Methods: Thirty patients undergoing head and neck radiotherapy were included in the study. Patients were screened for pain scores, distress scores, physical and psychological symptoms, and spiritual and emotional distress. Results: Significant increasing trend seen for pain score, distress score, and total number of symptoms during 2 nd week, 4 th week, and on completion of radiotherapy treatment (all P′s < 0.001 compared to pretreatment. Those who had chemotherapy (CT along with radiation had significantly greater pain score (t = 5.54, P = 0.03 and distress score (t = 3.9, P = 0.05 at 2 weeks into radiotherapy compared to those who did not receive CT. There was significantly higher grade of skin toxicity in those with spiritual distress (Somers′ d = 0.36, P = 0.02 and higher grade of mucositis in those with existential distress (d = 0.34, P = 0.02 at 4 weeks into radiotherapy. Conclusion: Positive correlation between distress score and pain score and occurrence of physical symptoms. Increasing trend seen for pain score, distress score, and total number of symptoms during 2 nd week, 4 th week, and completion of radiotherapy treatment compared to pretreatment. Increase in distress score in those with existential and spiritual distress.

  8. Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.

    Science.gov (United States)

    Bortvedt, Sarah F; Lund, P Kay

    2012-03-01

    To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.

  9. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  10. Temporal lobe injury after re-irradiation of locally recurrent nasopharyngeal carcinoma using intensity modulated radiotherapy: clinical characteristics and prognostic factors.

    Science.gov (United States)

    Liu, Shuai; Lu, Taixiang; Zhao, Chong; Shen, Jingxian; Tian, Yunming; Guan, Ying; Zeng, Lei; Xiao, Weiwei; Huang, Shaomin; Han, Fei

    2014-09-01

    Temporal lobe injury (TLI) is a debilitating complication after radiotherapy for nasopharyngeal carcinoma (NPC), especially in patients who suffer treatment relapses and receive re-irradiation. We explored the clinical characteristics and prognostic factors of TLI in locally recurrent NPC (rNPC) patients after re-irradiation using intensity modulated radiotherapy (IMRT). A total of 454 temporal lobes (TLs) from 227 locally rNPC patients were reviewed. The clinical characteristics of TLI were analyzed. In the two radiotherapy courses, the equivalent dose in 2 Gy per fraction (EQD2) for the TLs was recalculated to facilitate comparison of the individual data. The median follow-up time was 31 (range, 3-127) months. After re-irradiation using IMRT, 31.3 % (71/227) of patients developed TLI. The median latency of TLI was 15 (range, 4-100) months. Univariate and multivariate analysis showed that the interval time (IT) between the two courses of radiotherapy and the summation of the maximum doses of the two radiotherapy courses (EQD2 - ∑max) were independent factors influencing TLI. The 5-year incidence of TLI for an IT ≤26 or >26 months was 35.9 and 53.7 % respectively (p = 0.024). The median maximum doses delivered to the injured TLs were significantly higher than was the case for the uninjured TLs after two courses of radiotherapy (135.3 and 129.8 Gy, respectively: p 2-year interval was found to be relatively safe.

  11. In vitro cytotoxicity of human recombinant tumor necrosis factor alpha in association with radiotherapy in a human ovarian carcinoma cell line

    International Nuclear Information System (INIS)

    Manetta, A.; Lucci, J.; Soopikian, J.; Granger, G.; Berman, M.L.; DiSaia, P.J.

    1990-01-01

    It has been speculated that tumor necrosis factor alpha (TNF-alpha) may decrease the cytotoxicity of radiotherapy by increasing the scavenging of toxic superoxide radicals. Because of the possible clinical implications, the cytotoxicity of TNF-alpha in combination with radiotherapy (RT) was compared with that of RT alone in a human ovarian cancer cell line. NIH:OVCAR-3 cells were incubated with TNF-alpha at 10.0, 1.0, 0.1, and 0.01 microgram/ml. Plates were divided into two groups; one received 150 cGy of radiotherapy and the other received no further therapy. Seventy-two hours later, supernatants were aspirated and viable cells were stained with a 1% solution of crystal violet. Survival of cells treated with RT plus TNF-alpha was expressed as a percentage of surviving irradiated controls. Analysis of results revealed minimal additive cell killing effect between TNF-alpha and radiotherapy at all concentrations of tumor necrosis factor, with the greatest difference noted in the group treated with 10 micrograms/ml TNF-alpha. A continued radiotherapy dose-response study with TNF-alpha showed a similar additive, not radioprotective, effect. This may have implication as a potentiator of RT in some human tumors

  12. The role of radiotherapy in the management of POEMS syndrome

    OpenAIRE

    Suh, Yang-Gun; Kim, Young-Suk; Suh, Chang-Ok; Kim, Yu Ri; Cheong, June-Won; Kim, Jin Seok; Cho, Jaeho

    2014-01-01

    Background POEMS syndrome is a paraneoplastic syndrome caused by an underlying plasma cell proliferative disease. In this study, we examined the treatment outcomes and role of radiotherapy in the management of POEMS syndrome. Methods In total, 33 patients diagnosed with POEMS syndrome were analyzed. These patients presented with osteosclerotic myeloma (OSM, n = 13), Castleman’s disease (CD, n = 4), OSM with CD (n = 10), and vascular endothelial growth factor elevation without gross lesions (V...

  13. Prognostic impact of placenta growth factor and vascular endothelial growth factor A in patients with breast cancer

    DEFF Research Database (Denmark)

    Maae, Else; Olsen, Dorte Aalund; Steffensen, Karina Dahl

    2012-01-01

    Placenta growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A) are angiogenic growth factors interacting competitively with the same receptors. VEGF-A is essential in both normal and pathologic conditions, but the functions of PlGF seem to be restricted to pathologic conditions s...

  14. Effect of epidermal growth factor against radiotherapy-induced oral mucositis in rats

    International Nuclear Information System (INIS)

    Lee, Sang-wook; Jung, Kwon Il; Kim, Yeun Wha B.S.; Jung, Heun Don; Kim, Hyun Sook; Hong, Joon Pio

    2007-01-01

    Purpose: We tested the efficacy of oral recombinant human epidermal growth factor (rhEGF) against radiation-induced oral mucositis in a rat model. Methods and Materials: Each of 35 Sprague-Dawley rats, 7 to 8 weeks of age and weighing 178 ± 5 grams, was irradiated once in the head region with 25 Gy, using a 4-MV therapeutic linear accelerator at a rate of 2 Gy/min. The irradiated rats were randomly divided into four groups: those receiving no treatment (Group 1), those treated with vehicle only three times per day (Group 2), and those treated with 50 μg/mL (Group 3), or 100 μg/mL (Group 4) rhEGF three times per day. Results: Rats were monitored for survival rate and daily activity, including hair loss, sensitivity, and anorexia. We found that survival rate and oral intake were significantly increased and histologic changes were significantly decreased in the rhEGF-treated rats. There was no difference, however, between rats treated with 50 μg/mL or 100 μg/mL rhEGF. Conclusion: These findings suggest that orally administered rhEGF decreased radiation-induced oral mucositis in rats

  15. Role of tumor size in radiotherapy using modifiers

    International Nuclear Information System (INIS)

    Kozin, S.V.; Furmanchuk, A.V.

    1990-01-01

    Consideration is given to present-day knowledge about changes, taking place in malignant tumor tissues during their growth, important for results of radiotherapy, using modifiers, from a radiobiological viewpoint. It is shown that hypertermia (HT) is the most effective adjuvant of radiotherapy for medium - and large-size tumors. The combined application of artificial hyperglycemia (AH) and HT is investigated as the method for increasing efficiency of radiotherapy. Efficiency of using radioprotectors and electron-acceptor compounds (metronidazole, misonidazole) for large-size malignant tumors in combinations-metronidazole with AH and misonidazole with HT-is noted. Analysis of these data on radiotherapy efficiency depending on size of irradiated tumors will enable an evaluation of radiotherapy potential in different cases in determining the advisability of modifier application

  16. Release kinetics of platelet-derived and plasma-derived growth factors from autologous plasma rich in growth factors.

    Science.gov (United States)

    Anitua, Eduardo; Zalduendo, Mari Mar; Alkhraisat, Mohammad Hamdan; Orive, Gorka

    2013-10-01

    Many studies have evaluated the biological effects of platelet rich plasma reporting the final outcomes on cell and tissues. However, few studies have dealt with the kinetics of growth factor delivery by plasma rich in growth factors. Venous blood was obtained from three healthy volunteers and processed with PRGF-Endoret technology to prepare autologous plasma rich in growth factors. The gel-like fibrin scaffolds were then incubated in triplicate, in a cell culture medium to monitor the release of PDGF-AB, VEGF, HGF and IGF-I during 8 days of incubation. A leukocyte-platelet rich plasma was prepared employing the same technology and the concentrations of growth factors and interleukin-1β were determined after 24h of incubation. After each period, the medium was collected, fibrin clot was destroyed and the supernatants were stored at -80°C until analysis. The growth factor delivery is diffusion controlled with a rapid initial release by 30% of the bioactive content after 1h of incubation and a steady state release when almost 70% of the growth factor content has been delivered. Autologous fibrin matrix retained almost 30% of the amount of the growth factors after 8 days of incubation. The addition of leukocytes to the formula of platelet rich plasma did not increase the concentration of the growth factors, while it drastically increased the presence of pro-inflammatory IL-1β. Further studies employing an in vitro inflammatory model would be interesting to study the difference in growth factors and pro-inflammatory cytokines between leukocyte-free and leukocyte-rich platelet rich plasma. Copyright © 2013 Elsevier GmbH. All rights reserved.

  17. Fibroblast growth factor 2 and DNA repair involvement in the keratinocyte stem cells response to ionizing radiation

    International Nuclear Information System (INIS)

    Harfouche, L'Emira Ghida

    2010-02-01

    Keratinocyte stem cells (KSCs) from the human inter follicular epidermis are regarded as the major target to radiation during radiotherapy. We found herein that KSCs are more resistant to ionizing radiation than their direct progeny, and presented more rapid DNA damage repair kinetics than the progenitors. Furthermore, we provided evidence describing the effect of fibroblast growth factor 2 (FGF2) signaling on the ability of KSCs and progenitors to repair damaged DNA. Despite our knowledge of the fact, that FGF is an anti-apoptotic factor in multiple cell types, the direct link between DNA repair and FGF2 signaling has rarely been shown. Existence of such link is an important issue with implications not only to stem cell field but also to cancer therapy. (author)

  18. Evaluating predictive factors for determining enteral nutrition in patients receiving radical radiotherapy for head and neck cancer: A retrospective review

    International Nuclear Information System (INIS)

    Mangar, Stephen; Slevin, Nicholas; Mais, Kathleen; Sykes, Andrew

    2006-01-01

    Background and purpose: To identify objective pre-treatment clinical parameters that could be used to predict for patients at high risk of requiring enteral tube feeding prior to head and neck radiotherapy. Patients and methods: A retrospective study was conducted on 160 consecutive patients attending for radiotherapy assessment. Regression analysis was used to determine various pre-treatment nutritional and tumour specific parameters associated with the use of enteral nutrition either before (prophylactic) or during (reactive) radiotherapy (RT). The significant parameters identified were then selected into categorical variables and compared between those who needed reactive enteral nutrition and the remainder of the group who did not. These results were used to generate predictive factors that could be used to identify those at high risk of malnutrition during RT for whom early or prophylactic enteral nutrition should be considered. Results: Fifty patients required enteral feeding of which 60% required this prior to radiotherapy. Multivariate analysis identified the following factors to be significant-body mass index, performance status (PS), advanced stage, pre-treatment weight loss, low serum albumin and protein, age, and smoking. The most significant categorical predictive parameters for reactive enteral feeding were stage 3-4 disease, PS 2-3, and smoking >20/day. The combination of these factors predicted a 75% chance of needing enteral nutrition. Conclusion: Nutritional assessment is important prior to radiotherapy and is multifactorial. Using a combination of relatively simple and objective parameters (performance status, smoking and disease stage) it is possible to identify those at high risk of needing enteral nutrition prior to starting RT

  19. Impact of adjuvant inhibition of vascular endothelial growth factor receptor tyrosine kinases on tumor growth delay and local tumor control after fractionated irradiation in human squamous cell carcinomas in nude mice

    International Nuclear Information System (INIS)

    Zips, Daniel; Hessel, Franziska; Krause, Mechthild; Schiefer, Yvonne; Hoinkis, Cordelia; Thames, Howard D.; Haberey, Martin; Baumann, Michael

    2005-01-01

    Purpose: Previous experiments have shown that adjuvant inhibition of the vascular endothelial growth factor receptor after fractionated irradiation prolonged tumor growth delay and may also improve local tumor control. To test the latter hypothesis, local tumor control experiments were performed. Methods and materials: Human FaDu and UT-SCC-14 squamous cell carcinomas were studied in nude mice. The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 (50 mg/kg body weight b.i.d.) was administered for 75 days after irradiation with 30 fractions within 6 weeks. Tumor growth time and tumor control dose 50% (TCD 50 ) were determined and compared to controls (carrier without PTK787/ZK222584). Results: Adjuvant administration of PTK787/ZK222584 significantly prolonged tumor growth time to reach 5 times the volume at start of drug treatment by an average of 11 days (95% confidence interval 0.06;22) in FaDu tumors and 29 days (0.6;58) in UT-SCC-14 tumors. In both tumor models, TCD 50 values were not statistically significantly different between the groups treated with PTK787/ZK222584 compared to controls. Conclusions: Long-term inhibition of angiogenesis after radiotherapy significantly reduced the growth rate of local recurrences but did not improve local tumor control. This indicates that recurrences after irradiation depend on vascular endothelial growth factor-driven angiogenesis, but surviving tumor cells retain their clonogenic potential during adjuvant antiangiogenic treatment with PTK787/ZK222584

  20. Insulin-like growth factor I (IGF-1) Ec/Mechano Growth factor--a splice variant of IGF-1 within the growth plate.

    Science.gov (United States)

    Schlegel, Werner; Raimann, Adalbert; Halbauer, Daniel; Scharmer, Daniela; Sagmeister, Susanne; Wessner, Barbara; Helmreich, Magdalena; Haeusler, Gabriele; Egerbacher, Monika

    2013-01-01

    Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

  1. Hypoxia-targeted suicidal gene therapy system enhances antitumor effects of radiotherapy

    International Nuclear Information System (INIS)

    Liu Junye; Guo Yao; Guo Guozhen

    2006-01-01

    Objective: To explore the effects of hypoxia-targeted suicidal gene therapy system combined with radiotherapy on pancreatic cancer. Methods: The recombinant adenovirus Ad-5HRE/hCMVmp-BCD was constructed by DNA recombinant technique. Western blot was used to detect hypoxia-induced expression of bacterial cytosine deaminase (BCD). Cell growth inhibition assay was used to determine the sensitivity of human pancreatic cancer cells MIA-PACA2 to 5-fluorocytosine (5-FC). Tumor xenograft growth delay assays was used to evaluate the effects of Ad-5HRE/hCMVmp-BCD/5-FC combined with radiotherapy on pancreatic cancer. Results: Western blot analysis demonstrated that hypoxia-induced BCD protein expression was achieved in MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD. With hypoxia treatment, the sensitivity of MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD to 5-FC significantly increased. Administration of either Ad-5HRE/hCMVmp-BCD/5-FC or radiotherapy could inhibit the growth of MIA-PACA2 xenografts in nude mice. Moreover, combination of Ad-5HRE/hCMVmp-BCD/5-FC could significantly enhance suppressing effects of radiotherapy on MIA-PACA2 xenografts. Conclusion: Hypoxia-targeted suicidal gene therapy system Ad-5HRE/hCMVmp-BCD/5-FC could enhance antitumor effects of radiotherapy on pancreatic cancer and can be used as a powerful adjunct to conventional radiotherapy. (authors)

  2. Unintended exposure in radiotherapy: Identification of prominent causes

    International Nuclear Information System (INIS)

    Boadu, Mary; Rehani, Madan Mohan

    2009-01-01

    Background and purpose: Unintended exposures in radiotherapy are likely to occur when certain conditions that favour such exposures exist. Based on the frequency of occurrence of various causes of 100 events of unintended exposures in radiotherapy as derived from the analysis of published reports, a checklist for assessing the vulnerability of radiotherapy facilities for potential accidents has been prepared. The list presents items to be considered for safety critical assessments of a radiotherapy department for the improvement of patient safety and the entire radiotherapy processes. Materials and methods: The resources used for this paper consist of 100 unintended radiotherapy exposures and were derived from existing published reports. The analysis was performed by forming two templates: one consisting of 10 initiating events and another of 35 contributing factors. Results: Four most prominent initiating events were identified and together accounted for about 70% of all the unintended exposure events. Ten most prominent contributing factors were also identified and together accounted for about 70% of all the radiotherapy unintended exposure events covered under this study. Conclusion: With this knowledge of high frequency of occurrences, the identified four prominent initiating events and the 10 most prominent contributing factors must be checked and dealt with as a matter of priority when assessing the safety of a radiotherapy facility. A simple checklist for checking the quality assurance programmes of a radiotherapy department for every aspect of the design and delivery of radiation have been provided.

  3. Radiotherapy services in countries in transition: gross national income per capita as a significant factor

    International Nuclear Information System (INIS)

    Levin, Victor; Tatsuzaki, Hideo

    2002-01-01

    Background and purpose: The acquisition of radiotherapy by countries in transition (CITs) is an evolutionary process from having no resources whatsoever, to meeting the standards adopted by well-developed countries. The influence of the economic ability of a country to acquire and sustain this technology has intuitively been accepted as a major factor but has not before been subjected to analysis for a large group of countries. This information has been analysed to provide guidance to countries commencing and expanding radiotherapy services. Material and methods: The number of linear accelerators and 60 Co megavoltage teletherapy machines in 72 CITs, those with gross national income per capita (GNI/cap) $12000 pa were expressed as machines per million population (MEV/mil) and used as an index of the ability of the country to provide a service. This figure was related to GNI/cap. The average populations of 24 further countries without radiotherapy were compared with 21 countries with radiotherapy facilities having the same range of GNI/cap. Results: The relationship log 10 MEV/mil=-2.90+0.85 log 10 GNI/cap was identified between the machines and income. Also verified was that small low income countries were less likely to have the technology than those with large populations. Conclusions: The increase in the number of teletherapy machines is closely linked to the GNI/cap of a country. Our sample of well developed countries failed to demonstrate a levelling off of equipment acquisition with income. In the lower income group, smaller countries were less likely to have radiotherapy services than those with large populations

  4. Risk factors for voice quality after radiotherapy for early glottic cancer

    International Nuclear Information System (INIS)

    Hocevar-Boltezar, Irena; Zargi, Miha; Strojan, Primoz

    2009-01-01

    Background and purpose: In the majority of patients irradiated for early glottic cancer an abnormal voice was reported. The purpose of the study was to determine the factors influencing voice quality after radiotherapy for T1 glottic cancer. Methods: The voices of 75 male patients irradiated for T1 glottic carcinoma were assessed subjectively and objectively by acoustic analyses and aerodynamic measurements. The laryngeal function and morphology were evaluated by videolaryngostroboscopy. The data on smoking habits, the associated diseases influencing voice quality, the extent of the tumor, the type of biopsy, and the irradiation technique were collected from the medical records. The data on the factors influencing voice quality were compared for patients with a normal/near-normal voice and those with a hoarse voice. Results: Voice quality was at least slightly abnormal in 94.7% and 81.3% of patients, when assessed perceptively and objectively, respectively. Smoking after the completed treatment, more severe morphologic alterations of the vocal folds, dryness of the throat, incomplete closure of the vocal folds and functional voice disorders expressed as supraglottic activity adversely influenced the voice quality. A good correlation between the perceptive voice assessment and the acoustic analyses was established. Conclusions: After the successful irradiation for T1 glottic carcinoma, the great majority of the patients have at least a slightly hoarse voice. A better voice outcome could be achieved if radiotherapy was followed by the patient's cessation of smoking and the appropriate voice therapy.

  5. Arterial occlusive disease after radiotherapy

    International Nuclear Information System (INIS)

    Piedbois, P.; Mazeron, J.J.; Le Bourgeois, J.P.; Becquemin, J.P.; Blanc, I.; Lange, F.; Melliere, D.

    1990-01-01

    Fourteen cases of arterial occlusion or severe narrowing following radiotherapy are studied in order to assess the possible etiological role of such therapy in arterial lesion. Surgical results are also discussed in terms of long-term efficacy. The average time of occurrence after radiotherapy was 8 years post-radiotherapy. This series includes 7 supra-aortic trunk stenoses and 7 abdominal aorta trunk stenoses. The doses received in the volumes iradiated ranged from 47 to 70 Gy with standard fractionation. Association of atherosclerotic risk factors was present in 12 patients, but stenoses were usually confined to irradiated areas, and at imes occurred in uncommon sites. Surgical management included 11 by-passes, 2 endarterectomies and one percutaneous transluminal angioplasty. All patients experienced immediate and satisfactory functional improvements. Three patients were re-operated on because of the re-occlusion of the by-pass and graft infection. On the whole, stenoses in previously irradiated areas showed no particular difficulties for surgical treatment. It was concluded that radiotherapy seems to be a definite risk factor for arterial occlusion or narrowing, especially in association in association with atherosclerotic risk factors. (author). 45 refs.; 3 figs.; 2 tabs

  6. Serum platelet-derived growth factor and fibroblast growth factor in patients with benign and malignant ovarian tumors

    DEFF Research Database (Denmark)

    Madsen, Christine Vestergaard; Steffensen, Karina Dahl; Olsen, Dorte Aalund

    2012-01-01

    New biological markers with predictive or prognostic value are highly warranted in the treatment of ovarian cancer. The platelet-derived growth factor (PDGF) system and fibroblast growth factor (FGF) system are important components in tumor growth and angiogenesis....

  7. Vascular endothelial growth factor and basic fibroblast growth factor expression positively correlates with angiogenesis and peritumoural brain oedema in astrocytoma

    International Nuclear Information System (INIS)

    Jang, F.F.; Wei, W.

    2008-01-01

    Astrocytoma is the most malignant intracranial neoplasm and is characterized by high neovascularization and peritumoural brain oedema. Angiogenesis is a complicated process in oncogenesis regulated by the balance between angiogenic and antiangiogenic factors. The expression of two angiogenic growth factors, vascular endothelial growth factor and basic fibroblast growth factor were investigated using immunohistochemistry for astrocytoma from 82 patients and 11 normal human tissues. The expression of vascular endothelial growth factor and basic fibroblast growth factor positively correlate with the pathological grade of astrocytoma, microvessel density numbers and brain oedema, which may be responsible for the increased tumour neovascularization and peritumoural brain oedema. The results support the idea that inhibiting vascular endothelial growth factor and basic fibroblast growth factor are useful for the treatment of human astrocytoma and to improve patient's clinical outcomes and prognosis. (author)

  8. Solitary bone plasmacytoma: outcome and prognostic factors following radiotherapy

    International Nuclear Information System (INIS)

    Liebross, Robert H.; Ha, Chul S.; Cox, James D.; Weber, Donna; Delasalle, Kay; Alexanian, Raymond

    1998-01-01

    Purpose: To clarify the natural history of solitary plasmacytoma of bone (SBP) after radiation treatment. Methods and Materials: Between 1965-1996, we identified 57 previously untreated patients with a SBP. A serum myeloma protein was present in 33 patients (58%) and Bence Jones proteinuria was present in an additional eight patients (14%). The median radiotherapy dose was 50 Gy (range, 30-70 Gy). Overall survival, cause-specific survival, and freedom from progression to multiple myeloma were calculated actuarially. Results: Local control was achieved in 55 of 57 patients (96%). For those 29 patients (51%) who subsequently developed multiple myeloma, the median time to progression was 1.8 years. There was a direct correlation between persistence of abnormal protein following radiotherapy and the likelihood of developing multiple myeloma. Among 11 patients with disappearance of myeloma protein, only two developed multiple myeloma after 4 and 12 years, in contrast to progression in 57% of patients with a persistent protein peak and 63% of those with nonsecretory disease (p = 0.02). Among 23 patients with thoracolumbar spine disease, 7 of 8 patients staged with plain radiographs alone developed multiple myeloma in comparison with 1 of 7 patients who also had magnetic resonance imaging (MRI) (p = 0.08). For all patients, the median survival from radiotherapy was 11.0 years. The median cause-specific survival of patients with disappearance of myeloma protein was significantly longer than that of the remaining patients (p = 0.004). Conclusion: Results supported the importance of precise staging that includes MRI of the spine for optimum patient selection and the application of definitive radiotherapy. Those patients with myeloma protein that disappears following radiotherapy represent a category with a high likelihood of cure

  9. External radiotherapy of pituitary adenomas

    International Nuclear Information System (INIS)

    Zierhut, Dietmar; Flentje, Michael; Adolph, Juergen; Erdmann, Johannes; Raue, Friedhelm; Wannenmacher, Michael

    1995-01-01

    Purpose: To evaluate therapeutic outcome and side effects of radiotherapy in pituitary adenomas as sole or combined treatment. Methods and Materials: Retrospective analysis of 138 patients (74 male, 64 female) irradiated for pituitary adenoma from 1972 to 1991 was performed. Mean age was 49.7 years (15-80 years). Regular follow-up (in the mean 6.53 ± 3.99 years) included radiodiagnostical [computed tomography (CT), magnetic resonance imaging (MRI), x-ray], endocrinological, and ophthalmological examinations. Seventy patients suffered from nonfunctional pituitary adenoma, 50 patients suffered from growth-hormone producing adenomas, 11 had prolactinomas, and 7 patients had adrenocorticotropic hormone (ACTH) producing pituitary adenomas. In 99 patients surgery was followed by radiotherapy in case of suspected remaining tumor (invasive growth of the adenoma, assessment of the surgeon, pathologic CT after surgery, persisting hormonal overproduction). Twenty-three patients were treated for recurrence of disease after surgery and 16 patients received radiation as primary treatment. Total doses from 40-60 Gy (mean: 45.5 Gy) were given with single doses of 2 Gy 4 to five times a week. Results: Tumor control was achieved in 131 patients (94.9%). In seven patients, recurrence of disease was diagnosed in the mean 2.9 years (9-98 months) after radiotherapy and salvaged by surgery. A statistically significant dose-response relationship was found in favor of doses ≥ 45 Gy. Ninety percent of the patients with hormonally active pituitary adenomas had a benefit from radiotherapy in means of complete termination (38%) or at least reduction (52%) of hormonal overproduction. Partial or complete hypopituitarism after radiotherapy developed, depending on hormonal axis, in 12 (prolactin) to 27% (follicle-stimulating hormone FSH) of patients who had not already had hypopituitarism prior to radiation. Two out of 138 patients suffered reduction of visual acuity, which was, in part

  10. Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.

    Science.gov (United States)

    Ververis, J; Ku, L; Delafontaine, P

    1994-02-01

    Insulin-like growth factor I is an important mitogen for vascular smooth muscle cells, and its effects are regulated by several binding proteins. Western ligand blotting of conditioned medium from rat aortic smooth muscle cells detected a 24 kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent with insulin-like growth factor binding protein-4 by size. Low amounts of a glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31 kDa non-glycosylated protein also were present. Basic fibroblast growth factor markedly increased secretion of the 24 kDa binding protein and its 28 kDa glycosylated variant. This effect was dose- and time-dependent and was inhibited by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth factor I to cell monolayers revealed no surface-associated binding proteins, either basally or after agonist treatment. Induction of binding protein production by fibroblast growth factor at sites of vascular injury may be important in vascular proliferative responses in vivo.

  11. Demand for radiotherapy in Spain.

    Science.gov (United States)

    Rodríguez, A; Borrás, J M; López-Torrecilla, J; Algara, M; Palacios-Eito, A; Gómez-Caamaño, A; Olay, L; Lara, P C

    2017-02-01

    Assessing the demand for radiotherapy in Spain based on existing evidence to estimate the human resources and equipment needed so that every person in Spain has access to high-quality radiotherapy when they need it. We used data from the European Cancer Observatory on the estimated incidence of cancer in Spain in 2012, along with the evidence-based indications for radiotherapy developed by the Australian CCORE project, to obtain an optimal radiotherapy utilisation proportion (OUP) for each tumour. About 50.5 % of new cancers in Spain require radiotherapy at least once over the course of the disease. Additional demand for these services comes from reradiation therapy and non-melanoma skin cancer. Approximately, 25-30 % of cancer patients with an indication for radiotherapy do not receive it due to factors that include access, patient preference, familiarity with the treatment among physicians, and especially resource shortages, all of which contribute to its underutilisation. Radiotherapy is underused in Spain. The increasing incidence of cancer expected over the next decade and the greater frequency of reradiations necessitate the incorporation of radiotherapy demand into need-based calculations for cancer services planning.

  12. Insulin-like growth factor I (IGF-1 Ec/Mechano Growth factor--a splice variant of IGF-1 within the growth plate.

    Directory of Open Access Journals (Sweden)

    Werner Schlegel

    Full Text Available Human insulin-like growth factor 1 Ec (IGF-1Ec, also called mechano growth factor (MGF, is a splice variant of insulin-like growth factor 1 (IGF-1, which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

  13. Effect of integrated surgery + radiotherapy + chemotherapy treatment on survival status and serum indexes in patients with gallbladder carcinoma

    Directory of Open Access Journals (Sweden)

    Zhi-Li Wei

    2016-12-01

    Full Text Available Objective: To study the effect of integrated surgery + radiotherapy + chemotherapy treatment on the survival status and serum indexes in patients with gallbladder carcinoma. Methods: A total of 68 patients with gallbladder carcinoma were divided into observation group (received integrated surgery + radiotherapy + chemotherapy treatment and control group (received surgery + radiotherapy according to different treatments. Differences in the content of tumor markers, growth factors and adhesion molecules in serum as well as the median survival time and survival rate in 5 years of follow-up were compared between the two groups 1 month after treatment. Results: Tumor markers β2-MG, CA19-9, CA242, CA125, CA724, CEA and AFP content in serum of observation group after treatment were significantly lower than those of control group; growth factors VEGF, FGF, EGFR and HER2 content in serum were significantly lower than those of control group while IGFBP-2 and IGFBP-3 content were significantly higher than those of control group; adhesion molecules E-selectin, ICAM-1, VCAM-1 and sE-Cd content in serum were significantly lower than those of control group; the median survival time of 5-year follow-up as well as 1-, 3- and 5-year survival rate were significantly greater than those of control group. Conclusions: Integrated treatment of surgery + radiotherapy + chemotherapy can optimize the short-term and long-term curative effect in patients with gallbladder carcinoma.

  14. The incidence of postoperative radiotherapy-induced acute dermatitis in breast cancer and its influencing factors for Chinese women

    Directory of Open Access Journals (Sweden)

    Ding J

    2018-03-01

    Full Text Available Jingxian Ding,1,2,* Yonghong Guo,3,* Qingge Li,1 Jun Chen,4 Pinghua Hu,4 Qiuming Liu,4 Yali Cao,4 Jiong Wu5,6 1Department of Radiation Oncology, The Third Hospital of Nanchang, Nanchang, China; 2Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; 3Department of Radiation Oncology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China; 4Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, China; 5Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; 6Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China *These authors contributed equally to this work Purpose: To investigate the incidence of skin acute reaction and its influencing factors in postoperative breast cancer radiotherapy patients. Methods: One hundred and seventy three cases of breast cancer patients treated with postoperative radiotherapy were consecutively enrolled from June 1, 2016 to July 31, 2017 in our breast cancer center. Irradiation technology includes conformal intensity-modulated radiotherapy and a conventional two-dimensional one with conventional fraction. Any acute radiation dermatitis was recorded and the influencing factors were analyzed at the end of the radiation treatment. Results: Radiotherapy-induced acute dermatitis in patients with breast-conserving surgery was relatively mild. Among the 173 patients, 33 cases had no obvious changes in the skin (grade 0; 121 cases had grade 1 skin reactions, manifested as local dark erythema and dry peeling; 29 cases had grade 2 skin reactions, characterized by edema, hyperemia, or erosion part; no grade 3 cases of skin reactions were observed. The incidence of grade 0, grade 1, and grade 2 reactions in all patients was 19.1%, 69.9%, and 11.0%, respectively. The severity of skin acute reaction is independent of the tumor sites, molecular subtypes, patients’ age, and irradiation modalities, but it

  15. Effects of radiotherapy on anti-cancer immune response: mathematical modeling

    International Nuclear Information System (INIS)

    Isaeva, O.G.; Osipov, V.A.

    2009-01-01

    The influence of radiotherapy on the tumor-immune dynamics is studied within our recent model. Simulation of the standard course of radiotherapy shows that in the case of weak immune response a few months after cure the tumor achieves the maximum size, whereas the strong immune system is able to handle the growth of survived tumor cells population. Simulation of vaccine therapy after radiotherapy has been carried out. The high efficiency of vaccination is found provided that it is assigned during a certain period of time after radiotherapy. Different strategies of radiotherapy have been considered. It is shown that hyper rectification is more effective for treatment in comparison with other cures

  16. Acute myocardial infarction after mediastinal radiotherapy

    International Nuclear Information System (INIS)

    Gagliardi, Juan; Tezanos Pinto, Miguel; Avalos, Adolfo; Sarubbi, Augusto; Padilla, Lucio; Espinosa, Daniel

    2004-01-01

    Mediastinal radiotherapy can affect the heart and great vessels to different degrees. It may turn up as coronary heart disease and less frequently as acute myocardial infarction. We report the case of a patient without coronary risk factors and an antecedent of mediastinal radiotherapy for Hodgkin's lymphoma. Considerations about mediastinal radiation as a risk factor for early development of coronary heart diseases are exposed. (author) [es

  17. Postoperative radiotherapy of uterine sarcoma: A multicentric retrospective study; Radiotherapie postoperatoire dans les sarcomes uterins: etude retrospective multicentrique

    Energy Technology Data Exchange (ETDEWEB)

    Champetier, C.; Cowen, D. [Service de radiotherapie, hopital de la Timone, 264, rue Saint-Pierre, 13385 Marseille cedex 05 (France); Hannoun-Levi, J.M. [Centre Antoine-Lacassagne, 33, avenue Valombrose, 06100 Nice (France); Resbeut, M. [Centre de radiotherapie Saint-Louis, rue Andre-Blondel, 83100 Toulon (France); Azria, D. [Centre Val-d' Aurelle-Paul-Lamarque, 208, rue des Apothicaires, 34298 Montpellier cedex 5 (France); Salem, N. [Institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille (France); Tessier, E. [Centre azureen de radiotherapie, 1, place du Docteur-Jean-Luc-Broquerie, 06250 Mougins (France); Ellis, S. [Centre catalan de radiotherapie, 80, rue Pascal-Marie-Agasse, 66000 Perpignan (France)

    2011-04-15

    Purpose. - Surgery is the treatment of choice for localized uterine sarcomas. We conducted a retrospective study to define prognostic factors. Patients and methods. - We studied 111 cases of patients treated by adjuvant radiotherapy for uterine sarcoma in seven French centers. The median decline was 31 months. We conducted a univariate analysis to identify factors correlated with local recurrence. The statistically significant factors were studied in multivariate analysis by Cox model. Results. - The median dose of external beam radiotherapy was 45 Gy. Forty-three percent of patients had vaginal vault brachytherapy and 21 % chemotherapy. Only 6.3 % of patients had complications of acute grade III and 8.1 % of long-term sequelae of radiotherapy. The survival rate at 5 years was 74.6 %. They noted 12.6 % of isolated locoregional recurrences, against 29.7 % for distant recurrences, 80 % were pulmonary. Factors correlated with the risk of locoregional relapse were menopausal status (P = 0.045) and surgical margins suspicious or not healthy (P = 0.0095). The chemotherapy did not improve overall survival or disease free survival but the numbers were low. Conclusion. - The postoperative radiotherapy provides good local control in this disease. Brachytherapy is sometimes done, but it does not improve local control. Chemotherapy is not a standard localized stage but the rate of metastatic recurrence calls for the development of strategies involving systemic treatment with radiotherapy. (authors)

  18. Development of radiation pneumopathy and generalised radiological changes after radiotherapy are independent negative prognostic factors for survival in non-small cell lung cancer patients

    International Nuclear Information System (INIS)

    Farr, Katherina P.; Khalil, Azza A.; Knap, Marianne M.; Møller, Ditte S.; Grau, Cai

    2013-01-01

    Background and purpose: To investigate the risk factors for radiation pneumopathy (RP) and survival rate of non-small cell lung cancer patients with RP and generalised interstitial lung changes (gen-ILC). Material and methods: A total of 147 consecutive patients receiving curative radiotherapy were analysed. RP was graded according to Common Terminology Criteria for Adverse Events v. 3. Computed tomography images were assessed for the presence of gen-ILC after radiotherapy. Univariate and multivariate analyses were performed to identify significant factors. Results: Median follow-up was 16.2 months (range 1.4–58.6). Radiological changes after radiotherapy were confined to high dose irradiation volume in 111 patients, while 31 patients developed gen-ILC. Dosimetric parameters and level of C-reactive protein before radiotherapy were significantly associated with severe RP. Development of gen-ILC (p = 0.008), as well as severe RP (p = 0.03) had significant negative impact on patients’ survival. These two factors remained significant in the multivariate analysis. Conclusions: Severe radiation pneumopathy and generalised radiographic changes were significant independent prognostic factors for survival. More studies on pathophysiology of radiation induced damage are necessary to fully understand the mechanisms behind it

  19. Prognostic impact of placenta growth factor and vascular endothelial growth factor A in patients with breast cancer

    DEFF Research Database (Denmark)

    Maae, Else; Olsen, Dorte Aalund; Steffensen, Karina Dahl

    2012-01-01

    such as ischemic heart disease, arthritis and tumor growth. Angiogenesis is a complex process with several growth factors involved. Because PlGF modulates VEGF-A responses, we investigated their mutual relationship and impact on breast cancer prognosis. Quantitative PlGF and VEGF-A levels were measured in 229...... tumor tissue specimen from primarily operated patients with unilateral breast cancer. Non-malignant breast tissue was also dissected near the tumor and quantitative measurements were available for 211 patients. PlGF and VEGF-A protein levels in homogenized tissue lysates were analyzed using the Luminex......Placenta growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A) are angiogenic growth factors interacting competitively with the same receptors. VEGF-A is essential in both normal and pathologic conditions, but the functions of PlGF seem to be restricted to pathologic conditions...

  20. Urinary transforming growth factors in neoplasia: separation of 125I-labeled transforming growth factor-alpha from epidermal growth factor in human urine

    International Nuclear Information System (INIS)

    Stromberg, K.; Hudgins, W.R.

    1986-01-01

    Purified human epidermal growth factor (hEGF) from urine promotes anchorage-independent cell growth in soft agar medium. This growth is enhanced by transforming growth factor-beta (TGF-beta), and is specifically inhibited by hEGF antiserum. Transforming growth factors of the alpha type (TGF-alpha), potentially present in normal human urine or urine from tumor-bearing patients, also promote anchorage-independent cell growth and compete with EGF for membrane receptor binding. Consequently, TGF-alpha cannot be distinguished from urinary hEGF by these two functional assays. Therefore, a technique for separation of TGF-alpha and related peptides from urinary EGF based on biochemical characteristics would be useful. Radioiodination of characterized growth factors [mouse EGF (mEGF), hEGF, and rat TGF-alpha (rTGF-alpha)], which were then separately added to human urine, was used to evaluate a resolution scheme that separates TGF-alpha from the high level of background hEGF present in human urine. Methyl bonded microparticulate silica efficiently adsorbed the 125 I-labeled mEGF, 125 I-labeled hEGF, and 125 I-labeled rTGF-alpha that were added to 24-h human urine samples. Fractional elution with acetonitrile (MeCN) of the adsorbed silica released approximately 70 to 80% of the 125 I-labeled mEGF and 125 I-labeled hEGF between 25 and 30% MeCN, and over 80% of the 125 I-labeled rTGF-alpha between 15 and 25% MeCN, with retention after dialysis of less than 0.2 and 1.7% of the original urinary protein, respectively. A single-step enrichment of about 400-fold for mEGF and hEGF, and 50-fold for rTGF-alpha were achieved rapidly. 125 I-labeled mEGF and 125 I-labeled hEGF eluted later than would be predicted on the basis of their reported molecular weight of approximately 6000, whereas 125 I-labeled rTGF-alpha eluted from Bio-Gel P-10 at an approximate molecular weight of 8000 to 9000

  1. Novel Drosophila receptor that binds multiple growth factors

    International Nuclear Information System (INIS)

    Rosner, M.R.; Thompson, K.L.; Garcia, V.; Decker, S.J.

    1986-01-01

    The authors have recently reported the identification of a novel growth factor receptor from Drosophila cell cultures that has dual binding specificity for both insulin and epidermal growth factor (EGF). This 100 kDa protein is also antigenically related to the cytoplasmic region of the mammalian EGF receptor-tyrosine kinase. They now report that this protein binds to mammalian nerve growth factor and human transforming growth factor alpha as well as insulin and EGF with apparent dissociation constants ranging from 10 -6 to 10 -8 M. The 100 kDa protein can be affinity-labeled with these 125 I-labeled growth factors after immunoprecipitation with anti-EGF receptor antiserum. These four growth factors appear to share a common binding site, as evidenced by their ability to block affinity labelling by 125 I-insulin. No significant binding to the 100 kDa protein was observed with platelet-derived growth factor, transforming growth factor beta, or glucagon. The 100 kDa Drosophila protein has a unique ligand-binding spectrum with no direct counterpart in mammalian cells and may represent an evolutionary precursor of the mammalian receptors for these growth factors

  2. PSA Density as a prognostic factor in prostate cancer patients treated with radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lankford, Scott; Pollack, Alan; Zagars, Gunar K

    1995-07-01

    Purpose/Objective: The pretreatment serum prostate specific antigen level (PSAL) is the most significant predictor of biochemical failure in patients treated with definitive radiotherapy. While one report indicates that PSA density (PSAD) is an important prognostic factor for patients treated with radiotherapy, another claims that it adds nothing to that seen with PSAL. We describe here a comparative analysis of the prognostic value of PSAL and PSAD using the endpoints of local control (LC), freedom from distant metastasis (FFDM), freedom from biochemical failure (FFBF), and freedom from any failure (FFAF, biochemical and/or clinical failure). Materials and Methods: There were 353 patients who between 1987-1993 were treated for regionally localized adenocarcinoma of the prostate and in whom PSAL and pretreatment prostate volume by ultrasound were available. External beam radiotherapy was administered to 334 patients using a four field box with high energy photons to {<=}70 Gy in 35 fractions. The remainder received between 76-78 Gy using conformal radiotherapy. The mean and median doses were 66.8 Gy and 66.0 Gy. Median follow-up for those living was 27 mo. The mean PSAL was 12.0 ng/ml with a median of 9.3 ng/ml. The PSAL was divided into 4 groups that we have described previously as correlating strongly with LC, FFBF, and FFAF; there were 64 patients with a PSA of {<=}4, 133 with >4 and {<=}10, 107 with >10 and {<=}20, and 49 with >20 ng/ml. PSAD was calculated by dividing the PSAL by the pretreatment prostate volume (in cc). The PSAD was divided into 4 groups based on the frequency distribution, which was not normally distributed. The subdivisions were 110 patients with a PSAD of {<=}0.2, 113 with {<=}0.2 and {<=}0.4, 87 with >0.4 and {<=}0.8, and 43 with >0.8. Patient breakdown by Stage was 106 with T1, 130 with T2, and 117 with T3/T4 disease. Patient breakdown by Gleason score was 76 patients with tumor scores of 2-4, 151 with scores of 5 or 6, 83 with a score

  3. Outcomes of visual acuity in carbon ion radiotherapy: Analysis of dose-volume histograms and prognostic factors

    International Nuclear Information System (INIS)

    Hasegawa, Azusa; Mizoe, Jun-etsu; Mizota, Atsushi; Tsujii, Hirohiko

    2006-01-01

    Purpose: To analyze the tolerance dose for retention of visual acuity in patients with head-and-neck tumors treated with carbon ion radiotherapy. Methods and Materials: From June 1994 to March 2000, 163 patients with tumors in the head and neck or skull base region were treated with carbon ion radiotherapy. Analysis was performed on 54 optic nerves (ONs) corresponding to 30 patients whose ONs had been included in the irradiated volume. These patients showed no evidence of visual impairment due to other factors and had a follow-up period of >4 years. All patients had been informed of the possibility of visual impairment before treatment. We evaluated the dose-complication probability and the prognostic factors for the retention of visual acuity in carbon ion radiotherapy, using dose-volume histograms and multivariate analysis. Results: The median age of 30 patients (14 men, 16 women) was 57.2 years. Median prescribed total dose was 56.0 gray equivalents (GyE) at 3.0-4.0 GyE per fraction per day (range, 48-64 GyE; 16-18 fractions; 4-6 weeks). Of 54 ONs that were analyzed, 35 had been irradiated with max ]) resulting in no visual loss. Conversely, 11 of the 19 ONs (58%) irradiated with >57 GyE (D max ) suffered a decrease of visual acuity. In all of these cases, the ONs had been involved in the tumor before carbon ion radiotherapy. In the multivariate analysis, a dose of 20% of the volume of the ON (D 2 ) was significantly associated with visual loss. Conclusions: The occurrence of visual loss seems to be correlated with a delivery of >60 GyE to 20% of the volume of the ON

  4. The result of radiotherapy for pituitary adenoma

    International Nuclear Information System (INIS)

    Lee, H. J.; Yang, K. M.; Suh, S. H.

    1997-01-01

    To evaluate the prognostic factors for disease-free survival and long-term results of radiotherapy for pituitary adenoma. The study involved a retrospective review of outcome in a series of 27 patients with pituitary adenoma, between 1984 and 1995 at Paik hospital. The study included 20 patients treated with surgery and postoperative radiotherapy and 7 with radiotherapy alone. The patients were followed for 12-146 months (median: 97 months). Seventeen were men and 10 were women. The numbers of functioning and non-functioning pituitary adenoma were 22 and 5 respectively and those of microadenoma and macroadenoma were 4 and 23 respectively. The radiation doses of 5040-5580cGy(median: 5040cGy) were delivered over 5-7 weeks, using 4MV LINAC. The prognostic factors were analyzed by log-rank test. For radiation therapy alone, the 5 YSR was 100% and progression free survival rate was 85.8%. The tumor was controlled in 6/7 (85.8%). For surgery and postoperative radiotherapy , the 5YSR, progression free survival rate and local control rate were 95%, 84.8%, and 89.5% respectively. The parameters of tumor size, hormone secretion, radiation dose, radiotherapy field size were evaluated in a uni- and multivariate analysis and all the factors were not statistically significant (P>0.05). Eleven of 12 (92%) with visual field defect experienced normalization or improvement, and 5 for 7 evaluable patients with hyperprolactinoma achieved normalization in 4 and decrement in 5 patients. Only 2 patients developed mild degree of panhypopituitarism. The radiotherapy appears to be effective in controlling clinical symptoms and signs resulting from pituitary adenoma. Local control rate with radiotherapy alone or with surgery and postoperative radiotherapy was comparable. There was a trend toward high recurrence rate in patients with nonfunctioning or prolactin secreting tumor and larger radiation field sizes. (author)

  5. The result of radiotherapy for pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, H. J.; Yang, K. M.; Suh, S. H. [Inje Univ., Seoul (Korea, Republic of). Coll. of Medicine; Cho, H. L.; Shon, S. C. [Pusan Paik Hospital, Pusan (Korea, Republic of)

    1997-12-01

    To evaluate the prognostic factors for disease-free survival and long-term results of radiotherapy for pituitary adenoma. The study involved a retrospective review of outcome in a series of 27 patients with pituitary adenoma, between 1984 and 1995 at Paik hospital. The study included 20 patients treated with surgery and postoperative radiotherapy and 7 with radiotherapy alone. The patients were followed for 12-146 months (median: 97 months). Seventeen were men and 10 were women. The numbers of functioning and non-functioning pituitary adenoma were 22 and 5 respectively and those of microadenoma and macroadenoma were 4 and 23 respectively. The radiation doses of 5040-5580cGy(median: 5040cGy) were delivered over 5-7 weeks, using 4MV LINAC. The prognostic factors were analyzed by log-rank test. For radiation therapy alone, the 5 YSR was 100% and progression free survival rate was 85.8%. The tumor was controlled in 6/7 (85.8%). For surgery and postoperative radiotherapy , the 5YSR, progression free survival rate and local control rate were 95%, 84.8%, and 89.5% respectively. The parameters of tumor size, hormone secretion, radiation dose, radiotherapy field size were evaluated in a uni- and multivariate analysis and all the factors were not statistically significant (P>0.05). Eleven of 12 (92%) with visual field defect experienced normalization or improvement, and 5 for 7 evaluable patients with hyperprolactinoma achieved normalization in 4 and decrement in 5 patients. Only 2 patients developed mild degree of panhypopituitarism. The radiotherapy appears to be effective in controlling clinical symptoms and signs resulting from pituitary adenoma. Local control rate with radiotherapy alone or with surgery and postoperative radiotherapy was comparable. There was a trend toward high recurrence rate in patients with nonfunctioning or prolactin secreting tumor and larger radiation field sizes. (author).

  6. Growth hormone, growth factors, and acromegaly

    Energy Technology Data Exchange (ETDEWEB)

    Ludecke, D.K.; Tolis, G.T.

    1987-01-01

    This book contains five sections, each consisting of several papers. The section headings are: Biochemistry and Physiology of GH and Growth Factors, Pathology of Acromegaly, Clinical Endocrinology of Acromegaly, Nonsurgical Therapy of Acromegaly, and Surgical Therapy of Acromegaly.

  7. The role of radiotherapy for the induction of antitumor immune responses

    International Nuclear Information System (INIS)

    Multhoff, G.; Helmholtz-Zentrum Muenchen; Gaipl, U.S.; Niedermann, G.

    2012-01-01

    Effective radiotherapy is aimed to control the growth of the primary carcinoma and to induce a long-term specific antitumor immune response against the primary tumor, recurrence and metastases. The contribution covers the following issues: T cells and tumor specific immune responses, dendritic cells (DCs) start adaptive immune responses, NK (natural killer) cells for HLA independent tumor control, abscopal effects of radiotherapy, combination of radiotherapy and immune therapy, radiotherapy contribution to the induction of immunogenic cell death, combinability of radiotherapy and DC activation, combinability of radiotherapy and NK cell therapy. It turns out that the combination of radio-chemotherapy and immune therapy can change the microenvironment initiating antitumor immune reactions that inhibit the recurrence risk and the development of metastases.

  8. The selection of patients for accelerated radiotherapy on the basis of tumor growth kinetics and intrinsic radiosensitivity

    International Nuclear Information System (INIS)

    Tucker, S.L.; Kang-Sow Chan

    1990-01-01

    Mathematical modelling was used to reach qualitative conclusions concerning the relative rate of local tumor control that might be achieved by using accelerated fractionation to treat only the patients with the most rapidly growing rumors, compared with the control rated that could be expected from either conventional or accelerated radiotherapy alone. The results suggest that concomitant boost therapy is equally or more effective than conventional dose fractionation for all tumors, regardless of their growth kinetics. For tumors with very short clonogen doubling times, CHART (continuous hyperfractionated accelerated radiotherapy) may be even more effective than concomitant boost treatment, but CHART is less effective than conventional or concomitant boost therapy for tumors with longer clonogen doubling times. Thus, there is a rationale for using a predictive assay of tumor clonogen doubling times to identify the patients who should be treated with CHART. However, improvements in local tumor control resulting from concomitant boost treatment or the selective use of CHART are not likely to be apparent in the population as a whole, because the overall control rated are largely determined by refractory tumors having little chance of control with any of the treatments and by higher responsive tumors that are likely to be controlled regardless of the treatment choice. Differences in control rated with different treatment strategies are most apparent in the stochastic fraction of the population, which excludes those patients for whom there is either very little change (e.g. 99%) of achieving local control with both treatments. The stochastic fraction can be approximated by excluding those patients with the most radioresistant and the most radiosensitive tumors, since intrinsic tumor radiosensitivity appears to be the single most important factor determining treatment outcome. (author). 32 refs.; 4 figs.; 5 tabs

  9. Granulocyte macrophage-colony-stimulating factor mouthwashes heal oral ulcers during head and neck radiotherapy

    International Nuclear Information System (INIS)

    Rovirosa, Angeles; Ferre, Jorge; Biete, Albert

    1998-01-01

    Purpose: To evaluate the effectiveness of granulocyte macrophage-colony-stimulating factor GM-CSF mouthwashes in the epithelization of radiation-induced oral mucosal ulceration, control of pain, and weight loss. Methods and Materials: Twelve patients received curative radiotherapy for head and neck carcinoma. All had oropharyngeal and/or oral mucosa irradiation, with a median dose of 72 Gy (range 50-74), with conventional fractionation. A total of 300 μg of GM-CSF in 250 cc of water for 1 h of mouthwashing was prescribed. The procedure started once oral ulceration in the irradiation field was detected. Patients, examined twice a week, were evaluated for oral ulceration, pain, and weight loss. Blood tests were taken weekly during GM-CSF administration. A comparison was carried out with 12 retrospective case-matched controls. Results: In the GM-CSF group, mucosa ulcerations healed in 9 of 12 (75%) of the patients during the course of the radiotherapy. Fifty percent of the patients said they felt less pain during the GM-CSF treatment; 30% needed morphine. The mean and median weight loss as a percentage of baseline weight in addition to the actual weight were 4.2% and 3%, respectively (variation ranged between a gain of 1% and a loss of 13%). No GM-CSF-related side effects were found. In the case control group, in the 12 cases, oral ulcerations increased during radiotherapy and two patients needed intubation intake and hospital admission, as opposed to the GM-CSF group. The mean and median percentage of weight loss were 5.8% and 5%, respectively. Sixty percent of patients needed morphine, as opposed to 30% in the GM-CSF group. Conclusions: Granulocyte macrophage-colony-stimulating factor was effective in curing mucosal ulcerations during the course of radiotherapy. This is the first time we have seen a drug with this capacity. Although the GM-CSF seems to be effective in the control of pain, oral intake, and weight loss, we need further studies with a greater number

  10. Relative Expression of Apoptotic and Vascular Epithelial Growth Factor Receptor Genes in Gamma-Irradiated Rat Kidney

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hyang; Chun, Ki Jung; Kim, Jin Kyu [Korea Atomic research Institute, Deajeon (Korea, Republic of); Yoon, Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

    2005-07-01

    Biological process of wound healing, which occurs in three phases of revascularization (inflammatory, proliferative, and maturation) is an important essential step in regulating this process. Blood vessels serve as carriers for various cells, cytokines, and growth factors that are needed for tissue repair. The formation of new blood vessels is a necessary event during embryogenesis, but it occurs rarely in the adult with few exceptions, such as in the female reproductive system and wound healing. Angiogenesis is controlled by a variety of mitogenic, chemotactic, and inhibitory peptide and lipid factors that act on invading endothelial and smooth muscle cells. One of the most important angiogenic factors is the vascular endothelial growth factor (VEGF), a glycosylated protein of 46-48 kD composed of two disulphide linked subunits. The VEGF family consists of six members, five splicing forms of VEGF and the placenta-derived growth factor (PDGF). In normal, VEGF is expressed during embryogenesis and in a limited number of sites in adults. In disease states, VEGF can be detected in various tumor cells, the synovial pannus in rheumatoid arthritis, and in keratinocytes during wound healing. Five different VEGF isoforms, with 121, 145, 165, 189, and 106 amino acids, can be generated as a result of an alternative splicing from the single VEGF gene. The VEGF molecules bind to receptors known as VEFGR- 1 (FLT-1, fms-like tyrosine kinase 1), VEGFR-2 (KDR, kinase domain region/FLK-1, fetal liver kinase 1), VEGFR-2 (FLT-4), neurophilin-1, neurophilin-2, and heparan sulfate proteoglycans. Ionizing radiation can affect the angiogenesis and neovascularization on normal tissues in radiotherapy or by background radiation surrounding living beings. Kidney belongs to the urinary system and classified to the radio-resistant organ according to the previous studies. Therefore, the present study tested the effect of gamma irradiation and mercury chloride (MgCl{sub 2}) to the renal region

  11. Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I

    International Nuclear Information System (INIS)

    Drago, J.; Murphy, M.; Carroll, S.M.; Harvey, R.P.; Bartlett, P.F.

    1991-01-01

    Fibroblast growth factor stimulates proliferation and subsequent differentiation of precursor cells isolated from the neuroepithelium of embryonic day 10 mice in vitro. Here we show that fibroblast growth factor-induced proliferation is dependent on the presence of insulin-like growth factors (IGFs) and that IGF-I is endogenously produced by the neuroepithelial cells. Blocking of endogenous IGF-I activity with anti-IGF-I antibodies results in complete inhibition of fibroblast growth factor-mediated proliferation and in cell death. IGF-I alone acts as a survival agent. These observations correlate with the detection of transcripts for IGF-I and basic fibroblast growth factor in freshly isolated neuroepithelium and are consistent with an autocrine action of these factors in early brain development in vivo

  12. Cytokine levels as biomarkers of radiation fibrosis in patients treated with breast radiotherapy

    International Nuclear Information System (INIS)

    Westbury, Charlotte B; Yarnold, John R; Haviland, Joanne; Davies, Sue; Gothard, Lone; Abdi, Bahja Ahmed; Sydenham, Mark; Bowen, Jo; Stratton, Richard; Short, Susan C

    2014-01-01

    Radiation fibrosis is not easily measurable although clinical scores have been developed for this purpose. Biomarkers present an alternative more objective approach to quantification, and estimation in blood provides accessible samples. We investigated if blood cytokines could be used to measure established fibrosis in patients who have undergone radiotherapy for breast cancer. We studied two cohorts treated by breast-conserving surgery and radiotherapy in the UK START Trial A, one with breast fibrosis (cases) and one with no or minimal fibrosis (controls). Two candidate cytokines, plasma connective tissue growth factor (CTGF) and serum interleukin-6 (IL6) were estimated by ELISA. Comparisons between cases and controls used the t-test or Mann–Whitney test and associations between blood concentration and clinical factors were assessed using the Spearman rank correlation coefficient. Seventy patients were included (26 cases, 44 controls). Mean time since radiotherapy was 9.9 years (range 8.3-12.0). No statistically significant differences between cases and controls in serum IL6 (median (IQR) 0.84 pg/ml (0.57-1.14), 0.75 pg/ml (0.41-1.43) respectively) or plasma CTGF (331.4 pg/ml (234.8-602.9), 334.5 pg/ml (270.0-452.8) were identified. There were no significant associations between blood cytokine concentration and age, fibrosis severity, breast size or time since radiotherapy. No significant difference in IL6 or CTGF concentrations was detected between patients with breast fibrosis and controls with minimal or no fibrosis

  13. Integrated cancer therapy combined radiotherapy and immunotherapy. The challenge of using Gc protein-derived macrophage activating factor (GcMAF) as a key molecule

    International Nuclear Information System (INIS)

    Uto, Yoshihiro; Hori, Hitoshi

    2013-01-01

    Radiation oncologists know the conflict between radiotherapy and immunotherapy, but now challenged trails of the integrative cancer therapies combined radiation therapy and various immunoreaction/immune therapies begin. We therefore review the recent results of basic research and clinical trial of the integrated cancer therapies which combined radiotherapy and various immune therapies/immunoreaction, and the challenged studies of combined use of radiotherapy and our developed cancer immunotherapy using serum GcMAF which is human serum containing Gc protein-derived macrophage activating factor (GcMAF). (author)

  14. Assesment of prognostic factors in radical radiotherapy for patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    Chmielewska, E.

    2000-01-01

    Lung cancer is still the most severe problem of oncology throughout the word. In Poland there are some 20 000 new cases per annum, among them non-small cell lung cancer accounts for about 16 000 cases. The basic method of therapy of non-small cell lung cancers is surgery; however, in Polish conditions only about 15% of patients qualify for it. Therefore, there remains a large group of patients who are potential candidates for radiotherapy. Evaluation of a group of patients qualified for radical radiotherapy according to uniform rules, treated with the same protocol and assesed by the same group of physicians. The obtained results of therapy allow to evaluate the usefulness of radical radiotherapy in patients with non-operable non-small cell lung cancer and serve as a basis of search for more effective radiotherapy protocols. The aim of the study is to attempt to define the prognostic, therapeutical, clinical-and population-related factors for survival and local control in patients with non-operable, non-small cell lung cancer. Between January 1, 1990, and December 31, 1995, there were 2330 patients with non-small cell lung in the Ambulatory of the Cancer Centre in Warsaw. Basing on the results of clinical examination and additional examination, 260 patients qualified for radical radiotherapy. In this group there were 31 women (12%) and 229 men (88%). In a majority of cases the stage of the disease was advanced: stage IIIA was found in 114 patients (44%), and stage IIIB in 73 patients (28%). Retrospective analysis of the results of treatment was carried out. The material covered 260 patients. The survival time and the time to local progression were the basis for the analysis. The survival probability was calculated whit the Kaplan-Meier method. Multidimensional analysis of the prognostic factors (age, clinical advancement of the disease, performance status, loss of weight, LDH and haemoglobin level, tumour size, pulmonary function, prior exploratory thoracotomy

  15. Epidermal Growth Factor Receptor Is Related to Poor Survival in Glioblastomas: Single-Institution Experience

    Science.gov (United States)

    Choi, Youngmin; Lee, Hyung-Sik; Hur, Won-Joo; Sung, Ki-Han; Kim, Ki-Uk; Choi, Sun-Seob; Kim, Su-Jin; Kim, Dae-Cheol

    2013-01-01

    Purpose There are conflicting results surrounding the prognostic significance of epidermal growth factor receptor (EGFR) status in glioblastoma (GBM) patients. Accordingly, we attempted to assess the influence of EGFR expression on the survival of GBM patients receiving postoperative radiotherapy. Materials and Methods Thirty three GBM patients who had received surgery and postoperative radiotherapy at our institute, between March 1997 and February 2006, were included. The evaluation of EGFR expression with immunohistochemistry was available for 30 patients. Kaplan-Meier survival analysis and Cox regression were used for statistical analysis. Results EGFR was expressed in 23 patients (76.7%), and not expressed in seven (23.3%). Survival in EGFR expressing GBM patients was significantly less than that in non-expressing patients (median survival: 12.5 versus 17.5 months, p=0.013). Patients who received more than 60 Gy showed improved survival over those who received up to 60 Gy (median survival: 17.0 versus 9.0 months, p=0.000). Negative EGFR expression and a higher radiation dose were significantly correlated with improved survival on multivariate analysis. Survival rates showed no differences according to age, sex, and surgical extent. Conclusion The expression of EGFR demonstrated a significantly deleterious effect on the survival of GBM patients. Therefore, approaches targeting EGFR should be considered in potential treatment methods for GBM patients, in addition to current management strategies. PMID:23225805

  16. Locally Advanced Stage IV Squamous Cell Carcinoma of the Head and Neck: Impact of Pre-Radiotherapy Hemoglobin Level and Interruptions During Radiotherapy

    International Nuclear Information System (INIS)

    Rades, Dirk; Stoehr, Monika; Kazic, Nadja; Hakim, Samer G.; Walz, Annette; Schild, Steven E.; Dunst, Juergen

    2008-01-01

    Purpose: Stage IV head and neck cancer patients carry a poor prognosis. Clear understanding of prognostic factors can help to optimize care for the individual patient. This study investigated 11 potential prognostic factors including pre-radiotherapy hemoglobin level and interruptions during radiotherapy for overall survival (OS), metastases-free survival (MFS), and locoregional control (LC) after radiochemotherapy. Methods and Materials: Eleven factors were investigated in 153 patients receiving radiochemotherapy for Stage IV squamous cell head and neck cancer: age, gender, Karnofsky performance score (KPS), tumor site, grading, T stage, N stage, pre-radiotherapy hemoglobin level, surgery, chemotherapy type, and interruptions during radiotherapy >1 week. Results: On multivariate analysis, improved OS was associated with KPS 90-100 (relative risk [RR], 2.36; 95% confidence interval [CI], 1.20-4.93; p = .012), hemoglobin ≥12 g/dL (RR, 1.88; 95% CI, 1.01-3.53; p = .048), and no radiotherapy interruptions (RR, 2.59; 95% CI, 1.15-5.78; p = .021). Improved LC was significantly associated with lower T stage (RR, 2.17; 95% CI, 1.16-4.63; p = .013), hemoglobin ≥12 g/dL (RR, 4.12; 95% CI, 1.92-9.09; p 1 week. It appears important to avoid anemia and radiotherapy interruptions to achieve the best treatment results

  17. Investigation of anxiety about radiotherapy and development of the Categorical Anxiety Scale about Radiotherapy

    International Nuclear Information System (INIS)

    Shimotsu, Sakie; Karasawa, Kumiko; Ito, Kana; Saito, Anne-yuko I; Kawase, Eri; Imasato, Sakae; Matsuki, Hideyuki; Horikawa, Naoshi

    2006-01-01

    There are many patients with anxiety for radiotherapy though it is one of most important treatments for cancer, to which attention has not been fully paid. Authors investigated this anxiety to classify and quantitatively evaluate the problems. Firstly they asked 48 patients with various cancers about the concrete anxiety items related with radiotherapy, and the items were examined by the expert doctor of consultation-liaison psychiatry and of radiology to make up questions of 25 items about radiotherapy. Then those questions together with Hospital Anxiety and Depression Scale (HAD) were asked to in-(52 subjects) and out-(133) patients (106 males and 79 females of the mean age 62.58 years) to classify anxiety and to see the reliability and validity of items included. Factor analysis of the results revealed that three kinds of anxiety, i.e., adverse effects of radiation, environments at irradiation and effect of radiotherapy, were significant. Based on this, authors arranged the Categorical Anxiety Scale about Radiotherapy composed from 17 items, of which reliability and validity in contents and in parallelism with HAD had been assured. (T.I.)

  18. Melatonin prevents possible radiotherapy-induced thyroid injury.

    Science.gov (United States)

    Arıcıgil, Mitat; Dündar, Mehmet Akif; Yücel, Abitter; Eryılmaz, Mehmet Akif; Aktan, Meryem; Alan, Mehmet Akif; Fındık, Sıdıka; Kılınç, İbrahim

    2017-12-01

    We aimed to investigate the protective effect of melatonin in radiotherapy-induced thyroid gland injury in an experimental rat model. Thirty-two rats were divided into four groups: the control group, melatonin treatment group, radiotherapy group and melatonin plus radiotherapy group. The neck region of each rat was defined by simulation and radiated with 2 Gray (Gy) per min with 6-MV photon beams, for a total dose of 18 Gy. Melatonin was administered at a dose of 50 mg/kg through intraperitoneal injection, 15 min prior to radiation exposure. Thirty days after the beginning of the study, rats were decapitated and analyses of blood and thyroid tissue were performed. Tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) levels in the radiotherapy group were significantly higher than those in the melatonin plus radiotherapy group (p melatonin plus radiotherapy group (p melatonin plus radiotherapy group (p Melatonin helped protect thyroid gland structure against the undesired cytotoxic effects of radiotherapy in rats.

  19. Role of vascular endothelial growth factor and other growth factors in post-stroke recovery

    Directory of Open Access Journals (Sweden)

    Tanu Talwar

    2014-01-01

    Full Text Available Stroke is a major health problem world-wide and its burden has been rising in last few decades. Until now tissue plasminogen activator is only approved treatment for stroke. Angiogenesis plays a vital role for striatal neurogenesis after stroke. Administration of various growth factors in an early post ischemic phase, stimulate both angiogenesis and neurogenesis and lead to improved functional recovery after stroke. However vascular endothelial growth factors (VEGF is the most potent angiogenic factor for neurovascularization and neurogenesis in ischemic injury can be modulated in different ways and thus can be used as therapy in stroke. In response to the ischemic injury VEGF is released by endothelial cells through natural mechanism and leads to angiogenesis and vascularization. This release can also be up regulated by exogenous administration of Mesenchymal stem cells, by various physical therapy regimes and electroacupuncture, which further potentiate the efficacy of VEGF as therapy in post stroke recovery. Recent published literature was searched using PubMed and Google for the article reporting on methods of up regulation of VEGF and therapeutic potential of growth factors in stroke.

  20. Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF).

    Science.gov (United States)

    Masuki, Hideo; Okudera, Toshimitsu; Watanebe, Taisuke; Suzuki, Masashi; Nishiyama, Kazuhiko; Okudera, Hajime; Nakata, Koh; Uematsu, Kohya; Su, Chen-Yao; Kawase, Tomoyuki

    2016-12-01

    The development of platelet-rich fibrin (PRF) drastically simplified the preparation procedure of platelet-concentrated biomaterials, such as platelet-rich plasma (PRP), and facilitated their clinical application. PRF's clinical effectiveness has often been demonstrated in pre-clinical and clinical studies; however, it is still controversial whether growth factors are significantly concentrated in PRF preparations to facilitate wound healing and tissue regeneration. To address this matter, we performed a comparative study of growth factor contents in PRP and its derivatives, such as advanced PRF (A-PRF) and concentrated growth factors (CGF). PRP and its derivatives were prepared from the same peripheral blood samples collected from healthy donors. A-PRF and CGF preparations were homogenized and centrifuged to produce extracts. Platelet and white blood cell counts in A-PRF and CGF preparations were determined by subtracting those counts in red blood cell fractions, supernatant acellular serum fractions, and A-PRF/CGF exudate fractions from those counts of whole blood samples. Concentrations of growth factors (TGF-β1, PDGF-BB, VEGF) and pro-inflammatory cytokines (IL-1β, IL-6) were determined using ELISA kits. Compared to PRP preparations, both A-PRF and CGF extracts contained compatible or higher levels of platelets and platelet-derived growth factors. In a cell proliferation assay, both A-PRF and CGF extracts significantly stimulated the proliferation of human periosteal cells without significant reduction at higher doses. These data clearly demonstrate that both A-PRF and CGF preparations contain significant amounts of growth factors capable of stimulating periosteal cell proliferation, suggesting that A-PRF and CGF preparations function not only as a scaffolding material but also as a reservoir to deliver certain growth factors at the site of application.

  1. Growth factors, muscle function, and doping.

    Science.gov (United States)

    Goldspink, Geoffrey; Wessner, Barbara; Tschan, Harald; Bachl, Norbert

    2010-03-01

    This article discusses the inevitable use of growth factors for enhancing muscle strength and athletic performance. Much effort has been expended on developing a treatment of muscle wasting associated with a range of diseases and aging. Frailty in the aging population is a major socioeconomic and medical problem. Emerging molecular techniques have made it possible to gain a better understanding of the growth factor genes and how they are activated by physical activity. The ways that misuse of growth factors may be detected and verified in athletes and future challenges for detecting manipulation of signaling pathways are discussed. Copyright 2010. Published by Elsevier Inc.

  2. Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1

    International Nuclear Information System (INIS)

    Williams, Kaye J.; Telfer, Brian A.; Xenaki, Dia; Sheridan, Mary R.; Desbaillets, Isabelle; Peters, Hans J.W.; Honess, Davina; Harris, Adrian L.; Dachs, Gabi U.; Kogel, Albert van der; Stratford, Ian J.

    2005-01-01

    Background and purpose: To test the hypothesis that deficiency in expression of the transcription factor, HIF-1, renders tumours more radioresponsive than HIF-1 proficient tumours. Patients and methods: Tumours comprising mouse hepatoma cells lacking HIF-1β (and thereby HIF-1 function) were grown in nude mice and radiation-induced growth delay compared with that seen for wild-type tumours and tumours derived from HIF-1β negative cells where HIF-1 function had been restored. Results: The xenografts that lack HIF-1 activity take longer to establish their growth and are more radioresponsive than both parental xenografts and those with restored HIF-1 function. Pre-treatment of the HIF-1 deficient xenografts with the hypoxic radiosensitizer misonidazole, had little effect on radioresponse. In contrast this treatment radiosensitized the parental xenografts. In spite of this, no difference in oxygenation status was found between the tumour types as measured by Eppendorf O 2 -electrodes and by binding of the hypoxic cell marker NITP. Admixing wild type and HIF-1 deficient cells in the same tumour at ratios of 1 in 10 and 1 in 100 restores the growth of the mixed tumours to that of a 100% HIF-1 proficient cell population. However, when comparing the effects of radiation on the mixed tumours, radioresponsiveness is maintained in those tumours containing the high proportion of HIF-1 deficient cells. Conclusions: The differences in radioresponse do not correlate with tumour oxygenation, suggesting that the hypoxic cells within the HIF-1 deficient tumours do not contribute to the outcome of radiotherapy. Thus, hypoxia impacts on tumour radioresponsiveness not simply because of the physio-chemical mechanism of oxygen with radiation-induced radicals causing damage 'fixation', but also because hypoxia/HIF-1 promotes expression of genes that allow tumour cells to survive under these adverse conditions. Further, the results from the cell mixing experiments uncouple the growth

  3. The effect of endostatin gene in combination with radiotherapy on rats with implanted tumor

    International Nuclear Information System (INIS)

    Li Yong; Jin Ning; Yang Haishan; Piao Chunji; Lv Zhe

    2005-01-01

    Objective: To study the combination therapy effect of the radiotherapy with endostatin gene therapy on the rats with implanted tumor. Methods: Immediate Walker-256 cancerous ascetic injection method was used to make a rat tumor-bearing model, then the tumor was treated with saline, endostatin gene, irradiation or endostatin gene plus irradiation. The tumor growth rate and weight were observed, Western blot and RT-PCR were adopted to check the expressions of endostatin mRNA and protein. Results: The expressions of endostatin mRNA and protein were significant in the gene therapy group and the gene plus radiotherapy group, but there was a significant difference between these two groups. As compared with the control group, the tumor growth rate and weight decreased significantly in all the therapy groups (P 0.05). Conclusion: After the pCMV-Endostatin was induced, the expressions of endostatin mRNA and protein was significant in Walker-256 tumor and the tumor growth was inhibited. However, the effect of the endostatin gene plus radiotherapy was obviously better than that of the endostatin gene therapy group or the radiotherapy group for inhibiting tumor growth. (authors)

  4. Accuracy evaluation of the prescribed calibration factors for ionisation chambers belonging to radiotherapy centres

    International Nuclear Information System (INIS)

    Mohd Taufik Dolah; Supian Samat; Taiman Kadni

    1999-01-01

    Air kerma and exposure calibration factors of 14 ionisation chambers belonging to ten local radiotherapy centres have been determined by SSDL in the recent last ten month (1/10/1998 - 31/7/1999). The results obtained were compared either with previous SSDL results, or the chambers certificate values. The range of the percentage deviations obtained was -1.70% to 1.18%, which lies between the IAEA accepted value of range ±3.5%. (author)

  5. Transforming growth factor-beta1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Flyvbjerg, Allan; Eriksen, E F

    2001-01-01

    While transforming growth factor-beta1 (TGF-beta1) regulates proliferation and differentiation of human osteoblast precursor cells, the mechanisms underlying these effects are not known. Several hormones and locally acting growth factors regulate osteoblast functions through changes in the insulin......-like growth factors (IGFs) and IGF-binding proteins (IGFBPs). Thus, we studied the effects of TGF-beta1 on IGFs and IGFBPs in human marrow stromal (hMS) osteoblast precursor cells. TGF-beta1 increased the steady-state mRNA level of IGF-I up to 8.5+/-0.6-fold (P...

  6. Organisational Factors of Rapid Growth of Slovenian Dynamic Enterprises

    Directory of Open Access Journals (Sweden)

    Pšeničny Viljem

    2013-01-01

    Full Text Available The authors provide key findings on the internal and external environmental factors of growth that affect the rapid growth of dynamic enterprises in relation to individual key organisational factors or functions. The key organisational relationships in a growing enterprise are upgraded with previous research findings and identified key factors of rapid growth through qualitative and quantitative analysis based on the analysis of 4,511 dynamic Slovenian enterprises exhibiting growth potential. More than 250 descriptive attributes of a sample of firms from 2011 were also used for further qualitative analysis and verification of key growth factors. On the basis of the sample (the study was conducted with 131 Slovenian dynamic enterprises, the authors verify whether these factors are the same as the factors that were studied in previous researches. They also provide empirical findings on rapid growth factors in relation to individual organisational functions: administration - management - implementation (entrepreneur - manager - employees. Through factor analysis they look for the correlation strength between individual variables (attributes that best describe each factor of rapid growth and that relate to the aforementioned organisational functions in dynamic enterprises. The research findings on rapid growth factors offer companies the opportunity to consider these factors during the planning and implementation phases of their business, to choose appropriate instruments for the transition from a small fast growing firm to a professionally managed growing company, to stimulate growth and to choose an appropriate growth strategy and organisational factors in order to remain, or become, dynamic enterprises that can further contribute to the preservation, growth and development of the Slovenian economy

  7. Standard-Fractionated Radiotherapy for Optic Nerve Sheath Meningioma: Visual Outcome Is Predicted by Mean Eye Dose

    Energy Technology Data Exchange (ETDEWEB)

    Abouaf, Lucie [Neuro-Ophthalmology Unit, Pierre-Wertheimer Hospital, Hospices Civils de Lyon, Lyon (France); Girard, Nicolas [Radiotherapy-Oncology Department, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon (France); Claude Bernard University, Lyon (France); Lefort, Thibaud [Neuro-Radiology Department, Pierre-Wertheimer Hospital, Hospices Civils de Lyon, Lyon (France); D' hombres, Anne [Claude Bernard University, Lyon (France); Tilikete, Caroline; Vighetto, Alain [Neuro-Ophthalmology Unit, Pierre-Wertheimer Hospital, Hospices Civils de Lyon, Lyon (France); Claude Bernard University, Lyon (France); Mornex, Francoise, E-mail: francoise.mornex@chu-lyon.fr [Claude Bernard University, Lyon (France)

    2012-03-01

    Purpose: Radiotherapy has shown its efficacy in controlling optic nerve sheath meningiomas (ONSM) tumor growth while allowing visual acuity to improve or stabilize. However, radiation-induced toxicity may ultimately jeopardize the functional benefit. The purpose of this study was to identify predictive factors of poor visual outcome in patients receiving radiotherapy for ONSM. Methods and Materials: We conducted an extensive analysis of 10 patients with ONSM with regard to clinical, radiologic, and dosimetric aspects. All patients were treated with conformal radiotherapy and subsequently underwent biannual neuroophthalmologic and imaging assessments. Pretreatment and posttreatment values of visual acuity and visual field were compared with Wilcoxon's signed rank test. Results: Visual acuity values significantly improved after radiotherapy. After a median follow-up time of 51 months, 6 patients had improved visual acuity, 4 patients had improved visual field, 1 patient was in stable condition, and 1 patient had deteriorated visual acuity and visual field. Tumor control rate was 100% at magnetic resonance imaging assessment. Visual acuity deterioration after radiotherapy was related to radiation-induced retinopathy in 2 patients and radiation-induced mature cataract in 1 patient. Study of radiotherapy parameters showed that the mean eye dose was significantly higher in those 3 patients who had deteriorated vision. Conclusions: Our study confirms that radiotherapy is efficient in treating ONSM. Long-term visual outcome may be compromised by radiation-induced side effects. Mean eye dose has to be considered as a limiting constraint in treatment planning.

  8. Engineering growth factors for regenerative medicine applications.

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Aaron C.; Briquez, Priscilla S.; Hubbell, Jeffrey A.; Cochran, Jennifer R.

    2016-01-15

    Growth factors are important morphogenetic proteins that instruct cell behavior and guide tissue repair and renewal. Although their therapeutic potential holds great promise in regenerative medicine applications, translation of growth factors into clinical treatments has been hindered by limitations including poor protein stability, low recombinant expression yield, and suboptimal efficacy. This review highlights current tools, technologies, and approaches to design integrated and effective growth factor-based therapies for regenerative medicine applications. The first section describes rational and combinatorial protein engineering approaches that have been utilized to improve growth factor stability, expression yield, biodistribution, and serum half-life, or alter their cell trafficking behavior or receptor binding affinity. The second section highlights elegant biomaterial-based systems, inspired by the natural extracellular matrix milieu, that have been developed for effective spatial and temporal delivery of growth factors to cell surface receptors. Although appearing distinct, these two approaches are highly complementary and involve principles of molecular design and engineering to be considered in parallel when developing optimal materials for clinical applications.

  9. Immunohistochemical expression of Insulin-like growth factor-1, Transforming growth factor-beta1, and Vascular endothelial growth factor in parathyroid adenoma and hyperplasia

    Directory of Open Access Journals (Sweden)

    Hamide Sayar

    2014-01-01

    Full Text Available Background: Insulin-like growth factor (IGF, transforming growth factor-beta1 (TGF-β1, and vascular endothelial growth factor (VEGF are commonly studied growth factors, but little data are available on the immunohistochemical expression of these factors in parathyroid lesions. Materials and Methods: Tissue specimens from 36 patients with primary hyperparathyroidism (P-HPT (26 adenomas and 10 primary hyperplasias were examined. Normal parathyroid tissue adjacent to the adenoma or area of hyperplasia was used as control tissue. Preoperative laboratory testing [serum Ca and P, creatinine and parathormone levels (PTH] which led to the diagnosis of P-HPT had been performed, the size and weight of the parathyroid glands measured, and postoperative serum PTH levels determined. Paraffin-embedded parathyroid tissue specimens were stained with antibodies to IGF-1, VEGF, and TGF-β1 using standard immunohistochemical procedures. Results: IGF-1 immunoreactivity was seen in 50% of hyperplasia and in 46% of adenoma samples, but in 87% of normal parathyroid tissue in the vicinity of the adenomas (P = 0.005. TGF-β1 immunoreactivity was observed in 90% of hyperplasia, in 92% of adenoma samples, and in 95% of normal tissues around adenomas. VEGF immunoreactivity was observed in 70% of hyperplastic and 65% of adenomatous tissues, as well as in 54% of normal tissues in the vicinity of the adenoma. No significant differences in the expression of IGF-1, TGF-β1, and VEGF were observed between primary adenomas compared to hyperplasia samples (P > 0.05. Conclusions: Parathyroid tissue is clearly a site for production of IGF-1, TGF-β1, and VEGF. IGF-1 receptor activity was higher in normal parathyroid tissue compared to hyperplastic and adenomatous tissue.

  10. Secondary effects of radiotherapy on the orofacial sphere

    International Nuclear Information System (INIS)

    Guillaume, Nicolas

    2012-01-01

    The objective of this research is to determine the role of the dental surgeon in the taking into care of patients treated by head and neck radiotherapy. It also aims at giving information to the patient on secondary effects which radiotherapy may induce, and at determining which therapeutic behaviour to adopt to prevent or at least mitigate the appearance of complications. The author first presents some generalities on radiotherapy: presentation of upper aero-digestive tract cancers (surgery, radiotherapy, and chemotherapy), description of the different radiotherapy techniques (external radiotherapy, brachytherapy), discussion of factors influencing local secondary effects of radiotherapy. The second part addresses the specific case of early orofacial secondary effects, discusses their origin, clinic signs and prevention means: cutaneous effect, mucositis, xerostomia, candidiasis, taste disorders, relationship between early local reactions and anti-tumour treatment efficiency. The third part addresses late orofacial secondary effects: cervix sclerosis, limitation of mouth opening, dental effects, periodontal diseases, osteoradionecrosis. The last part discusses the evolution of radiotherapy: intensity modulated conformational radiotherapy, targeted therapeutics [fr

  11. Factors associated with changes in vaginal length and diameter during pelvic radiotherapy for cervical cancer.

    Science.gov (United States)

    Martins, Jumara; Vaz, Ana Francisca; Grion, Regina Celia; Esteves, Sérgio Carlos Barros; Costa-Paiva, Lúcia; Baccaro, Luiz Francisco

    2017-12-01

    This study reports the incidence and factors associated with vaginal stenosis and changes in vaginal dimensions after pelvic radiotherapy for cervical cancer. A descriptive longitudinal study with 139 women with cervical cancer was conducted from January 2013 to November 2015. The outcome variables were vaginal stenosis assessed using the Common Terminology Criteria for Adverse Events (CTCAE v3.0) and changes in vaginal diameter and length after the end of radiotherapy. Independent variables were the characteristics of the neoplasm, clinical and sociodemographic data. Bivariate analysis was carried out using χ 2 , Kruskal-Wallis and Mann-Whitney's test. Multiple analysis was carried out using Poisson regression and a generalized linear model. Most women (50.4%) had stage IIIB tumors. According to CTCAE v3.0 scale, 30.2% had no stenosis, 69.1% had grade 1 and 0.7% had grade 2 stenosis after radiotherapy. Regarding changes in vaginal measures, the mean variation in diameter was - 0.6 (± 1.7) mm and the mean variation in length was - 0.6 (± 1.3) cm. In the final statistical model, having tumoral invasion of the vaginal walls (coefficient + 0.73, p vaginal stenosis and lower reduction of vaginal dimensions. Advanced clinical stage (coefficient + 1.44; p = 0.02) and receiving brachytherapy/teletherapy (coefficient - 1.17, p vaginal dimensions. Most women had mild vaginal stenosis with slight reductions in both diameter and length of the vaginal canal. Women with tumoral invasion of the vagina have an increase in vaginal length soon after radiotherapy due to a reduction in tumoral volume.

  12. The prognostic factors affecting survival in muscle invasive bladder cancer treated with radiotherapy

    International Nuclear Information System (INIS)

    Chung, Woong Ki; Oh, Bong Ryoul; Ahn, Sung Ja; Nah, Byung Sik; Kwon, Dong Deuk; Park, Kwang Sung; Ryu, Soo Bang; Park, Yang Il

    2002-01-01

    This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Twenty eight patient with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were performed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uniformed in 3. Radiation therapy was performed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was performed on the prognostic factors affecting the survival rate. The survival rate was 76%, 46%, 33%, 33% at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, T-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uni- and multivariate analysis. In univariate analysis, the T-stage (ρ 0.078) and radiation dose (ρ = 0.051) were marginally significant, and the treatment response (ρ = 0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival rate. The

  13. The prognostic factors affecting survival in muscle invasive bladder cancer treated with radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Woong Ki; Oh, Bong Ryoul; Ahn, Sung Ja; Nah, Byung Sik; Kwon, Dong Deuk; Park, Kwang Sung; Ryu, Soo Bang; Park, Yang Il [Chonnam National University Medical School, Chonnam National University Hospital, Kwangju (Korea, Republic of)

    2002-06-15

    This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Twenty eight patient with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were performed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uniformed in 3. Radiation therapy was performed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was performed on the prognostic factors affecting the survival rate. The survival rate was 76%, 46%, 33%, 33% at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, T-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uni- and multivariate analysis. In univariate analysis, the T-stage ({rho} 0.078) and radiation dose ({rho} = 0.051) were marginally significant, and the treatment response ({rho} = 0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival

  14. Insulin-like growth factors and insulin-like growth factor binding proteins in mammary gland function

    International Nuclear Information System (INIS)

    Marshman, Emma; Streuli, Charles H

    2002-01-01

    Insulin-like growth factor (IGF)-mediated proliferation and survival are essential for normal development in the mammary gland during puberty and pregnancy. IGFs interact with IGF-binding proteins and regulate their function. The present review focuses on the role of IGFs and IGF-binding proteins in the mammary gland and describes how modulation of their actions occurs by association with hormones, other growth factors and the extracellular matrix. The review will also highlight the involvement of the IGF axis in breast cancer

  15. radiochemical studies on the growth of myeloma cells

    International Nuclear Information System (INIS)

    Elshershaby, H.M.M.

    2008-01-01

    cancer is a disease of unregulated cell growth. humans of all ages develop cancer, and a wide variety of organs are affected. multiple myeloma is a cancer in which antibody-producing plasma cells grow in an uncontrolled and invasive (malignant) manner. melphalan (DNA cross-linker), is one of the most widely used and effective drugs in the treatment of multiple myeloma. thalidomide as an immunomodulatory agent is clinically useful in a number of cancers. antitumor activity may be related to a number of known properties, including antitumor necrosis factor (TNF)-α and T-cell costimulatory and antiangiogenic effect. however, it may also involve direct antitumor effects. radiotherapy is an important modality in the treatment of cancer. the aim of radiotherapy is to deliver radiation doses and schedules that kill cancer cells, while preserving normal tissue function. the aim of these studies was to evaluate the therapeutic effects of some chemical substances (chemotherapy)such as melphalan and thalidomide and γ-radiation (radiotherapy)on the growth of myeloma cells. also some confirmatory tests such as β2-microglobulin, caspases enzymes 8 and 9 and flow cytometric analyses were performed for the obtained optimum doses.

  16. Cultured human foreskin fibroblasts produce a factor that stimulates their growth with properties similar to basic fibroblast growth factor

    International Nuclear Information System (INIS)

    Story, M.T.

    1989-01-01

    To determine if fibroblasts could be a source of fibroblast growth factor (FGF) in tissue, cells were initiated in culture from newborn human foreskin. Fibroblast cell lysates promoted radiolabeled thymidine uptake by cultured quiescent fibroblasts. Seventy-nine percent of the growth-promoting activity of lysates was recovered from heparin-Sepharose. The heparin-binding growth factor reacted on immunoblots with antiserum to human placenta-derived basic FGF and competed with iodinated basic FGF for binding to antiserum to (1-24)bFGF synthetic peptide. To confirm that fibroblasts were the source of the growth factor, cell lysates were prepared from cells incubated with radiolabeled methionine. Heparin affinity purified material was immunoprecipitated with basic FGF antiserum and electrophoresed. Radiolabeled material was detected on gel autoradiographs in the same molecular weight region as authentic iodinated basic FGF. The findings are consistant with the notion that cultured fibroblasts express basic FGF. As these cells also respond to the mitogen, it is possible that the regulation of their growth is under autocrine control. Fibroblasts may be an important source of the growth factor in tissue

  17. Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

    International Nuclear Information System (INIS)

    Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

    2011-01-01

    Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

  18. Problems of radiotherapy on the brain tumors in children less than two years of age

    Energy Technology Data Exchange (ETDEWEB)

    Miyagami, Mitsusuke; Tsubokawa, Takashi (Nihon Univ., Tokyo (Japan). School of Medicine); Nishimoto, Hiroshi; Ueno, Yuhichi

    1990-06-01

    Impaired growth and mental or developmental disturbance due to radiotherapy for 10 cases of brain tumors in the children ages less than 2 years old were evaluated. Six cases of brain tumor which did not involve the hypothalamic-pituitary axis, were followed more than 2 years after cranial or craniospinal irradiation. Four cases irradiated greater than 2900 rad to the whole brain all revealed markedly lower body heights than -2 SD of the medium. Growth impairment was found to be progressive over time, and markedly evident after 2 years following cranial or craniospinal radiotherapy. Somatomedin C in the blood was measured in 8 cases of brain tumors in childhood receiving radiotherapy. The measurement of Somatomedin C showed markedly low values measuring 0.19 to 0.54 U/ml (medium; 0.36 U/ml) in children having lower body height than -2 SD. Mental retardation or developmental disturbances were found in IQ or DQ tests in all of 5 infants or children younger than 2 years with brain tumors who got radiotherapy over 2900 rad to the whole brain. A case of craniopharyngioma, which had 5400 rad for tumor localization at the hypothalamus-pituitary axis and showed markedly low height, was given growth hormone and grew to normal height without distinct side effects. It was suggested that radiotherapy for brain tumors in infants or children should have special care in deciding the dose, field and time of radiation. If low height due to radiotherapy results, growth hormone therapy should be used for its treatment in childhood. (author).

  19. Factors associated with acute oral mucosal reaction induced by radiotherapy in head and neck squamous cell carcinoma: A retrospective single-center experience.

    Science.gov (United States)

    Tao, Zhenchao; Gao, Jin; Qian, Liting; Huang, Yifan; Zhou, Yan; Yang, Liping; He, Jian; Yang, Jing; Wang, Ru; Zhang, Yangyang

    2017-12-01

    To investigate risk factors for acute oral mucosal reaction during head and neck squamous cell carcinoma radiotherapy.A retrospective study of patients with head and neck squamous cell carcinoma who underwent radiotherapy from November 2013 to May 2016 in Anhui Provincial Cancer Hospital was conducted. Data on the occurrence and severity of acute oral mucositis were extracted from clinical records. Based on the Radiation Therapy Oncology Group (RTOG) grading of acute radiation mucosal injury, the patients were assigned into acute reaction (grades 2-4) and minimum reaction (grades 0-1) groups. Preradiotherapy characteristics and treatment factors were compared between the 2 groups. Multivariate logistic regression analysis was used to detect the independent factors associated with acute oral mucosal reactions.Eighty patients completed radiotherapy during the study period. Oral mucosal reactions were recorded as 25, 31, and 24 cases of grades 1, 2, and 3 injuries, respectively. Significant differences between acute reaction and minimum reaction groups were detected in cancer lymph node (N) staging, smoking and diabetes history, pretreatment platelet count and T-Helper/T-Suppressor lymphocyte (Th/Ts) ratio, concurrent chemotherapy, and total and single irradiation doses.Multivariate analysis showed that N stage, smoking history, single dose parapharyngeal irradiation, and pretreatment platelet count were independent risk factors for acute radiation induced oral mucosal reaction. Smoking history, higher grading of N stage, higher single dose irradiation, and lower preirradiation platelet count may increase the risk and severity of acute radiation oral mucosal reaction in radiotherapy of head and neck cancer patients. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  20. Factor-structure of economic growth in E-commerce

    Institute of Scientific and Technical Information of China (English)

    吴隽; 刘洪久; 栾天行

    2003-01-01

    In order to analyze the factors having effect on economic growth of E-commerce, the economic growthprocess of E-commerce is divided into three stages; growth stage, stabilization stage and re-growth stage. Thesethree different stages are analysed using several economic growth theories, a set of factor-structure is proposedfor each stage of the economic growth process of E-commerce.

  1. Economic growth factors system: theoretical and methodological aspect

    OpenAIRE

    H.Ya. Hlukha

    2014-01-01

    The aim of the article. The main objective of the article is to create theoretical grounds to build the system of economic growth factors, to modernize their classification, to define exogenous and endogenous factors, to analyze them within the state economic policy structure. The results of the analysis. The article focuses on economic growth factors theoretical studies: - economic growth factors classification characteristics have been highlighted; - various approaches to determine...

  2. Insulin-like growth factor-I in growth and metabolism

    DEFF Research Database (Denmark)

    Backeljauw, P; Bang, P; Dunger, D B

    2010-01-01

    Deficiency of insulin-like growth factor-I (IGF-I) results in growth failure. A variety of molecular defects have been found to underlie severe primary IGF-I deficiency (IGFD), in which serum IGF-I concentrations are substantially decreased and fail to respond to GH therapy. Identification of more...

  3. Assessment of psychological responses in patients about to receive radiotherapy

    International Nuclear Information System (INIS)

    Karasawa, Kumiko; Horikawa, Naoshi; Kawase, Eri

    2005-01-01

    Radiotherapy is considered to be associated with psychological distress. We assessed the mental status, anxiety, and the factors associated with these in cancer patients about to receive radiotherapy. Hospitalized patients about to receive radiotherapy participated. Psychological status was assessed by a psychiatrist, based on interview about the type of anxiety related to cancer or radiotherapy as well as self-rating questionnaires. Eligible data were collected from 94 patients. The incidence of mental disorders was 20%. The total mood disturbance scores were significantly higher in patients with poor performance status. The most common type of anxiety regarding radiotherapy was acute adverse effect, and the predictors were palliative treatment and living alone. Mental disorders, mood disturbance, and anxiety in patients cannot be neglected in radiation oncology practice. Especially careful attention should be paid to patients with these predictive factors. (author)

  4. Radiotherapy in supratentorial gliomas. A study of 821 cases

    International Nuclear Information System (INIS)

    Heesters, M.; Molenaar, W.; Go, G.K.

    2003-01-01

    Purpose: Analysis of the results of radiotherapy in a large group of cerebral gliomas with identification of prognostic factors and the outcome with respect to different decades of treatment. Patients and Methods: Two decades (1979-1999) of radiotherapy in supratentorial astrocytic and oligodendroglial tumors (n = 821) at the University Hospital Groningen were retrospectively evaluated. Prognostic factors for survival were analyzed. Two decades of radiotherapy treatment were compared with respect to radiotherapy dose and treatment-field design. Results: Glioblastoma multiforme, including gliosarcoma, was the most frequent supratentorial glioma (n = 442) with a poor survival, i.e., median survival time (MST) 7 months, especially in patients > 50 years of age and with poor performance. Patients with good performance were selected for radiotherapy with an optimum dose of 60 Gy local-field irradiation. However, in patients with poor prognosis, no radiotherapy was applied or a shorter treatment scheme was given. Anaplastic astrocytomas (n = 131) were treated in the same way as glioblastoma multiforme. Over time, a decrease in radiation dose (from 60 to 45 Gy) and from whole brain irradiation to local-field treatment was observed, following the literature. In low-grade gliomas, prognostic factors for survival were age, performance, and extent of resection. Gemistocytic astrocytoma (n = 15) had an inferior survival compared to astrocytoma (MST 46 vs. 54 months), but a superior survival compared to anaplastic astrocytoma (MST 10 months). The presence of an oligodendroglial component in a glioma implied a superior survival compared to the astrocytic gliomas. The inherent biology of the glioma is reflected by the study of recurrent tumors with progression to higher grades of malignancy in 32-40% and by the histology of recurrent oligodendroglial tumors. In comparing two decades of radiotherapy in gliomas, no differences in survival were observed despite the technological

  5. Radiotherapy in supratentorial gliomas. A study of 821 cases

    Energy Technology Data Exchange (ETDEWEB)

    Heesters, M. [Dept. of Radiotherapy, Groningen Univ. Hospital (Netherlands); Molenaar, W. [Dept. of Pathology, Groningen Univ. Hospital (Netherlands); Go, G.K. [Dept. of Neurosurgery, Groningen Univ. Hospital (Netherlands)

    2003-09-01

    Purpose: Analysis of the results of radiotherapy in a large group of cerebral gliomas with identification of prognostic factors and the outcome with respect to different decades of treatment. Patients and Methods: Two decades (1979-1999) of radiotherapy in supratentorial astrocytic and oligodendroglial tumors (n = 821) at the University Hospital Groningen were retrospectively evaluated. Prognostic factors for survival were analyzed. Two decades of radiotherapy treatment were compared with respect to radiotherapy dose and treatment-field design. Results: Glioblastoma multiforme, including gliosarcoma, was the most frequent supratentorial glioma (n = 442) with a poor survival, i.e., median survival time (MST) 7 months, especially in patients > 50 years of age and with poor performance. Patients with good performance were selected for radiotherapy with an optimum dose of 60 Gy local-field irradiation. However, in patients with poor prognosis, no radiotherapy was applied or a shorter treatment scheme was given. Anaplastic astrocytomas (n = 131) were treated in the same way as glioblastoma multiforme. Over time, a decrease in radiation dose (from 60 to 45 Gy) and from whole brain irradiation to local-field treatment was observed, following the literature. In low-grade gliomas, prognostic factors for survival were age, performance, and extent of resection. Gemistocytic astrocytoma (n = 15) had an inferior survival compared to astrocytoma (MST 46 vs. 54 months), but a superior survival compared to anaplastic astrocytoma (MST 10 months). The presence of an oligodendroglial component in a glioma implied a superior survival compared to the astrocytic gliomas. The inherent biology of the glioma is reflected by the study of recurrent tumors with progression to higher grades of malignancy in 32-40% and by the histology of recurrent oligodendroglial tumors. In comparing two decades of radiotherapy in gliomas, no differences in survival were observed despite the technological

  6. Postoperative radiotherapy of uterine sarcoma: A multicentric retrospective study

    International Nuclear Information System (INIS)

    Champetier, C.; Cowen, D.; Hannoun-Levi, J.M.; Resbeut, M.; Azria, D.; Salem, N.; Tessier, E.; Ellis, S.

    2011-01-01

    Purpose. - Surgery is the treatment of choice for localized uterine sarcomas. We conducted a retrospective study to define prognostic factors. Patients and methods. - We studied 111 cases of patients treated by adjuvant radiotherapy for uterine sarcoma in seven French centers. The median decline was 31 months. We conducted a univariate analysis to identify factors correlated with local recurrence. The statistically significant factors were studied in multivariate analysis by Cox model. Results. - The median dose of external beam radiotherapy was 45 Gy. Forty-three percent of patients had vaginal vault brachytherapy and 21 % chemotherapy. Only 6.3 % of patients had complications of acute grade III and 8.1 % of long-term sequelae of radiotherapy. The survival rate at 5 years was 74.6 %. They noted 12.6 % of isolated locoregional recurrences, against 29.7 % for distant recurrences, 80 % were pulmonary. Factors correlated with the risk of locoregional relapse were menopausal status (P = 0.045) and surgical margins suspicious or not healthy (P = 0.0095). The chemotherapy did not improve overall survival or disease free survival but the numbers were low. Conclusion. - The postoperative radiotherapy provides good local control in this disease. Brachytherapy is sometimes done, but it does not improve local control. Chemotherapy is not a standard localized stage but the rate of metastatic recurrence calls for the development of strategies involving systemic treatment with radiotherapy. (authors)

  7. Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection.

    Science.gov (United States)

    Lang, Charles H; Frost, Robert A

    2002-05-01

    The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance.

  8. On the calibration of radiotherapy dosemeters in Australia

    International Nuclear Information System (INIS)

    Huntley, R.; Kotler, L.; Webb, D.

    2000-01-01

    Full text: Dosemeters for external beam radiotherapy are calibrated in Australia by ARPANSA, against the national primary standards of exposure and absorbed dose. The primary standards are free air chambers for exposure at low and medium energy X-rays, a graphite cavity chamber for exposure at 60 Co, and a graphite calorimeter for absorbed dose at 60 Co and high energy (MV) X -rays. Radiotherapy dosemeters are calibrated against these standards using a well documented formalism to provide calibration factors suitable for use with dosimetry protocols. A dosemeter usually comprises an ionization chamber connected to an independent electrometer. These are calibrated separately if possible. A combined calibration factor is reported together with the electrometer calibration factor (sensitivity). The dosimetry protocol used in radiotherapy centres in Australia and New Zealand is currently the simplified version of the IAEA TRS277 protocol, published by the New Zealand NRL and recommended by the ACPSEM. This protocol requires the use of an exposure or air kerma calibration factor at 60 Co (Nx or Nk) to evaluate the absorbed dose to air calibration factor N D . The chamber is then placed in a water phantom with its centre displaced from the reference point by p eff . ARPANSA can also supply calibration factors in absorbed dose to water (N D,w ), as required as input to the new IAEA CoP. If an absorbed dose to water calibration factor is used by the radiotherapy centre, the chamber should be placed with its centre at the reference point in the water phantom. ARPANSA has for some years coordinated the participation of Australian radiotherapy centres in the IAEA TLD Quality Audit service. Note that this service does not represent a calibration and should not be referred to as such. The only calibration is that provided by ARPANSA for a reference dosemeter at each radiotherapy centre. As soon as the ANSTO SSDL is operational, calibrations of reference dosemeters will also be

  9. Livin expression is an independent factor in rectal cancer patients with or without preoperative radiotherapy

    International Nuclear Information System (INIS)

    Ding, Zhen-Yu; Zhang, Hong; Adell, Gunnar; Olsson, Birgit; Sun, Xiao-Feng

    2013-01-01

    This study was aimed to investigate the expression significance of Livin in relation to radiotherapy (RT), clinicopathological and biological factors of rectal cancer patients. This study included 144 primary rectal cancer patients who participated in a Swedish clinical trial of preoperative radiotherapy. Tissue microarray samples from the excised primary rectal cancers, normal mucosa and lymph node metastases were immunostained with Livin antibody. The proliferation of colon cancer cell lines SW620 and RKO was assayed after Livin knock-down. The expression of Livin was significantly increased from adjacent (P = 0.051) or distant (P = 0.028) normal mucosa to primary tumors. 15.4% (2/13) and 39.7% (52/131) patients with Livin-negative and positive tumors died at 180 months after surgery, and the difference tended to be statistically significant (P = 0.091). In multivariate analyses, the difference achieved statistical significance, independent of TNM stage, local and distant recurrence, grade of differentiation, gender, and age (odds ratio = 5.09, 95% CI: 1.01-25.64, P = 0.048). The in vitro study indicated colon cancer cells with Livin knock-down exhibited decreased proliferation compared with controls after RT. The expression of Livin was was independently related to survival in rectal cancer patients, suggesting Livin as a useful prognostic factor for rectal cancer patients

  10. Immunoreactive transforming growth factor alpha and epidermal growth factor in oral squamous cell carcinomas

    DEFF Research Database (Denmark)

    Therkildsen, M H; Poulsen, Steen Seier; Bretlau, P

    1993-01-01

    Forty oral squamous cell carcinomas have been investigated immunohistochemically for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF). The same cases were recently characterized for the expression of EGF-receptors. TGF-alpha was detected...... previous results confirms the existence of TGF-alpha, EGF, and EGF-receptors in the majority of oral squamous cell carcinomas and their metastases......., the cells above the basal cell layer were positive for both TGF-alpha and EGF. The same staining pattern was observed in oral mucosa obtained from healthy persons. In moderately to well differentiated carcinomas, the immunoreactivity was mainly confined to the cytologically more differentiated cells, thus...

  11. Silencing of the Wnt transcription factor TCF4 sensitizes colorectal cancer cells to (chemo-) radiotherapy

    Science.gov (United States)

    Kendziorra, Emil; Ahlborn, Kerstin; Spitzner, Melanie; Rave-Fränk, Margret; Emons, Georg; Gaedcke, Jochen; Kramer, Frank; Wolff, Hendrik A.; Becker, Heinz; Beissbarth, Tim; Ebner, Reinhard; Ghadimi, B.Michael; Pukrop, Tobias; Ried, Thomas; Grade, Marian

    2011-01-01

    A considerable percentage of rectal cancers are resistant to standard preoperative chemoradiotherapy. Because patients with a priori-resistant tumors do not benefit from multimodal treatment, understanding and overcoming this resistance remains of utmost clinical importance. We recently reported overexpression of the Wnt transcription factor TCF4, also known as TCF7L2, in rectal cancers that were resistant to 5-fluorouracil-based chemoradiotherapy. Because Wnt signaling has not been associated with treatment response, we aimed to investigate whether TCF4 mediates chemoradioresistance. RNA interference-mediated silencing of TCF4 was employed in three colorectal cancer (CRC) cell lines, and sensitivity to (chemo-) radiotherapy was assessed using a standard colony formation assay. Silencing of TCF4 caused a significant sensitization of CRC cells to clinically relevant doses of X-rays. This effect was restricted to tumor cells with high T cell factor (TCF) reporter activity, presumably in a β-catenin-independent manner. Radiosensitization was the consequence of (i) a transcriptional deregulation of Wnt/TCF4 target genes, (ii) a silencing-induced G2/M phase arrest, (iii) an impaired ability to adequately halt cell cycle progression after radiation and (iv) a compromised DNA double strand break repair as assessed by γH2AX staining. Taken together, our results indicate a novel mechanism through which the Wnt transcription factor TCF4 mediates chemoradioresistance. Moreover, they suggest that TCF4 is a promising molecular target to sensitize resistant tumor cells to (chemo-) radiotherapy. PMID:21983179

  12. Radiotherapy for head and neck malignancies is associated with increased salivary platelet-activating factor content

    International Nuclear Information System (INIS)

    Hlavaty, T.E.; Fisher, R.; Robbins, M.E.C.; Wheeler, J.; Funk, G.; Hussey, D.H.

    1996-01-01

    Purpose/Objective: Oral mucositis, characterized by pronounced erythema, edema, atrophy, and ulceration, remains a common complication of radiotherapeutic treatment of head and neck malignancies. These radiation-induced morbidities can cause a temporary cessation or indeed reduction in the extent of radiotherapy dose employed, compromising the likelihood of tumor cure. The precise pathogenic mechanisms involved in the development of radiation mucositis remain ill-defined. Platelet-activating factor (PAF), a pivotal mediator of acute inflammatory reactions, has been implicated in radiation-induced mucositis (McManus et al Lab Invest 68:118-124 1993). However, these data are limited in terms both of patient numbers, and time-course. The present study evaluated saliva PAF levels in patients receiving radiotherapy for head and neck malignancies in terms of levels prior to, during, and after the completion of radiotherapy. Materials and Methods: Saliva samples (1-2 mL) were obtained from 14 patients with oral cancer, and from 14 control non-malignant individuals. Saliva samples from the oral cancer patients were collected prior to the initiation of treatment, after the administration of 30 Gy, and at the completion of the course of radiotherapy. PAF was extracted from the saliva samples using a chloroform methanol mixture (2:1). Further purification was accomplished by washing the extracts through silica minicolumns. Measurements of PAF content were performed using a scintillation proximity assay system (Amersham, UK). This combined the use of a high specific activity 3 H-PAF with an antibody specific for PAF. Results: The PAF content of saliva obtained from patients prior to the initiation of radiotherapy was 226 ± 55 ng/mL, (mean ± SE). This was significantly greater than the value of 25 ± 11 ng/mL (p value = 0.003; 2-tail t test) measured in the saliva from the control individuals. Irradiation was associated with a significant increase in the PAF content of saliva

  13. Effects of growth-promoting factors on proliferation of mouse ...

    African Journals Online (AJOL)

    SSCs) in vitro are critical to our understanding of male infertility, genetic resources and endangered species conservation. To investigate the effects of growth-promoting factors, epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1) and ...

  14. Postmastectomy radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Shikama, Naoto; Koguchi, Masahiko; Sasaki, Shigeru; Kaneko, Tomoki; Shinoda, Atsunori; Nishikawa, Atsushi [Shinshu Univ., Matsumoto, Nagano (Japan). School of Medicine

    2000-10-01

    Since there have been few reports on postmastectomy radiotherapy having a high evidence level in Japan, the significance of postoperative radiotherapy and the irradiation techniques were reviewed based on reports from Western countries. Authors focused on the indications for postoperative irradiation, irradiation methods (irradiation sites, irradiation techniques; prosthetics, methods of irradiating the chest wall and lymph nodes, timing of irradiation), and complications, and discuss them. The factors thought to be adaptable to postmastectomy radiotherapy have been listed. Axillary lymph node metastasis and the size of the primary focus are thought to be important factors in locoregional recurrence. The chest wall and the supraclavicular lymph nodes are the usual sites of irradiation after mastectomy. The irradiation method consists of tangential irradiation of the chest wall and single-field irradiation of the supraclavicular lymph nodes, with 46-50 Gy in fractional doses of 1.8-2 Gy x 5/w is administered for 4.5-5.5 weeks. The timing of irradiation in the West is generally after chemotherapy. Adverse radiation effects include ischemic heart disease, pneumonitis, arm edema, rib fractures, and brachial plexus paralysis. The frequency of these complications is increased by the combined use of chemotherapy or surgery. The breast cancer cure rate in Japan is generally better than in the West. It remains to be determined whether the clinical data from Europe and America are applicable to the treatment of breast cancer in Japan. To address this issue, a clinical investigation should be performed in Japan with close cooperation between surgeons, physicians, pathologists, and radiotherapists. (K.H.)

  15. Tumor-infiltrating lymphocytes predict efficacy of preoperative radiotherapy for rectal cancer

    International Nuclear Information System (INIS)

    Xu Gang; Zhang Shanwen; Xu Bo

    2009-01-01

    Objective: To evaluate the effect of tumor infiltrating lymphocyte(TIL) on prognosis of rectal cancer treated with preoperative radiotherapy. Methods: From Jan. 1999 to Oct. 2007,107 patients with rectal cancer were treated with preoperative radiotherapy of 30 Gy/10f/12 days. The relationships among TIL, pathologic regression and prognosis were analyzed. Results: Before radiotherapy, TIL in rectal cancer was 75 patients (70.1%) in grade 1,16 (15.0%) in grade 2 and 16 (15.0%) in grade 3; While after radiotherapy, it changed to 19 (17.7%) in grade 1,43 (40.2%) in grade 2,35 (32.7%) in grade 3 and 10 (9.3%) in grade 4. After radiotherapy, pathologic regression was 36 (33.6%) in grade 1,57 (53.3%) in grade 2 and 14 (13.1%) in grade 3. Univariate analysis showed that TIL both before and after radiotherapy was the significant prognostic factor for local pathologic regression (χ 2 =36.80, P 2 = 14.00, P 2 =24.00, P 2 =12.17, P 2 =8.05, P<0.01). Conclusions: For rectal cancer treated with preoperative radiotherapy, TIL before and after radiotherapy is significantly related with local pathologic regression, and TIL after radiotherapy is a prognostic factor. (authors)

  16. Moving toward multi-dimensional radiotherapy and the role of radiobiology

    International Nuclear Information System (INIS)

    Oita, Masataka; Uto, Yoshihiro; Aoyama, Hideki

    2014-01-01

    Recent radiotherapy for cancer treatment enable the high-precision irradiation to the target under the computed image guidance. Developments of such radiotherapy has played large role in the improved strategy of cancer treatments. In addition, the molecular mechanistic studies related to proliferations of cancer cell contribute the multidisciplinary fields of clinical radiotherapies. Therefore, the combination of the image guidance and molecular targeting of cancer cells make it possible for individualized cancer treatment. Especially, the use of particle beam or boron neutron capture therapy (BNCT) has been spotlighted, and installations of such devices are planned widely. As the progress and collaborations of radiation biology and engineering physics, establishment of a new style of radiotherapy becomes available in post-genome era. In 2010s, the hi-tech machines controlling the spaciotemporal radiotherapy become in practice. Although, there still remains to be improved, e.g., more precise prediction of radiosensitivity or growth of individual tumors, and adverse outcomes after treatments, multi-dimensional optimizations of the individualized irradiations based on the molecular radiation biologies and medical physics are important for further development of radiotherapy. (author)

  17. Bone Health and Pelvic Radiotherapy.

    Science.gov (United States)

    Higham, C E; Faithfull, S

    2015-11-01

    Survivors who have received pelvic radiotherapy make up many of the long-term cancer population, with therapies for gynaecological, bowel, bladder and prostate malignancies. Individuals who receive radiotherapy to the pelvis as part of their cancer treatment are at risk of insufficiency fractures. Symptoms of insufficiency fractures include pelvic and back pain and immobility, which can affect substantially quality of life. This constellation of symptoms can occur within 2 months of radiotherapy up to 63 months post-treatment, with a median incidence of 6-20 months. As a condition it is under reported and evidence is poor as to the contributing risk factors, causation and best management to improve the patient's bone health and mobility. As radiotherapy advances, chronic symptoms, such as insufficiency fractures, as a consequence of treatment need to be better understood and reviewed. This overview explores the current evidence for the effect of radiotherapy on bone health and insufficiency fractures and identifies what we know and where gaps in our knowledge lie. The overview concludes with the need to take seriously complaints of pelvic pain from patients after pelvic radiotherapy and to investigate and manage these symptoms more effectively. There is a clear need for definitive research in this field to provide the evidence-based guidance much needed in practice. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  18. Development of radiation oncology learning system combined with multi-institutional radiotherapy database (ROGAD)

    International Nuclear Information System (INIS)

    Takemura, Akihiro; Iinuma, Masahiro; Kou, Hiroko; Harauchi, Hajime; Inamura, Kiyonari

    1999-01-01

    We have constructed and are operating a multi-institutional radiotherapy database ROGAD (Radiation Oncology Greater Area Database) since 1992. One of it's purpose is 'to optimize individual radiotherapy plans'. We developed Radiation oncology learning system combined with ROGAD' which conforms to that purpose. Several medical doctors evaluated our system. According to those evaluations, we are now confident that our system is able to contribute to improvement of radiotherapy results. Our final target is to generate a good cyclic relationship among three components: radiotherapy results according to ''Radiation oncology learning system combined with ROGAD.'; The growth of ROGAD; and radiation oncology learning system. (author)

  19. Radiotherapy

    International Nuclear Information System (INIS)

    Prosnitz, L.R.; Kapp, D.S.; Weissberg, J.B.

    1983-01-01

    This review highlights developments over the past decade in radiotherapy and attempts to summarize the state of the art in the management of the major diseases in which radiotherapy has a meaningful role. The equipment, radiobiology of radiotherapy and carcinoma of the lung, breast and intestines are highlighted

  20. Four R's of radiotherapy

    International Nuclear Information System (INIS)

    Withers, H.R.

    1975-01-01

    Radiotherapy given as multiple doses can be effective in sterilizing cancers, but the processes whereby the neoplasm is eradicated and the normal tissues are preserved are not fully understood. The differential between normal tissue and tumor response is enhanced by dose fractionation, single doses resulting in severe normal tissue injury when the dose is sufficient to control a proportion of treated tumors. Data are reviewed from radiobiological studies on laboratory animals and cultured cells that have thrown some light on four of the phenomena that influence the outcome of fractionated-dose radiotherapy, one or more of which may account for the relative sparing of normal tissues. These are repair of sublethal injury in normal and neoplastic cells, reoxygenation of the tumor, redistribution through the division cycle, and regeneration of surviving normal and malignant cells between dose fractions. These have been called the four R's of fractionated radiotherapy. Other factors are involved in the outcome of multifraction radiotherapy, including maintenance of the architectural integrity of the normal tissues, the volume of tissue irradi []ted, the tumor bed, and the immunocompetence of the host. (90 references) (CH)

  1. Preclinical evaluation of molecular-targeted anticancer agents for radiotherapy

    International Nuclear Information System (INIS)

    Krause, Mechthild; Zips, Daniel; Thames, Howard D.; Kummermehr, Johann; Baumann, Michael

    2006-01-01

    The combination of molecular-targeted agents with irradiation is a highly promising avenue for cancer research and patient care. Molecular-targeted agents are in themselves not curative in solid tumours, whereas radiotherapy is highly efficient in eradicating tumour stem cells. Recurrences after high-dose radiotherapy are caused by only one or few surviving tumour stem cells. Thus, even if a novel agent has the potential to kill only few tumour stem cells, or if it interferes in mechanisms of radioresistance of tumours, combination with radiotherapy may lead to an important improvement in local tumour control and survival. To evaluate the effects of novel agents combined with radiotherapy, it is therefore necessary to use experimental endpoints which reflect the killing of tumour stem cells, in particular tumour control assays. Such endpoints often do not correlate with volume-based parameters of tumour response such as tumour regression and growth delay. This calls for radiotherapy specific research strategies in the preclinical testing of novel anti-cancer drugs, which in many aspects are different from research approaches for medical oncology

  2. Prediction of lung density changes after radiotherapy by cone beam computed tomography response markers and pre-treatment factors for non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Bernchou, Uffe; Hansen, Olfred; Schytte, Tine

    2015-01-01

    BACKGROUND AND PURPOSE: This study investigates the ability of pre-treatment factors and response markers extracted from standard cone-beam computed tomography (CBCT) images to predict the lung density changes induced by radiotherapy for non-small cell lung cancer (NSCLC) patients. METHODS...... AND MATERIALS: Density changes in follow-up computed tomography scans were evaluated for 135 NSCLC patients treated with radiotherapy. Early response markers were obtained by analysing changes in lung density in CBCT images acquired during the treatment course. The ability of pre-treatment factors and CBCT...

  3. Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

  4. Processing and evaluation of image matching tools in radiotherapy; Mise en oeuvre et evaluation d'outils de fusion d'image en radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Bondiau, P Y

    2004-11-15

    Cancer is a major problem of public health. Treatment can be done in a general or loco-regional way, in this last case medical images are important as they specify the localization of the tumour. The objective of the radiotherapy is to deliver a curative dose of radiation in the target volume while sparing the organs at risks (O.A.R.). The determination of the accurate localization of the targets volume as well as O.A.R. make it possible to define the ballistic of irradiation beams. After the description of the principles of radiotherapy and cancers treatment, we specify the clinical stakes of ocular, cerebral and prostatic tumours. We present a state of the art of image matching, the various techniques reviewed with an aim of being didactic with respect to the medical community. The results of matching are presented within the framework of the planning of the cerebral and prostatic radiotherapy in order to specify the types of applicable matching in oncology and more particularly in radiotherapy. Then, we present the prospects for this type of application according to various anatomical areas. Applications of automatic segmentation and the evaluation of the results in the framework of brain tumour are described after a review of the various segmentation methods according to anatomical localizations. We will see an original application: the digital simulation of the virtual tumoral growth and the comparison with the real growth of a cerebral tumour presented by a patient. Lastly, we will expose the future developments possible of the tools for image processing in radiotherapy as well as the tracks of research to be explored in oncology. (author)

  5. Radiotherapy for carcinoma of the larynx

    International Nuclear Information System (INIS)

    Terhaard, C.H.J.

    1991-01-01

    Data of patients treated for laryngeal cancer with radiotherapy are analyzed by uni- and multivariate methods. Patients are subdivided into the various T-categories, obtaining more homogeneous groups of laryngeal cancer. Prognostic factors are defined for survival, local and regional control after radiotherapy, and for ultimate locoregional control after salvage surgery (partial or total laryngectomy and/or neck dissection). An attempt is made to set up a refined treatment recommendation, based on these prognostic factors, and to define an optimal fractionation schedule for advanced laryngeal cancer. Future prospects to improve the therapeutic ratio on advanced laryngeal cancer are discussed. (H.W.). 360 refs.; 28 figs.; 35 tabs

  6. Beta cell proliferation and growth factors

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis; Svensson, C; Møldrup, Annette

    1999-01-01

    Formation of new beta cells can take place by two pathways: replication of already differentiated beta cells or neogenesis from putative islet stem cells. Under physiological conditions both processes are most pronounced during the fetal and neonatal development of the pancreas. In adulthood little...... increase in the beta cell number seems to occur. In pregnancy, however, a marked hyperplasia of the beta cells is observed both in rodents and man. Increased mitotic activity has been seen both in vivo and in vitro in islets exposed to placental lactogen (PL), prolactin (PRL) and growth hormone (GH...... and activation of the tyrosine kinase JAK2 and the transcription factors STAT1 and 3. The activation of the insulin gene however also requires the distal part of the receptor and activation of calcium uptake and STAT5. In order to identify putative autocrine growth factors or targets for growth factors we have...

  7. Correlative study on anemia and radiotherapy effects in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Chen Jinsheng; Jiang Yuanshi; Cao Xibiao; Zhan Yongzhong; Yang Liye; Chen Jianxiu; Chen Chengwu; Li Yang

    2003-01-01

    Objective: To study the effect of oxygen-carrying ability of blood efficacy of radiotherapy for patients with nasopharyngeal carcinoma. Methods: Altogether 161 cases of patients with nasopharyngeal carcinoma were classified according to severity of anemia, and Hb, RBC, MCH, HCT, MCV, MCHC and RDW were tested before, during and after radiotherapy. The patients were followed-up for up to 5 years, the relationship and mechanism among anemia, radiotherapy effects and survival rate was discussed. Results: The survival rate between anemia group and non-anemia group was different significantly (P<0.05). Anemia before radiotherapy, anemia appearance or anemia deterioration during radiotherapy were sensitive factors affecting radiotherapy results. The anemia more severe, the radiotherapy worse. Conclusion: Anemia-hypohemoglobinemia leads to decrease of oxygen-carrying capacity of blood, resulting in oxygen deficiency of tumor cells and their radiotherapy resistance. Therefore this method is worthy of further studies

  8. Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer

    International Nuclear Information System (INIS)

    Marinko, Tanja; Dolenc, Jure; Bilban-Jakopin, Cvetka

    2014-01-01

    Trastuzumab therapy given in combination with one of several chemotherapy regimens is currently considered the standard of care for the treatment of early-stage, human epidermal growth factor receptor-2 (HER2) -positive breast cancer. The treatment with trastuzumab is due to a significant impact on the survival part of the standard adjuvant treatment of patients with HER2-positive breast cancer. Patients treated with postoperative breast or chest wall irradiation receive trastuzumab concomitant with radiotherapy. In a small proportion of patients trastuzumab causes cardiotoxicity. Preclinical findings indicate a radiosensibilizing effect of trastuzumab in breast cancer cells, but it is not yet clear whether it radiosensibilizes cells of healthy tissues too. Special attention is required when left breast or left thoracic wall is irradiated in patient receiving trastuzumab, because long-term effects of the concurrent treatment with trastuzumab and radiotherapy are not yet known. In an era where more patients are surviving a diagnosis of breast cancer, better understanding and earlier detection of therapy-induced cardiac toxicity will be of paramount importance

  9. Cardiotoxicity of concomitant radiotherapy and trastuzumab for early breast cancer.

    Science.gov (United States)

    Marinko, Tanja; Dolenc, Jure; Bilban-Jakopin, Cvetka

    2014-06-01

    Trastuzumab therapy given in combination with one of several chemotherapy regimens is currently considered the standard of care for the treatment of early-stage, human epidermal growth factor receptor-2 (HER2) -positive breast cancer. The treatment with trastuzumab is due to a significant impact on the survival part of the standard adjuvant treatment of patients with HER2-positive breast cancer. Patients treated with postoperative breast or chest wall irradiation receive trastuzumab concomitant with radiotherapy. In a small proportion of patients trastuzumab causes cardiotoxicity. Preclinical findings indicate a radiosensibilizing effect of trastuzumab in breast cancer cells, but it is not yet clear whether it radiosensibilizes cells of healthy tissues too. Special attention is required when left breast or left thoracic wall is irradiated in patient receiving trastuzumab, because long-term effects of the concurrent treatment with trastuzumab and radiotherapy are not yet known. In an era where more patients are surviving a diagnosis of breast cancer, better understanding and earlier detection of therapy-induced cardiac toxicity will be of paramount importance.

  10. Clinical Application of Growth Factors and Cytokines in Wound Healing

    Science.gov (United States)

    Barrientos, Stephan; Brem, Harold; Stojadinovic, Olivera; Tomic-Canic, Marjana

    2016-01-01

    Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of non-healing wounds (e.g. pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted a nonline search of Medline and Pub Medical and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies and future research possibilities. In this review we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include: granulocyte-macrophage colony stimulating factor (GM-CSF), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy. PMID:24942811

  11. Risk Factors to Growth Retardation in Major Thalassemia

    Directory of Open Access Journals (Sweden)

    Riva Uda

    2011-03-01

    Full Text Available The increasing in the life span of patients with major thalassemia should be followed by increased quality of life. There are factors which can affect growth retardation in these patients. The aim of this study was to find out the risk factors for growth retardation in patients with major thalassemia. An analytical study with cross-sectional design was conducted at Pediatric Thalassemia Clinics of Dr.Hasan Sadikin Hospital, Bandung, in June to July 2006. The subjects of this study were patients with major thalassemia. Inclusion criteria’s were age under 14 years old, had no chronic diseases like tuberculosis, cerebral palsy with complete medical records. Risk factors were the timing of diagnosis, initial and dose of deferoxamine, volume of transfused blood, mean pretransfusion hemoglobin level, family income, and age. Antropometric measurement indices were used to assess the growth which expressed in Z score. Growth evaluated based on height/age (H/A and growth retardation if H/A <-2 SD. Risk factors for growth retardation were analyzed separately using chi-square test and odds ratio (OR with 95% confidence interval (CI. Then they were analyzed simultaneously with logistic regression method. Subjects consisted of 152 patients with major thalassemia. Seventy three thalassemia patients were stunted. Analysis showed that age (OR: 5.42, 95% CI:2.32–12.65, p <0.001, dosage of deferoxamine (OR: 4.0, 95% CI: 1.29–12.41, p: 0.016, and family income (OR: 2.32, 95% CI: 1.06–5.06, p: 0.036 were risks factors for growth retardation. Conclusion, risk factors for growth retardation in major thalassemia are age, dosage of deferoxamine, and family income.

  12. Epidermal growth factor receptor inhibition reduces angiogenesis via hypoxia-inducible factor-1α and Notch1 in head neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Wei-Ming Wang

    Full Text Available Angiogenesis, a marker of cancer development, affects response to radiotherapy sensibility. This preclinical study aims to understand the receptor tyrosine kinase-mediated angiogenesis in head neck squamous cell carcinoma (HNSCC. The receptor tyrosine kinase activity in a transgenic mouse model of HNSCC was assessed. The anti-tumorigenetic and anti-angiogenetic effects of cetuximab-induced epidermal growth factor receptor (EGFR inhibition were investigated in xenograft and transgenic mouse models of HNSCC. The signaling transduction of Notch1 and hypoxia-inducible factor-1α (HIF-1α was also analyzed. EGFR was overexpressed and activated in the Tgfbr1/Pten deletion (2cKO mouse model of HNSCC. Cetuximab significantly delayed tumor onset by reducing tumor angiogenesis. This drug exerted similar effects on heterotopic xenograft tumors. In the human HNSCC tissue array, increased EGFR expression correlated with increased HIF-1α and micro vessel density. Cetuximab inhibited tumor-induced angiogenesis in vitro and in vivo by significantly downregulating HIF-1α and Notch1. EGFR is involved in the tumor angiogenesis of HNSCC via the HIF-1α and Notch1 pathways. Therefore, targeting EGFR by suppressing hypoxia- and Notch-induced angiogenesis may benefit HNSCC therapy.

  13. Extremity Regeneration of Soft Tissue Injury Using Growth Factor-Impregnated Gels

    Science.gov (United States)

    2017-10-01

    vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). Repeated injections of growth factor-alginate material are... Vascularized endothelial growth factor (VEGF) Insulin-like growth factor-1 (IGF-1) Alginate gel Ischemia-reperfusion Large animal model...operative complications including skin necrosis and seroma development. The IACUC protocol was reevaluated and modified thought multiple discussions

  14. Platelet-derived growth factor (PDGF)-signaling mediates radiation-induced apoptosis in human prostate cancer cells with loss of p53 function

    International Nuclear Information System (INIS)

    Kim, Harold E.; Han, Sue J.; Kasza, Thomas; Han, Richard; Choi, Hyeong-Seon; Palmer, Kenneth C.; Kim, Hyeong-Reh C.

    1997-01-01

    Platelet-derived growth factor (PDGF) signals a diversity of cellular responses in vitro, including cell proliferation, survival, transformation, and chemotaxis. PDGF functions as a 'competence factor' to induce a set of early response genes expressed in G 1 including p21 WAF1/CIP1 , a functional mediator of the tumor suppressor gene p53 in G 1 /S checkpoint. For PDGF-stimulated cells to progress beyond G 1 and transit the cell cycle completely, progression factors in serum such as insulin and IGF-1 are required. We have recently shown a novel role of PDGF in inducing apoptosis in growth-arrested murine fibroblasts. The PDGF-induced apoptosis is rescued by insulin, suggesting that G 1 /S checkpoint is a critical determinant for PDGF-induced apoptosis. Because recent studies suggest that radiation-induced signal transduction pathways interact with growth factor-mediated signaling pathways, we have investigated whether activation of the PDGF-signaling facilitates the radiation-induced apoptosis in the absence of functional p53. For this study we have used the 125-IL cell line, a mutant p53-containing, highly metastatic, and hormone-unresponsive human prostate carcinoma cell line. PDGF signaling is constitutively activated by transfection with a p28 v-sis expression vector, which was previously shown to activate PDGF α- and β- receptors. Although the basal level of p21 WAF1/CIP1 expression and radiation-induced apoptosis were not detectable in control 125-IL cells as would be predicted in mutant p53-containing cells, activation of PDGF-signaling induced expression of p21 WAF1/CIP1 and radiation-induced apoptosis. Our study suggests that the level of 'competence' growth factors including PDGF may be one of the critical determinants for radiation-induced apoptosis, especially in cells with loss of p53 function at the site of radiotherapy in vivo

  15. Development of radiation oncology learning system combined with multi-institutional radiotherapy database (ROGAD)

    Energy Technology Data Exchange (ETDEWEB)

    Takemura, Akihiro; Iinuma, Masahiro; Kou, Hiroko [Kanazawa Univ. (Japan). School of Medicine; Harauchi, Hajime; Inamura, Kiyonari

    1999-09-01

    We have constructed and are operating a multi-institutional radiotherapy database ROGAD (Radiation Oncology Greater Area Database) since 1992. One of it's purpose is 'to optimize individual radiotherapy plans'. We developed Radiation oncology learning system combined with ROGAD' which conforms to that purpose. Several medical doctors evaluated our system. According to those evaluations, we are now confident that our system is able to contribute to improvement of radiotherapy results. Our final target is to generate a good cyclic relationship among three components: radiotherapy results according to ''Radiation oncology learning system combined with ROGAD.'; The growth of ROGAD; and radiation oncology learning system. (author)

  16. Processing and evaluation of image matching tools in radiotherapy

    International Nuclear Information System (INIS)

    Bondiau, P.Y.

    2004-11-01

    Cancer is a major problem of public health. Treatment can be done in a general or loco-regional way, in this last case medical images are important as they specify the localization of the tumour. The objective of the radiotherapy is to deliver a curative dose of radiation in the target volume while sparing the organs at risks (O.A.R.). The determination of the accurate localization of the targets volume as well as O.A.R. make it possible to define the ballistic of irradiation beams. After the description of the principles of radiotherapy and cancers treatment, we specify the clinical stakes of ocular, cerebral and prostatic tumours. We present a state of the art of image matching, the various techniques reviewed with an aim of being didactic with respect to the medical community. The results of matching are presented within the framework of the planning of the cerebral and prostatic radiotherapy in order to specify the types of applicable matching in oncology and more particularly in radiotherapy. Then, we present the prospects for this type of application according to various anatomical areas. Applications of automatic segmentation and the evaluation of the results in the framework of brain tumour are described after a review of the various segmentation methods according to anatomical localizations. We will see an original application: the digital simulation of the virtual tumoral growth and the comparison with the real growth of a cerebral tumour presented by a patient. Lastly, we will expose the future developments possible of the tools for image processing in radiotherapy as well as the tracks of research to be explored in oncology. (author)

  17. The impact of vascular endothelial growth factor and basic fibroblast growth factor on cardiac fibroblasts grown under altered gravity conditions

    DEFF Research Database (Denmark)

    Ulbrich, Claudia; Leder, Annekatrin; Pietsch, Jessica

    2010-01-01

    Myocardium is very sensitive to gravitational changes. During a spaceflight cardiovascular atrophy paired with rhythm problems and orthostatic intolerance can occur. The aim of this study was to investigate the impact of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor...

  18. Impact of immunotherapy among patients with melanoma brain metastases managed with radiotherapy.

    Science.gov (United States)

    Stokes, William A; Binder, David C; Jones, Bernard L; Oweida, Ayman J; Liu, Arthur K; Rusthoven, Chad G; Karam, Sana D

    2017-12-15

    Patients with melanoma brain metastases (MBM) have been excluded from trials evaluating immunotherapy in melanoma. As such, immunotherapy's role in MBM is poorly understood, particularly in combination with radiotherapy. The National Cancer Database was queried for patients with MBM receiving brain radiotherapy. They were classified according to immunotherapy receipt. Multivariate Cox regression was performed to identify factors associated with survival. Among 1287 patients, 185 received immunotherapy. Factors associated with improved survival included younger age, academic facility, lower extracranial disease burden, stereotactic radiotherapy, chemotherapy, and immunotherapy. Adding immunotherapy to radiotherapy for MBM is associated with improved survival. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Growth factor effects on costal chondrocytes for tissue engineering fibrocartilage

    Science.gov (United States)

    Johns, D.E.; Athanasiou, K.A.

    2010-01-01

    Tissue engineered fibrocartilage could become a feasible option for replacing tissues like the knee meniscus or temporomandibular joint disc. This study employed five growth factors insulin-like growth factor-I, transforming growth factor-β1, epidermal growth factor, platelet-derived growth factor-BB, and basic fibroblast growth factor in a scaffoldless approach with costal chondrocytes, attempting to improve biochemical and mechanical properties of engineered constructs. Samples were quantitatively assessed for total collagen, glycosaminoglycans, collagen type I, collagen type II, cells, compressive properties, and tensile properties at two time points. Most treated constructs were worse than the no growth factor control, suggesting a detrimental effect, but the IGF treatment tended to improve the constructs. Additionally, the 6wk time point was consistently better than 3wks, with total collagen, glycosaminoglycans, and aggregate modulus doubling during this time. Further optimization of the time in culture and exogenous stimuli will be important in making a more functional replacement tissue. PMID:18597118

  20. Growth Factors and Breast Tumors, Comparison of Selected Growth Factors with Traditional Tumor Markers

    Czech Academy of Sciences Publication Activity Database

    Kučera, R.; Černá, M.; Ňaršanská, A.; Svobodová, Š.; Straková, M.; Vrzalová, J.; Fuchsová, R.; Třešková, I.; Kydlíček, T.; Třeška, V.; Pecen, Ladislav; Topolčan, O.; Padziora, P.

    2011-01-01

    Roč. 31, č. 12 (2011), s. 4653-4656 ISSN 0250-7005 Grant - others:GA MZd(CZ) NS9727; GA MZd(CZ) NS10238; GA MZd(CZ) NS10253 Institutional research plan: CEZ:AV0Z10300504 Keywords : growth factor * breast cancer * tumor markers * CA 15-3 * CEA * IGF1 * EGF * HGF Subject RIV: FD - Oncology ; Hematology Impact factor: 1.725, year: 2011

  1. Reirradiation for recurrent head and neck cancers using charged particle or photon radiotherapy.

    Science.gov (United States)

    Yamazaki, Hideya; Demizu, Yusuke; Okimoto, Tomoaki; Ogita, Mikio; Himei, Kengo; Nakamura, Satoaki; Suzuki, Gen; Yoshida, Ken; Kotsuma, Tadayuki; Yoshioka, Yasuo; Oh, Ryoongjin

    2017-07-01

    To examine the outcomes of reirradiation for recurrent head and neck cancers using different modalities. This retrospective study included 26 patients who received charged particle radiotherapy (CP) and 150 who received photon radiotherapy (117 CyberKnife radiotherapy [CK] and 36 intensity-modulated radiotherapy [IMRT]). Inverse probability of treatment weighting (IPTW) involving propensity scores was used to reduce background selection bias. Higher prescribed doses were used in CP than photon radiotherapy. The 1‑year overall survival (OS) rates were 67.9% for CP and 54.1% for photon radiotherapy (p = 0.15; 55% for CK and 51% for IMRT). In multivariate Cox regression, the significant prognostic factors for better survival were nasopharyngeal cancer, higher prescribed dose, and lower tumor volume. IPTW showed a statistically significant difference between CP and photon radiotherapy (p = 0.04). The local control rates for patients treated with CP and photon radiotherapy at 1 year were 66.9% (range 46.3-87.5%) and 67.1% (range 58.3-75.9%), respectively. A total of 48 patients (27%) experienced toxicity grade ≥3 (24% in the photon radiotherapy group and 46% in the CP group), including 17 patients with grade 5 toxicity. Multivariate analysis revealed that younger age and a larger planning target volume (PTV) were significant risk factors for grade 3 or worse toxicity. CP provided superior survival outcome compared to photon radiotherapy. Tumor volume, primary site (nasopharyngeal), and prescribed dose were identified as survival factors. Younger patients with a larger PTV experienced toxicity grade ≥3.

  2. The dynamics of plasma transforming growth factor beta 1 (TGF-beta1) level

    Czech Academy of Sciences Publication Activity Database

    Feltl, D.; Závadová, E.; Pála, M.; Hozák, Pavel

    2005-01-01

    Roč. 41, č. 2 (2005), s. 208-213 ISSN 1368-8375 R&D Projects: GA AV ČR(CZ) IAA5039202 Institutional research plan: CEZ:AV0Z50390512 Keywords : Head and neck cancer * radiotherapy Subject RIV: EA - Cell Biology Impact factor: 2.266, year: 2005

  3. Long-term effects of megavoltage radiotherapy in acromegaly

    International Nuclear Information System (INIS)

    Lam, K.S.L.; Wang, C.; Ma, J.T.C.; Yeung, R.T.T.; Choi, P.

    1989-01-01

    The progress of 41 Chinese patients with acromegaly treated with megavoltage radiotherapy was reviewed after a mean follow-up of 4.5 (one-ten) years. Nine received prior surgery. Radiotherapy was delivered by a 3-field technique to a total of 4000-5000 cGy in 25 fractions. By life table analysis successful treatment of growth hormone (GH) hypersecretion, as defined by a mean GH concentration of ≤ 10 mu/L, could be expected in 6, 11, 26, 64 and 67% of the patients after one, two, five, eight and ten years respectively. Median intervals before achieving a mean GH level of ≤ 10 Mu/L were 6.6 and 8.6 years following radiotherapy with the higher (4500-5000 cGy) and lower (4000 cGy) doses respectively, suggesting a tendency towards earlier response following radiotherapy with the higher dose. The prevalence of acquired hypopituitarism in patients followed up for over five years was 40% for gonadotrophins, 30% for TSH and 20% for ACTH deficiency respectively. In the majority of patients, acquired hypopituitarism was not apparent within five years after radiotherapy. No mortality or major side effects were noted following radiotherapy. In 34 patients on longterm bromocriptine treatment, mean GH concentrations were normalised in 26.5% of patients. We conclude that with judicious selection of patients and use of adjunctive medical therapy, megavoltage radiotherapy remains a safe and satisfactory form of treatment for acromegaly especially if expert transphenoidal surgery is not readily available. 19 refs., 3 figs., 2 tabs

  4. Diffusion tensor magnetic resonance imaging driven growth modeling for radiotherapy target definition in glioblastoma.

    Science.gov (United States)

    Jensen, Morten B; Guldberg, Trine L; Harbøll, Anja; Lukacova, Slávka; Kallehauge, Jesper F

    2017-11-01

    The clinical target volume (CTV) in radiotherapy is routinely based on gadolinium contrast enhanced T1 weighted (T1w + Gd) and T2 weighted fluid attenuated inversion recovery (T2w FLAIR) magnetic resonance imaging (MRI) sequences which have been shown to over- or underestimate the microscopic tumor cell spread. Gliomas favor spread along the white matter fiber tracts. Tumor growth models incorporating the MRI diffusion tensors (DTI) allow to account more consistently for the glioma growth. The aim of the study was to investigate the potential of a DTI driven growth model to improve target definition in glioblastoma (GBM). Eleven GBM patients were scanned using T1w, T2w FLAIR, T1w + Gd and DTI. The brain was segmented into white matter, gray matter and cerebrospinal fluid. The Fisher-Kolmogorov growth model was used assuming uniform proliferation and a difference in white and gray matter diffusion of a ratio of 10. The tensor directionality was tested using an anisotropy weighting parameter set to zero (γ0) and twenty (γ20). The volumetric comparison was performed using Hausdorff distance, Dice similarity coefficient (DSC) and surface area. The median of the standard CTV (CTVstandard) was 180 cm 3 . The median surface area of CTVstandard was 211 cm 2 . The median surface area of respective CTV γ0 and CTV γ20 significantly increased to 338 and 376 cm 2 , respectively. The Hausdorff distance was greater than zero and significantly increased for both CTV γ0 and CTV γ20 with respective median of 18.7 and 25.2 mm. The DSC for both CTV γ0 and CTV γ20 were significantly below one with respective median of 0.74 and 0.72, which means that 74 and 72% of CTVstandard were included in CTV γ0 and CTV γ20, respectively. DTI driven growth models result in CTVs with a significantly increased surface area, a significantly increased Hausdorff distance and decreased overlap between the standard and model derived volume.

  5. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

    LENUS (Irish Health Repository)

    Sands, Michelle

    2011-01-25

    Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF) family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF) and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2) or hypoxia (10% O2) for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA), VEGFB, placenta growth factor (PlGF), VEGF receptor 1 (VEGFR1) and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or potentiate the

  6. Endogenous versus exogenous growth factor regulation of articular chondrocytes.

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G; Mercer, Scott; Eckert, George J; Trippel, Stephen B

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-β1 stimulated these reparative functions, while endogenous TGF-β1 had little effect. Endogenous TGF-β1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-β1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. This article is a U.S. Government work and is in the public domain in the USA.

  7. Experimental radiotherapy and clinical radiobiology. Vol. 17. Proceedings

    International Nuclear Information System (INIS)

    Baumann, M.; Dahm-Daphi, J.; Dikomey, E.; Petersen, C.; Rodemann, H.P.; Zips, D.

    2008-01-01

    The proceedings contain the lectures and poster sessions on the following topics: modulation of the immune system for the improvement of tumor radiotherapy; molecular factors and predictors of radiation sensitivity of tumor cells; DNA repair; molecular factors and modulation of radiation reactions of normal tissue; biological studies with differential experimental radiations; tumor stem cells: importance for the radiotherapy; DNA repair and its importance for the radiation sensitivity of tumor cells; biological modification of the radiation sensitivity of tumor cells; biological imaging and tumor microenvironment

  8. Radiotherapy-induced hypopituitarism in nasopharyngeal carcinoma: the tip of an iceberg.

    Science.gov (United States)

    Ipekci, S H; Cakir, M; Kiyici, A; Koc, O; Artac, M

    2015-07-01

    Radiation-induced hypopituitarism is an important late complication of cranial radiotherapy in children and adults. The purpose of this cross-sectional study was to evaluate the effects of radiotherapy on pituitary function in adult nasopharyngeal carcinoma patients. Pituitary function was evaluated in 30 patients after cranial radiotherapy for nasopharyngeal carcinoma. Somatotroph and corticotroph axes were assessed by insulin tolerance test while gonadotroph and thyroid axes were evaluated by basal pituitary and end organ hormone levels at 10-133 months after radiotherapy. At least one hormonal disorder was observed in 28 (93%) patients after radiotherapy. 26 (87%) patients had one or more anterior pituitary hormone deficiencies. The rates of pituitary hormone deficiencies were 77% for growth hormone, followed by adrenocorticotropic hormone (73%), thyroid-stimulating hormone (27%) and gonadotropins (7%). Hyperprolactinemia was present in 13 (43%) patients. Radiation-induced hypopituitarism is more common than expected in patients with nasopharyngeal carcinoma. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: predictive clinical and dosimetric factors

    International Nuclear Information System (INIS)

    Ciammella, Patrizia; Podgornii, Ala; Galeandro, Maria; Micera, Renato; Ramundo, Dafne; Palmieri, Tamara; Cagni, Elisabetta; Iotti, Cinzia

    2014-01-01

    The objective of this study is to evaluate toxicity and cosmetic outcome in breast cancer patients treated with adjuvant hypo fractionated radiotherapy to the whole breast, and to identify the risk factors for toxicity. Two hundred twelve women with early breast cancer underwent conserving surgery were enrolled in the study. The patients received 40.05 Gy in 15 daily fractions, 2.67 Gy per fraction. The boost to the tumor bed was administered with a total dose of 9 Gy in 3 consecutive fractions in 55 women. Physician-rated acute and late toxicity and cosmetic outcome (both subjective and objective) were prospectively assessed during and after radiotherapy. In our population study the mean age was 63 with the 17% (36 pts) of the women younger than 50 years. The median follow-up was 34 months. By the end of RT, 35 patients out of 212 (16%) no acute toxicity, according to the RTOG criteria, while 145 (68%) and 31 patients (15%) developed grade 1 and grade 2 acute skin toxicity, respectively. Late skin toxicity evaluation was available for all 212 patients with a minimum follow up of 8 months. The distribution of toxicity was: 39 pts (18%) with grade 1 and 2 pts (1%) with grade 2. No worse late skin toxicity was observed. Late subcutaneous grade 0-1 toxicity was recorded in 208 patients (98%) and grade 2 toxicity in 3 patients (2%), while grade 3 was observed in 1 patient only. At last follow up, a subjective and objective good or excellent cosmetic outcome was reported in 93% and 92% of the women, respectively. At univariate and multivariate analysis, the late skin toxicity was correlated with the additional boost delivery (p=0.007 and p=0.023). Regarding the late subcutaneous tissue, a correlation with diabetes was found (p=0.0283). These results confirm the feasibility and safety of the hypofractionated radiotherapy in patients with early breast cancer. In our population the boost administration was resulted to be a significant adverse prognostic factor for acute

  10. Factors Influencing Neurocognitive Outcomes in Young Patients With Benign and Low-Grade Brain Tumors Treated With Stereotactic Conformal Radiotherapy

    International Nuclear Information System (INIS)

    Jalali, Rakesh; Mallick, Indranil; Dutta, Debnarayan

    2010-01-01

    Purpose: To present the effect of radiotherapy doses to different volumes of normal structures on neurocognitive outcomes in young patients with benign and low-grade brain tumors treated prospectively with stereotactic conformal radiotherapy (SCRT). Methods and Materials: Twenty-eight patients (median age, 13 years) with residual/progressive brain tumors (10 craniopharyngioma, 8 cerebellar astrocytoma, 6 optic pathway glioma and 4 cerebral low-grade glioma) were treated with SCRT to a dose of 54 Gy in 30 fractions over 6 weeks. Prospective neuropsychological assessments were done at baseline before RT and at subsequent follow-up examinations. The change in intelligence quotient (IQ) scores was correlated with various factors, including dose-volume to normal structures. Results: Although the overall mean full-scale IQ (FSIQ) at baseline before RT remained unchanged at 2-year follow-up after SCRT, one third of patients did show a >10% decline in FSIQ as compared with baseline. Logistic regression analysis demonstrated that patients aged 10% drop in FSIQ than older patients (53% vs. 10%, p = 0.03). Dosimetric comparison in patients showing a >10% decline vs. patients showing a 43.2 Gy to >13% of volume of the left temporal lobe were the ones to show a significant drop in FSIQ (p = 0.048). Radiotherapy doses to other normal structures, including supratentorial brain, right temporal lobe, and frontal lobes, did not reveal any significant correlation. Conclusion: Our prospectively collected dosimetric data show younger age and radiotherapy doses to left temporal lobe to be predictors of neurocognitive decline, and may well be used as possible dose constraints for high-precision radiotherapy planning.

  11. The radiotherapy value in recurrence control mammary neoplasm

    International Nuclear Information System (INIS)

    Torres Lopez, M.; Santini Blasco, A.

    1996-01-01

    In base on the retrospective analysis of 250 patient carrying of mammals neoplasms recurrence, their general characteristics are determined and the results are emphasized obtained by the radiotherapy, as well as the list that the indicative predict. It culminates in the necessity of indicating the adyuvance postoperative radiotherapy when factors unfavorable presage of recurrence(AU ) [es

  12. Early Response Monitoring with 18F-FDG PET and Cetuximab-F(ab')2-SPECT After Radiotherapy of Human Head and Neck Squamous Cell Carcinomas in a Mouse Model

    NARCIS (Netherlands)

    Dijk, L.K. van; Boerman, O.C.; Franssen, G.M.; Lok, J.; Kaanders, J.H.A.M.; Bussink, J.

    2014-01-01

    Only a subset of patients with head and neck squamous cell carcinomas (HNSCCs) benefit from radiotherapy and concurrent epidermal growth factor receptor (EGFR) inhibitor therapy with cetuximab, indicating the need for patient selection. The aim of this study was to visualize the change in

  13. Radiotherapy with concomitant chemotherapy superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the EORTC radiotherapy and gastrointestinal tract cooperative groups

    International Nuclear Information System (INIS)

    Bartelink, H.; Roelofsen, F.; Bosset, J.F.; Eschwege, F.; Rougier, Ph.; Peiffert, D.; Glabbeke, M. van; Pierart, M.

    1996-01-01

    Purpose: To investigate the potential gain of the concomitant use of radiotherapy and chemotherapy in improving local control and reducing the need for colostomy, a randomized phase-III trial was performed in patients with locally advanced anal cancer. Material and methods: In the period 1987-1994 110 patients were randomized between radiotherapy alone and a combination of radiotherapy and chemotherapy. The patients had tumors larger than 4 cm, or T 3-4 N 0-3 , or T 1-2 N 1-3 anal cancer. Radiotherapy consisted of 45 Gy given in 5 weeks, with a daily dose of 1.8 Gy. After a rest period of 6 weeks a boost of 15 Gy or 20 Gy was given in case of partial or complete response respectively. Chemotherapy was given during radiotherapy, 750 mg/m2 daily as continuous infusion on day 1-5 and 29-33, a single dose of Mitomycin C 15 mg/m 2 was administered on day 1. Results: The addition of chemotherapy to radiotherapy has resulted in an increase in the complete remission rate from 54% to 80%, and from 83% to 94% if results are considered after surgical resections. This has led to a significant improvement in loco-regional control and colostomy free survival (P=0.04, P=0.003 resp.) both in favor of the combined modality treatment. No significant difference was found when severe side effects were considered. The survival rate remained similar in both treatment arms. Skin ulceration, nodal involvement and sex were the most important prognostic factors for both local control and survival. These remained significant after multivariate analysis. The improvement seen in local control by adding chemotherapy to radiotherapy remained also significant after adjusting for prognostic factors in the multivariate analysis. Conclusions: The concomitant use of radiotherapy and chemotherapy resulted in an improved local control rate and a reduction in the need for colostomy in patients with locally advanced anal cancer

  14. Radiotherapy Results of Early Uterine Cervix Cancer

    International Nuclear Information System (INIS)

    Choi, Doo Ho; Huh, Seung Jae

    1996-01-01

    Purpose : This study was done to analyze survivals, patterns of failure, and complications of early uterine cervix cancer after curative radiotherapy. Methods and Materials : Eighty patients with uterine cervix cancer FIGO Stage IB (48 cases) and Stage IIA (32 cases) treated with radiotherapy were analyzed retrospectively. Patients were treated from November 1985 to May 1993, and minimum follow up period was 24 months. and 6 cases were lost to follow up. All of them were treated with external radiotherapy and different fractions of high dose rate intracavitary radiotherapy. Survival rates, failure patterns, complication rates and degrees of severity were analyzed according to several factors. Results : Overall 5 year survival rate and relapse free survival rate were 72.3%, and 72.8% respectively. Prognostic factors were stage, size, pathology, RT response and there was no significant survival difference among the reasons of radiotherapy choice. There were 19 cases of treatment failure, another 3 cases were not tumor related death, and most of treatment related failure occurred within 24 months. Late complication rate of bladder and rectum were 8.8%, 15% respectively, frequency and severity of complication were correlated with ICR fractionation dose and total dose. Conclusion : These results showed that survival rates of early stage radiation treated cervix cancer patients were comparable to surgical series, but more aggressive treatment methods needed for stage IIA poor prognostic patients, To decrease late complication, choice of proper ICR dose and meticulous vaginal packing is needed

  15. Radiotherapy treatment results of bladder cancer: study of 458 patients

    International Nuclear Information System (INIS)

    Vara Santos, J.; Torre Tomas, A. de la; Romero Fernandez, J.; Regueiro Otero, C.; Clavo Varas, B.; Magallan Sebastian, R.; Valcarcel Sancho, F.; Polo Tolosana, E.; Aragon de la Cruz, G.

    1994-01-01

    Between 1964 to 1990, 458 patients diagnosed of bladder cancer have been treated with radical radiotherapy in our department. The 5-years and 10-years actuarial survival rates were 37% and 27% respectively. The 5-years and 10-years actuarial local control rates, evaluated in 404 patients, were 41% and 38%. In regard to survival, T stage (p=0.013), advanced intravesical extension or multicentrity (p>0.0001), and squamous differentiation (p<0.0001), reached statistical significance as adverse prognostic factors. In 248 patients, with invasive transitional carcinoma, radical radiotherapy alone was used. In this group of patients, T stage (p=0.006) and advanced intravesical extension or multicentrity (p=0.0002) were adverse prognostic factors for survival. Our results suggest that radical radiotherapy must be considered and alternative to surgery in management of bladder cancer. On the basis of prognostic factors evidenced in this series a subgroup of patients with low probability of survival when treated with exclusive radiotherapy are defined. This patients must be included in clinical research protocols. (Author) 44 refs

  16. Fibroblast growth factor 23

    African Journals Online (AJOL)

    Dr Olaleye

    Systemic phosphate homeostasis is maintained through several hormonal mechanisms which involve fibroblast growth factor 23 (FGF-23), α-klotho, vitamin D and parathyroid hormone. FGF-23 is known to be the major regulator of phosphate balance (Mirams et al., 2004). FGF-23 is a phosphaturic hormone, which is.

  17. Radiotherapy in breast cancer and its prognosis

    International Nuclear Information System (INIS)

    Mitter, Mihir

    1980-01-01

    Various aspects of breast cancer are discussed. These include clinical staging, histological grading, site of growth, frequency and lactation, immunological response and prognosis, and survival of untreated cases. Importance of early detection is emphasised and prognosis after radiotherapy alone or in combination with surgery is briefly discussed. (M.G.B.)

  18. Malignant fibrous histiocytoma: outcome and prognostic factors following conservation surgery and radiotherapy

    International Nuclear Information System (INIS)

    Zagars, Gunar K.; Mullen, John R.; Pollack, Alan

    1996-01-01

    Purpose: Malignant fibrous histiocytoma is the most common type of soft tissue sarcoma. This communication presents an analysis of outcome and prognostic factors based on a retrospective review of patients with this disease treated by conservation surgery and radiotherapy. Methods and Materials: From 1966 to 1991, 271 consecutive patients with malignant fibrous histiocytoma were treated with conservation surgery and radiotherapy. The outcome with local control, metastatic relapse, and survival as end points was evaluated by univariate and multivariate statistics to delineate independently significant prognostic factors. Results: Postoperative radiation at a mean dose of 62.8 Gy was used in 195 patients and preoperative radiation at a mean dose of 50 Gy was used in 76 patients. At a median follow-up of 7.3 years, 123 patients (45%) developed disease relapse at some site. Fifty-seven (21%) developed local recurrence leading to an actuarial local relapse rate of 26% at 10 years, 83 (31%) developed metastatic relapse for a 10-year actuarial metastatic rate of 33%, and the 5-, 10-, and 15-year survival rates were 68, 60, and 46%, respectively. For local control, prior local recurrence (in 53 patients) was identified as an adverse factor, yielding a 10-year recurrence rate of 42% compared to 22% for 218 patients without prior disease (p 5 cm), and histology (myxoid vs. nonmyxoid) were not significant determinants of local outcome. For metastatic relapse, the major determinants of outcome were histology (myxoid vs. nonmyxoid) and tumor size. Myxoid tumors (59 patients) had a low metastatic propensity (13% 10-year metastatic rate) compared to nonmyxoid tumors (212 patients) (40% 10-year metastatic rate) (p 5 cm) were the only independent determinants of outcome. Conclusion: Malignant fibrous histiocytoma is a heterogeneous disease and its myxoid variant must be recognized as a distinct entity. Both variants are locally aggressive and require equally aggressive local

  19. Epidermal growth factor in the rat prostate

    DEFF Research Database (Denmark)

    Tørring, Niels; Jørgensen, P E; Poulsen, Steen Seier

    1998-01-01

    Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate.......Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate....

  20. Adjuvant radiotherapy for stage I endometrial cancer.

    Science.gov (United States)

    Kong, A; Johnson, N; Cornes, P; Simera, I; Collingwood, M; Williams, C; Kitchener, H

    2007-04-18

    The role of adjuvant radiotherapy (both pelvic external beam radiotherapy and vaginal intracavity brachytherapy) in stage I endometrial cancer following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO) remains unclear. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CancerLit, Physician Data Query (PDQ) of National Cancer Institute. Handsearching was also carried out where appropriate. Randomised controlled trials (RCTs) which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer were included. Quality of the studies was assessed and data collected using a predefined data collection form. The primary endpoint was overall survival. Secondary endpoints were locoregional recurrence, distant recurrence and endometrial cancer death. Data on quality of life (QOL) and morbidity were also collected. A meta-analysis on included trials was performed using the Cochrane Collaboration Review Manager Software 4.2. The meta-analysis was performed on four trials (1770 patients). The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 (95% confidence interval (CI) 0.17 to 0.44, p ASTEC; Lukka) are awaited. External beam radiotherapy carries a risk of toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors.

  1. Processing and evaluation of image matching tools in radiotherapy; Mise en oeuvre et evaluation d'outils de fusion d'image en radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Bondiau, P.Y

    2004-11-15

    Cancer is a major problem of public health. Treatment can be done in a general or loco-regional way, in this last case medical images are important as they specify the localization of the tumour. The objective of the radiotherapy is to deliver a curative dose of radiation in the target volume while sparing the organs at risks (O.A.R.). The determination of the accurate localization of the targets volume as well as O.A.R. make it possible to define the ballistic of irradiation beams. After the description of the principles of radiotherapy and cancers treatment, we specify the clinical stakes of ocular, cerebral and prostatic tumours. We present a state of the art of image matching, the various techniques reviewed with an aim of being didactic with respect to the medical community. The results of matching are presented within the framework of the planning of the cerebral and prostatic radiotherapy in order to specify the types of applicable matching in oncology and more particularly in radiotherapy. Then, we present the prospects for this type of application according to various anatomical areas. Applications of automatic segmentation and the evaluation of the results in the framework of brain tumour are described after a review of the various segmentation methods according to anatomical localizations. We will see an original application: the digital simulation of the virtual tumoral growth and the comparison with the real growth of a cerebral tumour presented by a patient. Lastly, we will expose the future developments possible of the tools for image processing in radiotherapy as well as the tracks of research to be explored in oncology. (author)

  2. Growth Factors and Tension-Induced Skeletal Muscle Growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1994-01-01

    The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we

  3. Growth factors II: insuline-like growth binging proteins (GFBPs Factores de crecimiento II: factores insulinoides de crecimiento

    Directory of Open Access Journals (Sweden)

    Hilda Norha Jaramillo Londoño

    1996-03-01

    Full Text Available This review summarizes recent knowledge concerning Insulin.like growth factors I and II, with emphasis on their biochemical structure, concentrations, binding proteins, receptors, mechanisms of action, biological effects, and alterations of their concentrations in biological fluids. Se revisan los Factores Insulinoides de Crecimiento, también denominados ";Factores de Crecimiento Similares a la Insulina";, sobre los cuales se dispone de abundante información. Se sintetizan conocimientos recientes sobre dichos factores con énfasis en los siguientes aspectos: estructura bioquímica, concentraciones y sus cambios en los líquidos biológicos, proteínas fijadoras, receptores, mecanismos de acción y efectos biológicos.

  4. Effect of radiotherapy on immunity function of cancer patients receiving radiotherapy

    International Nuclear Information System (INIS)

    Li Xinli; Zhu Shentao; Xu Jiuhong

    2003-01-01

    Objective: In order to observe the effect of radiotherapy on immunity function of cancer patients receiving radiotherapy. Methods: Cellular immunity is determined by APAAP; Humoral immunity is determined by transmission method. Results: The items of cellular immunity is lower than the control after radiotherapy. These items decrease continually. The difference between before and after radiotherapy has statistic significance. Of all Humoral immunity items, IgA, IgM decreased after radiotherapy and the difference has statistic significance. Conclusions: Radiotherapy can damage patients' immunity function

  5. Gender Factors and Inclusive Economic Growth: The Silent Revolution

    Directory of Open Access Journals (Sweden)

    Laura Cabeza-García

    2018-01-01

    Full Text Available The gender factors that trigger economic growth in both high- and low-income countries were investigated in this study. To address these gender factors, four characteristic dimensions of gender inclusion were considered: education, access to the labor market, fertility, and democracy. The relationship between economic growth and gender factors was analyzed in a sample of 127 countries. Value and robustness were added to the results using dynamic models applied to panel data while accounting for endogeneity. We conclude that high fertility in women has negative effects on economic growth. However, when women have greater access to secondary education and the labor market in conditions of equality, the effects are positive. Similarly, the access of women to active political participation has significant effects on economic growth. Overall, this study helps identify which gender factors may promote inclusive economic growth, which is economic growth achieved when both men and women are incorporated in equal conditions.

  6. Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor

    International Nuclear Information System (INIS)

    Matsumoto, K.; Hashimoto, K.; Yoshikawa, K.; Nakamura, T.

    1991-01-01

    Effect of hepatocyte growth factor (HGF) on normal human epidermal keratinocytes cultured under conditions of low Ca2+ (0.1 mM, growth-promoting condition) and physiological Ca2+ (1.8 mM, differentiation-promoting condition) was investigated. In low Ca2+, HGF markedly enhanced the migration of keratinocytes while it suppressed cell growth and DNA synthesis in a dose-dependent manner. In contrast, HGF enhanced the migration, cell growth, and DNA synthesis of keratinocytes cultured under conditions of physiological Ca2+. The maximal stimulation of DNA synthesis (2.4-fold stimulation) in physiological Ca2+ was seen at 2.5-5 ng/ml HGF and the stimulatory effect of HGF was suppressed by transforming growth factor-beta 1. Analysis of the HGF receptor using 125I-HGF as a ligand showed that human keratinocytes expressed a single class of specific, saturable receptor for HGF in both low and physiological Ca2+ conditions, exhibiting a Kd = 17.3 pM and approximately 690 binding sites/cell under physiological Ca2+. Thus, HGF is a potent factor which enhances growth and migration of normal human keratinocytes under conditions of physiological Ca2+. HGF may play an important role in epidermal tissue repair as it enhances both the migration and growth of keratinocytes

  7. Chronic treatment with epidermal growth factor induces growth of the rat ventral prostate

    DEFF Research Database (Denmark)

    Tørring, N; Jensen, L V; Wen, J G

    2001-01-01

    the hyperplastic growth phase of the prostate in newborn rats.MATERIAL AND METHODS: Newborn rats were treated for 8 weeks with EGF (150 microg/kg body weight per day), administered as daily subcutaneous injections. Sections of the prostate tissue were examined by a stereological technique to determine tissue......OBJECTIVE: The epidermal growth factor (EGF) system is expressed in the rat prostate, and growth factors from this system induce proliferation in prostate epithelial and stromal cell cultures. The aim of the study was to investigate the possible growth-promoting effects of the system during...... of the prostate epithelium, the stroma and the lumen following EGF treatment, in a pattern resembling physiological growth of the ventral prostate. A significant correlation (r = 0.78, p

  8. Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Nahyun Choi

    2018-02-01

    Full Text Available Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs. We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif ligand 1 (CXCL1, platelet-derived endothelial cell growth factor (PD-ECGF, and platelet-derived growth factor-C (PDGF-C. Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2 phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration.

  9. Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

    Science.gov (United States)

    Choi, Nahyun; Shin, Soyoung; Song, Sun U.; Sung, Jong-Hyuk

    2018-01-01

    Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration. PMID:29495622

  10. Hepatocyte and keratinocyte growth factors and their receptors in human lung emphysema

    Directory of Open Access Journals (Sweden)

    Marchal Joëlle

    2005-10-01

    Full Text Available Abstract Background Hepatocyte and keratinocyte growth factors are key growth factors in the process of alveolar repair. We hypothesized that excessive alveolar destruction observed in lung emphysema involves impaired expression of hepatocyte and keratinocyte growth factors or their respective receptors, c-met and keratinocyte growth factor receptor. The aim of our study was to compare the expression of hepatocyte and keratinocyte growth factors and their receptors in lung samples from 3 groups of patients: emphysema; smokers without emphysema and non-smokers without emphysema. Methods Hepatocyte and keratinocyte growth factor proteins were analysed by immunoassay and western blot; mRNA expression was measured by real time quantitative polymerase chain reaction. Results Hepatocyte and keratinocyte growth factors, c-met and keratinocyte growth factor receptor mRNA levels were similar in emphysema and non-emphysema patients. Hepatocyte growth factor mRNA correlated negatively with FEV1 and the FEV1/FVC ratio both in emphysema patients and in smokers with or without emphysema. Hepatocyte and keratinocyte growth factor protein concentrations were similar in all patients' groups. Conclusion The expression of hepatocyte and keratinocyte growth factors and their receptors is preserved in patients with lung emphysema as compared to patients without emphysema. Hepatocyte growth factor mRNA correlates with the severity of airflow obstruction in smokers.

  11. Computerised tomography in radiotherapy planning

    International Nuclear Information System (INIS)

    Badcock, P.C.

    1983-01-01

    This study evaluates the effectiveness of computed tomography as an adjunct to radiotherapy planning. Until recently, acquisition of accurate data concerning tumour anatomy lagged behind other developments in radiotherapy. With the advent of computer-tomography (CT), these data can be displayed and transmitted to a treatment planning computer. It is concluded that the greatest inaccuracies in the radiation treatment of patients are to be found in both the inadequate delineation of the target volume within the patient and changes in body outline relative to the target volume over the length of the irradiated volume. The technique was useful in various subgroups (pelvic, intra-thoracic and chest-wall tumours) and for those patients being treated palliatively. With an estimated improvement in cure rate of 4.5% and cost-effective factors of between 3.3 and 5, CT-assisted radiotherapy planning appears to be a worthwhile procedure. (orig.)

  12. Radiotherapy-induced hypopituitarism: a review.

    Science.gov (United States)

    Sathyapalan, Thozhukat; Dixit, Sanjay

    2012-05-01

    Hypopituitarism is a disorder caused by impaired hormonal secretions from the hypothalamic-pituitary axis. Radiotherapy is the most common cause of iatrogenic hypopituitarism. The hypothalamic-pituitary axis inadvertently gets irradiated in patients receiving prophylactic cranial radiotherapy for leukemia, total body irradiation and radiotherapy for intracranial, base skull, sinonasal and nasopharyngeal tumors. Radiation-induced hypopituitarism (RIH) is insidious, progressive and largely nonreversible. Mostly, RIH involves one hypothalamic-pituitary axis; however, multiple hormonal axes deficiency starts developing at higher doses. Although the clinical effects of the hypopituitarism are more profound in children and young adults, its implications in older adults are being increasingly recognized. The risk continues to persist or increase up to 10 years following radiation exposure. The clinical management of hypopituitarism is challenging both for the patients and healthcare providers. Here we have reviewed the scale of the problem, the risk factors and the management of RIH.

  13. Dental status, dental rehabilitation procedures, demographic and oncological data as potential risk factors for infected osteoradionecrosis of the lower jaw after radiotherapy for oral neoplasms: a retrospective evaluation

    International Nuclear Information System (INIS)

    Niewald, Marcus; Fleckenstein, Jochen; Mang, Kristina; Holtmann, Henrik; Spitzer, Wolfgang J; Rübe, Christian

    2013-01-01

    Retrospective evaluation of the dental status of patients with oral cancer before radiotherapy, the extent of dental rehabilitation procedures, demographic and radiotherapy data as potential risk factors for development of infected osteoradionecrosis of the lower jaw. A total of 90 patients who had undergone radiotherapy for oral cancer were included into this retrospective evaluation. None of them had distant metastases. After tumour surgery the patients were referred to an oral and maxillofacial surgeon for dental examination and the necessary dental rehabilitation procedures inclusive potential tooth extraction combined with primary soft tissue closure. Adjuvant radiotherapy was started after complete healing of the gingiva (> 7 days after potential extraction). The majority of patients (n = 74) was treated with conventionally fractionated radiotherapy with total doses ranging from 50-70Gy whereas further 16 patients received hyperfractionated radiotherapy up to 72Gy. The records of the clinical data were reviewed. Furthermore, questionnaires were mailed to the patients’ general practitioners and dentists in order to get more data concerning tumour status and osteoradionecrosis during follow-up. The patients’ dental status before radiotherapy was generally poor. On average 10 teeth were present, six of them were regarded to remain conservable. Extensive dental rehabilitation procedures included a mean of 3.7 tooth extractions. Chronic periodontitis with severe attachment loss was found in 40%, dental biofilm in 56%. An infected osteoradionecrosis (IORN) grade II according to (Schwartz et al., Am J Clin Oncol 25:168-171, 2002) was diagnosed in 11 of the 90 patients (12%), mostly within the first 4 years after radiotherapy. We could not find significant prognostic factors for the occurrence of IORN, but a trendwise correlation with impaired dental status, rehabilitation procedures, fraction size and tumour outcome. The occurrence of IORN is an important long

  14. Dental status, dental rehabilitation procedures, demographic and oncological data as potential risk factors for infected osteoradionecrosis of the lower jaw after radiotherapy for oral neoplasms: a retrospective evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Niewald, Marcus; Fleckenstein, Jochen [Department of Radiotherapy and Radiooncology, Saarland University Medical Center, Kirrberger Str. 1, D-66421 Homburg (Germany); Mang, Kristina [Dental Practice, Duisburg (Germany); Holtmann, Henrik; Spitzer, Wolfgang J [Department of Oral and Maxillofacial Surgery, Saarland University Medical Center, Kirrberger Str. 1, D-66421 Homburg (Germany); Rübe, Christian [Department of Radiotherapy and Radiooncology, Saarland University Medical Center, Kirrberger Str. 1, D-66421 Homburg (Germany)

    2013-10-02

    Retrospective evaluation of the dental status of patients with oral cancer before radiotherapy, the extent of dental rehabilitation procedures, demographic and radiotherapy data as potential risk factors for development of infected osteoradionecrosis of the lower jaw. A total of 90 patients who had undergone radiotherapy for oral cancer were included into this retrospective evaluation. None of them had distant metastases. After tumour surgery the patients were referred to an oral and maxillofacial surgeon for dental examination and the necessary dental rehabilitation procedures inclusive potential tooth extraction combined with primary soft tissue closure. Adjuvant radiotherapy was started after complete healing of the gingiva (> 7 days after potential extraction). The majority of patients (n = 74) was treated with conventionally fractionated radiotherapy with total doses ranging from 50-70Gy whereas further 16 patients received hyperfractionated radiotherapy up to 72Gy. The records of the clinical data were reviewed. Furthermore, questionnaires were mailed to the patients’ general practitioners and dentists in order to get more data concerning tumour status and osteoradionecrosis during follow-up. The patients’ dental status before radiotherapy was generally poor. On average 10 teeth were present, six of them were regarded to remain conservable. Extensive dental rehabilitation procedures included a mean of 3.7 tooth extractions. Chronic periodontitis with severe attachment loss was found in 40%, dental biofilm in 56%. An infected osteoradionecrosis (IORN) grade II according to (Schwartz et al., Am J Clin Oncol 25:168-171, 2002) was diagnosed in 11 of the 90 patients (12%), mostly within the first 4 years after radiotherapy. We could not find significant prognostic factors for the occurrence of IORN, but a trendwise correlation with impaired dental status, rehabilitation procedures, fraction size and tumour outcome. The occurrence of IORN is an important long

  15. Radiotherapy in the treatment of solitary plasmacytoma.

    Science.gov (United States)

    Jyothirmayi, R; Gangadharan, V P; Nair, M K; Rajan, B

    1997-05-01

    Solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are rare. High local control rates are reported with radiotherapy, although the optimal dose and extent of radiotherapy portals remains controversial. Between 1983 and 1993, 30 patients with solitary plasmacytoma were seen at the Regional Cancer Centre, Trivandrum, India. 23 patients had SPB and seven EMP. The mean age was 52 years and the male to female ratio 3.2:1. Diagnosis of SPB was confirmed by biopsy in 16 patients and tumour excision in seven. 20 patients received megavoltage radiotherapy to the bone lesion with limited margins, and one received chemotherapy. Two patients who underwent complete tumour excision received no further treatment. All seven patients with EMP received megavoltage radiotherapy, four following biopsy and three after tumour excision. Local control was achieved in all patients with SPB. Nine progressed to multiple myeloma and one developed a solitary plasmacytoma in another bone. Six patients with EMP achieved local control. Three later progressed to multiple myeloma and one had local relapse. Median time to relapse was 28 months in SPB and 30 months in EMP. 5-year overall survival rates were 82% and 57% for patients with SPB and EMP, respectively. The corresponding progression free survival rates were 55% and 50%, respectively. Age, sex, site of tumour, serum M protein and haemoglobin levels did not significantly influence progression free survival. The extent of surgery, radiotherapy dose or time to relapse were not significant prognostic factors. Radiotherapy appears to be an effective modality of treatment of solitary plasmacytoma. No dose-response relationship is observed, and high local control rates are achieved with limited portals. Progression to multiple myeloma is the commonest pattern of failure, although no prognostic factors for progression are identified. The role of chemotherapy in preventing disease progression needs further evaluation.

  16. Predictive factors for the response of pulmonary tumours treated by robotic stereotactic radiotherapy; Facteurs predictifs pour la reponse des tumeurs pulmonaires traitees par radiotherapie stereotaxique robotisee

    Energy Technology Data Exchange (ETDEWEB)

    Doyen, J.; Benezery, K.; Thariat, J.; Angellier, G.; Poudenx, M.; Bondiau, P.Y. [Centre Antoine-Lacassagne, 06 - Nice (France); Beckendorf, V. [Centre Alexis-Vautrin, 54 - Nancy (France); Venissac, N. [Centre hospitalo-universitaire Pasteur, 06 - Nice (France)

    2010-10-15

    The authors report a study which aimed at identifying factors influencing the response to radiotherapy performed in robotic stereotactic conditions with CyberKnife within the frame of treatment of primitive or secondary pulmonary tumours. Thirty eight stage I cancers, 22 metastases including 17 epidermoid carcinomas, and 43 adenocarcinomas have been treated this way. The analysis of data and results reveals that feminine gender, a biological dose greater than 140 Gy, and an age greater than 65 year old are associated with a better tumour response. Short communication

  17. Dosimetric Factors Associated With Long-Term Dysphagia After Definitive Radiotherapy for Squamous Cell Carcinoma of the Head and Neck

    International Nuclear Information System (INIS)

    Caudell, Jimmy J.; Schaner, Philip E.; Desmond, Renee A.; Meredith, Ruby F.; Spencer, Sharon A.; Bonner, James A.

    2010-01-01

    Purpose: Intensification of radiotherapy and chemotherapy for head-and-neck cancer may lead to increased rates of dysphagia. Dosimetric predictors of objective findings of long-term dysphagia were sought. Methods and Materials: From an institutional database, 83 patients were identified who underwent definitive intensity-modulated radiotherapy for squamous cell carcinoma of the head and neck, after exclusion of those who were treated for a second or recurrent head-and-neck primary lesion, had locoregional recurrence at any time, had less than 12 months of follow-up, or had postoperative radiotherapy. Dosimetric parameters were analyzed relative to three objective endpoints as a surrogate for severe long-term dysphagia: percutaneous endoscopic gastrostomy (PEG) tube dependence at 12 months, aspiration on modified barium swallow, or pharyngoesophageal stricture requiring dilation. Results: Mean dose greater than 41 Gy and volume receiving 60 Gy (V 60 ) greater than 24% to the larynx were significantly associated with PEG tube dependence and aspiration. V 60 greater than 12% to the inferior pharyngeal constrictor was also significantly associated with increased PEG tube dependence and aspiration. V 65 greater than 33% to the superior pharyngeal constrictor or greater than 75% to the middle pharyngeal constrictor was associated with pharyngoesophageal stricture requiring dilation. Conclusions: Doses to the larynx and pharyngeal constrictors predicted long-term swallowing complications, even when controlled for other clinical factors. The addition of these structures to intensity-modulated radiotherapy optimization may reduce the incidence of dysphagia, although cautious clinical validation is necessary.

  18. Inhibitory effect of sequential combined chemotherapy and radiotherapy on growth of implanted tumor in mice

    International Nuclear Information System (INIS)

    Okada, Kouji

    1983-01-01

    Sequential chemotherapy using FT-207, adriamycin and mitomycin C followed by radiotherapy was attempted to achieve effective inhibition against implanted tumor in C57BL/6 black mice bearing YM-12 tumors. Sequential combined chemotherapy was more effective than single drug chemotherapy or combined chemotherapy of other drugs. Addition of radiotherapy to the sequential combined chemotherapy was successful for enhancing therapeutic effect. (author)

  19. Factors influencing bowel sparing in intensity modulated whole pelvic radiotherapy for gynaecological malignancies

    International Nuclear Information System (INIS)

    Georg, Petra; Georg, Dietmar; Hillbrand, Martin; Kirisits, Christian; Poetter, Richard

    2006-01-01

    Background and purpose: To evaluate the influence of uterus and bladder size on large and small bowel sparing with intensity modulated whole pelvic radiotherapy (IM-WPRT) in gynecologic patients. Patients and methods: Twenty patients were selected; 10 women with cervical cancer treated with definitive radiotherapy (group 'DEF') and 10 endometrial cancer patients treated postoperatively (group 'POST'). Bladder, rectal wall, small (SB) and large bowel (LB) were delineated as organs at risk. A conformal four field technique and a seven field IMRT plan (prescription dose 50.4 Gy) were compared in terms of DVH and various target parameters. Results: At doses between 40 and 50.4 Gy statistically significant improvements (P<0.05) were observed for IM-WPRT for irradiated volume of rectal wall and bladder. In both patient groups, with IMRT the average irradiated volume of SB was reduced by a factor of 6 at 50.4 Gy. This ratio was 2 for LB. In the DEF group the effect of SB-sparing with IMRT correlated with bladder size (correlation coefficient 0.70) while it did not correlate in the postoperative group. The effect of LB-sparing decreased with increasing bladder size in both groups but the impact of IMRT was larger for postoperative patients. Conclusions: IMRT significantly reduced the absolute volume of rectal wall, bladder and bowel irradiated at the prescribed dose level in gynaecologic patients. Main differences between POST and DEF patients receiving IM-WPRT were absolute volumes of LB irradiated to doses between 35 and 50 Gy, suggesting an impact of intact uterus on LB volume in the pelvis. POST patients seem to benefit most from elective nodal IMRT. Bladder filling is an important co-factor influencing the benefit of IMRT with respect to OAR sparing

  20. In silico modelling of radiation effects towards personalised treatment in radiotherapy

    Science.gov (United States)

    Marcu, Loredana G.; Marcu, David

    2017-12-01

    In silico models applied in medical physics are valuable tools to assist in treatment optimization and personalization, which represent the ultimate goal of today's radiotherapy. Next to several biological and biophysical factors that influence tumour response to ionizing radiation, hypoxia and cancer stem cells are critical parameters that dictate the final outcome. The current work presents the results of an in silico model of tumour growth and response to radiation developed using Monte Carlo techniques. We are presenting the impact of partial oxygen tension and repopulation via cancer stem cells on tumour control after photon irradiation, highlighting some of the gaps that clinical research needs to fill for better customized treatment.

  1. Dose response relationship in local radiotherapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok

    2001-01-01

    In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2±7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver

  2. Chronic fatigue in cancer patients treated with radiotherapy

    International Nuclear Information System (INIS)

    Rucinska, M.; Wojtukiewicz, M.Z.; Tokajuk, P.

    2004-01-01

    Fatigue is one of the most prevalent and profound symptoms related to both malignancy and anti-neoplastic treatment. It is being reported in 60% to 80% of cancer patients. We review the correlation between the cancer-related fatigue syndrome and radiotherapy. In patients undergoing radiotherapy, fatigue is often cumulative and may reach its peak during the last weeks of treatment. The presence of fatigue prior to therapy initiation is the most important predictive factor of the occurrence of radiotherapy-related cancer fatigue syndrome. Occasionally, fatigue persists for a prolonged period of months and even years beyond radiotherapy. Anemia may be one of major causative factors responsible for the development of the cancer-related fatigue syndrome. Fatigue has an enormous physical, mental, emotional, and economic impact on cancer patients, their families and care-providers. The treatment of radiation-related fatigue remains unknown. The initial approach should cover efforts aimed at the correction of potential etiologies, especially anemia. Education concerning fatigue greatly benefits some patients. It seems that exercise may be beneficial in relieving fatigue, bearing in mind that the exercise program for cancer patients should be initiated gradually and significantly individualized. (author)

  3. Efficacy of Traditional Chinese Medicine in Treatment and Prophylaxis of Radiation-Induced Oral Mucositis in Patients Receiving Radiotherapy: A Randomized Controlled Trial.

    Science.gov (United States)

    Wang, Cong; Wang, Peiguo; Ouyang, Huaqiang; Wang, Jing; Sun, Lining; Li, Yanwei; Liu, Dongying; Jiang, Zhansheng; Wang, Bin; Pan, Zhanyu

    2018-06-01

    To estimate the efficacy of traditional Chinese medicine (Chining decoction, CHIN) for radiation-induced oral mucositis in patients with head and neck cancer. From May 2014 to December 2015, 70 consecutive patients were randomly assigned to receive CHIN (treatment group) or recombinant human epidermal growth factor (rhEGF) spray (control group) at a 1:1 ratio. CHIN was administered to treatment group from the first day of radiotherapy until the completion of radiotherapy. Simultaneously, the rhEGF spray was administered to control group on the oral mucosa of irradiated area. The clinical benefit was determined by gradation of mucositis (Common Terminology Criteria for Adverse Events v4.0), oral pain, and xerostomia (visual analysis scale) for each week during radiotherapy. Body mass index was evaluated before and after radiotherapy. Patients in the treatment group had prominent remission of oral pain and grade of mucositis on each observing point compared with those in control group ( P .05). CHIN presented an obvious advantage in preventing radiation-induced oral mucositis compared with rhEGF spray.

  4. Preliminary analysis of the risk factors for radiation pneumonitis in patients with non- small-cell lung cancer treated with concurrent erlotinib and thoracic radiotherapy

    Directory of Open Access Journals (Sweden)

    Zhuang H

    2014-05-01

    Full Text Available Hongqing Zhuang,* Hailing Hou,* Zhiyong Yuan, Jun Wang, Qingsong Pang, Lujun Zhao, Ping WangDepartment of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, and Tianjin Lung Cancer Center, Tianjin, People's Republic of China*These authors contributed equally to this workPurpose: The aim of this study was to investigate radiation pneumonitis and its associated risk factors in patients with non-small-cell lung cancer treated with concurrent erlotinib and thoracic radiotherapy.Materials and methods: We conducted an analysis of patients with nonoperable stage IIIA–IV non-small-cell lung cancer who were treated with concurrent thoracic radiotherapy and erlotinib (ClinicalTrials.gov identifier: NCT00973310. The Common Terminology Criteria for Adverse Events version 3.0 grading system was applied to evaluate the incidence of radiation pneumonitis. The lung dosimetric parameters were recorded in accordance with the treatment plan, and the study endpoint was radiation pneumonitis at grade 2 or more.Results: Among the 24 selected clinical cases, nine were identified with radiation pneumonitis of grade 2 or above (37.5%. This included four cases with grade 2 (16.7%, two cases with grade 3 (8.3%, and three cases with grade 5 (12.5%. The results showed that the planning target volume was a significant factor affecting the incidence of radiation pneumonitis. All lung dosimetric parameters exhibited statistically significant differences between patients with pneumonitis and patients without pneumonitis. The receiver operating characteristic (ROC curve analysis showed that all lung dosimetric parameters were useful in predicting the incidence of radiation pneumonitis. In addition, the threshold values of V5, V10, V15, V20, V30, and mean lung dose were >4%, >29%, >27%, >22%, >17% and >1,027 cGy, respectively.Conclusion: Special attention

  5. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

    Directory of Open Access Journals (Sweden)

    McLoughlin Paul

    2011-01-01

    Full Text Available Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2 or hypoxia (10% O2 for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA, VEGFB, placenta growth factor (PlGF, VEGF receptor 1 (VEGFR1 and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or

  6. The Relationships Between Spiritual Well-Being, Quality of Life, and Psychological Factors Before Radiotherapy for Prostate Cancer.

    Science.gov (United States)

    Walker, Sara J; Chen, Yiyi; Paik, Kyungjeen; Mirly, Brandy; Thomas, Charles R; Hung, Arthur Y

    2017-10-01

    Given shifting trends of religious identities in the USA, better understanding the impact of patients' religious identities on health-related quality of life (QOL) may help tailor the use of psychological interventions. Men with prostate cancer (N = 43) completed measures of quality of life (QOL), spiritual well-being in two domains (i.e., Faith and Meaning/Peace), psychological state, and psychological trait before undergoing radiotherapy. We hypothesized that (1) higher existential Meaning/Peace would correlate with higher QOL and psychological trait protective factors (e.g., Agreeableness) and that (2) higher existential Meaning/Peace would correlate with lower depression, anxiety, and Neuroticism (i.e., a psychological trait risk factor). We did not anticipate similar relationships between religious Faith and QOL, depression, anxiety, or psychological traits and consider related analyses to be exploratory in nature. Meaning/Peace was indeed negatively associated with depression, anxiety, and Neuroticism. Meaning/Peace was positively correlated with Physical, Social, Functional, and Emotional well-being, as well as Extraversion. Religious Faith was positively associated with Functional well-being, but not the other state, trait, or QOL domains. In sum, prostate cancer patients' sense of existential Meaning/Peace prior to radiotherapy was associated with well-being in many domains, whereas religious Faith appeared less so.

  7. Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma

    International Nuclear Information System (INIS)

    Schoenfeld, Gordon O.; Amdur, Robert J.; Schmalfuss, Ilona M.; Morris, Christopher G.; Keole, Sameer R.; Mendenhall, William M.; Marcus, Robert B.

    2006-01-01

    Purpose: To report outcomes of patients with localized intracranial germinoma treated with low-dose craniospinal irradiation (CSI) followed by a boost to the ventricular system and primary site. Methods and Materials: Thirty-one patients had pathologically confirmed intracranial germinoma and no spine metastases. Low-dose CSI was administered in 29 patients: usually 21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at 1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor size on magnetic resonance images before, during, and after radiotherapy. Results: With a median follow-up of 7.0 years, 29 of 31 patients (94%) are disease free. One failure had nongerminomatous histology; the initial diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1 died. No patient developed myelopathy, visual deficits, dementia, or skeletal growth problems. In locally controlled patients, tumor response according to magnetic resonance scan was nearly complete within 6 months after radiotherapy. Conclusions: Radiotherapy alone with low-dose prophylactic CSI cures almost all patients with localized intracranial germinoma. Complications are rare when the daily dose of radiotherapy is limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a near-complete response to radiotherapy should undergo resection to rule out a nongerminomatous element

  8. The role of primary radiotherapy in acromegaly (abstract)

    International Nuclear Information System (INIS)

    Ali, M.; Knob, G.

    1998-01-01

    The aim of the study was to evaluate the role of primary radiotherapy in acromegaly. Fifteen cases were randomly included in this study from 1989 to 1998. The patients were given external radiotherapy using Co/sup 60/ source and 200 cGy/F, 5F/week up to 5000 cGy, Tumor dose (TD). The target volume was irradiated by opposite parallel lateral field. The field size ranged from 4.5 to 6.5 cm. depending upon the tumor size and its extensions. These patients were continuously followed up for variable period depending upon the history of the patient and compliance by serial Growth Hormone (GH) assay and Clinical and Radiological evaluation. Out of these fifteen patients one died of cardiac sequelae. In the remaining treated patients majority has normal or continuously decreasing GH levels. The treatment of Acromegaly includes surgery, radiotherapy, medical treatment or the combination of these with variable success and non is perfect. We used radiotherapy as the primary modality, due to medical contraindication or refusal of patient for surgery and found that this is an effective modality in the treatment of acromegaly even in patients with extra sellar extension of the tumor. (author)

  9. Growth and Growth hormone - Insulin Like Growth Factor -I (GH-IGF-I) Axis in Chronic Anemias.

    Science.gov (United States)

    Soliman, Ashraf T; De Sanctis, Vincenzo; Yassin, Mohamed; Adel, Ashraf

    2017-04-28

    Anaemia is a global public health problem affecting both developing and developed countries with major consequences for human health as well as social and economic development. It occurs at all stages of the life cycle, but is more prevalent in pregnant women and young children. Iron deficiency anaemia (IDA) was considered to be among the most important contributing factors to the global burden of disease. Prolonged and/or chronic anemia has a negative effect on linear growth especially during the rapid phases (infancy and puberty). Additionally infants with chronic IDA have delayed cognitive, motor, and affective development that may be long-lasting. In view of the significant impact of chronic anemias on growth, pediatricians endocrinologists and hematologists should advocate primary prevention and screening for growth disturbance in these forms of anemias. The extent of the negative effect of different forms of chronic anemias on linear growth and its possible reversibilty is addressed in this review. The possible mechanisms that may impair growth in the different forms of anemias are addressed with special attention to their effect on the growth hormone (GH) - insulin like growth factor -I (IGF-I).

  10. Endothelial trans-differentiation in glioblastoma recurring after radiotherapy.

    Science.gov (United States)

    De Pascalis, Ivana; Morgante, Liliana; Pacioni, Simone; D'Alessandris, Quintino Giorgio; Giannetti, Stefano; Martini, Maurizio; Ricci-Vitiani, Lucia; Malinverno, Matteo; Dejana, Elisabetta; Larocca, Luigi M; Pallini, Roberto

    2018-04-30

    We hypothesized that in glioblastoma recurring after radiotherapy, a condition whereby the brain endothelium undergoes radiation-induced senescence, tumor cells with endothelial phenotype may be relevant for tumor neovascularization. Matched glioblastoma samples obtained at primary surgery and at surgery for tumor recurrence after radiotherapy, all expressing epidermal growth factor receptor variant III (EGFRvIII), were assessed by a technique that combines fluorescent in situ hybridization (FISH) for the EGFR/CEP7 chromosomal probe with immunostaining for endothelial cells (CD31) and activated pericytes (α Smooth Muscle Actin). Five EGFRvIII-expressing paired primary/recurrent glioblastoma samples, in which the tumor cells showed EGFR/CEP7 amplification, were then assessed by CD31 and α Smooth Muscle Actin immunofluorescence. In glomeruloid bodies, the ratio between CD31+ cells with amplified EGFR/CEP7 signal and the total CD31+ cells was 0.23 ± 0.09 (mean ± sem) and 0.63 ± 0.07 in primary tumors and in recurrent ones, respectively (p < 0.002, Student-t test). In capillaries, the ratio of CD31+ cells with amplified EGFR/CEP7 over the total CD31+ cells lining the capillary lumen was 0.21 ± 0.06 (mean ± sem) and 0.42 ± 0.07 at primary surgery and at recurrence, respectively (p < 0.005, Student-t test). Expression of α Smooth Muscle Actin by cells with EGFR/CEP7 amplification was not observed. Then, in glioblastoma recurring after radiotherapy, where the brain endothelium suffers from radiation-induced cell senescence, tumor-derived endothelium plays a role in neo-vascularization.

  11. Comparison of metastatic disease after local tumour treatment with radiotherapy or surgery in various tumour models

    International Nuclear Information System (INIS)

    Ruiter, J. de; Cramer, S.J.; Lelieveld, P.; Putten, L.M. van

    1982-01-01

    Spontaneous metastases in lymph nodes and/or the lung were obtained after tumour cell inoculation of four mouse tumours and one rat tumour into the foot-pads of syngeneic animals or their F 1 hybrids. Following local radiotherapy with doses of 45-80 Gy, significantly more mice died with metastases than following local amputation of the tumour-bearing foot when the 2661 carcinoma was involved. No significant difference was observed after these treatments for the other tumours. The enhancement of metastatic growth after local radiotherapy in the 2661 carcinoma seems not to be due to incomplete killing of tumour cells in the foot. The presence of irradiated normal structures and tumour tissue after radiotherapy promoted the outgrowth of 2661 carcinoma cells which were outside the radiation field at the time of treatment. Evidently, even under similar experimental conditions, radiotherapy may enhance the growth of metastases from some tumours and not from others. (author)

  12. Friends Turned Foes: Angiogenic Growth Factors beyond Angiogenesis.

    Science.gov (United States)

    Matkar, Pratiek N; Ariyagunarajah, Ramya; Leong-Poi, Howard; Singh, Krishna K

    2017-10-02

    Angiogenesis, the formation of new blood vessels from pre-existing ones is a biological process that ensures an adequate blood flow is maintained to provide the cells with a sufficient supply of nutrients and oxygen within the body. Numerous soluble growth factors and inhibitors, cytokines, proteases as well as extracellular matrix proteins and adhesion molecules stringently regulate the multi-factorial process of angiogenesis. The properties and interactions of key angiogenic molecules such as vascular endothelial growth factors (VEGFs), fibroblast growth factors (FGFs) and angiopoietins have been investigated in great detail with respect to their molecular impact on angiogenesis. Since the discovery of angiogenic growth factors, much research has been focused on their biological actions and their potential use as therapeutic targets for angiogenic or anti-angiogenic strategies in a context-dependent manner depending on the pathologies. It is generally accepted that these factors play an indispensable role in angiogenesis. However, it is becoming increasingly evident that this is not their only role and it is likely that the angiogenic factors have important functions in a wider range of biological and pathological processes. The additional roles played by these molecules in numerous pathologies and biological processes beyond angiogenesis are discussed in this review.

  13. Isolated limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma : The value of adjuvant radiotherapy

    NARCIS (Netherlands)

    Thijssens, KMJ; van Ginkel, RJ; Pras, E; Suurmeijer, AJH; Hoekstra, HJ

    Background: The aim was to investigate the value of adjuvant radiotherapy for locally advanced soft tissue sarcoma after hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan followed by limb-saving surgery. Methods: From 1991 to 2003, 73 patients (median age, 54

  14. Alterations of Growth Factors in Autism and Attention-Deficit/Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Alma Y. Galvez-Contreras

    2017-07-01

    Full Text Available Growth factors (GFs are cytokines that regulate the neural development. Recent evidence indicates that alterations in the expression level of GFs during embryogenesis are linked to the pathophysiology and clinical manifestations of attention-deficit/hyperactivity disorder (ADHD and autism spectrum disorders (ASD. In this concise review, we summarize the current evidence that supports the role of brain-derived neurotrophic factor, insulin-like growth factor 2, hepatocyte growth factor (HGF, glial-derived neurotrophic factor, nerve growth factor, neurotrophins 3 and 4, and epidermal growth factor in the pathogenesis of ADHD and ASD. We also highlight the potential use of these GFs as clinical markers for diagnosis and prognosis of these neurodevelopmental disorders.

  15. Alterations of Growth Factors in Autism and Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Galvez-Contreras, Alma Y.; Campos-Ordonez, Tania; Gonzalez-Castaneda, Rocio E.; Gonzalez-Perez, Oscar

    2017-01-01

    Growth factors (GFs) are cytokines that regulate the neural development. Recent evidence indicates that alterations in the expression level of GFs during embryogenesis are linked to the pathophysiology and clinical manifestations of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). In this concise review, we summarize the current evidence that supports the role of brain-derived neurotrophic factor, insulin-like growth factor 2, hepatocyte growth factor (HGF), glial-derived neurotrophic factor, nerve growth factor, neurotrophins 3 and 4, and epidermal growth factor in the pathogenesis of ADHD and ASD. We also highlight the potential use of these GFs as clinical markers for diagnosis and prognosis of these neurodevelopmental disorders. PMID:28751869

  16. Radiotherapy Boost Following Conservative Surgery for Locally Advanced Breast Cancer

    International Nuclear Information System (INIS)

    Cendales, Ricardo; Ospino, Rosalba; Torres, Felipe; Cotes, Martha

    2009-01-01

    Nearly half of breast cancer patients in developing countries present with a locally advanced cancer. Treatment is centered on a multimodal approach based on chemotherapy, surgery and radiotherapy. The growing use of neoadjuvant chemotherapy has led to a more conservative surgical approach; nonetheless, it is not yet considered as a standard. There are no clear recommendations on the use of a radiotherapy boost in such situation. A Medline search was developed. Most articles are retrospective series. Survival free of locoregional relapse in patients treated with neoadjuvant chemotherapy, breast conserving surgery and radiotherapy is good. All articles described a boost administered to nearly all patients without regard to their prognostic factors, given that a locally advanced tumor is already considered as a poor prognostic factor. Even tough the poor level of evidence, a recommendation can be made: radiotherapy boost should be administered to all patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and breast conserving surgery.

  17. Epidermal growth factor in alkali-burned corneal epithelial wound healing.

    Science.gov (United States)

    Singh, G; Foster, C S

    1987-06-15

    We conducted a double-masked study to evaluate the effect of epidermal growth factor on epithelial wound healing and recurrent erosions in alkali-burned rabbit corneas. Epithelial wounds 10 mm in diameter healed completely under the influence of topical epidermal growth factor, whereas the control corneas did not resurface in the center. On reversal of treatment, the previously nonhealing epithelial defects healed when treated with topical epidermal growth factor eyedrops. Conversely, the epidermal growth factor-treated and resurfaced corneas developed epithelial defects when treatment was discontinued. Histopathologic examination disclosed hyperplastic epithelium growing over the damaged stroma laden with polymorphonuclear leukocytes when treated with epidermal growth factor eyedrops, but it did not adhere to the underlying tissue. Hydropic changes were seen intracellularly as well as between the epithelial cells and the stroma.

  18. Human corpus luteum: presence of epidermal growth factor receptors and binding characteristics

    International Nuclear Information System (INIS)

    Ayyagari, R.R.; Khan-Dawood, F.S.

    1987-01-01

    Epidermal growth factor receptors are present in many reproductive tissues but have not been demonstrated in the human corpus luteum. To determine the presence of epidermal growth factor receptors and its binding characteristics, we carried out studies on the plasma cell membrane fraction of seven human corpora lutea (days 16 to 25) of the menstrual cycle. Specific epidermal growth factor receptors were present in human corpus luteum. Insulin, nerve growth factor, and human chorionic gonadotropin did not competitively displace epidermal growth factor binding. The optimal conditions for corpus luteum-epidermal growth factor receptor binding were found to be incubation for 2 hours at 4 degrees C with 500 micrograms plasma membrane protein and 140 femtomol 125 I-epidermal growth factor per incubate. The number (mean +/- SEM) of epidermal growth factor binding sites was 12.34 +/- 2.99 X 10(-19) mol/micrograms protein; the dissociation constant was 2.26 +/- 0.56 X 10(-9) mol/L; the association constant was 0.59 +/- 0.12 X 10(9) L/mol. In two regressing corpora lutea obtained on days 2 and 3 of the menstrual cycle, there was no detectable specific epidermal growth factor receptor binding activity. Similarly no epidermal growth factor receptor binding activity could be detected in ovarian stromal tissue. Our findings demonstrate that specific receptors for epidermal growth factor are present in the human corpus luteum. The physiologic significance of epidermal growth factor receptors in human corpus luteum is unknown, but epidermal growth factor may be involved in intragonadal regulation of luteal function

  19. Local Delivery of Growth Factors Using Coated Suture Material

    Directory of Open Access Journals (Sweden)

    T. F. Fuchs

    2012-01-01

    Full Text Available The optimization of healing processes in a wide range of tissues represents a central point for surgical research. One approach is to stimulate healing processes with growth factors. These substances have a short half-life and therefore it seems useful to administer these substances locally rather than systemically. One possible method of local delivery is to incorporate growth factors into a bioabsorbable poly (D, L-lactide suspension (PDLLA and coat suture material. The aim of the present study was to establish a procedure for the local delivery of growth factors using coated suture material. Sutures coated with growth factors were tested in an animal model. Anastomoses of the colon were created in a rat model using monofilament sutures. These were either untreated or coated with PDLLA coating alone or coated with PDLLA incorporating insulin—like growth factor-I (IGF-I. The anastomoses were subjected to biomechanical, histological, and immunohistochemical examination. After 3 days the treated groups showed a significantly greater capacity to withstand biomechanical stress than the control groups. This finding was supported by the results of the histomorphometric. The results of the study indicate that it is possible to deliver bioactive growth factors locally using PDLLA coated suture material. Healing processes can thus be stimulated locally without subjecting the whole organism to potentially damaging high systemic doses.

  20. Keratinocyte growth factor mRNA expression in periodontal ligament fibroblasts

    DEFF Research Database (Denmark)

    Dabelsteen, S; Wandall, H H; Grøn, B

    1997-01-01

    Keratinocyte growth factor (KGF) is a fibroblast growth factor which mediates epithelial growth and differentiation. KGF is expressed in subepithelial fibroblasts, but generally not in fibroblasts of deep connective tissue, such as fascia and ligaments. Here we demonstrate that KGF mRNA is expres......Keratinocyte growth factor (KGF) is a fibroblast growth factor which mediates epithelial growth and differentiation. KGF is expressed in subepithelial fibroblasts, but generally not in fibroblasts of deep connective tissue, such as fascia and ligaments. Here we demonstrate that KGF m......RNA is expressed in periodontal ligament fibroblasts, and that the expression is increased upon serum stimulation. Fibroblasts from human periodontal ligament, from buccal mucosa, from gingiva, and from skin were established from explants. Alkaline phosphatase activity was used as an indicator of the periodontal...

  1. Experimental study on combination of chemotherapy and radiotherapy

    International Nuclear Information System (INIS)

    Tanaka, Juichi

    1986-01-01

    Recently, by applying multidrug therapy using cisplatin and bleomycin to the treatment of head and neck cancer, the response rate of chemotherapy has been markedly increased and thus, chemotherapy has taken an important part in the treatment of head and neck cancer. In this paper a clinical application of chemotherapy in combination with radiotherapy was evaluated from the point of the cure rate and also preservation of the structures and the functions of the head and neck region. In order to test the advantage or usefulness of initial chemotherapy followed by radiotherapy (= pre-radiation chemotherapy), the experimental study on combination of chemotherapy and radiotherapy was designed by using ICR mice and Ehrlich solid carcinoma. Cisplatin and peplomycin, a newly developed derivative of bleomycin, were used as chemotherapeutic agents. Tumor growth delay rate was chosen as a parameter to indicate the effectiveness. Results obtained are as follows. 1. Combination chemotherapy of cisplatin and peplomycin was more effective than each single agent on Ehrlich solid carcinoma. Synergistic effect was obtained by higher dose. So, the combination of cisplatin and peplomycin was proved to be eligible for pre-radiation chemotherapy. 2. Synergistic effect of chemotherapy and radiotherapy was observed when chemotherapy was used prior to radiotherapy on Ehrlich solid carcinoma. 3. Even their additional effect was not recognized when radiotherapy preceded to chemotherapy on Ehrlich solid carcinoma. 4. No severe toxic effect was seen in the mice. The experimental results made it clear that pre-radiation chemotherapy is beneficial to the treatment of head and neck cancer. (author)

  2. Effects of growth-promoting factors on proliferation of mouse ...

    African Journals Online (AJOL)

    AJL

    2012-02-16

    Feb 16, 2012 ... Key words: Growth-promoting factors, mouse spermatogonial stem cells (SSCs), proliferation. INTRODUCTION ... insulin-like growth factor-1 (IGF-1) can stimulate mitotic ...... A Model for Analysis of Spermatogenesis. Zool. Sci.

  3. Survival and prognostic factors after moderately hypofractionated palliative thoracic radiotherapy for non-small cell lung cancer

    International Nuclear Information System (INIS)

    Oorschot, B. van; Assenbrunner, B.; Beckmann, G.; Flentje, M.; Schuler, M.

    2014-01-01

    Survival and prognostic variables in patients with advanced or metastatic non-small cell lung cancer (NSCLC) requiring thoracic palliative radiotherapy using a moderately hypofractionated regime (13-15 x 3 Gy) were evaluated. From March 2006 to April 2012, 120 patients with a physician estimated prognosis of 6-12 months were treated with this regime using CT-based 3D conformal radiotherapy. We collected data on patient characteristics, comorbidities, toxicity, and treatment parameters. Radiotherapy was completed as prescribed in 114 patients (95.0 %, premature termination 5.0 %). Acute grade 3 toxicity was seen in 6.4 % of patients. The median survival of all patients was 5.8 months. Nonmetastatic patients survived significantly longer than patients with metastatic disease (median 11.7 months vs 4.7 months, p = 0.0001) and 18.6 % of nonmetastatic patients survived longer than 2 years. In 12.7 % radiotherapy started less than 30 days before death and 14.2 % of patients received radiotherapy within 14 days before death. In the multivariate analysis, good general condition, nonmetastatic disease, and a stable or improved general condition at the end of radiotherapy were significant. The treatment parameters, age, and comorbidities were not statistically significant. Our data confirm considerable effectiveness of 13 x 3 Gy with conformal radiotherapy for patients with locally confined NSCLC not fit for radical treatment and raise doubt for this regimen in metastatic patients and ECOG ≥ 2 when burden, acute toxicity, and resources are considered. (orig.) [de

  4. Predictive factors for intrauterine growth restriction.

    Science.gov (United States)

    Albu, A R; Anca, A F; Horhoianu, V V; Horhoianu, I A

    2014-06-15

    Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies.

  5. Systemic administration of insulin-like growth factor I (IGF-I) causes growth of the rat prostate

    DEFF Research Database (Denmark)

    Tørring, N; Vinter-Jensen, L; Pedersen, S B

    1997-01-01

    PURPOSE: To investigate the effects of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) on the rat prostate. In addition, we investigated the effect of ornithine decarboxylase (ODC) inhibition with alpha-diflouromethylornitine (DFMO) on the expected growth of the prostate.MA...

  6. ANALYSIS OF FACTORS WHICH AFFECTING THE ECONOMIC GROWTH

    Directory of Open Access Journals (Sweden)

    Suparna Wijaya

    2017-03-01

    Full Text Available High economic growth and sustainable process are main conditions for sustainability of economic country development. They are also become measures of the success of the country's economy. Factors which tested in this study are economic and non-economic factors which impacting economic development. This study has a goal to explain the factors that influence on macroeconomic Indonesia. It used linear regression modeling approach. The analysis result showed that Tax Amnesty, Exchange Rate, Inflation, and interest rate, they jointly can bring effect which amounted to 77.6% on economic growth whereas the remaining 22.4% is the influenced by other variables which not observed in this study. Keywords: tax amnesty, exchange rates, inflation, SBI and economic growth

  7. The distribution of alternative agents for targeted radiotherapy within human neuroblastoma spheroids

    International Nuclear Information System (INIS)

    Mairs, R.J.; Gaze, M.N.; Murray, T.; Reid, R.; McSharry, C.; Babich, J.W.

    1991-01-01

    This study aims to select the radiopharmaceutical vehicle for targeted radiotherapy of neuroblastoma which is most likely to penetrate readily the centre of micrometastases in vivo. The human neuroblastoma cell line NB1-G, grown as multicellular spheroids provided an in vitro model for micrometastases. The radiopharmaceuticals studied were the catecholamine analogue metaiodobenzyl guanidine (mIBG), a specific neuroectodermal monoclonal antibody (UJ13A) and β nerve growth factor (βNGF). Following incubation of each drug with neuroblastoma spheroids, autoradiographs of frozen sections were prepared to demonstrate their relative distributions. mIBG and βNGF were found to penetrate the centre of spheroids readily although the concentration of mIBG greatly exceeded that of βNGF. In contrast, UJ13A was only bound peripherally. We conclude that mIBG is the best available vehicle for targeted radiotherapy of neuroblastoma cells with active uptake mechanisms for catecholimines. It is suggested that radionuclides with a shorter range of emissions than 131 I may be conjugated to benzyl guanidine to constitute more effective targeting agents with potentially less toxicity to adjacent normal tissues. (author)

  8. Physiological factors influencing capillary growth.

    Science.gov (United States)

    Egginton, S

    2011-07-01

    (1) Angiogenesis (growth of new capillaries from an existing capillary bed) may result from a mismatch in microvascular supply and metabolic demand (metabolic error signal). Krogh examined the distribution and number of capillaries to explore the correlation between O(2) delivery and O(2) consumption. Subsequently, the heterogeneity in angiogenic response within a muscle has been shown to reflect either differences in fibre type composition or mechanical load. However, local control leads to targetted angiogenesis in the vicinity of glycolytic fibre types following muscle stimulation, or oxidative fibres following endurance training, while heterogeneity of capillary spacing is maintained during ontogenetic growth. (2) Despite limited microscopy resolution and lack of specific markers, Krogh's interest in the structure of the capillary wall paved the way for understanding the mechanisms of capillary growth. Angiogenesis may be influenced by the response of perivascular or stromal cells (fibroblasts, macrophages and pericytes) to altered activity, likely acting as a source for chemical signals modulating capillary growth such as vascular endothelial growth factor. In addition, haemodynamic factors such as shear stress and muscle stretch play a significant role in adaptive remodelling of the microcirculation. (3) Most indices of capillarity are highly dependent on fibre size, resulting in possible bias because of scaling. To examine the consequences of capillary distribution, it is therefore helpful to quantify the area of tissue supplied by individual capillaries. This allows the spatial limitations inherent in most models of tissue oxygenation to be overcome generating an alternative approach to Krogh's tissue cylinder, the capillary domain, to improve descriptions of intracellular oxygen diffusion. © 2010 The Author. Acta Physiologica © 2010 Scandinavian Physiological Society.

  9. Radiotherapy of bronchogenic carcinoma

    International Nuclear Information System (INIS)

    Heilmann, H.P.

    1982-01-01

    Radiotherapy of branchogenic carcinoma comprises; palliative treatment, postoperative or pre-operative radiotherapy, radiotherapy as part of a combination of chemotherapy and radiotherapy of small cell carcinoma and curative radiotherapy of non-operable non-small cell carcinoma. Atelectasis and obstruction are indications for palliative radiotherapy. Postoperative radiotherapy is given only in cases of incomplete resection or mediastinal metastases. In the treatment of small cell carcinoma by combined irradiation and chemotherapy the mediastinum and primary tumour are irradiated, generally after chemotherapy, and the C.N.S. receives prophylactic radiotherapy. Curative radiotherapy is indicated in cases of non-operable small cell carcinoma. Irradiation with doses of 60-70 Gy produced 5-years-survival rates of 10-14% in cases classified as T 1 -T 2 N 0 M 0 . (orig.) [de

  10. Prognostic factors of inoperable localized lung cancer treated by high dose radiotherapy

    International Nuclear Information System (INIS)

    Schaake-Koning, C.S.; Schuster-Uitterhoeve, L.; Hart, G.; Gonzalez, D.G.

    1983-01-01

    A retrospective study was made of the results of high dose radiotherapy (greater than or equal to 50 Gy) given to 171 patients with inoperable, intrathoracic non small cell lung cancer from January 1971-April 1973. Local control was dependent on the total tumor dose: after one year local control was 63% for patients treated with >65 Gy, the two year local control was 35%. If treated with 2 , the one year local control was 72%; the two year local control was 44%. Local control was also influenced by the performance status, by the localization of the primary tumor in the left upper lobe and in the periphery of the lung. Local control for tumors in the left upper lobe and in the periphery of the lung was about 70% after one year, and about 40% after two years. The one and two years survival results were correlated with the factors influencing local control. The dose factor, the localization factors and the performance influenced local control independently. Tumors localized in the left upper lobe did metastasize less than tumors in the lower lobe, or in a combination of the two. This was not true for the right upper lobe. No correlation between the TNM system, pathology and the prognosis was found

  11. Radiotherapy physics

    International Nuclear Information System (INIS)

    Chen, G.T.Y.; Collier, J.M.; Lyman, J.T.; Pitluck, S.

    1982-01-01

    The Radiotherapy Physics Group works on the physical and biophysical aspects of charged particle radiotherapy. Our activities include the development of isosurvival beams (beams of uniform biological effect), computerized treatment planning development for charged particle radiotherapy, design of compensation to shape dose distributions, and development of dosimetry techniques to verify planned irradiations in both phantoms and patients

  12. Postoperative radiotherapy in salivary ductal carcinoma: a single institution experience

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Hyung; Kim, Mi Sun; Choi, Seo Hee; Suh, Yang Gun; Koh, Yoon Woo; Kim, Se Hun; Choi, Eun Chang; Keum, Ki Chang [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-09-15

    We reviewed treatment outcomes and prognostic factors for patients with salivary ductal carcinoma (SDC) treated with surgery and postoperative radiotherapy from 2005 to 2012. A total of 16 patients were identified and 15 eligible patients were included in analysis. Median age was 61 years (range, 40 to 71 years) and 12 patients (80%) were men. Twelve patients (80%) had a tumor in the parotid gland, 9 (60%) had T3 or T4 disease, and 9 (60%) had positive nodal disease. All patients underwent surgery and postoperative radiotherapy. Postoperative radiotherapy was delivered using 3-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Locoregional failure-free survival (LRFFS), distant failure-free survival (DFFS), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Differences in survival based on risk factors were tested using a log-rank test. Median total radiotherapy dose was 60 Gy (range, 52.5 to 63.6 Gy). Four patients received concurrent weekly chemotherapy with cisplatin. Among 10 patients who underwent surgery with neck dissection, 7 received modified radical neck dissection. With a median follow-up time of 38 months (range, 24 to 105 months), 4-year rates were 86% for LRFFS, 51% for DFFS, 46% for PFS, and 93% for OS. Local failure was observed in 2 patients (13%), and distant failure was observed in 7 (47%). The lung was the most common involved site of distant metastasis. Surgery and postoperative radiotherapy in SDC patients resulted in good local control, but high distant metastasis remained a major challenge.

  13. New algorithm for risk analysis in radiotherapy

    International Nuclear Information System (INIS)

    Torres, Antonio; Montes de Oca, Joe

    2015-01-01

    Risk analyses applied to radiotherapy treatments have become an undeniable necessity, considering the dangers generated by the combination of using powerful radiation fields on patients and the occurrence of human errors and equipment failures during these treatments. The technique par excellence to execute these analyses has been the risk matrix. This paper presents the development of a new algorithm to execute the task with wide graphic and analytic potentialities, thus transforming it into a very useful option for risk monitoring and the optimization of quality assurance. The system SECURE- MR, which is the basic software of this algorithm, has been successfully used in risk analysis regarding different kinds of radiotherapies. Compared to previous methods, It offers new possibilities of analysis considering risk controlling factors as the robustness of reducers of initiators frequency and its consequences. Their analytic capacities and graphs allow novel developments to classify risk contributing factors, to represent information processes as well as accidental sequences. The paper shows the application of the proposed system to a generic process of radiotherapy treatment using a lineal accelerator. (author)

  14. Neural Stem Cell Differentiation Using Microfluidic Device-Generated Growth Factor Gradient.

    Science.gov (United States)

    Kim, Ji Hyeon; Sim, Jiyeon; Kim, Hyun-Jung

    2018-04-11

    Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro , we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.

  15. Esophageal perforation during or after conformal radiotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Chen Haiyan; Ma Xiumei; Ye Ming; Hou Yanli; Xie Huaying; Bai Yongrui

    2014-01-01

    The aim of this study was to analyze the risk factors and prognosis for patients with esophageal perforation occurring during or after radiotherapy for esophageal carcinoma. We retrospectively analyzed 322 patients with esophageal carcinoma. These patients received radiotherapy for unresectable esophageal tumors, residual tumors after operation, or local recurrence. Of these, 12 had radiotherapy to the esophagus before being admitted, 68 patients had concurrent chemoradiotherapy (CRT), and 18 patients had esophageal perforation after RT (5.8%). Covered self-expandable metallic stents were placed in 11 patients. Two patients continued RT after stenting and control of infection; one of these suffered a new perforation, and the other had a massive hemorrhage. The median overall survival was 2 months (0-3 months) compared with 17 months in the non-perforation group. In univariate analysis, the Karnofsky performance status (KPS) being ≤ 70, age younger than 60, T4 stage, a second course of radiotherapy to the esophagus, extracapsular lymph nodes (LN) involving the esophagus, a total dose > 100 Gy (biologically effective dose -10 ), and CRT were risk factors for perforation. In multivariate analysis, age younger than 60, extracapsular LN involving the esophagus, T4 stage, and a second course of radiotherapy to the esophagus were risk factors. In conclusion, patients with T4 stage, extracapsular LN involving the esophagus, and those receiving a second course of RT should be given particular care to avoid perforation. The prognosis after perforation was poor. (author)

  16. Cervix cancer: clinical aspects of tumoral control and radiotherapy treatment time

    International Nuclear Information System (INIS)

    Petitto, J.V.

    1994-01-01

    The author analyzed 35 patients with recurrence or residual tumor at the end of the radiotherapy program. These patients were selected out of a group of 338 patients cervix cancer who had also undergone on the same radiotherapy program. Those patients were compared with control group of 30 patients without clinical evidence of the disease, from the same group of 338 patients. It has studied the clinical results considering the total radiotherapy time to developed the radiation program and factors that could modify the time for a longer program, and also modify the final survival results. No significant difference was shown in this study, but it should be taken in consideration the total radiotherapy time, because this is a factor that could change the final results if the time would be longer than what was shown in this work. (author). 26 refs, 10 tabs

  17. Cow placenta extract promotes murine hair growth through enhancing the insulin - like growth factor-1

    Directory of Open Access Journals (Sweden)

    Dongliang Zhang

    2011-01-01

    Full Text Available Background: Hair loss is seen as an irreversible process. Most research concentrates on how to elongate the anagen, reduce the negative factors of obstructing hair growth and improve the hair number and size. Aim: In our experiment, we tried to prove that the cow placenta extract can promote hair growth by elongating hair shaft and increasing hair follicle number. Materials and Methods: Cow placenta extract (CPE, water and minoxidil applied separately on the back of depilated B57CL/6 mice for the case, negative and positive control respectively. We checked the proliferation of cells which are resident in hair sheath, and the expression of a few growth factors which stimulate hair growth. Results: Result shows that placenta extract more efficiently accelerates cell division and growth factor expression, by raising the insulin-like growth factor (IGF-1 mRNA and protein level to increase HF size and hair length. Conclusions: The extract is not a purified product; so, it is less effective than minoxidil, which is approved by the US FDA for the treatment of male pattern baldness. If refinement is done, the placenta extract would be a good candidate medicine for hair loss.

  18. Bilateral Rhegmatogenous Retinal Detachment during External Beam Radiotherapy

    Directory of Open Access Journals (Sweden)

    Takako Hidaka

    2016-06-01

    Full Text Available Herein, we report a case of nontraumatic bilateral rhegmatogenous retinal detachment (RRD during external beam radiotherapy for nonocular tumor, presented as an observational case study in conjunction with a review of the relevant literature. A 65-year-old male was referred to our hospital due to bilateral RRD. He underwent a biopsy for a tumor of the left frontal lobe 4 months prior to presentation, and the tumor had been diagnosed as primary central nerve system B-cell type lymphoma. He received chemotherapy and external beam radiotherapy for 1 month. There were no traumatic episodes. Bilateral retinal detachment occurred during a series of radiotherapies. Simultaneous nontraumatic bilateral retinal detachment is rare. The effects of radiotherapy on ocular functionality, particularly in cases involving retinal adhesion and vitreous contraction, may include RRD. Thus, it is necessary to closely monitor the eyes of patients undergoing radiotherapy, particularly those undergoing surgery for retinal detachment and those with a history of photocoagulation for retinal tears, a relevant family history, or risk factors known to be associated with RRD.

  19. Nerve growth factor mRNA in brain: localization by in situ hybridization

    International Nuclear Information System (INIS)

    Rennert, P.D.; Heinrich, G.

    1986-01-01

    Nerve Growth Factor is a 118 amino acid polypeptide that plays an important role in the differentiation and survival of neurons. The recent discovery that a mRNA that encodes beta Nerve Growth Factor is present in brain suggests that the Nerve Growth Factor gene may not only regulate gene expression of peripheral but also of central neurons. To identify the site(s) of Nerve Growth Factor mRNA production in the brain and to determine which cells express the Nerve Growth Factor gene, the technique of in situ hybridization was employed. A 32P-labeled RNA probe complementary to Nerve Growth Factor mRNA hybridized to cells in the stratum granulosum of the dentate gyrus and the stratum pyramidale of the hippocampus. These observations identify for the first time cellular sites of Nerve Growth Factor gene expression in the central nervous system, and suggest that Nerve Growth Factor mRNA is produced by neurons

  20. Molecular characterization of transforming growth factor-beta3

    NARCIS (Netherlands)

    Dijke, ten P.

    1991-01-01

    Normal tissue homeostasis is controlled by a critical balance of positive and negative modulators. Chapter 2 gives an overview of the molecular aspects of growth control, in particular the role of growth factors and oncogene and anti-oncogene products. Uncontrolled growth of cancer cells

  1. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor beta induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  2. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  3. Epidermal Growth Factor and Intestinal Barrier Function

    Directory of Open Access Journals (Sweden)

    Xiaopeng Tang

    2016-01-01

    Full Text Available Epidermal growth factor (EGF is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.

  4. Effects of basic fibroblast growth factor and insulin-like growth factor on cultured cartilage cells from skate Raja porasa

    Science.gov (United States)

    Fan, Tingjun; Jin, Lingyun; Wang, Xiaofeng

    2003-12-01

    Effects of basic fibroblast growth factor (bFGF) and insulin-like growth factor II (IGF-II) on cartilage cells from proboscis of skate, Raja porasa Günther, were investigated in this study. The cartilage cells were cultured in 20% FBS-supplemented MEM medium at 24°C. Twelve hours after culture initiation, the cartilage cells were treated with bFGF and IGF-II at different concentration combinations. It was found that 20 ng/ml of bFGF or 80 ng/ml of IGF-II was enough to have obvious stimulating effect on the growth and division of skate cartilage cells. Test of bFGF and IGF-II together, revealed that 20 ng/ml of bFGF and 80 ng/ml of IGF-II together had the best stimulating effect on the growth and division of skate cartilage cells. The cartilage cells cultured could form a monolayer at day 7.

  5. The effects of radiotherapy and surgery on the sexual function of women treated for cervical cancer

    International Nuclear Information System (INIS)

    Flay, Linda D.; Matthews, John H.L.

    1995-01-01

    Purpose: This study investigated the short- and medium-term effects of pelvic radiotherapy and surgery on the sexual function of women treated for cervical cancer. Methods and Materials: Sixteen women with Stages I, II, or III disease referred for radiotherapy treatment were assessed. Six had undergone prior hysterectomy. The women were assessed with questionnaires prior to radiotherapy, at completion of radiotherapy, and at 6 weeks and 14 weeks after radiotherapy treatment. The clinical findings at routine follow-up were noted. Results: The study showed significant changes in sexual activity and satisfaction as a result of treatment. This was due to a number of physical and psychological factors. The level of sexual activity was lowest at completion of radiotherapy treatment. A feeling of vaginal shortening was the most frequent reason and was more common in women who were treated with surgery and radiotherapy. Dyspareunia, bleeding, and concern of bleeding and/or recurrence were all significant factors. Conclusions: The questionnaires were an effective way of assessing women's sexual function. Radiotherapy caused sexual dysfunction in one-half of women. Combined treatment with radiotherapy and surgery results in a higher risk than radiotherapy alone. Women with cervical cancer and undergoing radiotherapy treatment require considerable counseling and support

  6. Photodynamic therapy-generated vaccines prevent tumor recurrence after radiotherapy

    International Nuclear Information System (INIS)

    Korbelik, M.; Sun, J.

    2003-01-01

    Photodynamic therapy (PDT), an established clinical modality for a variety of malignant and non-malignant diseases, inflicts photoreactive drug-mediated oxidative stress that prompts the engagement of host inflammatory and immune responses which contribute to the therapy outcome. Recently, it has become evident that in vitro PDT-treated tumor cells or their lysates can be utilized as an effective vaccine against established tumors of the same origin. The mechanism underlying the vaccine action appears to be based on eliciting immune recognition of the tumor and developing an efficient immune response even against poorly immunogenic tumors. This study examined whether PDT-generated vaccines can be effectively combined with radiotherapy. Subcutaneous SCCVII tumors (squamous cell carcinomas) growing in syngeneic C3H/HeN mice were treated by radiotherapy (60 Gy x-ray dose). PDT-vaccine treatment, done by peritumoral injection of in vitro PDT-treated SCCVII cells (20 million/mouse), was performed either immediately after radiotherapy or ten days later. The mice were then observed for tumor regression/recurrence. The tumors treated with radiotherapy alone shrunk and became impalpable for a brief period after which they all recurred. In contrast, vaccination performed at 10 days post radiotherapy delayed tumor recurrence and prevented it in one of six mice. Even better results were obtained with mice vaccinated immediately after radiotherapy, with mice showing not only a delayed tumor recurrence but also no sign of tumor in 50% of mice. The PDT-vaccine treatment without radiotherapy produced in this trial a significant tumor growth retardation but no complete regressions. These results indicate that PDT-generated vaccines can ensure immune rejection of cancer once the lesion size is reduced by radiotherapy. Even without obtaining a systemic immunity for the elimination of disseminated malignant deposits, these findings suggest that PDT-vaccines can improve local control

  7. Radiotherapy

    International Nuclear Information System (INIS)

    Zedgenidze, G.A.; Kulikov, V.A.; Mardynskij, Yu.S.

    1984-01-01

    The technique for roentgenotopometric and medicamentous preparation of patients for radiotherapy has been reported in detail. The features of planning and performing of remote, intracavitary and combined therapy in urinary bladder cancer are considered. The more effective methods of radiotherapy have been proposed taking into account own experience as well as literature data. The comparative evaluation of treatment results and prognosis are given. Radiation pathomorphism of tumors and tissues of urinary bladder is considered in detail. The problems of diagnosis, prophylaxis and treatment of complications following radiodiagnosis and radiotherapy in patients with urinary bladder cancer are illustrated widely

  8. Dosimetry audits and intercomparisons in radiotherapy: A Malaysian profile

    International Nuclear Information System (INIS)

    Noor, Noramaliza M.; Nisbet, A.; Hussein, M.; Chu S, Sarene; Kadni, T.; Abdullah, N.; Bradley, D.A.

    2017-01-01

    Quality audits and intercomparisons are important in ensuring control of processes in any system of endeavour. Present interest is in control of dosimetry in teletherapy, there being a need to assess the extent to which there is consistent radiation dose delivery to the patient. In this study we review significant factors that impact upon radiotherapy dosimetry, focusing upon the example situation of radiotherapy delivery in Malaysia, examining existing literature in support of such efforts. A number of recommendations are made to provide for increased quality assurance and control. In addition to this study, the first level of intercomparison audit i.e. measuring beam output under reference conditions at eight selected Malaysian radiotherapy centres is checked; use being made of 9 µm core diameter Ge-doped silica fibres (Ge-9 µm). The results of Malaysian Secondary Standard Dosimetry Laboratory (SSDL) participation in the IAEA/WHO TLD postal dose audit services during the period between 2011 and 2015 will also been discussed. In conclusion, following review of the development of dosimetry audits and the conduct of one such exercise in Malaysia, it is apparent that regular periodic radiotherapy audits and intercomparison programmes should be strongly supported and implemented worldwide. The programmes to-date demonstrate these to be a good indicator of errors and of consistency between centres. A total of ei+ght beams have been checked in eight Malaysian radiotherapy centres. One out of the eight beams checked produced an unacceptable deviation; this was found to be due to unfamiliarity with the irradiation procedures. Prior to a repeat measurement, the mean ratio of measured to quoted dose was found to be 0.99 with standard deviation of 3%. Subsequent to the repeat measurement, the mean distribution was 1.00, and the standard deviation was 1.3%. - Highlights: • We review significant factors that impact upon radiotherapy dosimetry, • We carried out the

  9. All delays before radiotherapy risk progression of Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Tsang, G.; O'Brien, P.; Robertson, R.; Hamilton, C.; Wratten, C.; Denham, J.

    2004-01-01

    Prolonged waiting times for radiotherapy have resulted in many centres assigning priorities to various patient or diagnostic groups. A high risk of progression on a waiting list is one factor that would reasonably influence the priority. The present descriptive study of 27 patients with Merkel cell carcinoma (MCC) found that a median wait of 24 days for radiotherapy is associated with a high risk of progression. Eleven (41%) of 27 patients developed progressive disease, including five (45%) of 11 patients waiting for adjuvant radiotherapy. Patients treated adjuvantly also had longer waiting times prior to their initial radiotherapy consultation (median 41 days), which may have contributed to the rate of progression. Merkel cell carcinoma is an aggressive but curable malignancy and appropriate management should include efforts to minimize all potential delays prior to the commencement of radiotherapy. Copyright (2004) Blackwell Science Pty Ltd

  10. Factors influencing the treatment outcome for patients with T2N0 glottic carcinoma treated by definitive radiotherapy

    International Nuclear Information System (INIS)

    Fukuda, Ichiro; Kanehira, Chihiro; Kobayashi, Masao; Aoki, Manabu; Takagi, Sayako; Shirahama, Jun; Honda, Chikara

    2007-01-01

    The purpose of this study was to determine the prognostic factors affecting local outcomes for patients with T2N0 glottic carcinoma treated by definitive radiotherapy. A total of 48 patients with T2N0 squamous cell carcinoma treated by definitive radiotherapy between 1992 and 2005 were studied. Cumulative probability of overall survival, cause-specific survival, local control and larynx-preserving were calculated according the Kaplan-Meier method, and the prognostic significance of patient's age, number of subsites involved, impaired cord mobility, anterior commisure involved, total dose and overall treatment time were analyzed using the log-rank test in univariate analysis and Cox regression in multivariate analysis. Follow-up ranged from 13 to 141 months (median, 62 months). Five-year survivals were: overall, 95.3%; cause-specific, 97.9% and five years rates were local control, 61.4%; larynx-preserving, 76.4%. Multivariate analyses of the six parameters showed that overall treatment time significantly influenced the probability of local control, and impaired mobility and overall treatment time affected the probability of larynx-preserving. Our study showed that longer overall treatment time significantly worsened the percentage of local control and larynx-preserving for patients with T2N0 glottic carcinoma treated with definitive radiotherapy. Therefore, we suggest treating, the patients in a shorter treatment course. (author)

  11. Proposal for development of a system for planning radiotherapy of gliomas

    International Nuclear Information System (INIS)

    Caldeira, Alexandre D.

    2015-01-01

    In the last three years, discussions were held on several topics in Nuclear Medicine area, starting with the nuclear data processing, passing by deterministic and stochastic mathematical methods, and finalizing with computer simulations of the following phenomena: neutron transport, applied to boron neutron capture therapy, and neutron diffusion, to study growth of tumor cells. From a mathematical model applied to radiotherapy of gliomas available in literature, it is proposed a strategy for development of a computer system to assist the planning radiotherapy of gliomas. (author)

  12. Vascular endothelial growth factors and angiogenesis in eye disease

    NARCIS (Netherlands)

    Witmer, A. N.; Vrensen, G. F. J. M.; van Noorden, C. J. F.; Schlingemann, R. O.

    2003-01-01

    The vascular endothelial growth factor (VEGF) family of growth factors controls pathological angiogenesis and increased vascular permeability in important eye diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). The purpose of this review is to develop new insights

  13. Platelet-derived growth factor inhibits platelet activation in heparinized whole blood.

    Science.gov (United States)

    Selheim, F; Holmsen, H; Vassbotn, F S

    1999-08-15

    We previously have demonstrated that human platelets have functionally active platelet-derived growth factor alpha-receptors. Studies with gel-filtered platelets showed that an autocrine inhibition pathway is transduced through this tyrosine kinase receptor during platelet activation. The physiological significance of this inhibitory effect of platelet-derived growth factor on gel-filtered platelets activation is, however, not known. In the present study, we investigated whether platelet-derived growth factor inhibits platelet activation under more physiological conditions in heparinized whole blood, which represents a more physiological condition than gel-filtered platelets. Using flow cytometric assays, we demonstrate here that platelet-derived growth factor inhibits thrombin-, thrombin receptor agonist peptide SFLLRN-, and collagen-induced platelet aggregation and shedding of platelet-derived microparticles from the platelet plasma membrane during platelet aggregation in stirred heparinized whole blood. The inhibitory effect of platelet-derived growth factor was dose dependent. However, under nonaggregating conditions (no stirring), we could not demonstrate any significant effect of platelet-derived growth factor on thrombin- and thrombin receptor agonist peptide-induced platelet surface expression of P-selectin. Our results demonstrate that platelet-derived growth factor appears to be a true antithrombotic agent only under aggregating conditions in heparinized whole blood.

  14. Role of peptide growth factors in the rhythm of change hair

    Directory of Open Access Journals (Sweden)

    A. A. Kubanov

    2015-01-01

    Full Text Available The article presents current data on the role growth factors play in hair physiology. Based on a review of literature, the authors described the role growth factors play for initiating, suppressing the growth and differentiating hair follicles. According to them, each morphologic development stage of hair follicles is characterized by its own factor expression pattern. Referring to experimental and clinical studies, the authors describe the role some growth factors play for mechanisms promoting the development of androgynous and focal alopecia.

  15. Radiotherapy of brain metastases and glioblastomas in elderly patients; Radiotherapie des metastases cerebrales et des glioblastomes chez le sujet age

    Energy Technology Data Exchange (ETDEWEB)

    Lauche, O.; Kerr, C.; Riou, O.; Dhermain, F. [Institut Gustave-Roussy, Villejuif (France)

    2011-10-15

    As the occurrence of malignant gliomas and brain metastases is increasing in elderly people, the authors report the definition of an optimal therapeutic strategy for these patients. For patients in good health condition, a prospective randomized showed a modest benefit of radiotherapy alone with respect to support cares in terms of survival. The radiotherapy scheme is discussed in terms of dose and number of fractions. It seems that the physiological age is a strong prognosis factor. Short communication

  16. Evaluation of Risk Factors for Vertebral Compression Fracture after Carbon-Ion Radiotherapy for Primary Spinal and Paraspinal Sarcoma

    Directory of Open Access Journals (Sweden)

    Yoshihiro Matsumoto

    2017-01-01

    Full Text Available Background and Purpose. Carbon-ion radiotherapy (C-ion RT was effective therapy for inoperable spinal and paraspinal sarcomas. However, a significant adverse event following radiotherapies is vertebral compression fractures (VCFs. In this study, we investigated the incidence of and risk factors for post-C-ion RT VCFs in patients with spinal or paraspinal sarcomas. Material and Methods. Thirty consecutive patients with spinal or paraspinal sarcomas treated with C-ion RT were retrospectively reviewed. Various clinical parameters and the Spinal Instability Neoplastic Score (SINS were used to evaluate the risk factors for post-C-ion RT VCFs. Results. The overall incidence of VCFs was 23% (median time: 7 months. Patients with VCFs showed a markedly higher SINS score (median value, 9 points than those without VCF (5 points. The area under the receiver operating characteristic curve for the SINS score was 0.88, and the optimum SINS cut-off score was 8 points. The cumulative incidence of VCFs at 1 year was 9% for patients with a SINS score under 8 points, versus 80% for those with a SINS score of 8 points or higher (p<0.0001. Conclusions. In patients with a SINS score of 8 points or higher, referral to a spine surgeon for stabilization and multidisciplinary discussion is appropriate.

  17. Quinones are growth factors for the human gut microbiota.

    Science.gov (United States)

    Fenn, Kathrin; Strandwitz, Philip; Stewart, Eric J; Dimise, Eric; Rubin, Sarah; Gurubacharya, Shreya; Clardy, Jon; Lewis, Kim

    2017-12-20

    The human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables growth of uncultured species, suggesting the existence of growth factors in the natural environment not found in traditional cultivation media. One source of growth factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial growth factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel growth factors. By testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an "induced" isolate formed a gradient of growth around a cultivatable "helper." This set included two novel species Faecalibacterium sp. KLE1255-belonging to the anti-inflammatory Faecalibacterium genus-and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically. Our data show that menaquinones are a major class of growth factors for bacteria

  18. Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats

    DEFF Research Database (Denmark)

    Olsen, Peter Skov; Boesby, S.; Kirkegaard, P.

    2013-01-01

    The role of epidermal growth factor on liver regeneration after partial hepatectomy in rats was investigated. After a 70% hepatectomy in rats, the concentration of epidermal growth factor in portal venous blood was unchanged compared with unoperated controls. However, small amounts of epidermal...... growth factor could be identified in portal venous blood after intestinal instillation of epidermal growth factor. Brunner's glands and the submandibular glands secrete epidermal growth factor. Extirpation of Brunner's glands decreased liver regeneration, whereas removal of the submandibular glands had...... no effect on liver regeneration. Epidermal growth factor antiserum reduced liver regeneration significantly. Oral or s.c. administration of epidermal growth factor had no effect on liver regeneration, whereas epidermal growth factor enhanced the effect of insulin and glucagon on liver regeneration...

  19. Effect of radiation in radiotherapy

    International Nuclear Information System (INIS)

    Hirata, Hideki; Fujibuchi, Toshio; Saito, Tsutomu

    2013-01-01

    The title subject is easily explained for the deterministic effect, secondary cancer formation and case reports of accidental exposure at radiotherapy. For the deterministic effect, the dose-effect relationship is sigmoidal in normal and cancer tissues, and the more separated are their curves, the more favorable is the radiotherapy. TD 5/5 is the tolerable dose to yield <5% of irreversible radiation injury to the normal tissue within 5 years after the therapy and is generally dose-limiting. The curves are of various shapes depending on the tissue composition that its functional subunit (FSU) is parallel like lobules of the liver, or in series like neuron. Symptoms appear complicated on these factors. Recent development of CT-based therapeutic planning has made it possible to analyze the partial tissue volume to be irradiated and its absorbed dose by the relationship (dose volume histogram, DVH) between the electron density vs CT value regardless to anatomy. The normal tissue complication probability is a model composed from the physical DVH and biological factors of FSU composition and cellular radiation susceptibility, and is a measure of the irreversible late effect manifested in normal tissues. Epidemiology has shown the increased risk of secondary cancer formation by radiotherapy. Children are highly susceptible to this, and in adults undergoing the therapy of a certain cancer, it is known that the risk of radiation carcinogenesis is increased in the particular tissue. There are presented such case reports of accidental excessive exposure at radiotherapy as caused by an inappropriate use of detector, partial loss of data in a therapeutic planning device, reading of reversed MRI image, and too much repeated use of the old-type electric portal imaging device. (T.T.)

  20. Age is not a limiting factor for radical radiotherapy in pelvic malignancies

    International Nuclear Information System (INIS)

    Pignon, T.; Horiot, J.C.; Bolla, M.; Poppel, H. van; Bartelink, H.; Roelofsen, F.; Pene, F.; Gerard, A.; Einhorn, N.; Nguyen, T.D.; Vanglabbeke, M.; Scalliet, P.

    1997-01-01

    Background and purpose: Pelvic radiotherapy (RT) toxicity in the elderly is poorly documented. We developed a study aiming to evaluate whether or not a limit of age could be identified beyond which toxicities in patients receiving pelvic RT were more frequent or more severe. Material and methods: 1619 patients with pelvic cancers enrolled in nine EORTC trials, RT arms, were retrospectively studied. Patients were split into six age ranges from 50 years to 70 years and over. Survivals and late toxicity occurrence were calculated with the Kaplan-Meier method and comparison between age groups with the logrank test. A trend test was done to examine if chronological age had an impact on acute toxicity occurrence. Results: Survival was comparable in each age group for prostate (P=0.18), uterus (0.41), anal canal cancer (P=0.6) and slightly better for the younger group of rectum cancer (P=0.04). A total of 1722 acute and 514 late grade ≥1 were recorded. Acute nausea/vomiting, skin complications and performance status deterioration were significantly more frequent in younger patients. There was no trend toward more aged patients to experience diarrhea (P=0.149) and after adjustment on RT dose, acute urinary complications were observed equally in each age range (P=0.32). Eighty percent of patients were free of late complication at 5 years in each age range (P=0.79). For the grade >2 late side-effects, a plateau was observed after 1 year at near 9% without any difference (P=0.06) nor trend (P=0.13) between age-groups. Conclusion: Age per se is not a limiting factor for radical radiotherapy in pelvic malignancies

  1. Results of radiotherapy for brain metastases in old-aged patients

    International Nuclear Information System (INIS)

    Nieder, C.; Niewald, M.; Schnabel, K.

    1995-01-01

    To evaluate which patients older tahn 70 years will benefit by radiotherapy for their brain metastases the data of 35 patients in this age-group who were treated between 1983 and 1994 were retrospectivley analyzed. All patients were previously untreated and received a whole-brain irradiation and concomitantly corticosteroids. The median total dose was 30 Gy (fractionation: 10 times 3 Gy in 2 weeks). Six patients each received lower or higher total doses with 50.4 Gy at maximum. Six patients failed to complete their prescribed treatment (17%). The median survival of all patients who completed their radiotherapy course was 67 days only. Patients with extracerebral metastases had a median survival of 31 days. Survival was not dependent on total dose of radiotherapy. In 56% of all cases the general condition of the patients improved or remained stable at a high level. Karnofsky-performance status was the most important prognostic factor. Advanced age is an unfavourable prognostic factor. Only patients in good general condition without extracerebral metastases had survival times which justify radiotherapy for their brain metastases. (orig./MG) [de

  2. Nasopharynx carcinoma treatment: from the conventional radiotherapy to the conformal radiotherapy with intensity modulation; Traitement du carcinome du nasopharynx: de la radiotherapie conventionnelle a la radiotherapie conformationnelle avec modulation d'intensite

    Energy Technology Data Exchange (ETDEWEB)

    Mokaouim, K.; Grehange, G.; Truc, G.; Peingnaux, K.; Martin, E.; Zanetta, S.; Bruchon, Y.; Bonnetain, F.; Maingon, P. [Centre Georges-Francois Leclerc, 21 - Dijon (France)

    2009-10-15

    The objective of this study was to evaluate retrospectively the impact of factors linked to the radiotherapy realisation on the local and locoregional control, the global survival, the survival without disease of patients suffering of naso-pharynx carcinoma. Conclusion: the patients suffering of a nasopharynx carcinoma treated by irradiation associated to chemotherapy have an improved global survival and an improved survival without disease. The conformal radiotherapy with or without modulated intensity reduce the risk of serous otitis, trismus and xerostomia at long term. It seems necessary to realize multi centric studies with a longer period of follow up before asserting the advantages of the I.M.R.T. in comparison to the classical and conformal technique in the treatment of naso-pharynx carcinomas. (N.C.)

  3. National arrangements for radiotherapy

    International Nuclear Information System (INIS)

    2007-01-01

    After a presentation of several letters exchanged between the French health ministry and public agencies in charge of public health or nuclear safety after a radiotherapy accident in Epinal, this report comments the evolution of needs in cancerology care and the place given to radiotherapy. It outlines the technological and organisational evolution of radiotherapy and presents the distribution of radiotherapy equipment, of radio-therapists and other radiotherapy professionals in France. Within the context of radiotherapy accidents which occurred in 2007, it presents the regulatory arrangements which aimed at improving the safety, short term and middle term arrangements which are needed to support and structure radiotherapy practice quality. It stresses the fact that the system will deeply evolve by implementing a radiotherapy vigilance arrangement and a permanent follow-on and adaptation plan based on surveys and the creation of a national committee

  4. Whither radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ross, W M

    1987-03-01

    The 1986 Glyn Evans Memorial Lecture, given at the Joint Provincial Meeting of the Royal College of Radiologists, Sheffield, September 1986, sketches an outline of the history of radiotherapy and discusses the future development of the art. Topics included are siting of centres, training needs, the relationship of radiotherapy to other medical specialities, and the advantages and disadvantages of radiotherapy practitioners forming a separate medical College. (U.K.)

  5. Radiotherapy in bladder cancer

    International Nuclear Information System (INIS)

    Rozan, R.

    1992-01-01

    In 1992, the problem of the vesical radiotherapy is not resolved. The author presents the situation and the different techniques of radiotherapy in bladder cancers: external radiotherapy, only and associated with surgery, interstitial curietherapy and non-classical techniques as per operative radiotherapy, neutron therapy and concurrent radiotherapy with chemotherapy. In order to compare their efficiency, the five-year survival are given in all cases.(10 tabs)

  6. Radiotherapy of adult nodal non Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Gamen, G.; Thirion, P.

    1999-01-01

    The role of radiotherapy in the treatment of nodal non-Hodgkin's lymphoma has been modified by the introduction of efficient chemotherapy and the development of different pathological classifications. The recommended treatment of early-stage aggressive lymphomas is primarily a combination chemotherapy. The interest of adjuvant radiotherapy remains unclear and has to be established through large prospective trials. If radiation therapy has to be delivered, the historical results of exclusive radiation therapy showed that involved-fields and a dose of 35-40 Gy (daily fraction of 1.8 Gy, 5 days a week) are the optimal schedule. The interest of radiotherapy in the treatment of advanced-stage aggressive lymphoma is yet to be proven. Further studies had to stratify localized stages according to the factors of the International Prognostic Index. For easy-stage low-grade lymphoma, radiotherapy remains the standard treatment. However, the appropriate technique to use is controversial. Involved-field irradiation at a dose of 35 Gy seems to be the optimal schedule, providing a 10 year disease-free survival rate of 50 % and no major toxicity. There is no standard indication of radiotherapy in the treatment advanced-stage low-grade lymphoma. For 'new' nodal lymphoma's types, the indication of radiotherapy cannot be established (mantle-zone lymphoma, marginal zone B-cell lymphoma) or must take into account the natural history (Burkitt's lymphoma, peripheral T-cell lymphoma) and the sensibility to others therapeutic methods. (authors)

  7. Factors associated with acute and late dysphagia in the DAHANCA 6 & 7 randomized trial with accelerated radiotherapy for head and neck cancer

    DEFF Research Database (Denmark)

    Mortensen, Hanna R; Overgaard, Jens; Jensen, Kenneth

    2013-01-01

    Dysphagia is a common and debilitating side effect in head and neck radiotherapy (RT). Prognostic factors are numerous and their interrelationship not well understood. The aim of this study was to establish a multivariate prognostic model for acute and late dysphagia after RT, based on information...

  8. Rib fracture after stereotactic radiotherapy for primary lung cancer: prevalence, degree of clinical symptoms, and risk factors

    International Nuclear Information System (INIS)

    Nambu, Atsushi; Marino, Kan; Koshiishi, Tsuyota; Sawada, Eiichi; Araki, Tsutomu; Onishi, Hiroshi; Aoki, Shinichi; Tominaga, Licht; Kuriyama, Kengo; Araya, Masayuki; Saito, Ryoh; Maehata, Yoshiyasu; Komiyama, Takafumi

    2013-01-01

    As stereotactic body radiotherapy (SBRT) is a highly dose-dense radiotherapy, adverse events of neighboring normal tissues are a major concern. This study thus aimed to clarify the frequency and degree of clinical symptoms in patients with rib fractures after SBRT for primary lung cancer and to reveal risk factors for rib fracture. Appropriate α/β ratios for discriminating between fracture and non-fracture groups were also investigated. Between November 2001 and April 2009, 177 patients who had undergone SBRT were evaluated for clinical symptoms and underwent follow-up thin-section computed tomography (CT). The time of rib fracture appearance was also assessed. Cox proportional hazard modeling was performed to identify risk factors for rib fracture, using independent variables of age, sex, maximum tumor diameter, radiotherapeutic method and tumor-chest wall distance. Dosimetric details were analyzed for 26 patients with and 22 randomly-sampled patients without rib fracture. Biologically effective dose (BED) was calculated with a range of α/β ratios (1–10 Gy). Receiver operating characteristics analysis was used to define the most appropriate α/β ratio. Rib fracture was found on follow-up thin-section CT in 41 patients. The frequency of chest wall pain in patients with rib fracture was 34.1% (14/41), and was classified as Grade 1 or 2. Significant risk factors for rib fracture were smaller tumor-chest wall distance and female sex. Area under the curve was maximal for BED at an α/β ratio of 8 Gy. Rib fracture is frequently seen on CT after SBRT for lung cancer. Small tumor-chest wall distance and female sex are risk factors for rib fracture. However, clinical symptoms are infrequent and generally mild. When using BED analysis, an α/β ratio of 8 Gy appears most effective for discriminating between fracture and non-fracture patients

  9. Rib fracture after stereotactic radiotherapy for primary lung cancer: prevalence, degree of clinical symptoms, and risk factors

    Directory of Open Access Journals (Sweden)

    Nambu Atsushi

    2013-02-01

    Full Text Available Abstract Background As stereotactic body radiotherapy (SBRT is a highly dose-dense radiotherapy, adverse events of neighboring normal tissues are a major concern. This study thus aimed to clarify the frequency and degree of clinical symptoms in patients with rib fractures after SBRT for primary lung cancer and to reveal risk factors for rib fracture. Appropriate α/β ratios for discriminating between fracture and non-fracture groups were also investigated. Methods Between November 2001 and April 2009, 177 patients who had undergone SBRT were evaluated for clinical symptoms and underwent follow-up thin-section computed tomography (CT. The time of rib fracture appearance was also assessed. Cox proportional hazard modeling was performed to identify risk factors for rib fracture, using independent variables of age, sex, maximum tumor diameter, radiotherapeutic method and tumor-chest wall distance. Dosimetric details were analyzed for 26 patients with and 22 randomly-sampled patients without rib fracture. Biologically effective dose (BED was calculated with a range of α/β ratios (1–10 Gy. Receiver operating characteristics analysis was used to define the most appropriate α/β ratio. Results Rib fracture was found on follow-up thin-section CT in 41 patients. The frequency of chest wall pain in patients with rib fracture was 34.1% (14/41, and was classified as Grade 1 or 2. Significant risk factors for rib fracture were smaller tumor-chest wall distance and female sex. Area under the curve was maximal for BED at an α/β ratio of 8 Gy. Conclusions Rib fracture is frequently seen on CT after SBRT for lung cancer. Small tumor-chest wall distance and female sex are risk factors for rib fracture. However, clinical symptoms are infrequent and generally mild. When using BED analysis, an α/β ratio of 8 Gy appears most effective for discriminating between fracture and non-fracture patients.

  10. Rib fracture after stereotactic radiotherapy for primary lung cancer: prevalence, degree of clinical symptoms, and risk factors

    Science.gov (United States)

    2013-01-01

    Background As stereotactic body radiotherapy (SBRT) is a highly dose-dense radiotherapy, adverse events of neighboring normal tissues are a major concern. This study thus aimed to clarify the frequency and degree of clinical symptoms in patients with rib fractures after SBRT for primary lung cancer and to reveal risk factors for rib fracture. Appropriate α/β ratios for discriminating between fracture and non-fracture groups were also investigated. Methods Between November 2001 and April 2009, 177 patients who had undergone SBRT were evaluated for clinical symptoms and underwent follow-up thin-section computed tomography (CT). The time of rib fracture appearance was also assessed. Cox proportional hazard modeling was performed to identify risk factors for rib fracture, using independent variables of age, sex, maximum tumor diameter, radiotherapeutic method and tumor-chest wall distance. Dosimetric details were analyzed for 26 patients with and 22 randomly-sampled patients without rib fracture. Biologically effective dose (BED) was calculated with a range of α/β ratios (1–10 Gy). Receiver operating characteristics analysis was used to define the most appropriate α/β ratio. Results Rib fracture was found on follow-up thin-section CT in 41 patients. The frequency of chest wall pain in patients with rib fracture was 34.1% (14/41), and was classified as Grade 1 or 2. Significant risk factors for rib fracture were smaller tumor-chest wall distance and female sex. Area under the curve was maximal for BED at an α/β ratio of 8 Gy. Conclusions Rib fracture is frequently seen on CT after SBRT for lung cancer. Small tumor-chest wall distance and female sex are risk factors for rib fracture. However, clinical symptoms are infrequent and generally mild. When using BED analysis, an α/β ratio of 8 Gy appears most effective for discriminating between fracture and non-fracture patients. PMID:23391264

  11. Rib fracture after stereotactic radiotherapy for primary lung cancer: prevalence, degree of clinical symptoms, and risk factors.

    Science.gov (United States)

    Nambu, Atsushi; Onishi, Hiroshi; Aoki, Shinichi; Tominaga, Licht; Kuriyama, Kengo; Araya, Masayuki; Saito, Ryoh; Maehata, Yoshiyasu; Komiyama, Takafumi; Marino, Kan; Koshiishi, Tsuyota; Sawada, Eiichi; Araki, Tsutomu

    2013-02-07

    As stereotactic body radiotherapy (SBRT) is a highly dose-dense radiotherapy, adverse events of neighboring normal tissues are a major concern. This study thus aimed to clarify the frequency and degree of clinical symptoms in patients with rib fractures after SBRT for primary lung cancer and to reveal risk factors for rib fracture. Appropriate α/β ratios for discriminating between fracture and non-fracture groups were also investigated. Between November 2001 and April 2009, 177 patients who had undergone SBRT were evaluated for clinical symptoms and underwent follow-up thin-section computed tomography (CT). The time of rib fracture appearance was also assessed. Cox proportional hazard modeling was performed to identify risk factors for rib fracture, using independent variables of age, sex, maximum tumor diameter, radiotherapeutic method and tumor-chest wall distance. Dosimetric details were analyzed for 26 patients with and 22 randomly-sampled patients without rib fracture. Biologically effective dose (BED) was calculated with a range of α/β ratios (1-10 Gy). Receiver operating characteristics analysis was used to define the most appropriate α/β ratio. Rib fracture was found on follow-up thin-section CT in 41 patients. The frequency of chest wall pain in patients with rib fracture was 34.1% (14/41), and was classified as Grade 1 or 2. Significant risk factors for rib fracture were smaller tumor-chest wall distance and female sex. Area under the curve was maximal for BED at an α/β ratio of 8 Gy. Rib fracture is frequently seen on CT after SBRT for lung cancer. Small tumor-chest wall distance and female sex are risk factors for rib fracture. However, clinical symptoms are infrequent and generally mild. When using BED analysis, an α/β ratio of 8 Gy appears most effective for discriminating between fracture and non-fracture patients.

  12. Therapeutic effect of angiogenesis inhibitor combined with radiotherapy on liver metastasis model of colon cancer

    International Nuclear Information System (INIS)

    Jin Liugen; Zhou Shifu

    2005-01-01

    Objective: To observe the therapeutic effect of angiogenesis inhibitor combined with radiotherapy on liver metastasis model of colon cancer. Methods: Nude mice liver metastasis model of colon cancer was established with human colon cancer cells line (LS174T) inoculated into mice' spleen and followed by splenectomy. Angiogenesis inhibitor 2-ME and radiotherapy were administered after-wads. The growth inhibition effect on metastases and neovessel was examined. Results: The incidences of liver metastasis were 100% in this intrasplenic injection model. The mean weight and microvessel density 4 weeks after inoculation were 53.6 ± 4.7 mg, 8.4 ± 1.7 in treatment group as compared to 173.9 ± 11.6 mg, 41.2 ± 6.3 in control group respectively. Conclusion: 2-ME combined with radiotherapy has significant inhibition on the growth of liver metastases. Angiogenesis inhibition is one of the mechanisms of its efficiency. (authors)

  13. National arrangements for radiotherapy; Mesures nationales pour la radiotherapie. Travail collectif des missions

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    After a presentation of several letters exchanged between the French health ministry and public agencies in charge of public health or nuclear safety after a radiotherapy accident in Epinal, this report comments the evolution of needs in cancerology care and the place given to radiotherapy. It outlines the technological and organisational evolution of radiotherapy and presents the distribution of radiotherapy equipment, of radio-therapists and other radiotherapy professionals in France. Within the context of radiotherapy accidents which occurred in 2007, it presents the regulatory arrangements which aimed at improving the safety, short term and middle term arrangements which are needed to support and structure radiotherapy practice quality. It stresses the fact that the system will deeply evolve by implementing a radiotherapy vigilance arrangement and a permanent follow-on and adaptation plan based on surveys and the creation of a national committee.

  14. Aftereffect of radiotherapy of upper aero-digestive tracts in odontological care

    International Nuclear Information System (INIS)

    Schiochet, Luc

    2010-01-01

    In its first part, this thesis proposes a detailed presentation of the upper aero-digestive tract cancer. The author defines the cancerous process, describes anatomic aspects, and discusses epidemiological aspects (occurrence, mortality, survival, and epidemiological data in different countries). In the second part, the author discusses the role of radiotherapy and of dental surgery in taking a cancerous patient into care (general principles of radiotherapy, therapeutic options and choices, association of radiotherapy, chemotherapy and surgery). Principles of radiotherapy are then more precisely addressed: physical principles (X rays, gamma rays, electrons, neutrons, and protons), radioactivity doses, radiotherapy effect, main equipment, radiotherapy techniques (conformational or intensity-modulated radiotherapy, computed tomography, Cyberknife, external radiotherapy, brachytherapy). The third part addresses early oral-facial complications induced by radiotherapy: factors favouring these complications, nervous effects, effects on the blood system and on the skin, hyposialia and xerostomia, radio-induced mucositis of upper aero-digestive tracts. The next part addresses late effects: late cutaneous after-effects, late radio-mucositis, limitation of mouth opening, tooth decays, osteoradionecrosis. The last part addresses the role of the dental surgeon in taking into care a patient whose head and neck have been irradiated: role before irradiation, during irradiation, and after irradiation [fr

  15. Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

    Science.gov (United States)

    Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

    2017-05-01

    Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

  16. To understand radiotherapy

    International Nuclear Information System (INIS)

    2009-01-01

    Dealing with the use of radiotherapy for adults, this guide indicates when a radiotherapy is suggested, how it acts, how the treatment is chosen, which are the professionals involved. It describes how an external radiotherapy takes place and its various techniques, the different types of side effects (general, specific to the treated zone, late effects). It indicates which organs can be treated by curie-therapy, the different curie-therapy treatment modalities, how a curie-therapy takes place and which are its side effects. It outlines how to better cope with radiotherapy (how to be supported, the important role of relatives, everyday life questions, rights). It indicates and comments the different measures adopted for the safety and quality of radiotherapy

  17. Detection of macroglobulins in mammary tissue prior to and following radiotherapy

    International Nuclear Information System (INIS)

    Kozlov, D.V.

    1996-01-01

    Specimens of breast cancer tissue obtained during operation were immunohistochemically examined before and after radiotherapy and compared with fibroadenoma and intact mammary gland. Statistically reliable shifts on the microglobulin protein levels were revealed in fibroadenoma: the content of alpha 2 -microglobulin (AMG) and pregnancy-associated alpha 2 -glycoprotein (PAG) was increased in the parenchyma, whereas in the stroma the level of this latter protein was decreased. In breast cancer the increase of PAG level in the parenchyma and decrease of AMG biosynthesis were still more expressed. Radiotherapy inverted the time course of these protein in cancer parenchyma and stroma. Remembering about the important role of macroglobulins in tumor growth, measurements thereof may be used as additional tests in the diagnosis of breast tumors and in assessment of radiotherapy efficacy [ru

  18. Analysis of oral cancer treated by preoperative radiotherapy

    International Nuclear Information System (INIS)

    Hosokawa, Yoichiro; Kaneko, Masayuki; Yasuda, Motoaki

    1997-01-01

    Fifty-eight patients with squamous cell carcinoma of the oral region, treated by preoperative radiotherapy between January 1988 and December 1993, were reviewed to evaluate the relation between prognosis and pathological findings after preoperative radiotherapy. All patients underwent external radiotherapy of up to 40 Gy in 16 fractions (2.5 Gy a day, 4 fractions a week) before surgery, and the average term from the end of preoperative radiotherapy to surgery were 27.3 days. According to pathological findings during surgery, the patients were divided into a radiation effective group and a radiation noneffective group. There was a significant difference in the survival rates of the two groups, but there was no difference in local control rates. After surgery, regional lymph node metastasis and distant metastasis were more common in the radiation noneffective group than in the radiation effective group. It was considered that regional lymph node metastasis after treatment in the noneffective group is the determining factor in the progress. (author)

  19. Risk of cancer formation by radiotherapy

    International Nuclear Information System (INIS)

    Fuji, Hiroshi

    2011-01-01

    Described are the difference between exposures to radiation for medical purpose and to environmental radiation at low dose, estimation of carcinogenic risk by medical radiation, and notice for referring the risk at clinical practice. ICRP employs linear non-threshold (LNT) model for risk of cancer formation even at <200 mSv for safety, with a recognition that it is scientifically obscure. The model essentially stands on data of A-bomb survivors (the Gold Standard), where the relationship between 5-10% excess relative risk (ERR) of cancer formation and dose 0.05-2.5 Sv is linear. Analyses of the secondary carcinogenesis after radiotherapy have begun to be reported since around 2005: e.g., the secondary thyroid cancer risk in pediatric patients treated with radiotherapy has a peak at 20 Gy, suggesting the actual risk depends both on the linearity of carcinogenic increase and on the exponential probability of cell death increase. On this concept, the risk of cancer formation is not always linear to dose. At the practical radiotherapy, its secondary carcinogenic risk should be estimated not only on the dose but also on other factors such as the individual organ, patient's age and attainable age/time after the treatment. In treated teen-ager patients, ERRs of mortality/Gy are 2.28 for cancers of the skin of non-malignant melanoma, 1.32 of bladder and 1.21 of thyroid and in patients of fifties, 1.15 of bladder and lung. The EER tends to become lower as the treated age is older. Pediatric cancer patients to be treated with radiotherapy should be informed about the secondary cancer that the low dose risk given by ICRP is not always appropriate, a certain cancer risk has a peak dose, and ERR of cancer mortality is not a cancer risk of an organ. Many factors like anticancers and immuno-modifiers, modify the outcome of radiotherapy and should be carefully speculated for evaluating the outcome. (T.T.)

  20. Isolation of a cDNA for a Growth Factor of Vascular Endothelial Cells from Human Lung Cancer Cells: Its Identity with Insulin‐like Growth Factor II

    Science.gov (United States)

    Hagiwara, Koichi; Kobayashi, Tatsuo; Tobita, Masato; Kikyo, Nobuaki; Yazaki, Yoshio

    1995-01-01

    We have found growth‐promoting activity for vascular endothelial cells in the conditioned medium of a human lung cancer cell line, T3M‐11. Purification and characterization of the growth‐promoting activity have been carried out using ammonium sulfate precipitation and gel‐exclusion chromatography. The activity migrated as a single peak just after ribonuclease. It did not bind to a heparin affinity column. These results suggest that the activity is not a heparin‐binding growth factor (including fibroblast growth factors) or a vascular endothelial growth factor. To identify the molecule exhibiting the growth‐promoting activity, a cDNA encoding the growth factor was isolated through functional expression cloning in COS‐1 cells from a cDNA library prepared from T3M‐11 cells. The nucleotide sequence encoded by the cDNA proved to be identical with that of insulin‐like growth factor II. PMID:7730145

  1. Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

    Science.gov (United States)

    Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

    2017-04-01

    Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O 2 , 6 h; postnatal day 7 , P7) at P14. Exposure to hypoxia led to reduced body weight ( P controls and was associated with significantly reduced plasma levels of mouse GH ( P controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain. Copyright © 2017 the American Physiological Society.

  2. Expression of transforming growth factor alpha and epidermal growth factor receptor in rat lung neoplasms induced by plutonium-239

    International Nuclear Information System (INIS)

    Stegelmeier, B.L.; Gillett, N.A.; Hahn, F.F.; Kelly, G.; Rebar, A.H.

    1994-01-01

    Ninety-two rat lung proliferative lesions and neoplasms induced by inhaled 239 PuO 2 were evaluated for aberrant expression of transforming growth factor alpha (TGF-α) and epidermal growth factor receptor (EGFR). Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the squamous cell carcinomas and 87% of the foci of alveolar epithelial squamous metaplasia than that exhibited by the normal-appearing, adjacent lung parenchyma. In contrast, only 20% of adenocarcinomas and foci of epithelial hyperplasia expressed elevated levels of TGF-α. Many neoplasms expressing TGF-α also expressed excessive levels of EGFR mRNA. Southern and DNA slot blot analyses showed that the elevated EGFR expression was not due to amplification of the EGFR gene. These data suggest that increased amounts of TGF-α were early alterations in the progression of plutonium-induced squamous cell carcinoma, and these increases may occur in parallel with overexpression of the receptor for this growth factor. Together, these alterations create a potential autocrine loop for sustaining clonal expansion of cells initiated by high-LET radiation. 44 refs., 4 figs., 1 tab

  3. Compound list: transforming growth factor beta 1 [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available transforming growth factor beta 1 TGFB1 00182 ftp://ftp.biosciencedbc.jp/archive/op...en-tggates/LATEST/Human/in_vitro/transforming_growth_factor_beta_1.Human.in_vitro.Liver.zip ...

  4. Systemic analysis of different colorectal cancer cell lines and TCGA datasets identified IGF-1R/EGFR-PPAR-CASPASE axis as important indicator for radiotherapy sensitivity.

    Science.gov (United States)

    Chen, Lin; Zhu, Zhe; Gao, Wei; Jiang, Qixin; Yu, Jiangming; Fu, Chuangang

    2017-09-05

    Insulin-like growth factor 1 receptor (IGF-1R) is proved to contribute the development of many types of cancers. But, little is known about its roles in radio-resistance of colorectal cancer (CRC). Here, we demonstrated that low IGF-1R expression value was associated with the better radiotherapy sensitivity of CRC. Besides, through Quantitative Real-time PCR (qRT-PCR), the elevated expression value of epidermal growth factor receptor (EGFR) was observed in CRC cell lines (HT29, RKO) with high radio-sensitivity compared with those with low sensitivity (SW480, LOVO). The irradiation induced apoptosis rates of wild type and EGFR agonist (EGF) or IGF-1R inhibitor (NVP-ADW742) treated HT29 and SW480 cells were quantified by flow cytometry. As a result, the apoptosis rate of EGF and NVP-ADW742 treated HT29 cells was significantly higher than that of those wild type ones, which indicated that high EGFR and low IGF-1R expression level in CRC was associated with the high sensitivity to radiotherapy. We next conducted systemic bioinformatics analysis of genome-wide expression profiles of CRC samples from the Cancer Genome Atlas (TCGA). Differential expression analysis between IGF-1R and EGFR abnormal CRC samples, i.e. CRC samples with higher IGF-1R and lower EGFR expression levels based on their median expression values, and the rest of CRC samples identified potential genes contribute to radiotherapy sensitivity. Functional enrichment of analysis of those differential expression genes (DEGs) in the Database for Annotation, Visualization and Integrated Discovery (DAVID) indicated PPAR signaling pathway as an important pathway for the radio-resistance of CRC. Our study identified the potential biomarkers for the rational selection of radiotherapy for CRC patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Association of Polymorphisms in Connective Tissue Growth Factor and Epidermal Growth Factor Receptor Genes With Human Longevity.

    Science.gov (United States)

    Donlon, Timothy A; Morris, Brian J; He, Qimei; Chen, Randi; Masaki, Kamal H; Allsopp, Richard C; Willcox, D Craig; Tranah, Gregory J; Parimi, Neeta; Evans, Daniel S; Flachsbart, Friederike; Nebel, Almut; Kim, Duk-Hwan; Park, Joobae; Willcox, Bradley J

    2017-08-01

    Growth pathways play key roles in longevity. The present study tested single-nucleotide polymorphisms (SNPs) in the connective tissue growth factor gene (CTGF) and the epidermal growth factor receptor gene (EGFR) for association with longevity. Comparison of allele and genotype frequencies of 12 CTGF SNPs and 41 EGFR SNPs between 440 American men of Japanese ancestry aged ≥95 years and 374 men of average life span revealed association with longevity at the p cases, consistent with heterozygote advantage in living to extreme old age. No associations of the most significant SNPs were observed in whites or Koreans. In conclusion, the present findings indicate that genetic variation in CTGF and EGFR may contribute to the attainment of extreme old age in Japanese. More research is needed to confirm that genetic variation in CTGF and EGFR contributes to the attainment of extreme old age across human populations. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Nerve growth factor promotes human hemopoietic colony growth and differentiation

    International Nuclear Information System (INIS)

    Matsuda, H.; Coughlin, M.D.; Bienenstock, J.; Denburg, J.A.

    1988-01-01

    Nerve growth factor (NGF) is a neurotropic polypeptide necessary for the survival and growth of some central neurons, as well as sensory afferent and sympathetic neurons. Much is now known of the structural and functional characteristics of NGF, whose gene has recently been clones. Since it is synthesized in largest amounts by the male mouse submandibular gland, its role exclusively in nerve growth is questionable. These experiments indicate that NGF causes a significant stimulation of granulocyte colonies grown from human peripheral blood in standard hemopoietic methylcellulose assays. Further, NGF appears to act in a relatively selective fashion to induce the differentiation of eosinophils and basophils/mast cells. Depletion experiments show that the NGF effect may be T-cell dependent and that NGF augments the colony-stimulating effect of supernatants from the leukemic T-cell (Mo) line. The hemopoietic activity of NGF is blocked by 125 I-polyclonal and monoclonal antibodies to NGF. The authors conclude that NGF may indirectly act as a local growth factor in tissues other than those of the nervous system by causing T cells to synthesize or secrete molecules with colony-stimulating activity. In view of the synthesis of NGF in tissue injury, the involvement of basophils/mast cells and eosinophils in allergic and other inflammatory processes, and the association of mast cells with fibrosis and tissue repair, they postulate that NGF plays an important biological role in a variety of repair processes

  7. Differential modulation of growth and phenotypic expression of chondrocytes in sparse and confluent cultures by growth factors in cartilage

    International Nuclear Information System (INIS)

    Hiraki, Y.; Inoue, H.; Asada, A.; Suzuki, F.

    1990-01-01

    The growth-promoting actions of cartilage extracts (CE) on rabbit cultured chondrocytes were studied to assess the role of local acting growth factors in the generation and expansion of highly differentiated cells. In the present study, DNA synthesis and proteoglycan synthesis in the cultured chondrocytes were monitored by flow cytofluorometry and double-isotope autoradiography by using ( 3 H)thymidine and ( 35 S)sulfate. We report here that actions of the same set of growth factors extracted from cartilage evokes differential cellular responses depending upon cell density. Growth factors in the optimal dose of CE (2 micrograms/ml) or epidermal growth factor (EGF, 40 ng/ml) did not reveal such a cell density-dependent effect on cellular proliferation. However, growth factors in CE induced proteoglycan synthesis selectively in nonproliferating and expressing cells in confluent culture

  8. Estimation of cancer risks from radiotherapy of benign diseases

    International Nuclear Information System (INIS)

    Trott, K.R.; Kamprad, F.

    2006-01-01

    Background: The effective-dose method which was proposed by the ICRP (International Commission of Radiation Protection) for the estimation of risk to the general population from occupational or environmental, low-dose radiation exposure is not adequate for estimating the risk of cancer induction by radiotherapy of malignant or nonmalignant diseases. Methods:The risk of cancer induction by radiotherapy of benign diseases should be based on epidemiologic data directly derived from follow-up studies of patients who had been given radiotherapy for nonmalignant diseases in the past. Results: Risk factors were derived from epidemiologic studies of patients treated with irradiation for nonmalignant diseases to be used for selecting treatment options and optimizing treatment procedures. Conclusion: In most cases, cancer risks estimated by the effective-dose method may overestimate the true risks by one order of magnitude, yet in other cases even may underestimate it. The proposed method using organ-specific risk factors may be more suitable for treatment planning. (orig.)

  9. Insulin-like growth factor 1 (IGF-1): a growth hormone

    Science.gov (United States)

    Laron, Z

    2001-01-01

    Aim—To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process. Methods—To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice. Results—Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100–136 cm for female and 109–138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8–9 cm in the first year of treatment, compared with 10–12 cm/year during GH treatment of IGHD. The growth rate in following years was 5–6.5 cm/year. Conclusion—IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting effect of pituitary GH. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH. PMID:11577173

  10. Increased Melanoma Growth and Metastasis Spreading in Mice Overexpressing Placenta Growth Factor

    Science.gov (United States)

    Marcellini, Marcella; De Luca, Naomi; Riccioni, Teresa; Ciucci, Alessandro; Orecchia, Angela; Lacal, Pedro Miguel; Ruffini, Federica; Pesce, Maurizio; Cianfarani, Francesca; Zambruno, Giovanna; Orlandi, Augusto; Failla, Cristina Maria

    2006-01-01

    Placenta growth factor (PlGF), a member of the vascular endothelial growth factor family, plays an important role in adult pathological angiogenesis. To further investigate PlGF functions in tumor growth and metastasis formation, we used transgenic mice overexpressing PlGF in the skin under the control of the keratin 14 promoter. These animals showed a hypervascularized phenotype of the skin and increased levels of circulating PlGF with respect to their wild-type littermates. Transgenic mice and controls were inoculated intradermally with B16-BL6 melanoma cells. The tumor growth rate was fivefold increased in transgenic animals compared to wild-type mice, in the presence of a similar percentage of tumor necrotic tissue. Tumor vessel area was increased in transgenic mice as compared to controls. Augmented mobilization of endothelial and hematopoietic stem cells from the bone marrow was observed in transgenic animals, possibly contributing to tumor vascularization. The number and size of pulmonary metastases were significantly higher in transgenic mice compared to wild-type littermates. Finally, PlGF promoted tumor cell invasion of the extracellular matrix and increased the activity of selected matrix metalloproteinases. These findings indicate that PlGF, in addition to enhancing tumor angiogenesis and favoring tumor growth, may directly influence melanoma dissemination. PMID:16877362

  11. Factors responsible for the growth of small business

    Directory of Open Access Journals (Sweden)

    JA Döckel

    2015-01-01

    Full Text Available Entrepreneurial conduct holds the key to economic growth. Thus those business that show growth and development are considered entrepreneurial, implying that SMME policy initiatives should focus on businesses with growth potential, and not the small business sector as a whole.  The success of a small business seems to depend on the intentions of the owner, together with factors associated with the ability of, and opportunity for, the specific business to grow.  The aim of this article is to make use of a multiple linear regression model to determine the variables that impact positively on business growth.  In addition to demand factors, it was established that smaller and younger businesses are the ones that grow faster. A successful business also shows a positive correlation between business management skills and entrepreneurial conduct.

  12. Experimental radiotherapy and clinical radiobiology. Vol. 18. Proceedings

    International Nuclear Information System (INIS)

    Baumann, Michael; Dahm-Daphi, Jochen; Dikomey, Ekkehard; Petersen, Cordula; Rodemann, H. Peter; Zips, Daniel

    2009-01-01

    The proceedings on experimental radiotherapy and clinical radiobiology contain two review articles (prediction of normal tissue reactions after radiotherapy, ?H2AX foci as a marker for DNA double-strand breaks) and 34 contributions to the following topics: Hypoxia and molecular mechanisms of radiation resistance; biological imaging of the tumor micromilieu; DNA repair, genomic instability and carcerogenesis; molecular factors of radiation resistance; actual controversial discussion on possible irradiation caused metastasis risk enhancement; EGFR inhibition and irradiation; biology of experimental radiation/ normal tissue toxicity

  13. Mitochondrial respiratory control is lost during growth factor deprivation.

    Science.gov (United States)

    Gottlieb, Eyal; Armour, Sean M; Thompson, Craig B

    2002-10-01

    The ability of cells to maintain a bioenergetically favorable ATP/ADP ratio confers a tight balance between cellular events that consume ATP and the rate of ATP production. However, after growth factor withdrawal, the cellular ATP/ADP ratio declines. To investigate these changes, mitochondria from growth factor-deprived cells isolated before the onset of apoptosis were characterized in vitro. Mitochondria from growth factor-deprived cells have lost their ability to undergo matrix condensation in response to ADP, which is accompanied by a failure to perform ADP-coupled respiration. At the time of analysis, mitochondria from growth factor-deprived cells were not depleted of cytochrome c and cytochrome c-dependent respiration was unaffected, demonstrating that the inhibition of the respiratory rate is not due to loss of cytochrome c. Agents that disrupt the mitochondrial outer membrane, such as digitonin, or maintain outer membrane exchange of adenine nucleotide, such as Bcl-x(L), restored ADP-dependent control of mitochondrial respiration. Together, these data suggest that the regulation of mitochondrial outer membrane permeability contributes to respiratory control.

  14. The effectiveness of external beam radiotherapy for acromegaly is not affected by previous pituitary ablative treatments

    International Nuclear Information System (INIS)

    Reed, P.I.; Joplin, G.F.; Speirs, C.J.; Morrison, R.; Aber, V.

    1990-01-01

    Thirty-three acromegalic patients were treated with radiotherapy and followed up for at least 3 years (mean 6 years, range 3 to 12). Seventeen had not had previous pituitary ablative therapy and 16 had. The mean GH level for these two groups before radiotherapy was comparable at 98 and 119 mlU/l. The observed frequency of reaching <10 mlU/L was 53% and 75% of patients in the two groups, respectively, the mean observed falls in growth hormone level were 81 and 85% of the initial level, and the calculated exponential decline rate of GH level was 72 and 52% per fyear. Considering all 35 patients, requirement for pituitary hormone replacement therapy increased from 15 patients before radiotherapy to 20 after radiotherapy, being mostly those who had had prior ablative therapies. There were no complications attributable to the radiotherapy treatment. It appears that radiotherapy is equally efficacious whether a prior unsuccessful ablative procedure had been used or not. (author)

  15. The effectiveness of external beam radiotherapy for acromegaly is not affected by previous pituitary ablative treatments

    Energy Technology Data Exchange (ETDEWEB)

    Reed, P.I.; Joplin, G.F. (Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London (UK)); Speirs, C.J. (Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London (UK)); Morrison, R. (Department of Radiotherapy, Royal Postgraduate Medical School, Hammersmith Hospital, London (UK)); Aber, V. (Department of Medical Physics, Royal Postgraduate Medical School, Hammersmith Hospital, London (UK))

    1990-01-01

    Thirty-three acromegalic patients were treated with radiotherapy and followed up for at least 3 years (mean 6 years, range 3 to 12). Seventeen had not had previous pituitary ablative therapy and 16 had. The mean GH level for these two groups before radiotherapy was comparable at 98 and 119 mlU/l. The observed frequency of reaching <10 mlU/L was 53% and 75% of patients in the two groups, respectively, the mean observed falls in growth hormone level were 81 and 85% of the initial level, and the calculated exponential decline rate of GH level was 72 and 52% per fyear. Considering all 35 patients, requirement for pituitary hormone replacement therapy increased from 15 patients before radiotherapy to 20 after radiotherapy, being mostly those who had had prior ablative therapies. There were no complications attributable to the radiotherapy treatment. It appears that radiotherapy is equally efficacious whether a prior unsuccessful ablative procedure had been used or not. (author).

  16. Transforming growth factor-beta, but not ciliary neurotrophic factor, inhibits DNA synthesis of adrenal medullary cells in vitro

    DEFF Research Database (Denmark)

    Wolf, N; Krohn, K; Bieger, S

    1999-01-01

    by the neuroendocrine chromaffin cells, which also express the transforming growth factor-beta receptor type II. In contrast to the developmentally related sympathetic neurons, chromaffin cells continue to proliferate throughout postnatal life. Using 5-bromo-2'-deoxyuridine pulse labeling and tyrosine hydroxylase...... immunocytochemistry as a marker for young postnatal rat chromaffin cells, we show that treatment with fibroblast growth factor-2 (1 nM) and insulin-like growth factor-II (10 nM) increased the fraction of 5-bromo-2'-deoxyuridine-labeled nuclei from 1% to about 40% of the cells in the absence of serum. In the presence...... of fibroblast growth factor-2 and insulin-like growth factor-II, transforming growth factor-beta1 (0.08 nM) reduced 5-bromo-2'-deoxyuridine labeling by about 50%, without interfering with chromaffin cell survival or death. Doses lower and higher than 0.08 nM were less effective. Similar effects were seen...

  17. Relationship among expression of basic-fibroblast growth factor ...

    African Journals Online (AJOL)

    Relationship among expression of basic-fibroblast growth factor, MTDH/Astrocyte elevated gene-1, adenomatous polyposis coli, matrix metalloproteinase 9,and COX-2 markers with prognostic factors in prostate carcinomas.

  18. Effectiveness of accelerated radiotherapy for patients with inoperable non-small cell lung cancer (NSCLC) and borderline prognostic factors without distant metastasis: a retrospective review

    International Nuclear Information System (INIS)

    Nguyen, Linh N.; Komaki, Ritsuko; Allen, Pamela; Schea, Randi A.; Milas, Luka

    1999-01-01

    Purpose: The standard treatment for patients with unresectable or medically inoperable non-small cell lung cancer (NSCLC) and good prognostic factors (e.g., weight loss [WL] ≤5% and Karnofsky performance status [KPS] ≥70) is induction chemotherapy followed by definitive radiotherapy to the primary site at 1.8-2.0 Gy per fraction with a total dose of 60-63 Gy to the target volume. Patients with poor prognostic factors usually receive radiotherapy alone, but the fractionation schedule and total dose have not been standardized. To attempt to optimize irradiation doses and schedule, we compared the effectiveness of accelerated radiotherapy (ACRT) alone to 45 Gy at 3 Gy per fraction with standard radiation therapy (STRT) of 60-66 Gy at 2 Gy per fraction in regard to tumor response, local control, distant metastasis, toxicity, and survival. Methods and Materials: Fifty-five patients treated with radiation for NSCLC at The University of Texas M. D. Anderson Cancer Center between 1990 and 1994 were identified. All 55 patients had node-positive, and no distant metastasis (N+, M0) of NSCLC. Two cohorts were identified. One cohort (26 patients) had borderline poor prognostic factors (KPS less than 70 but higher than 50, and/or WL of more than 5%) and was treated with radiotherapy alone to 45 Gy over 3 weeks at 3 Gy/fraction (ACRT). The second cohort (29 patients) had significantly better prognostic factors (KPS ≥70 and WL ≤5%) and was treated to 60-66 Gy over 6 to 6((1)/(2)) weeks at 2 Gy per fraction (STRT) during the same period. Results: In the first cohort treated by ACRT, the distribution of patients by AJCC stage was IIB 8%, IIIA 19%, and IIIB 73%. Sixty-two percent had KPS 5%. The maximum response rate as determined by chest X-ray was 60% among 45 of 55 patients who were evaluable for response: combined complete responses (20%) and partial responses (40%). Overall survival in these patients was 13% at 2 and 5 years, with a locoregional control rate of 42% and a

  19. Quality assurance of radiotherapy and its clinical assessment

    International Nuclear Information System (INIS)

    Inoue, Toshihiko

    2002-01-01

    We investigated the clinical quality assurance (QA) of radiotherapy in Japan since 1981. The aim of this study was to establish the QA of a radiotherapy system and its clinical assessment in Japan. We introduced the Patterns of Care Study (PCS) into Japan to perform this study in 1996. The PCS is a retrospective study designed to establish the national practice for cancer patients during a specific period and should be a complementary study to a prospective randomized controlled study. We collected precise data for 4399 patients with carcinomas of the breast, cervix, esophagus, lung and prostate by means of external audits for 96 institutes from 1998 through 2001. Patients were randomly sampled with two-stage cluster sampling. We stratified 556 institutes into four categories according to the academic condition and annual number of radiotherapy patients. National and regional averages of various factors of radiotherapy could be calculated and were used to measure QA of radiotherapy. Using a standard score, we could compare the process of individual institutions with national averages and feed back the evaluation score to each institution. With a PCS process survey, we could observe the dissemination of the treatment method under evidence-based medicine from the prospective randomized controlled study. We proposed future prediction of the number of radiotherapy patients and a counter plan for equipment and personnel. The first US-Japan PCS Workshop was held at San Francisco in 2001. We could establish QA of a radiotherapy system using PCS 1995-97 in Japan. (author)

  20. Radiotherapy for Locoregional Recurrent Cervix Cancer after Surgery

    International Nuclear Information System (INIS)

    Yang, Mi Gyoung

    1994-01-01

    Purpose: The role of radiotherapy in the management of patients with locoregional recurrent cervix cancer after radical surgery were retrospectively analyzed. Methods and materials: Twenty-eight patients treated with radiotherapy for locoregional recurrence after primary surgery for carcinoma of the cervix between 1989 and 1993 were analyzed. The median follow-up of survivors was 15 months (ranged 7-43 months). Eight patients had their disease confined to the vagina and 19 patients(68%) had pelvic mass as part of their locoregional recurrent disease. Within 24 months after the initial surgery, 82% of recurrences manifested themselves. All patients had whole pelvic irradiation with or without intracavitary radiotherapy(ICR). Results: Complete response(CR) was achieved in 18 patients(64%). Five of eighteen patients(28%) with initial CR developed second locoregional recurrence. Response to radiotherapy correlated strongly with tumor volume, site of recurrence and total radiation dose. The overall 2 year survival rate was 43% and the disease free survival was 31%. Survival rate was significantly influenced by the factors of interval from operation to recurrence, size and site of recurrent tumor, radiation dose, response of radiotherapy, lymph node status as initial presentation. The principal cause of death was lung metastasis(36%). Conclusion: Radiotherapy is an excellent modality for control of locoregional recurrent cervix cancer. To improve local control and survival rate, whole pelvic external radiotherapy in addition to ICR with more than 75.0Gy at the depth of 1.0cm from vaginal mucosa is needed and frequent follow up and early detection of recurrence is suggested as well

  1. Experimental study on anti-tumor effect of pcEgr-IFNγ gene-radiotherapy

    International Nuclear Information System (INIS)

    Wu Congmei; Li Xiuyi; Liu Shuzheng

    2001-01-01

    Objective: To study the anti-tumor effect of IFN γ gene-radiotherapy to murine melanoma and its immunologic mechanism. Methods: pcEgr-IFNγ plasmids were injected locally into tumor, and 36 hours later, the tumors were given 20 Gy X-ray irradiation. Tumor growth at different time, IFN γ expression 3 days later and immunologic indexes 15 days later were detected. Results: At 3-15 days after pcEgr-IFNγ gene-radiotherapy, the tumor growth rate was lower than that of irradiation alone group. It was also lower than that of gene therapy alone group and control plasmid combined with X-ray irradiation group significantly. Day 3 tumor IFN γ expression was higher than that of plasmid treatment alone group. NK activity, IL-2 and IFN γ secretion activities were higher than those of gene therapy alone and irradiation alone groups significantly. Conclusion: The antitumor effect of IFN γ gene-radiotherapy is better than that of either of them applied solely. Its mechanism might be concerned with the higher expression of IFN γ induced by irradiation in tumors and activation of anti-tumor immunologic functions

  2. Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Malemud Charles J

    2004-10-01

    Full Text Available Abstract Background Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects. Methods Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay. Results Serum growth hormone levels failed to correlate with age (r2 = 3.03 in the entire group of normal subjects (i.e. 20 – 80 years. In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r2 = 0.092. Of note, serum growth hormone was positively correlated with age (adjusted r2 = 0.269 in the 20 – 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 – 80 yrs or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p 55 yrs systemic lupus erythematosus patients. Conclusions These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal

  3. PLANNING NATIONAL RADIOTHERAPY SERVICES

    Directory of Open Access Journals (Sweden)

    Eduardo eRosenblatt

    2014-11-01

    Full Text Available Countries, states and island nations often need forward planning of their radiotherapy services driven by different motives. Countries without radiotherapy services sponsor patients to receive radiotherapy abroad. They often engage professionals for a feasibility study in order to establish whether it would be more cost-beneficial to establish a radiotherapy facility. Countries where radiotherapy services have developed without any central planning, find themselves in situations where many of the available centres are private and thus inaccessible for a majority of patients with limited resources. Government may decide to plan ahead when a significant exodus of cancer patients travel to another country for treatment, thus exposing the failure of the country to provide this medical service for its citizens. In developed countries the trigger has been the existence of highly visible waiting lists for radiotherapy revealing a shortage of radiotherapy equipment.This paper suggests that there should be a systematic and comprehensive process of long-term planning of radiotherapy services at the national level, taking into account the regulatory infrastructure for radiation protection, planning of centres, equipment, staff, education pr

  4. Safe Anesthesia for Radiotherapy in Pediatric Oncology: St. Jude Children's Research Hospital Experience, 2004-2006

    International Nuclear Information System (INIS)

    Anghelescu, Doralina L.; Burgoyne, Laura L.; Liu Wei; Hankins, Gisele M.; Cheng, Cheng; Beckham, Penny A. C.R.N.A.; Shearer, Jack; Norris, Angela L.; Kun, Larry E.; Bikhazi, George B.

    2008-01-01

    Purpose: To determine the incidence of anesthesia-related complications in children undergoing radiotherapy and the associated risk factors. Methods and Materials: We retrospectively investigated the incidence and types of anesthesia-related complications and examined their association with age, weight, oncology diagnosis, type of anesthetic (propofol vs. propofol and adjuncts), total propofol dose, anesthetic duration, type of radiotherapy procedure (simulation vs. radiotherapy) and patient position (prone vs. supine). Results: Between July 2004 and June 2006, propofol was used in 3,833 procedures (3,611 radiotherapy sessions and 222 simulations) in 177 patients. Complications occurred during 49 anesthetic sessions (1.3%). On univariate analysis, four factors were significantly associated with the risk of complications: procedure duration (p <0.001), total propofol dose (p <0.001), use of adjunct agents (vs. propofol alone; p = 0.029), and simulation (vs. radiotherapy; p = 0.014). Patient position (prone vs. supine) was not significantly associated with the frequency of complications (odds ratio, 0.71; 95% confidence interval, 0.33-1.53; p = 0.38). On multivariate analysis, the procedure duration (p <0.0001) and total propofol dose (p ≤0.03) were the most significant risk factors after adjustment for age, weight, anesthetic type, and procedure type. We found no evidence of the development of tolerance to propofol. Conclusion: The rate of anesthesia-related complications was low (1.3%) in our study. The significant risk factors were procedure duration, total propofol dose, the use of adjunct agents with propofol, and simulation (vs. radiotherapy)

  5. The Optimal Level and Impact of Internal Factors on Growth

    OpenAIRE

    Li, Kui-Wai

    2011-01-01

    This paper empirically uses data from the world economy to show that performance of domestic factors are equally important to external factors when comes to growth. Various external and domestic factors are used to construct two separate indices and the principal component method is applied in the analysis. The empirical results show that given a different level of performance in the economy’s external factors, a higher performance in the internal factors will produce a higher growth rate....

  6. Design and characteristics of cytotoxic fibroblast growth factor 1 conjugate for fibroblast growth factor receptor-targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    Szlachcic A

    2016-08-01

    Full Text Available Anna Szlachcic, Malgorzata Zakrzewska, Michal Lobocki, Piotr Jakimowicz, Jacek Otlewski Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland Abstract: Fibroblast growth factor receptors (FGFRs are attractive candidate cancer therapy targets as they are overexpressed in multiple types of tumors, such as breast, prostate, bladder, and lung cancer. In this study, a natural ligand of FGFR, an engineered variant of fibroblast growth factor 1 (FGF1V, was conjugated to a potent cytotoxic drug, monomethyl auristatin E (MMAE, and used as a targeting agent for cancer cells overexpressing FGFRs, similar to antibodies in antibody–drug conjugates. The FGF1V–valine–citrulline–MMAE conjugate showed a favorable stability profile, bound FGFRs on the cell surface specifically, and efficiently released the drug (MMAE upon cleavage by the lysosomal protease cathepsin B. Importantly, the conjugate showed a prominent cytotoxic effect toward cell lines expressing FGFR. FGF1V–vcMMAE was highly cytotoxic at concentrations even an order of magnitude lower than those found for free MMAE. This effect was FGFR-specific as cells lacking FGFR did not show any increased mortality. Keywords: fibroblast growth factor 1, FGF receptor, targeted cancer therapy, cytotoxic conjugates, FGFR-dependent cancer, MMAE, auristatin

  7. Radiotherapy of malignant growths in the eosophagus with clinical and radiological course control

    International Nuclear Information System (INIS)

    Holzhausen, B.

    1981-01-01

    This paper reports on clinical and radiological symptoms observed before during and after radiotherapy of 172 patients treated under high-voltage conditions at the radiological clinic in Muenster in the time from 1962 to 1977. The 1, 2, and 5 year survival rates are 26.5%, 13%, and 5.9%. The examination carried out retrospectively showed in 52% of the patients (46/90) after radiotherapy an expansion of the tumour stenosis. In 67% of the patients (67/101), the disphagia which had been stated before decreased. Thus the palliative effect of the treatment is the most important issue of the therapy. In the case of polypous and diffusely infiltrating tumours, the average survival rate was 11.2 months and 12.3 months which is significantly better than the results obtained with circular-stenosing tumours (6.4 months). (orig./APR) [de

  8. Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review).

    Science.gov (United States)

    Agrogiannis, Georgios D; Sifakis, Stavros; Patsouris, Efstratios S; Konstantinidou, Anastasia E

    2014-08-01

    The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

  9. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Pedersen, A T

    1997-01-01

    Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH-I...

  10. Preoperative radiotherapy of maxillary sinus cancer

    International Nuclear Information System (INIS)

    Kim, Jae Chul; Park, In Kyu

    1998-01-01

    .7%, respectively. The only factors associated with the overall survival rate was the response to radiotherapy (p<0.01). The only factors associated with the overall survival rate was the response to radiotherapy. We could omit a radical mutilating surgery by preoperative irradiation in 7 of 42 patients (21.4%) so as to preserve their facial integrity

  11. Preoperative radiotherapy of maxillary sinus cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Chul; Park, In Kyu [College of Medicine, Kyungpook National Univ., Taegu (Korea, Republic of)

    1998-09-01

    .7%, respectively. The only factors associated with the overall survival rate was the response to radiotherapy (p<0.01). The only factors associated with the overall survival rate was the response to radiotherapy. We could omit a radical mutilating surgery by preoperative irradiation in 7 of 42 patients (21.4%) so as to preserve their facial integrity.

  12. Growth factor delivery: How surface interactions modulate release in vitro and in vivo

    Science.gov (United States)

    King, William J.; Krebsbach, Paul H.

    2013-01-01

    Biomaterial scaffolds have been extensively used to deliver growth factors to induce new bone formation. The pharmacokinetics of growth factor delivery has been a critical regulator of their clinical success. This review will focus on the surface interactions that control the non-covalent incorporation of growth factors into scaffolds and the mechanisms that control growth factor release from clinically relevant biomaterials. We will focus on the delivery of recombinant human bone morphogenetic protein-2 from materials currently used in the clinical practice, but also suggest how general mechanisms that control growth factor incorporation and release delineated with this growth factor could extend to other systems. A better understanding of the changing mechanisms that control growth factor release during the different stages of preclinical development could instruct the development of future scaffolds for currently untreatable injuries and diseases. PMID:22433783

  13. Insulin-like growth factor binding protein 3 in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Kirman, Irena; Whelan, Richard Larry; Jain, Suvinit

    2005-01-01

    Epithelial cell growth regulation has been reported to be altered in inflammatory bowel disease (IBD) patients. The cell growth regulatory factor, insulin-like growth factor binding protein 3 (IGFBP-3), may be partly responsible for this phenomenon. So far, IGFBP-3 levels have been assessed...

  14. DEGRO practical guidelines for radiotherapy of breast cancer IV. Radiotherapy following mastectomy for invasive breast cancer

    International Nuclear Information System (INIS)

    Wenz, Frederik; Sperk, Elena; Budach, Wilfried; Dunst, Juergen; Feyer, Petra; Fietkau, Rainer; Sauer, Rolf; Haase, Wulf; Harms, Wolfgang; Piroth, Marc D.; Sautter-Bihl, Marie-Luise; Sedlmayer, Felix; Fussl, Christoph; Souchon, Rainer

    2014-01-01

    Since the last recommendations from the Breast Cancer Expert Panel of the German Society for Radiation Oncology (DEGRO) in 2008, evidence for the effectiveness of postmastectomy radiotherapy (PMRT) has grown. This growth is based on updates of the national S3 and international guidelines, as well as on new data and meta-analyses. New aspects were considered when updating the DEGRO recommendations. The authors performed a comprehensive survey of the literature. Data from recently published (meta-)analyses, randomized clinical trials and international cancer societies' guidelines yielding new aspects compared to 2008 were reviewed and discussed. New aspects were included in the current guidelines. Specific issues relating to particular PMRT constellations, such as the presence of risk factors (lymphovascular invasion, blood vessel invasion, positive lymph node ratio > 20 %, resection margins 2 cm or a combination of ≥ 2 risk factors) and 1-3 positive lymph nodes are emphasized. The evidence for improved overall survival and local control following PMRT for T4 tumors, positive resection margins, > 3 positive lymph nodes and in T3 N0 patients with risk factors such as lymphovascular invasion, G3 grading, close margins, and young age has increased. Recently identified risk factors such as invasive lobular subtype and negative hormone receptor status were included. For patients with 1-3 positive lymph nodes, the recommendation for PMRT has reached the 1a level of evidence. PMRT is mandatory in patients with T4 tumors and/or positive lymph nodes and/or positive resection margins. PMRT should be strongly considered in patients with T3 N0 tumors and risk factors, particularly when two or more risk factors are present. (orig.) [de

  15. Epidermal growth factor in mammary glands and milk from rats

    DEFF Research Database (Denmark)

    Thulesen, J; Raaberg, Lasse; Nexø, Ebba

    1993-01-01

    Epidermal growth factor (EGF) is one of the major growth-promoting agents in milk. Using immunohistochemistry we localized EGF in the mammary glands of lactating rats to the luminal border of the secretory cells. Following proteolytic pretreatment of the histological sections, the EGF-immunoreact......Epidermal growth factor (EGF) is one of the major growth-promoting agents in milk. Using immunohistochemistry we localized EGF in the mammary glands of lactating rats to the luminal border of the secretory cells. Following proteolytic pretreatment of the histological sections, the EGF...

  16. Cytokines and growth factors which regulate bone cell function

    Science.gov (United States)

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

  17. Regulation of insulin-like growth factor I receptors on vascular smooth muscle cells by growth factors and phorbol esters.

    Science.gov (United States)

    Ververis, J J; Ku, L; Delafontaine, P

    1993-06-01

    Insulin-like growth factor I (IGF I) is an important mitogen for vascular smooth muscle cells. To characterize regulation of vascular IGF I receptors, we performed radioligand displacement experiments using rat aortic smooth muscle cells (RASMs). Serum deprivation for 48 hours caused a 40% decrease in IGF I receptor number. Exposure of quiescent RASMs to platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), or angiotensin II (Ang II) caused a 1.5-2.0-fold increase in IGF I receptors per cell. After FGF exposure, there was a marked increase in the mitogenic response to IGF I. IGF I downregulated its receptors in the presence of platelet-poor plasma. Stimulation of protein kinase C (PKC) by exposure of quiescent RASMs to phorbol 12-myristate 13-acetate caused a biphasic response in IGF I binding; there was a 42% decrease in receptor number at 45 minutes and a 238% increase at 24 hours. To determine the role of PKC in growth factor-induced regulation of IGF I receptors, we downregulated PKC by exposing RASMs to phorbol 12,13-dibutyrate (PDBu) for 48 hours. PDGF- and FGF- but not Ang II-mediated upregulation of IGF I receptors was completely inhibited in PDBu-treated cells. Thus, acute PKC activation by phorbol esters inhibits IGF I binding, whereas chronic PKC activation increases IGF I binding. PDGF and FGF but not Ang II regulate vascular IGF I receptors through a PKC-dependent pathway. These data provide new insights into the regulation of vascular smooth muscle cell IGF I receptors in vitro and are of potential importance in characterizing vascular proliferative responses in vivo.

  18. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer

    DEFF Research Database (Denmark)

    Vaidya, Jayant S; Wenz, Frederik; Bulsara, Max

    2014-01-01

    The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival....

  19. Impact of radiotherapy for pediatric CNS atypical teratoid/rhabdoid tumor (single institute experience)

    International Nuclear Information System (INIS)

    Chen, Y.-W.; Wong, T.-T.; Ho, Donald Ming-Tak; Huang, P.-I.; Chang, K.-P.; Shiau, C.-Y.; Yen, S.-H.

    2006-01-01

    Purpose: To assess outcomes and prognostic factors in radiotherapy of pediatric central nervous system atypical teratoid/rhabdoid tumor (AT/RT). Methods and Materials: Seventeen patients with central nervous system AT/RT were retrospectively reviewed after curative radiotherapy as primary or adjuvant therapy between January 1990 and December 2003. Overall and failure-free survival rates were calculated using the Kaplan-Meier method. The log-rank method was used to compare the effects of dosage (>50 Gy or ≤50 Gy) and treatment duration (>45 days or ≤45 days). Multivariate analysis was performed for prognostic factors. Results: Median overall survival and failure-free survival were 17 and 11 months, respectively. The 3 longest-surviving patients were older, underwent gross tumor removal, and completed both craniospinal and focal boost irradiation. Multivariate analysis revealed a significant relationship between the following: overall survival and performance status (p = 0.019), failure-free survival and total irradiation dose (p = 0.037), time interval between surgery and radiotherapy initiation (p = 0.031), and time interval between surgery and radiotherapy end point (p = 0.047). Conclusion: Radiotherapy is crucial in the treatment of AT/RT. We recommend initiating radiotherapy immediately postoperatively and before systemic chemotherapy in pediatric patients ≥3 years of age

  20. Treatment outcome in patients with vulvar cancer: comparison of concurrent radiotherapy to postoperative radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ja Young; Kim, Sung Hwan; Kim, Ki Won; Park, Dong Choon; Yoon, Joo Hee; Yoon, Sei Chul [St. Vincent' s Hospital, The Catholic University of Korea School of Medicine, Seoul (Korea, Republic of); Yu, Mina [St. Mary' s Hospital, The Catholic University of Korea School of Medicine, Seoul (Korea, Republic of)

    2012-03-15

    To evaluate outcome and morbidity in patients with vulvar cancer treated with radiotherapy, concurrent chemoradiotherapy or postoperative radiotherapy. The records of 24 patients treated with radiotherapy for vulvar cancer between July 1993 and September 2009 were retrospectively reviewed. All patients received once daily 1.8-4 Gy fractions external beam radiotherapy to median 51.2 Gy (range, 19.8 to 81.6 Gy) on pelvis and inguinal nodes. Seven patients were treated with primary concurrent chemoradiotherapy, one patient was treated with primary radiotherapy alone, four patients received palliative radiotherapy, and twelve patients were treated with postoperative radiotherapy. Twenty patients were eligible for response evaluation. Response rate was 55% (11/20). The 5-year disease free survival was 42.2% and 5-year overall survival was 46.2%, respectively. Fifty percent (12/24) experienced with acute skin complications of grade III or more during radiotherapy. Late complications were found in 8 patients. 50% (6/12) of patients treated with lymph node dissection experienced severe late complications. One patient died of sepsis from lymphedema. However, only 16.6% (2/12) of patients treated with primary radiotherapy developed late complications. Outcome of patients with vulvar cancer treated with radiotherapy showed relatively good local control and low recurrence. Severe late toxicities remained higher in patients treated with both node dissection and radiotherapy.

  1. Radiotherapy of chondrosarcoma of bone

    International Nuclear Information System (INIS)

    Harwood, A.R.; Krajbich, J.I.; Fornasier, V.L.

    1980-01-01

    A retrospective analysis of 31 cases of chondrosarcoma of bone treated by radiotherapy is presented. In comparison with other large series, our group of patients were found to have been unfavourably selected with respect to the known prognostic factors: histology site, adequacy of operative treatment, and presenting symptoms. Twelve patients with primary chondrosarcoma were radically irradiated; 6 of these 12 have been alive and well without tumor for periods ranging from three and a half to 16 years and 3 of these are alive and well for 15 years or more following radiotherapy. The other 6 patients responded or desease stabilized following radiotherapy for periods ranging from 16 months to eight years. One poorly differentiated tumor was radically irradiated and did not respond. Eleven patients were irradiated palliatively, generally with low doses of irradiation, and only 4 responded transiently for periods ranging from three to 12 months. Seven patients with mesenchymal and dedifferentiated tumors were radically irradiated. Four responded or disease stabilized, and 1 of these patients was alive and well at 3 years; 3 did not respond. Six died with distant metastasis. It is concluded that chondrosarcoma of bone is a radioresponsive tumor and the place of radiotherapy in the treatment of this disease and the reason for its being labelled a radioresistant tumor are discussed. The problems of assessing response of chondrosarcoma to therapy are also discussed. It is suggested that chemotherapy may have a role in the management of mesenchymal and dedifferentiated chondrosarcoma

  2. Delayed airway stenosis after radiotherapy for head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yuta, Atsushi; Tatematsu, Masanori; Ishinaga, Hajime; Harada, Teruhiko; Majima, Yuichi [Mie Univ., Tsu (Japan). School of Medicine

    2002-03-01

    Seven cases of delayed airway stenosis after radiotherapy for early staged head and neck cancers during 1989 and 1999 were evaluated (aged 54-77 yrs, 6 male and a female). The cases included five glottic laryngeal cancers (T1a, T1b, and three T2), a subglottic laryngeal cancer, and an unknown origin, but strongly suspected laryngeal cancer, with neck metastasis. Radio injury was found from 3 months to 47 months after radiotherapy. {sup 60}Co for radiotherapy was used in all seven cases, although {sup 60}Co radionuclide was changed to Liniac in 1997. The total dose was 60 Gy for 3 cases, and 70 Gy for 4 cases. Tracheostomy was performed in 3 cases due to bilateral vocal cord impairment. Background, treatment, and response to radiotherapy were compared to those of 90 patients of a control group with early staged laryngeal cancer who did not fail radiation injury during the same period. As a result, radionuclide ({sup 60}Co), total dose, cervical surgery, antiinflammatory drugs, laryngeal edema during radiotherapy were risk factors. The intensity and the period of mucositis by radiotherapy was important for indicating delayed airway stenosis. (author)

  3. Delayed airway stenosis after radiotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Yuta, Atsushi; Tatematsu, Masanori; Ishinaga, Hajime; Harada, Teruhiko; Majima, Yuichi

    2002-01-01

    Seven cases of delayed airway stenosis after radiotherapy for early staged head and neck cancers during 1989 and 1999 were evaluated (aged 54-77 yrs, 6 male and a female). The cases included five glottic laryngeal cancers (T1a, T1b, and three T2), a subglottic laryngeal cancer, and an unknown origin, but strongly suspected laryngeal cancer, with neck metastasis. Radio injury was found from 3 months to 47 months after radiotherapy. 60 Co for radiotherapy was used in all seven cases, although 60 Co radionuclide was changed to Liniac in 1997. The total dose was 60 Gy for 3 cases, and 70 Gy for 4 cases. Tracheostomy was performed in 3 cases due to bilateral vocal cord impairment. Background, treatment, and response to radiotherapy were compared to those of 90 patients of a control group with early staged laryngeal cancer who did not fail radiation injury during the same period. As a result, radionuclide ( 60 Co), total dose, cervical surgery, antiinflammatory drugs, laryngeal edema during radiotherapy were risk factors. The intensity and the period of mucositis by radiotherapy was important for indicating delayed airway stenosis. (author)

  4. Fatigue Crack Growth Rate and Stress-Intensity Factor Corrections for Out-of-Plane Crack Growth

    Science.gov (United States)

    Forth, Scott C.; Herman, Dave J.; James, Mark A.

    2003-01-01

    Fatigue crack growth rate testing is performed by automated data collection systems that assume straight crack growth in the plane of symmetry and use standard polynomial solutions to compute crack length and stress-intensity factors from compliance or potential drop measurements. Visual measurements used to correct the collected data typically include only the horizontal crack length, which for cracks that propagate out-of-plane, under-estimates the crack growth rates and over-estimates the stress-intensity factors. The authors have devised an approach for correcting both the crack growth rates and stress-intensity factors based on two-dimensional mixed mode-I/II finite element analysis (FEA). The approach is used to correct out-of-plane data for 7050-T7451 and 2025-T6 aluminum alloys. Results indicate the correction process works well for high DeltaK levels but fails to capture the mixed-mode effects at DeltaK levels approaching threshold (da/dN approximately 10(exp -10) meter/cycle).

  5. The role and principles of radiotherapy in prostate cancer in the elderly subject

    International Nuclear Information System (INIS)

    Richaud, P.; Salomon, L.; Mongiat-Artus, P.; Gaschignard, N.; Beuzeboc, P.; Peyromaure, M.; Bastide, C.; Cornud, F.; Molinie, V.; Rozet, F.; Staerman, F.; Soulie, M.

    2009-01-01

    The aging of the population has resulted in an increase in the number of elderly patients with prostate cancer. Among the curative treatment options in the elderly subject, external radiotherapy is the most frequently chosen option. Combined treatment including radiotherapy and hormone therapy should be preferred to hormonal therapy alone, including in elderly patients, whenever life expectancy surpasses 4-5 years. The indications for this radiotherapy should be defined in an attempt to prevent excessive or insufficient treatment, to adapt the treatment modalities to the patient's age by assessing its potential toxicity, and to discuss the possible alternatives. In cases of localized prostate cancer in men who are aging well, a standard treatment should be proposed, preferring radiotherapy possibly associated with hormone therapy in cases with negative prognostic factors. Patients with a reversible health problems can also receive standard treatment, notably in cases with aggressive prognostic factors. (authors)

  6. Patterns of Pelvic Radiotherapy in Patients with Stage II/III Rectal Cancer

    International Nuclear Information System (INIS)

    Fitzgerald, T. L.; Zervos, E.; Wong, J. H.; Fitzgerald, T. L.; Zervos, E.; Wong, J. H.; Fitzgerald, T. L.; Zervos, E.; Wong, J. H.

    2013-01-01

    High-level evidence supports adjuvant radiotherapy for rectal cancer. We examined the influence of socio demographic factors on patterns of adjuvant radiotherapy for resected Stage II/III rectal cancer. Methods. Patients undergoing surgical resection for stage II/III rectal cancer were identified in SEER registry. Results. A total of 21,683 patients were identified. Majority of patients were male (58.8%), white (83%), and with stage III (54.9%) and received radiotherapy (66%). On univariate analysis, male gender, stage III, younger age, year of diagnosis, and higher socioeconomic status (SES) were associated with radiotherapy. Radiotherapy was delivered in 84.4% of patients <50; however, only 32.8% of those are >80 years. Logistic regression demonstrated a significant increase in the use of radiotherapy in younger patients who are 50 (OR, 10.3), with stage III (OR, 1.21), males (OR, 1.18), and with higher SES. Conclusions. There is a failure to conform to standard adjuvant radiotherapy in one-third of patients, and this is associated with older age, stage II, area-level of socioeconomic deprivation, and female sex.

  7. Measuring side effects after radiotherapy for pharynx cancer

    DEFF Research Database (Denmark)

    Jensen, Kenneth

    2007-01-01

    Data on side effects after radiotherapy is needed to establish the benefits and drawbacks of new treatments, but side effects are not quantified as easily as survival or local control. Side effects may be quantified using physical measures. Unfortunately, only few endpoints exist where a physical...... measure is obtainable, and the case of a patient-relevant measure is even rarer. Radiotherapy is often followed by complex symptoms not easily quantifiable by the observer. Quantitative patient reported side effects can be retrieved using validated questionnaires, but this kind of data is often difficult...... to interpret and the correlation with clinically observable or measurable changes not straightforward. The exploitation of the possibilities of highly conformal radiotherapy and multimodality treatment depends on a better understanding of the correlation between dose, volume, modifying factors, and side...

  8. Item 141 Radiotherapy. Radiobiological notions; main secondary effects

    International Nuclear Information System (INIS)

    Azria, David; Dubois, Jean-Bernard

    2006-11-01

    This document first gives definitions of ionizing radiations, photons, electrons and Gray (as a dose unit). It describes the mechanisms of action of ionizing radiations: physical, chemical, cellular actions, actions on tissues. It analyses and discusses the factors influencing the effects of radiations: intrinsic radio-sensitivity, cellular cycle, oxygen, time (session fractioning and organisation in time), and dose. The different types of radiotherapy are then presented: external radiotherapy, brachytherapy, radio-immunotherapy of internal radiotherapy. It discusses tissues tolerance doses and doses required to sterilize tumours, and discusses the various and main secondary effects: stochastic secondary effects and deterministic secondary effects. A table indicates possible early and late reactions for different organs (skin, lung, brain, medulla, nerves, oesophagus, heart, pancreas, stomach, liver, intestine, kidney, bladder, rectum, ENT, or eye's lens)

  9. Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization.

    Science.gov (United States)

    Tsunoda, Satoshi; Nakamura, Toshiyuki; Sakurai, Hiroaki; Saiki, Ikuo

    2007-04-01

    Fibroblast growth factor (FGF)-2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF-2 in B16-BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF-2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF-2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF-2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF-2 into the footpad inoculation site. In contrast, repeated injections of FGF-2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF-2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF-2 are associated with FGF-2-induced tumor progression. In addition, although FGF-2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16-BL6 cells in vitro, FGF-2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF-2 in vivo. These results indicate that abundant FGF-2 during the initial phase of tumor growth induces VEGFA-dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis.

  10. Radiotherapy in small countries.

    Science.gov (United States)

    Barton, Michael B; Zubizarreta, Eduardo H; Polo Rubio, J Alfredo

    2017-10-01

    To examine the availability of radiotherapy in small countries. A small country was defined as a country with a population less than one million persons. The economic status of each country was defined using the World Bank Classification. The number of cancers in each country was obtained from GLOBOCAN 2012. The number of cancer cases with an indication or radiotherapy was calculated using the CCORE model. There were 41 countries with a population of under 1 million; 15 were classified as High Income, 15 Upper Middle Income, 10 Lower Middle Income and one Low Income. 28 countries were islands. Populations ranged from 799 (Holy See) to 886450 (Fiji) and the total number of cancer cases occurring in small countries was 21,043 (range by country from 4 to 2476). Overall the total number of radiotherapy cases in small countries was 10982 (range by country from 2 to 1239). Radiotherapy was available in all HIC islands with 80 or more new cases of cancer in 2012 but was not available in any LMIC island. Fiji was the only LMIC island with a large radiotherapy caseload. Similar caseloads in non-island LMIC all had radiotherapy services. Most non-island HIC did not have radiotherapy services presumably because of the easy access to radiotherapy in neighbouring countries. There are no radiotherapy services in any LMIC islands. Copyright © 2017. Published by Elsevier Ltd.

  11. Sequential growth factor application in bone marrow stromal cell ligament engineering.

    Science.gov (United States)

    Moreau, Jodie E; Chen, Jingsong; Horan, Rebecca L; Kaplan, David L; Altman, Gregory H

    2005-01-01

    In vitro bone marrow stromal cell (BMSC) growth may be enhanced through culture medium supplementation, mimicking the biochemical environment in which cells optimally proliferate and differentiate. We hypothesize that the sequential administration of growth factors to first proliferate and then differentiate BMSCs cultured on silk fiber matrices will support the enhanced development of ligament tissue in vitro. Confluent second passage (P2) BMSCs obtained from purified bone marrow aspirates were seeded on RGD-modified silk matrices. Seeded matrices were divided into three groups for 5 days of static culture, with medium supplement of basic fibroblast growth factor (B) (1 ng/mL), epidermal growth factor (E; 1 ng/mL), or growth factor-free control (C). After day 5, medium supplementation was changed to transforming growth factor-beta1 (T; 5 ng/mL) or C for an additional 9 days of culture. Real-time RT-PCR, SEM, MTT, histology, and ELISA for collagen type I of all sample groups were performed. Results indicated that BT supported the greatest cell ingrowth after 14 days of culture in addition to the greatest cumulative collagen type I expression measured by ELISA. Sequential growth factor application promoted significant increases in collagen type I transcript expression from day 5 of culture to day 14, for five of six groups tested. All T-supplemented samples surpassed their respective control samples in both cell ingrowth and collagen deposition. All samples supported spindle-shaped, fibroblast cell morphology, aligning with the direction of silk fibers. These findings indicate significant in vitro ligament development after only 14 days of culture when using a sequential growth factor approach.

  12. Transitioning from conventional radiotherapy to intensity-modulated radiotherapy for localized prostate cancer. Changing focus from rectal bleeding to detailed quality of life analysis

    International Nuclear Information System (INIS)

    Yamazaki, Hideya; Nakamura, Satoaki; Nishimura, Takuya; Yoshida, Ken; Yoshioka, Yasuo; Koizumi, Masahiko; Ogawa, Kazuhiko

    2014-01-01

    With the advent of modern radiation techniques, we have been able to deliver a higher prescribed radiotherapy dose for localized prostate cancer without severe adverse reactions. We reviewed and analyzed the change of toxicity profiles of external beam radiation therapy (EBRT) from the literature. Late rectal bleeding is the main adverse effect, and an incidence of >20% of Grade ≥2 adverse events was reported for 2D conventional radiotherapy of up to 70 Gy. 3D conformal radiation therapy (3D-CRT) was found to reduce the incidence to ∼10%. Furthermore, intensity-modulated radiation therapy (IMRT) reduced it further to a few percentage points. However, simultaneously, urological toxicities were enhanced by dose escalation using highly precise external radiotherapy. We should pay more attention to detailed quality of life (QOL) analysis, not only with respect to rectal bleeding but also other specific symptoms (such as urinary incontinence and impotence), for two reasons: (1) because of the increasing number of patients aged >80 years, and (2) because of improved survival with elevated doses of radiotherapy and/or hormonal therapy; age is an important prognostic factor not only for prostate-specific antigen (PSA) control but also for adverse reactions. Those factors shift the main focus of treatment purpose from survival and avoidance of PSA failure to maintaining good QOL, particularly in older patients. In conclusion, the focus of toxicity analysis after radiotherapy for prostate cancer patients is changing from rectal bleeding to total elaborate quality of life assessment. (author)

  13. Role of growth factors in the growth of normal and transformed cells

    International Nuclear Information System (INIS)

    Lokeshwar, V.B.

    1989-01-01

    Growth factors play an important role in the growth of normal cells. However, their untimely and/or excess production leads to neoplastic transformation. The role of growth factors in the growth of normal cells was studied by investigating the mechanism of transmodulation of the cell surface EGF receptor number by protamine. Protamine increased the EGF stimulated mitogenic response in Swiss mouse 3T3 cells and A431 cells by increasing the number of functionally active EGF receptors. Protamine also increased EGF receptor number in plasma membranes and solubilized membranes. This was evidenced by an increase in both 125 I-EGF-EGF-receptor complex and EGF stimulated phosphorylation of the EGF receptor. The solubilized EGF receptor was retained on a protamine-agarose gel indicating that protamine might increase EGF receptor number by directly activating cryptic EGF receptors in the plasma membranes. The role of growth factors in neoplastic transformation was studied by investigating the role of the oncogene v-sis in the growth of Simian sarcoma virus (SSV) transformed cells. The product of the oncogene v-sis is 94% homologous to the B chain of PDGF. This study found that (i) v-sis gene product is synthesized as a 32 kDa unglycosylated monomer which is glycosylated, dimerized and proteolytically processed into p36, p72, p68, p58, p44 and p27 mol. wt. species respectively. (ii) p36, p72, p68 and p58 are very likely formed in the endoplasmic reticulum and/or Golgi complex. A fraction of newly synthesized p72, p68 and p58 is degraded intracellularly at a fast rate. (iii) p44 is a secretory product which remains tightly associated with the cell surface. p44 is recaptured by the cells through interaction with cell surface PDGF receptors and degraded into p27. (iv) During long term cultures p44 is extracellularly cleaved into a 27 kDa product

  14. Concomitant chemo-radiotherapy and local dose of radiation as risk factors for second malignant neoplasms after cancer in childhood: a case control study

    International Nuclear Information System (INIS)

    Guerin, S.; Guibout, C.; Vathaire, F. de; Shamsaldin, A.; Diallo, I.; Oberlin, O.; Hartmann, O.; Le Deley, M.C.; Dondon, M.G.; Hawkins, M.

    2006-01-01

    Radiotherapy and chemotherapy are associated with an increased risk of a second malignant neoplasm. after a cancer during childhood. This study specified the dose effect relationship between the local dose of radiation received at the site of the second malignant neoplasm and the risk of a second malignant neoplasm.It also investigated the effect of chemo radiotherapy on the risk of second malignant neoplasm. An European cohort of 4581 patients, treated for a solid cancer during childhood have been included in the study. 153 cases with a second malignant neoplasm, and 442 controls were matched according to sex, age at first cancer, calendar year, type of first cancer and follow-up. The local dose of radiation was estimated at the site of the second malignant neoplasm, for each case and at the same site, for his matched control. In conclusion, radiation was the foremost treatment related risk factor for the occurrence of a second malignant neoplasm. Compared to sequential treatment, concomitant chemo radiotherapy may lead to a higher risk of a second malignant neoplasm. (N.C.)

  15. The effect of oral sucralfate on the acute proctitis associated with prostate radiotherapy: a double-blind, randomized trial

    International Nuclear Information System (INIS)

    Kneebone, Andrew; Mameghan, Hedy; Bolin, Terry; Berry, Martin; Turner, Sandra; Kearsley, John; Graham, Peter; Fisher, Richard; Delaney, Geoff

    2001-01-01

    Purpose: Acute rectal complications occur in the majority of patients receiving external-beam radiotherapy for carcinoma of the prostate. Sucralfate has been proposed to reduce radiation-induced mucosal injury by forming a protective barrier on ulcer bases, binding local growth factors, and stimulating angiogenesis. However, there is conflicting clinical evidence as to whether sucralfate, taken prophylactically during radiotherapy, can ameliorate the symptoms of acute radiation proctitis. Methods and Materials: A double-blind randomized trial was conducted at four Radiation Oncology Departments in Sydney, Australia, between February 1995 and June 1997. A total of 338 patients with clinically localized prostate cancer receiving small volume radiotherapy, of whom 335 were evaluable, were randomized to receive either 3 g of oral sucralfate suspension or placebo twice a day during radiotherapy. Patients kept a daily record of their bowel symptoms and were graded according to the RTOG/EORTC acute toxicity criteria. Results: One hundred sixty-four patients received sucralfate and 171 received placebo. Both groups were well balanced with regard to patient, tumor, treatment factors, and baseline symptoms, except that the placebo group had a significantly more liquid baseline stool consistency score (p=0.004). Patients kept a daily diary of symptoms during radiotherapy. After adjusting for baseline values, there was no significant difference between the two groups with regard to stool frequency (p=0.41), consistency (p=0.20), flatus (p=0.25), mucus (p=0.54), and pain (p=0.73). However, there was more bleeding in the sucralfate group, with 64% of patients noticing rectal bleeding, compared with 47% in the placebo group (p=0.001). There was no significant difference between the two groups with respect to RTOG/EORTC acute toxicity (p=0.88; sucralfate 13%, 44%, 43% and placebo 15%, 44%, 40% for grade 0, 1, and 2, respectively). Conclusion: This study suggests that oral

  16. Complete remission through icotinib treatment in Non-small cell lung cancer epidermal growth factor receptor mutation patient with brain metastasis: A case report

    Directory of Open Access Journals (Sweden)

    Wang Tao

    2016-01-01

    Full Text Available Brain metastasis (BM has been universally recognized as a poor prognostic factor in non-small cell lung cancer (NSCLC. Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs have shown efficacy in treating BM with an EGFR mutation. This paper reports a case of BM patient with EGFR-mutated NSCLC. According to the findings, a complete remission (CR of the BM was achieved by icotinib treatment without conducting a radiotherapy, which was followed by a resection of the primary lung cancer lesion and lymph nodes. After one-year follow-up, the disease progressed to liver metastasis and liver lesion biopsy showed a T790M mutation. The patient responded well to the combination treatment of AZD9291 and icotinib after the failure of transcatheter arterial chemoembolization (TACE. This case report suggests that icotinib has a sustainable anticancer response to BM and the combination with icotinib and AZD9291 is effective for liver metastasis with T790M.

  17. Hyperthermia and radiotherapy

    International Nuclear Information System (INIS)

    Fitspatrick, C.

    1990-01-01

    Hyperthermia and radiotherapy have for long been used to assist in the control of tumours, either as separate entities, or, in a combined treatment scheme. This paper outlines why hyperthermia works, thermal dose and the considerations required in the timing when hyperthermia is combined with radiotherapy. Previously reported results for hyperthermia and radiotherapy used together are also presented. 8 refs., 8 tabs

  18. Cortactin involvement in the keratinocyte growth factor and fibroblast growth factor 10 promotion of migration and cortical actin assembly in human keratinocytes

    International Nuclear Information System (INIS)

    Ceccarelli, Simona; Cardinali, Giorgia; Aspite, Nicaela; Picardo, Mauro; Marchese, Cinzia; Torrisi, Maria Rosaria; Mancini, Patrizia

    2007-01-01

    Keratinocyte growth factor (KGF/FGF7) and fibroblast growth factor 10 (FGF10/KGF2) regulate keratinocyte proliferation and differentiation by binding to the tyrosine kinase KGF receptor (KGFR). KGF induces keratinocyte motility and cytoskeletal rearrangement, whereas a direct role of FGF10 on keratinocyte migration is not clearly established. Here we analyzed the motogenic activity of FGF10 and KGF on human keratinocytes. Migration assays and immunofluorescence of actin cytoskeleton revealed that FGF10 is less efficient than KGF in promoting migration and exerts a delayed effect in inducing lamellipodia and ruffles formation. Both growth factors promoted phosphorylation and subsequent membrane translocation of cortactin, an F-actin binding protein involved in cell migration; however, FGF10-induced cortactin phosphorylation was reduced, more transient and delayed with respect to that promoted by KGF. Cortactin phosphorylation induced by both growth factors was Src-dependent, while its membrane translocation and cell migration were blocked by either Src and PI3K inhibitors, suggesting that both pathways are involved in KGF- and FGF10-dependent motility. Furthermore, siRNA-mediated downregulation of cortactin inhibited KGF- and FGF10-induced migration. These results indicate that cortactin is involved in keratinocyte migration promoted by both KGF and FGF10

  19. Prediction of lung density changes after radiotherapy by cone beam computed tomography response markers and pre-treatment factors for non-small cell lung cancer patients.

    Science.gov (United States)

    Bernchou, Uffe; Hansen, Olfred; Schytte, Tine; Bertelsen, Anders; Hope, Andrew; Moseley, Douglas; Brink, Carsten

    2015-10-01

    This study investigates the ability of pre-treatment factors and response markers extracted from standard cone-beam computed tomography (CBCT) images to predict the lung density changes induced by radiotherapy for non-small cell lung cancer (NSCLC) patients. Density changes in follow-up computed tomography scans were evaluated for 135 NSCLC patients treated with radiotherapy. Early response markers were obtained by analysing changes in lung density in CBCT images acquired during the treatment course. The ability of pre-treatment factors and CBCT markers to predict lung density changes induced by radiotherapy was investigated. Age and CBCT markers extracted at 10th, 20th, and 30th treatment fraction significantly predicted lung density changes in a multivariable analysis, and a set of response models based on these parameters were established. The correlation coefficient for the models was 0.35, 0.35, and 0.39, when based on the markers obtained at the 10th, 20th, and 30th fraction, respectively. The study indicates that younger patients without lung tissue reactions early into their treatment course may have minimal radiation induced lung density increase at follow-up. Further investigations are needed to examine the ability of the models to identify patients with low risk of symptomatic toxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Changes in mast cell number and stem cell factor expression in human skin after radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    Westbury, Charlotte B.; Freeman, Alex; Rashid, Mohammed; Pearson, Ann; Yarnold, John R.; Short, Susan C.

    2014-01-01

    Background and purpose: Mast cells are involved in the pathogenesis of radiation fibrosis and may be a therapeutic target. The mechanism of increased mast cell number in relation to acute and late tissue responses in human skin was investigated. Materials and methods: Punch biopsies of skin 1 and 15–18 months after breast radiotherapy and a contralateral control biopsy were collected. Mast cells were quantified by immunohistochemistry using the markers c-Kit and tryptase. Stem cell factor (SCF) and collagen-1 expression was analysed by qRT-PCR. Clinical photographic scores were performed at post-surgical baseline and 18 months and 5 years post-radiotherapy. Primary human dermal microvascular endothelial cell (HDMEC) cultures were exposed to 2 Gy ionising radiation and p53 and SCF expression was analysed by Western blotting and ELISA. Results: Dermal mast cell numbers were increased at 1 (p = 0.047) and 18 months (p = 0.040) using c-Kit, and at 18 months (p = 0.024) using tryptase immunostaining. Collagen-1 mRNA in skin was increased at 1 month (p = 0.047) and 18 months (p = 0.032) and SCF mRNA increased at 1 month (p = 0.003). None of 16 cases scored had a change in photographic appearance at 5 years, compared to baseline. SCF expression was not increased in HDMECs irradiated in vitro. Conclusions: Increased mast cell number was associated with up-regulated collagen-1 expression in human skin at early and late time points. This increase could be secondary to elevated SCF expression at 1 month after radiotherapy. Although mast cells accumulate around blood vessels, no endothelial cell secretion of SCF was seen after in vitro irradiation. Modification of mast cell number and collagen-1 expression may be observed in skin at 1 and 18 months after radiotherapy in breast cancer patients with no change in photographic breast appearance at 5 years

  1. Role of DNA damage and repair as predeterminant factor in the development of radiotherapy induced acute adverse reactions

    International Nuclear Information System (INIS)

    Satish Rao, B.S.; Kamalesh, D.M.; Goutham, H.V.; Donald, J.F.; Sharan, Krishna; Vadhiraja, B.M.; Satyamoorthy, K.

    2013-01-01

    Radiotherapy induced normal tissue toxicity is one of the major limitations for the compromised the therapeutic outcome and also worsens the quality of life of survivors. Further, the clinical experience demonstrated inter-individual variability with respect to their normal tissue toxicity. Therefore, the discovery of contributing key factors of variability or predicting the risk of developing acute reactions before the initiation of radiation therapy may serve as a powerful predictive biomarker for individualizing radiotherapy, anticipating increased therapeutic effect. DNA double-strand break (DSB) induction and its repair in lymphocytes of head-and-neck and breast cancer patients undergoing chemoradiation or radiation therapy alone were analyzed by performing γ-H2AX foci, neutral comet and a modified neutral filter elution assays. Treatment induced normal tissue adverse reactions (acute skin reaction, oral mucositis) were assessed by the criteria of Radiation Therapy Oncology Group. The residual damage (RD) at 6 hrs of post irradiation was used as parameters to measure cellular radiosensitivity and for its correlation with radiotherapy induced acute reactions in patients stratified as non-over responders (NOR) and over responders (OR). A large inter-individual variation in the radiosensitivity was observed in the cancer individuals with respect to their lymphocyte radiosensitivity and the severity of normal tissue adverse reactions. There was a significant difference in RD (p<0.05) between the NOR and OR in breast cancer radiotherapy. Further, the increased normal tissue toxicity such as oral mucositis and skin reactions was associated with the reduced DSB repair (p<0.05) in head-and-neck cancer patients. The percentile analysis was found to be useful in predicting the OR amongst the head-and-neck cancer patients. Our results suggest that γ-H2AX analysis may have its potential to be developed into a clinically useful predictive assay for identifying the

  2. Radiotherapy

    International Nuclear Information System (INIS)

    Wannenmacher, M.; Debus, J.; Wenz, F.

    2006-01-01

    The book is focussed on the actual knowledge on the clinical radiotherapy and radio-oncology. Besides fundamental and general contributions specific organ systems are treated in detail. The book contains the following contributions: Basic principles, radiobiological fundamentals, physical background, radiation pathology, basics and technique of brachytherapy, methodology and technique of the stereotactic radiosurgery, whole-body irradiation, operative radiotherapy, hadron therapy, hpyerthermia, combined radio-chemo-therapy, biometric clinical studies, intensity modulated radiotherapy, side effects, oncological diagnostics; central nervous system and sense organs, head-neck carcinomas, breast cancer, thorax organs, esophagus carcinoma, stomach carcinoma, pancreas carcinoma, heptabiliary cancer and liver metastases, rectal carcinomas, kidney and urinary tract, prostate carcinoma, testicular carcinoma, female pelvis, lymphatic system carcinomas, soft tissue carcinoma, skin cancer, bone metastases, pediatric tumors, nonmalignant diseases, emergency in radio-oncology, supporting therapy, palliative therapy

  3. A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy

    NARCIS (Netherlands)

    van Geest, Rob J.; Lesnik-Oberstein, Sarit Y.; Tan, H. Stevie; Mura, Marco; Goldschmeding, Roel; van Noorden, Cornelis J. F.; Klaassen, Ingeborg; Schlingemann, Reinier O.

    2012-01-01

    Introduction In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) may cause blindness by neovascularisation followed by fibrosis of the retina. It has previously been shown that a shift in the balance between levels of CTGF

  4. Increased vascular endothelial growth factor (VEGF) expression in ...

    African Journals Online (AJOL)

    User

    2011-05-16

    May 16, 2011 ... Vascular endothelial growth factor (VEGF), a well known angiogenic factor, has been shown to have direct and/or ... Endogenous repair efforts fail to repair ... Spinal cord injury model preparation and intramedullary spinal.

  5. Large breast size as a risk factor for late adverse effects of breast radiotherapy: Is residual dose inhomogeneity, despite 3D treatment planning and delivery, the main explanation?

    International Nuclear Information System (INIS)

    Goldsmith, Christy; Haviland, Joanne; Tsang, Yat; Sydenham, Mark; Yarnold, John

    2011-01-01

    Background and Purpose: Large breast size is associated with an increased risk of late adverse effects after breast conservation surgery and radiotherapy, even when 3D dosimetry is used. The purpose of this study is to test the hypothesis that residual dose inhomogeneity is sufficient to explain the association. Methods: Patients previously treated after breast conservation surgery with whole breast radiotherapy using 3D dosimetry and followed up in the UK FAST hypofractionation trial were selected for this analysis. The residual level of dose inhomogeneity across the whole breast treatment volume was used to test for association between residual dosimetry and post-treatment change in breast appearance at 2 years post-radiotherapy. Results: At 2 years, 201/279 (72%) of women had no change in photographic breast appearance, 61 (22%) had mild change and 17 (6%) had marked change. Breast size and dosimetry were both significantly associated with late effects in univariate analyses, but only breast size remained an independent significant risk factor for change in breast appearance when included in a multiple regression model together with other prognostic factors (p = 0.006 for trend). Conclusion: Large-breasted women are more likely to suffer change in breast size and shape after whole breast radiotherapy delivered using 3D dosimetry, but residual dose inhomogeneity is insufficient to explain the association.

  6. Insulin-like growth factors and pancreas beta cells.

    NARCIS (Netherlands)

    Haeften, T.W. van; Twickler, M.

    2004-01-01

    Abstract Insulin-like growth factors (IGFs) have been implicated in normal growth, and especially foetal pancreas beta-cell development. As low birth weight has been implicated in the development of obesity and type 2 diabetes, much research has evolved into the importance of IGF and their

  7. Insulin-like growth factors and pancreas beta cells

    NARCIS (Netherlands)

    van Haeften, T. W.; Twickler, TB

    Insulin-like growth factors (IGFs) have been implicated in normal growth, and especially foetal pancreas beta-cell development. As low birth weight has been implicated in the development of obesity and type 2 diabetes, much research has evolved into the importance of IGF and their signalling

  8. Insulin-like growth factors and pancreas beta cells

    NARCIS (Netherlands)

    van Haeften, T. W.; Twickler, Th B.

    2004-01-01

    Abstract Insulin-like growth factors (IGFs) have been implicated in normal growth, and especially foetal pancreas beta-cell development. As low birth weight has been implicated in the development of obesity and type 2 diabetes, much research has evolved into the importance of IGF and their

  9. Radiotherapy in supraglottic carcinoma -with respect to locoregional control and survival-

    International Nuclear Information System (INIS)

    Nam, Taek Keun; Oh, Yoon Kyeong; Chung, Woong Ki; Cho, Jae Shik; Ahn, Sung Ja; Nah, Byung Sik

    2002-01-01

    was 100% vs 68% (ρ 0.29), 67% vs 55% (ρ =0.23), 81% vs 20% (ρ < 0.001), respectively. In the radiotherapy alone group, the 5YLCR of the patients with a complete, partial, and minimal response were 76%, 20%, 0%, respectively (ρ < 0.001). In all patients, multivariate analysis showed that the N-stage, surgery or not, and age were significant factors affecting the survival rate and that the N-stage, surgery or not, and the ECOG performance index were significant factors affecting the locoregional control. In the radiotherapy alone group, multivariate analysis showed that the radiation response and N-stage were significant factors affecting the overall survival rate as well as locoregional control. In early stage supraglottic carcinoma, conventional radiotherapy alone is an equally effective modality compared to surgery plus radiotherapy and could preserve the laryngeal function. However, in the advanced stages, radiotherapy combined with concurrent chemotherapy for laryngeal preservations or surgery should be considered. In bulky neck disease, all the possible planned neck dissections after induction chemotherapy or before radiotherapy should be attempted

  10. Growth factor receptors as molecular targets for cancer diagnosis and therapy

    International Nuclear Information System (INIS)

    Zalutsky, M. R.

    1997-01-01

    Growth factor receptors are of great interest as molecular targets for the diagnosis and treatment of cancer. Growth factor receptors are frequently over expressed on malignant cell populations since many cellular oncogenes encode either growth factors of their receptors. The wild-type epidermal growth factor receptor has a molecular weight of 170 kD and is over expressed on gliomas, bladder tumors, squamous cells carcinomas and breast carcinomas. Another growth factor oncogene, c-erb B-2, encodes a 185-kD glycoprotein found on the surface of gliomas, breast and ovarian cancers as well as other carcinomas of epithelial origin. In addition to causing over expression, oncogenic transformation also can result in genomic re-arrangements. An important example from the perspective of targeting is EGFRvIII, a deletion mutant which lacks amino acids 6-273 in the extracellular domain of the epiderma growth factor receptor. The EGFRvIII molecule (145 kD) may be of great value for targeting because it appears to be tumor-specific. Antibodies have been developed with specific reactivity with these growth factor receptors. Since these antibodies are internalized into the cell after receptor binding, it is necessary to use radiolabeling methods which residualize the radioactivity in the tumor cell after intracellular catabolism. To investigate this problem they have evaluated the effect of radioiodination method on the in vitro an in vivo properties of an anti-EGFRvIII antibody. Methods studied were Iodogen, tyramine-cellobiose, and N-succinimidyl 5-iodo-3-pyridine-carboxylate with the last offering optimal localization in a human xenograft model

  11. Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC

    International Nuclear Information System (INIS)

    Langer, Corey J.

    2004-01-01

    Combination chemotherapy regimens have emerged as the standard approach in advanced non-small-cell lung cancer. Meta-analyses have demonstrated a 2-month increase in median survival after platinum-based therapy vs. best supportive care, and an absolute 10% improvement in the 1-year survival rate. Just as importantly, cytotoxic therapy has produced benefits in symptom control and quality of life. Newer agents, including the taxanes, vinorelbine, gemcitabine, and irinotecan, have expanded our therapeutic options in the treatment of advanced non-small-cell lung cancer. Despite their contributions, we have reached a therapeutic plateau, with response rates seldom exceeding 30-40% in cooperative group studies and 1-year survival rates stable between 30% and 40%. It is doubtful that substituting one agent for another in various combinations will lead to any further improvement in these rates. The thrust of current research has focused on targeted therapy, and epidermal growth factor receptor inhibition is one of the most promising clinical strategies. Epidermal growth factor receptor inhibitors currently under investigation include the small molecules gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, OSI-774), as well as monoclonal antibodies such as cetuximab (IMC-225, Erbitux). Agents that have only begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, and PKI166 and GW572016, both examples of dual kinase inhibitors (inhibiting epidermal growth factor receptor and Her2). Preclinical models have demonstrated synergy for all these agents in combination with either chemotherapy or radiotherapy, leading to great enthusiasm regarding their ultimate contribution to lung cancer therapy. However, serious clinical challenges persist. These include the identification of the optimal dose(s); the proper integration of these agents into popular, established cytotoxic regimens; and the selection of the optimal setting(s) in which

  12. Differential expression of growth factors in irradiated mouse testes

    International Nuclear Information System (INIS)

    Mauduit, Claire; Siah, Ahmed; Foch, Marie; Chapet, Olivier; Clippe, Sebastien; Gerard, Jean-Pierre; Benahmed, Mohamed

    2001-01-01

    Purpose: By using as an experimental model the male mouse gonad, which contains both radiosensitive (germ) and radioresistant (somatic) cells, we have studied the growth factor (and/or receptor) expression of transforming growth factor-β receptor (TGFβ RI), stem cell factor (SCF), c-kit, Fas-L, Fas, tumor necrosis factor receptor (TNF R55), and leukemia inhibiting factor receptor (LIF-R) after local irradiation. Methods and Materials: Adult male mice were locally irradiated on the testes. Induction of apoptosis in the different testicular cell types following X-ray radiation was identified by the TdT-mediated dUTP Nick End Labeling (TUNEL) approach. Growth factor expression was evidenced by semiquantitative RT-PCR and Western blot analyses. Results: Apoptosis, identified through the TUNEL approach, occurred in radiosensitive testicular (premeotic) germ cells with the following kinetics: the number of apoptotic cells increased after 24 h (p<0.001) and was maximal 48 h after a 2-Gy ionizing radiation (p<0.001). Apoptotic cells were no longer observed 72 h after a 2-Gy irradiation. The number of apoptotic cells increased with the dose of irradiation (1-4 Gy). In the seminiferous tubules, the growth factor expression in premeiotic radiosensitive germ cells was modulated by irradiation. Indeed Fas, c-kit, and LIF-R expression, which occurs in (radiosensitive) germ cells, decreased 24 h after a 2-Gy irradiation, and the maximal decrease was observed with a 4-Gy irradiation. The decrease in Stra8 expression occurred earlier, at 4 h after a 2-Gy irradiation. In addition, a significant (p<0.03) decrease in Stra8 mRNA levels was observed at the lowest dose used (0.5 Gy, 48 h). Moreover, concerning a growth factor receptor, such as TGFβ RI, which is expressed both in radiosensitive and radioresistant cells, we observed a differential expression depending on the cell radiosensitivity after irradiation. Indeed, TGFβ RI expression was increased after irradiation in

  13. Radiotherapy for pediatric brain stem tumors

    International Nuclear Information System (INIS)

    Shcherbenko, O.I.; Parkhomenko, R.A.; Govorina, E.V.; Zelinskaya, N.I.; Ardatova, G.V.; Nechaeva, V.N.

    2000-01-01

    The immediate and short-term results of gamma therapy of brain stem tumors in 24 children were evaluated. All the patients were able to sustain treatment due to adjuvant support with dehydrating and hormonal drugs, and beneficial clinical effect was recorded in 80%. However, magnetic resonance tomography showed no decrease in tumor size. Tumor growth relapsed 3-8 months after radiotherapy. Although total dose ranged 60-72 Gy in 19 patients, there was no clinical evidence of radiation injury [ru

  14. SU-E-J-159: Analysis of Total Imaging Uncertainty in Respiratory-Gated Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, J; Okuda, T [Toyota memorial hospital, Toyota, Aichi (Japan); Sakaino, S; Yokota, N [Suzukake central hospital, Hamamatsu, Shizuoka (Japan)

    2015-06-15

    Purpose: In respiratory-gated radiotherapy, the gating phase during treatment delivery needs to coincide with the corresponding phase determined during the treatment plan. However, because radiotherapy is performed based on the image obtained for the treatment plan, the time delay, motion artifact, volume effect, and resolution in the images are uncertain. Thus, imaging uncertainty is the most basic factor that affects the localization accuracy. Therefore, these uncertainties should be analyzed. This study aims to analyze the total imaging uncertainty in respiratory-gated radiotherapy. Methods: Two factors of imaging uncertainties related to respiratory-gated radiotherapy were analyzed. First, CT image was used to determine the target volume and 4D treatment planning for the Varian Realtime Position Management (RPM) system. Second, an X-ray image was acquired for image-guided radiotherapy (IGRT) for the BrainLAB ExacTrac system. These factors were measured using a respiratory gating phantom. The conditions applied during phantom operation were as follows: respiratory wave form, sine curve; respiratory cycle, 4 s; phantom target motion amplitude, 10, 20, and 29 mm (which is maximum phantom longitudinal motion). The target and cylindrical marker implanted in the phantom coverage of the CT images was measured and compared with the theoretically calculated coverage from the phantom motion. The theoretical position of the cylindrical marker implanted in the phantom was compared with that acquired from the X-ray image. The total imaging uncertainty was analyzed from these two factors. Results: In the CT image, the uncertainty between the target and cylindrical marker’s actual coverage and the coverage of CT images was 1.19 mm and 2.50mm, respectively. In the Xray image, the uncertainty was 0.39 mm. The total imaging uncertainty from the two factors was 1.62mm. Conclusion: The total imaging uncertainty in respiratory-gated radiotherapy was clinically acceptable. However

  15. SU-E-J-159: Analysis of Total Imaging Uncertainty in Respiratory-Gated Radiotherapy

    International Nuclear Information System (INIS)

    Suzuki, J; Okuda, T; Sakaino, S; Yokota, N

    2015-01-01

    Purpose: In respiratory-gated radiotherapy, the gating phase during treatment delivery needs to coincide with the corresponding phase determined during the treatment plan. However, because radiotherapy is performed based on the image obtained for the treatment plan, the time delay, motion artifact, volume effect, and resolution in the images are uncertain. Thus, imaging uncertainty is the most basic factor that affects the localization accuracy. Therefore, these uncertainties should be analyzed. This study aims to analyze the total imaging uncertainty in respiratory-gated radiotherapy. Methods: Two factors of imaging uncertainties related to respiratory-gated radiotherapy were analyzed. First, CT image was used to determine the target volume and 4D treatment planning for the Varian Realtime Position Management (RPM) system. Second, an X-ray image was acquired for image-guided radiotherapy (IGRT) for the BrainLAB ExacTrac system. These factors were measured using a respiratory gating phantom. The conditions applied during phantom operation were as follows: respiratory wave form, sine curve; respiratory cycle, 4 s; phantom target motion amplitude, 10, 20, and 29 mm (which is maximum phantom longitudinal motion). The target and cylindrical marker implanted in the phantom coverage of the CT images was measured and compared with the theoretically calculated coverage from the phantom motion. The theoretical position of the cylindrical marker implanted in the phantom was compared with that acquired from the X-ray image. The total imaging uncertainty was analyzed from these two factors. Results: In the CT image, the uncertainty between the target and cylindrical marker’s actual coverage and the coverage of CT images was 1.19 mm and 2.50mm, respectively. In the Xray image, the uncertainty was 0.39 mm. The total imaging uncertainty from the two factors was 1.62mm. Conclusion: The total imaging uncertainty in respiratory-gated radiotherapy was clinically acceptable. However

  16. Complications of Radiotherapy after Immediate Breast Reconstruction with Implant: Risk Factors and Management - Our Institute’s Experience

    Directory of Open Access Journals (Sweden)

    Heba G. El-Sheredy

    2016-01-01

    Full Text Available Background: Breast cancer is the most frequent malignant tumor in women worldwide. In recent years, defined reconstruction principles along with numerous surgical techniques with volume replacement have been published. Autologous breast reconstruction is more natural but leaves donor site morbidity. It provides the opportunity to restore the breast mound without the need for scars. This study aims to evaluate the complications of radiotherapy after immediate breast reconstruction with implants in breast cancer patients who submitted to skin sparing mastectomy and nipple sparing mastectomy by taking into consideration the risk factors and management at our institution. Methods: The current study prospectively included patients with invasive breast cancer admitted between January and June 2012 who were scheduled for skin sparing mastectomy or nipple sparing mastectomy and axillary dissection followed by immediate breast reconstruction with implant. Patients received adjuvant chemotherapy followed by conventional fractionated radiation. Complications were classified as either minor or major. The minor complications included capsular contracture (Baker 1-2, seroma, minor skin infection and skin dehiscence without exposure of the implant. Major complications included capsular contracture (Baker 3-4, severe infection and major wound dehiscence with implant exposure. Capsular contracture was scored according to the modified Baker classification. Results: The study included 38 patients. Of these, 28 had skin sparing mastectomy while 10 underwent nipple sparing mastectomy. The overall complication rate was 71%. We observed minor complications in 18 patients while 9 patients had major complications. Complications occurred with a median time of 13 months following radiotherapy completion. All minor complications were managed conservatively whereas all major complications required repeat surgery. No loco-regional recurrences occurred during the follow up

  17. Retrospective study of 48 cases of post-operative radiotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Mnejja, W.; Yahiaoui, S.; Siala, W.; Daoud, J.; Ghorbel, A.; Frikha, M.

    2011-01-01

    The authors report a study which aimed at assessing therapeutic results after post-operative radiotherapy of 48 patients suffering from head and neck cancers. The analysis is made in terms of cancer control, survival without recurrence and global survival. The post-operative radiotherapy improves the disease control rate. Ganglionary attack and capsular failure are survival prognosis factors. The concomitant association of chemo-therapy and radiotherapy should improve therapeutic results. Short communication

  18. Therapeutic Results of Radiotherapy in Rectal Carcinoma -Comparison of Sandwich Technique Radiotherapy with Postoperative Radiotherapy

    International Nuclear Information System (INIS)

    Huh, Gil Cha; Suh, Hyun Suk; Lee, Hyuk Sang; Kim, Re Hwe; Kim, Chul Soo; Kim, Hong Yong; Kim, Sung Rok

    1996-01-01

    Purpose : To evaluate the potential advantage for 'sandwich' technique radiotherapy compared to postoperative radiotherapy in respectable rectal cancer. Between January 1989 and May 1994, 60 patients with respectable rectal cancer were treated at Inje University Seoul and Sanggye Paik Hospital.Fifty one patients were available for analysis : 20 patients were treated with sandwich technique radiotherapy and 31 patients were treated with postoperative radiotherapy. In sandwich technique radiotherapy(RT), patients were treated with preoperative RT 1500 cGy/5fx followed by immediate curative resection. Patients staged as Astler-Coller B2, C were considered for postoperative RT with 2500-4500 cGy. In postoperative RT, total radiation dose of 4500-6120 cGy, 180 cGy daily at 4-6 weeks was delivered. Patients were followed for median period of 25 months. Results : The overall 5-year survival rates for sandwich technique RT group and postoperative RT group were 60% and 71%, respectively(p>0.05). The 5-year disease free survival rates for each group were 63%. There was no difference in local failure rate between two groups(11% versus 7%). Incidence of distant metastasis was 11%(2/20) in the sandwich technique RT group and 20%(6/31) in the postoperative RT group(p>0.05). The frequencies of acute and chronic complications were comparable in both groups. Conclusion : The sandwich technique radiotherapy group shows local recurrence and survival similar to those of postoperative RT alone group but reduced distant metastasis compared to postoperative RT group. But long term follow-up and large number of patients is needed to make an any firm conclusion regarding the value of this sandwich technique RT

  19. A Case of Post-Radiotherapy Gastritis: Radiation Does Not Explain Everything

    Directory of Open Access Journals (Sweden)

    André Abrunhosa-Branquinho

    2014-01-01

    Full Text Available Hemorrhagic gastritis is a possible late toxicity outcome after radical radiotherapy but it is nowadays a very rare condition and most likely depends on other clinical factors. We report the case of a 77-year-old woman with a symptomatic solitary extramedullary intra-abdominal plasmacytoma and multiple gastric comorbidities, treated with external beam radiotherapy. Despite the good response to radiotherapy, the patient experienced multiple gastric bleeding a few months later, with the need of multiple treatments for its control. In this paper we will discuss in detail all aspects related to the different causes of hemorrhagic gastritis.

  20. Elective radiotherapy of the regional lymph node areas in breast cancer

    International Nuclear Information System (INIS)

    Poortmans, P.M.P.

    2006-01-01

    In breast cancer patients, the incidence of involvement of the regional lymph nodes and the risk for developing a locoregional recurrence are highly influenced by several prognostic factors. A meta-analysis of the EBCTCG showed a reduction of about 70% of the locoregional recurrence rate with radiotherapy for all patients, independent of age, characteristics of the tumour or the administration of systemic treatment. At the same time, this meta-analysis confirmed that radiotherapy can lead to an increased risk for developing contralateral breast cancer and to an increase in the risk of non-breast cancer related mortality, mainly due to cardiac and pulmonary toxicity. Because of this, the net effect of regional radiotherapy will be strongly influenced by the individual risk factors of the patients and by the quality of the technical aspects of the radiotherapy. The thin line between the benefits of elective regional lymph node irradiation and the possible late toxicity for patients with early stage breast cancer is currently the subject of several prospective randomized trials, the results of which will only become available in several years. Moreover, recent developments in the field of novel prognostic factors will open completely new ways to be explored, which might give bus new tools for estimating the individual benefit/risk ratio for every single patient. (author)

  1. Expression of FXYD-3 is an Independent Prognostic Factor in Rectal Cancer Patients With Preoperative Radiotherapy

    International Nuclear Information System (INIS)

    Loftas, Per; Onnesjoe, Sofia; Widegren, Emma; Adell, Gunnar; Kayed, Hany; Kleeff, Joerg; Zentgraf, Hanswalter; Sun Xiaofeng

    2009-01-01

    Purpose: FXYD-3 (MAT-8) is overexpressed in several types of cancers; however, its clinical relevance in rectal cancers has not been studied. Therefore, we examined FXYD-3 expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative radiotherapy (RT) to determine whether FXYD-3 was overexpressed in rectal cancers and correlated with RT, survival, and other clinicopathologic variables. Methods and Materials: The study included 140 rectal cancer patients who participated in a clinical trial of preoperative RT, 65 with and 75 without RT before surgery. FXYD-3 expression was immunohistochemically examined in distant (n = 70) and adjacent (n = 101) normal mucosa, primary tumors (n = 140), and lymph node metastasis (n = 36). Results: In the whole cohort, strong FXYD-3 expression was correlated with infiltrative tumor growth (p = 0.02). In the RT group, strong FXYD-3 expression alone (p = 0 .02) or combined with phosphatase of regenerating liver was associated with an unfavorable prognosis (p = 0.02), independent of both TNM stage and tumor differentiation. In tumors with strong FXYD-3 expression, there was less tumor necrosis (p = 0.02) and a trend toward increased incidence of distant metastasis (p = 0.08) after RT. None of these effects was seen in the non-RT group. FXYD-3 expression in the primary tumors tended to be increased compared with normal mucosa regardless of RT. Conclusion: FXYD-3 expression was a prognostic factor independent of tumor stage and differentiation in patients receiving preoperative RT for rectal cancer.

  2. Prognostic impact of HIF-1{alpha} expression in patients with definitive radiotherapy for cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dellas, K.; Bache, M.; Kappler, M.; Haensgen, G. [Halle-Wittenberg Univ., Halle (Germany). Dept. of Radiotherapy; Pigorsch, S.U. [Technische Univ. Muenchen (Germany). Dept. of Radiotherapy and Radiation Oncology; Taubert, H.; Holzhausen, H.J. [Halle-Wittenberg Univ., Halle (Germany). Inst. of Pathology; Holzapfel, D.; Zorn, E. [Halle-Wittenberg Univ., Halle (Germany). Dept. of Radiotherapy; Halle-Wittenberg Univ., Halle (Germany). Inst. of Pathology

    2008-03-15

    Purpose: To investigate the relationship between the hypoxia-inducible factor-(HIF-)1{alpha} expression in tumor tissue, tumor oxygenation and hemoglobin levels in patients with advanced cervical cancers prior to radiotherapy and the effect on clinical outcome. Patients and Methods: The investigation included 44 patients who underwent definitive radiotherapy for advanced cervical cancers between May 1995 and March 1999. Tumor biopsies were taken prior to treatment, and HIF-1{alpha} expression was determined by immunohistochemistry. In the same tumor area, tumor tissue oxygenation (pO{sub 2}) was measured using the Eppendorf device. Results: The 5-year cancer-specific survival of all patients was 60%. Twelve of 44 tumor specimens were HIF-1{alpha}-negative with a significantly better 5-year survival (92 {+-} 8%) versus 32 patients who were HIF-1{alpha}-positive (45 {+-} 10%; p < 0.02). There was no correlation between HIF-1{alpha} expression and tumor oxygenation (p = 0.57 both for pO{sub 2} median and hypoxic fraction < 5 mmHg vs. HIF-1{alpha} expression). However, patients with hemoglobin levels < 11 g/dl showed elevated HIF-1{alpha} expression compared to patients with hemoglobin levels > 12.5 g/dl (p = 0.04). Furthermore, HIF-1{alpha} correlated with vascular endothelial growth factor expression (p = 0.002). In a multivariate Cox regression model, HIF-1{alpha} expression (relative risk [RR] = 7.5; p = 0.05) revealed an increased risk of tumor-related death. Conclusion: The study indicates, that endogenous tumor markers such as HIF-1{alpha} may serve as prognostic markers of clinical outcome concerning cervical cancer after primary radiotherapy. (orig.)

  3. Better compliance with hypofractionation vs. conventional fractionation in adjuvant breast cancer radiotherapy. Results of a single, institutional, retrospective study

    International Nuclear Information System (INIS)

    Rudat, Volker; Nour, Alaa; Hammoud, Mohamed; Abou Ghaida, Salam

    2017-01-01

    The aim of the study was to identify factors significantly associated with the occurrence of unintended treatment interruptions in adjuvant breast cancer radiotherapy. Patients treated with postoperative radiotherapy of the breast or chest wall between March 2014 and August 2016 were evaluated. The radiotherapy regimens and techniques applied were either conventional fractionation (CF; 28 daily fractions of 1.8 Gy or 25 fractions of 2.0 Gy) or hypofractionation (HF; 15 daily fractions of 2.67 Gy) with inverse planned intensity-modulated radiotherapy (IMRT) or three-dimensional planned conformal radiotherapy (3DCRT). Logistic regression analysis was used to identify factors associated with noncompliance. Noncompliance was defined as the missing of at least one scheduled radiotherapy fraction. In all, 19 of 140 (13.6%) patients treated with HF and 39 of 146 (26.7%) treated with CF experienced treatment interruptions. Of 23 factors tested, the fractionation regimen emerged as the only independent significant prognostic factor for noncompliance on multivariate analysis (CF; p = 0.007; odds ratio, 2.3; 95% confidence interval, 1.3-4.2). No statistically significant differences concerning the reasons for treatment interruptions could be detected between patients treated with CF or HF. HF is significantly associated with a better patient compliance with the prescribed radiotherapy schedule compared with CF. The data suggest that this finding is basically related to the shorter overall treatment time of HF. (orig.) [de

  4. Effects of a synthetic bioactive peptide on neurite growth and nerve growth factor release in chondroitin sulfate hydrogels

    OpenAIRE

    Conovaloff, Aaron W.; Beier, Brooke L.; Irazoqui, Pedro P.; Panitch, Alyssa

    2011-01-01

    Previous work has revealed robust dorsal root ganglia neurite growth in hydrogels of chondroitin sulfate. In the current work, it was determined whether addition of a synthetic bioactive peptide could augment neurite growth in these matrices via enhanced binding and sequestering of growth factors. Fluorescence recovery after photobleaching studies revealed that addition of peptide slowed nerve growth factor diffusivity in chondroitin sulfate gels, but not in control gels of hyaluronic acid. F...

  5. Transcription factor control of growth rate dependent genes in Saccharomyces cerevisiae: A three factor design

    DEFF Research Database (Denmark)

    Fazio, Alessandro; Jewett, Michael Christopher; Daran-Lapujade, Pascale

    2008-01-01

    , such as Ace2 and Swi6, and stress response regulators, such as Yap1, were also shown to have significantly enriched target sets. Conclusion: Our work, which is the first genome-wide gene expression study to investigate specific growth rate and consider the impact of oxygen availability, provides a more......Background: Characterization of cellular growth is central to understanding living systems. Here, we applied a three-factor design to study the relationship between specific growth rate and genome-wide gene expression in 36 steady-state chemostat cultures of Saccharomyces cerevisiae. The three...... factors we considered were specific growth rate, nutrient limitation, and oxygen availability. Results: We identified 268 growth rate dependent genes, independent of nutrient limitation and oxygen availability. The transcriptional response was used to identify key areas in metabolism around which m...

  6. Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth.

    Science.gov (United States)

    Wu, Shufang; Yang, Wei; De Luca, Francesco

    2015-07-01

    GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated (TamCart)Igf1r(flox/flox) mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. (TamCart)Igf1r(flox/flox) tamoxifen-treated mice [knockout (KO) mice] and their Igf1r(flox/flox) control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-κB p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects.

  7. Adenovirus E4-ORF1 Dysregulates Epidermal Growth Factor and Insulin/Insulin-Like Growth Factor Receptors To Mediate Constitutive Myc Expression

    OpenAIRE

    Kong, Kathleen; Kumar, Manish; Taruishi, Midori; Javier, Ronald T.

    2015-01-01

    The E4-ORF1 protein encoded by human adenovirus stimulates viral replication in human epithelial cells by binding and activating cellular phosphatidylinositol 3-kinase (PI3K) at the plasma membrane and cellular Myc in the nucleus. In this study, we showed that E4-ORF1 hijacks the tyrosine kinase activities of cellular epidermal growth factor receptor (EGFR) and insulin receptor (InsR)/insulin-like growth factor receptor 1 (IGF1R), as well as the lipid kinase activity of PI3K, to mediate const...

  8. Radiotherapy in the management of cervical cancer in elderly patients

    International Nuclear Information System (INIS)

    Lindegaard, J.C.; Thranov, I.R.; Engelholm, S.A.

    2000-01-01

    One hundred and fourteen elderly patients (median 75.5 years, range 70.0-85.9) consecutively referred for curative radiotherapy in the period 1987-1996 were prospectively followed with regard to tumour control and complications. The importance of age, stage (FIGO), tumour size, histology, tumour fixation, haemoglobin, concurrent disease, performance status (WHO) and type of radiotherapy were assessed using univariate and multivariate analyses. Treatment was completed as planned in 68%, delayed in 29% and stopped prematurely in 3%. The frequency of grade 3 late complications was 11% and the actuarial probability at 5 years was 20%. Overall 5-year survival according to FIGO was 61% (I), 34% (II) and 25% (III). Cox multivariate analysis identified tumour size as independent prognostic factor for tumour control, disease-free survival and overall survival. FIGO stage was predictive for late grade 2 complications. We were unable to identify significant factors with respect to grade 3 complications. Age was not a significant parameter for any of the investigated endpoints. Elderly patients in good performance status with advanced cancer of the uterine may tolerate radical radiotherapy with acceptable morbidity and reasonable survival. Radiotherapy may also be a good alternative in early stage disease for surgically unfit elderly patients. (author)

  9. Gene expression of fibroblast growth factors in human gliomas and meningiomas: Demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues

    International Nuclear Information System (INIS)

    Takahashi, J.A.; Mori, Hirotaka; Fukumoto, Manabu; Oda, Yoshifumi; Kikuchi, Haruhiko; Hatanaka, Masakazu; Igarashi, Koichi; Jaye, M.

    1990-01-01

    The growth autonomy of human tumor cells is considered due to the endogenous production of growth factors. Transcriptional expression of candidates for autocrine stimulatory factors such as basic fibroblast growth factor (FGF), acidic FGF, and transforming growth factor type β were determined in human brain tumors. Basic FGF was expressed abundantly in 17 of 18 gliomas, 20 of 22 meningiomas, and 0 of 5 metastatic brain tumors. The level of mRNA expression of acidic FGF in gliomas was significant. In contrast, transforming growth factor type β1 was expressed in all the samples investigated. The mRNA for basic FGF and its peptide were localized in tumor cells in vivo by in situ hybridization and immunohistochemistry, showing that basic FGF is actually produced in tumor cells. The results suggest that tumor-derived basic FGF is involved in the progression of gliomas and meningiomas in vivo, whereas acidic FGF is expressed in a tumor origin-specific manner, suggesting that acidic FGF works in tandem with basic FGF in glioma tumorigenesis

  10. Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

    International Nuclear Information System (INIS)

    Xu, Ling; Hausmann, Martin; Dietmaier, Wolfgang; Kellermeier, Silvia; Pesch, Theresa; Stieber-Gunckel, Manuela; Lippert, Elisabeth; Klebl, Frank; Rogler, Gerhard

    2010-01-01

    Cholangiocarcinoma (CC) is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro. Expression of EGFR (epithelial growth factor receptor), HGFR (hepatocyte growth factor receptor) IGF1R (insulin-like growth factor 1 receptor), IGF2R (insulin-like growth factor 2 receptor) and VEGFR1-3 (vascular endothelial growth factor receptor 1-3) were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1). The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations. EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml), with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D). HuH28, OZ and TFK-1 lacked KRAS mutation. CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab

  11. Expression of growth factor receptors and targeting of EGFR in cholangiocarcinoma cell lines

    Directory of Open Access Journals (Sweden)

    Kellermeier Silvia

    2010-06-01

    Full Text Available Abstract Background Cholangiocarcinoma (CC is a malignant neoplasm of the bile ducts or the gallbladder. Targeting of growth factor receptors showed therapeutic potential in palliative settings for many solid tumors. The aim of this study was to determine the expression of seven growth factor receptors in CC cell lines and to assess the effect of blocking the EGFR receptor in vitro. Methods Expression of EGFR (epithelial growth factor receptor, HGFR (hepatocyte growth factor receptor IGF1R (insulin-like growth factor 1 receptor, IGF2R (insulin-like growth factor 2 receptor and VEGFR1-3 (vascular endothelial growth factor receptor 1-3 were examined in four human CC cell lines (EGI-1, HuH28, OZ and TFK-1. The effect of the anti-EGFR-antibody cetuximab on cell growth and apoptosis was studied and cell lines were examined for KRAS mutations. Results EGFR, HGFR and IGFR1 were present in all four cell lines tested. IGFR2 expression was confirmed in EGI-1 and TFK-1. No growth-inhibitory effect was found in EGI-1 cells after incubation with cetuximab. Cetuximab dose-dependently inhibited growth in TFK-1. Increased apoptosis was only seen in TFK-1 cells at the highest cetuximab dose tested (1 mg/ml, with no dose-response-relationship at lower concentrations. In EGI-1 a heterozygous KRAS mutation was found in codon 12 (c.35G>A; p.G12D. HuH28, OZ and TFK-1 lacked KRAS mutation. Conclusion CC cell lines express a pattern of different growth receptors in vitro. Growth factor inhibitor treatment could be affected from the KRAS genotype in CC. The expression of EGFR itself does not allow prognoses on growth inhibition by cetuximab.

  12. The surgical treatment of failure in cervical lymph nodes after radiotherapy for nasopharyngeal carcinoma: an analysis of 83 patients

    International Nuclear Information System (INIS)

    Gu Wendong; Ji Qinghai; Lu Xueguan; Feng Yan

    2003-01-01

    Objective: To analyze the results of neck dissection in patients who failed in cervical lymph nodes after radiotherapy for nasopharyngeal carcinoma. Methods: Eighty-three patients who received neck dissection due to lymph node persistence or recurrence after definitive radiotherapy were analyzed retrospectively according to the following relevant factors: age, sex, the interval between completion of radiotherapy and surgery, rN stage, postoperative radiotherapy given or not, the adjacent tissues involved or not and the number of positive nodes. Kaplan-Meier method, Log-rank method and Cox method were used in the statistical analysis. Results: The 1-, 3- and 5-year overall survival rates were 80.7%, 47.1% and 34.9%. The interval between completion of radiotherapy and surgery, postoperative radiotherapy given or not, the adjacent tissues involved or not were significantly prognostic factors in statistic analysis. Conclusions: Neck dissection can be applied in the management of cervical lymph node failure in nasopharyngeal carcinoma after radiotherapy. Postoperative radiotherapy should be considered in patients with capsular invasion and/or adjacent tissue involvement

  13. Historical review of radiotherapy

    International Nuclear Information System (INIS)

    Onai, Yoshio

    1993-01-01

    The techniques of radiotherapy have been improved by development of particle accelerators, radionuclides and computers. This paper presents a historical review of the physical and technical aspects of radiotherapy in Japan. Changes in the kinds of radiation, such as X-rays, gamma rays, electrons, neutrons and protons used for external radiotherapy, and the equipment involved are described chronologically, and historical changes in the quality of radiotherapy apparatus are outlined. Patient data acquisition equipment, such as X-ray simulator and X-ray CT, beam modifying devices, patient setup devices, and devices to verify treatment fields and patient doses are reviewed historically. Radiation sources for brachytherapy and internal radiotherapy, and remotely controlled afterloading systems are reviewed chronologically. Historical changes in methods to evaluate absorbed doses, dose monitor systems and beam data acquisition systems are outlined. Changes in methods of calculating dose distributions for external X-ray and electron therapy, brachytherapy and internal radiotherapy by unsealded radionuclides are described and calculation techniques for treatment planning system are reviewed. Annual figures in the numbers of radiotherapy equipment, such as telecobalt and telecesium units, linear accelerators, betatrons, microtrons, stereotactic gamma units, conformation radiotherapy units, remotely controlled afterloading systems, and associated equipment such as X-ray simulators and treatment planning systems are provided, as are changes in the number of accelerators by maximum X-ray energy and maximum electron energy, and in the number of licensed hospitals and clinics using small sealed sources. Changes in techniques of external radiotherapy and brachytherapy are described briefly from the point of view of dose distributions. (author)

  14. Supramolecular Nanofibers Enhance Growth Factor Signaling by Increasing Lipid Raft Mobility

    Energy Technology Data Exchange (ETDEWEB)

    Newcomb, Christina J.; Sur, Shantanu; Lee, Sungsoo S.; Yu, Jeong Min; Zhou, Yan; Snead, Malcolm L.; Stupp, Samuel I. (NWU); (USC)

    2016-04-12

    The nanostructures of self-assembling biomaterials have been previously designed to tune the release of growth factors in order to optimize biological repair and regeneration. We report here on the discovery that weakly cohesive peptide nanostructures in terms of intermolecular hydrogen bonding, when combined with low concentrations of osteogenic growth factor, enhance both BMP-2 and Wnt mediated signaling in myoblasts and bone marrow stromal cells, respectively. Conversely, analogous nanostructures with enhanced levels of internal hydrogen bonding and cohesion lead to an overall reduction in BMP-2 signaling. We propose that the mechanism for enhanced growth factor signaling by the nanostructures is related to their ability to increase diffusion within membrane lipid rafts. The phenomenon reported here could lead to new nanomedicine strategies to mediate growth factor signaling for translational targets.

  15. The HYP-RT Hypoxic Tumour Radiotherapy Algorithm and Accelerated Repopulation Dose per Fraction Study

    Directory of Open Access Journals (Sweden)

    W. M. Harriss-Phillips

    2012-01-01

    Full Text Available The HYP-RT model simulates hypoxic tumour growth for head and neck cancer as well as radiotherapy and the effects of accelerated repopulation and reoxygenation. This report outlines algorithm design, parameterisation and the impact of accelerated repopulation on the increase in dose/fraction needed to control the extra cell propagation during accelerated repopulation. Cell kill probabilities are based on Linear Quadratic theory, with oxygenation levels and proliferative capacity influencing cell death. Hypoxia is modelled through oxygen level allocation based on pO2 histograms. Accelerated repopulation is modelled by increasing the stem cell symmetrical division probability, while the process of reoxygenation utilises randomised pO2 increments to the cell population after each treatment fraction. Propagation of 108 tumour cells requires 5–30 minutes. Controlling the extra cell growth induced by accelerated repopulation requires a dose/fraction increase of 0.5–1.0 Gy, in agreement with published reports. The average reoxygenation pO2 increment of 3 mmHg per fraction results in full tumour reoxygenation after shrinkage to approximately 1 mm. HYP-RT is a computationally efficient model simulating tumour growth and radiotherapy, incorporating accelerated repopulation and reoxygenation. It may be used to explore cell kill outcomes during radiotherapy while varying key radiobiological and tumour specific parameters, such as the degree of hypoxia.

  16. Conformal radiotherapy by intensity modulation of pediatrics tumors; Radiotherapie conformationnelle par modulation d'intensite des tumeurs pediatriques

    Energy Technology Data Exchange (ETDEWEB)

    Leseur, J.; Le Prise, E. [Centre Eugene-Marquis, 35 - Rennes (France); Carrie, C. [Centre Leon Berard, 69 - Lyon (France); Bernier, V. [Centre Alexis-Vautrin, 54 - Nancy (France); Beneyton, V. [Centre Paul-Strauss, 67 - Strasbourg (France); Mahe, M.A.; Supiot, S. [Centre Rene-Gauducheau, 44 - Nantes (France)

    2009-10-15

    The objective of this study is to take stock on the validated and potential indications of the conformal radiotherapy with intensity modulation ( intensity modulated radiotherapy I.M.R.T.) in pediatrics and to propose recommendations for its use as well as the adapted dose constraints. About 40 to 50% of children treated for a cancer are irradiated. The I.M.R.T., by linear accelerator or helical tomo-therapy has for aim to give a homogenous dose to the target volume and to save organs at risk. Its use in pediatrics seems particularly interesting because of the complexity of target volumes and the closeness of organs at risk. In compensation for these positive elements, the importance of low doses irradiation given in big volumes makes fear event consequences on growth and an increased incidence of secondary cancers in children suffering from tumors with high cure rates and long life expectancy. (N.C.)

  17. Growth and puberty after treatment for acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Alves Claudia Helena Bastos da Silva

    2004-01-01

    Full Text Available Over the last 20 years, after combining treatment of chemotherapy and radiotherapy, there has been an improvement in the survival rate of acute lymphoblastic leukemia patients, with a current cure rate of around 70%. Children with the disease have been enrolled into international treatment protocols designed to improve survival and minimize the serious irreversible late effects. Our oncology unit uses the international protocol: GBTLI LLA-85 and 90, with the drugs methotrexate, cytosine, arabinoside, dexamethasone, and radiotherapy. However, these treatments can cause gonadal damage and growth impairment. PATIENTS AND METHOD: The authors analyzed 20 children off therapy in order to determine the role of the various doses of radiotherapy regarding endocrinological alterations. They were divided into 3 groups according to central nervous system prophylaxis: Group A underwent chemotherapy, group B underwent chemotherapy plus radiotherapy (18 Gy, and group C underwent chemotherapy plus radiotherapy (24 Gy. Serum concentrations of LH, FSH, GH, and testosterone were determined. Imaging studies included bone age, pelvic ultrasound and scrotum, and skull magnetic resonance imaging. RESULTS: Nine of the patients who received radiotherapy had decreased pituitary volume. There was a significant difference in the response to GH and loss of predicted final stature (Bayley-Pinneau between the 2 irradiated groups and the group that was not irradiated, but there was no difference regarding the radiation doses used (18 or 24 Gy. The final predicted height (Bayley-Pinneau was significantly less (P = 0.0071 in both groups treated with radiotherapy. Two girls had precocious puberty, and 1 boy with delayed puberty presented calcification of the epididymis. CONCLUSION: Radiotherapy was been responsible for late side effects, especially related to growth and puberty.

  18. Silencing of osteopontin promotes the radiosensitivity of breast cancer cells by reducing the expression of hypoxia inducible factor 1 and vascular endothelial growth factor

    Institute of Scientific and Technical Information of China (English)

    YANG Li; ZHAO Wei; ZUO Wen-shu; WEI Ling; SONG Xian-rang; WANG Xing-wu; ZHENG Gang; ZHENG Mei-zhu

    2012-01-01

    Background Osteopontin (OPN) is a secreted phosphoglycoprotein (SSP) that is overexpressed in a variety of tumors and was regarded as a molecular marker of tumors.In this study,we intended to demonstrate the role of OPN in human breast cancer cell line MDA-MB-231.Methods Recombinant plasmid expressing small interfering RNA (siRNA) specific to OPN mRNA was transfected into MDA-MB-231 cells to generate the stable transfected cell line MDA-MB-343,and the empty plasmid tansfected cells (MDA-MB-neg) or wildtype MDA-MB-231 cells were used as control cells respectively.Expression of OPN,hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) proteins was analyzed by Western blotting analysis.The radiosensitivity of cells was determined by detecting cell apoptosis,cell proliferation and cell senescence.Results HIF-1 and VEGF proteins in MDA-MB-343 cells were significantly downregulated upon the efficient knockdown of OPN expression under either hypoxia or normoxia environment.Moreover,expression of OPN protein was upregualted upon hypoxic culture.Stable OPN-silencing also decreased cell invasion,increased cell apoptosis and cell senescence,as well as reduced clonogenic survival,resulting in increase radiation tolerance.Conclusions Suppression of OPN gene expression can enhance radiosensitivity and affect cell apoptosis in breast cancer cells.OPN seems to be an attractive target for the improvement of radiotherapy.

  19. Evaluation of different in vitro assays of inherent sensitivity as predictors of radiotherapy response

    International Nuclear Information System (INIS)

    Schwartz, J.L.; Chicago Univ., IL; Beckett, M.A.; Mustafi, R.; Weichselbaum, R.R.; Vaughan, A.T.M.

    1991-01-01

    The inherent sensitivity of cells within a tumor plays an important role in the response of the tumor to radiotherapy. Clonogenic assays show that cells established from in-field radiotherapy failures are significantly more resistant to radiation than cell lines established from pre-treatment samples. Clonogenic assays fail to predict tumor response to radiotherapy, however. The failure might be due to the small sample size in this study, or the complicating factors of staging, surgery, and chemotherapy, and/or in vivo selection by radiotherapy for resistant tumor cells. In vitro selection for resistant cell lines does not appear to be a complicating factor. Nonclonogenic assays such as those that measure DNA strand break rejoining rates (filter elution, pulse-field gel electrophoresis) or chromosome structure (flow cytometric analysis) show promise as alternative rapid assays of radiation sensitivity and possibly tumor response. 16 refs., 2 figs

  20. Big Data Analytics for Prostate Radiotherapy.

    Science.gov (United States)

    Coates, James; Souhami, Luis; El Naqa, Issam

    2016-01-01

    Radiation therapy is a first-line treatment option for localized prostate cancer and radiation-induced normal tissue damage are often the main limiting factor for modern radiotherapy regimens. Conversely, under-dosing of target volumes in an attempt to spare adjacent healthy tissues limits the likelihood of achieving local, long-term control. Thus, the ability to generate personalized data-driven risk profiles for radiotherapy outcomes would provide valuable prognostic information to help guide both clinicians and patients alike. Big data applied to radiation oncology promises to deliver better understanding of outcomes by harvesting and integrating heterogeneous data types, including patient-specific clinical parameters, treatment-related dose-volume metrics, and biological risk factors. When taken together, such variables make up the basis for a multi-dimensional space (the "RadoncSpace") in which the presented modeling techniques search in order to identify significant predictors. Herein, we review outcome modeling and big data-mining techniques for both tumor control and radiotherapy-induced normal tissue effects. We apply many of the presented modeling approaches onto a cohort of hypofractionated prostate cancer patients taking into account different data types and a large heterogeneous mix of physical and biological parameters. Cross-validation techniques are also reviewed for the refinement of the proposed framework architecture and checking individual model performance. We conclude by considering advanced modeling techniques that borrow concepts from big data analytics, such as machine learning and artificial intelligence, before discussing the potential future impact of systems radiobiology approaches.

  1. Radiotherapy for Merkel cell carcinoma of the skin

    International Nuclear Information System (INIS)

    Tai, P.; Pacella, J.; Yu, E.

    2006-01-01

    We examine the impact of radiotherapy in the treatment of Merkel cell carcinomas (MCC) of the skin. Data at two Canadian institutions (Allan Blair Cancer Centre and Regional Cancer Program) were collected and charts were retrieved from the registry of 1997 to 2005. A total of 79 patients with definite MCC were studied. All expect three had a primary skin lesion. Six patients presented with nodal metastases and three patients with distant metastases. Fourteen patients were referred to the cancer centers at the time of recurrence. The series consisted of 40 males and 39 females with a median age of 80 years (range 48-94). The median follow up was 21 months (range 0.5-150.4). Twenty -two patient ass (group A) received radiotherapy at the time of presentation, being post-operative adjuvant treatment an done being primary treatment without surgery.The 5-year cause-specific survival rate (CSSR) was 42%. The 5-year rates equals the 10-year rate since the CSSR plateaus at a survival of 4,5 years and there after, patients died from causes other than MCC. The 5-year overall survival rate (OSR) was 19% for group A. Fifty-seven patients (group B) had surgery alone without post-operative adjuvant radiotherapy. 5-year and 10-year CSSRs were both 63% (P=0.8, using the logrank test when comparing the two groups of patients). The 5-year OSR was 30% and the 10-year OSR was 13% (P=0.6, group A versus group B). Morbidity from radiotherapy was minimal. Only patient had lymphoedema of the arm (which required a pressure garment) after axillary dissection and radiotherapy of 50 Gy in fractions over 35 days. Radiotherapy after surgical excision is well tolerated. It is recommended there are high risk factors for recurrence and radiotherapy should be started as soon as possible after referral. (author)

  2. Changes in performance status of elderly patients after radiotherapy

    International Nuclear Information System (INIS)

    Yamazaki, Hideya; Inoue, Takehiro; Yoshida, Ken

    2001-01-01

    The purpose of this study was to examine the feasibility of external radiation therapy for patients 80 years old and older. We analyzed changes in the performance status (PS) of 1353 patients by external radiotherapy at Osaka Teishin Hospital. In addition, factors influencing PS change and interruption of treatment were assessed in patients undergoing radical and palliative radiotherapy. Among elderly patients aged 80 years or more (n=67), two patients showed deterioration in PS (3%), whereas 128 (10%) did so among those 79 years old or younger. The rate of treatment completion was 90% (60/67) for patients aged 80 years and over compared with 89% (1146/1286) for younger patients. Changes in PS were more frequent for palliative treatment (improvement 83/683, 12%; deterioration 77/683, 11%) than for radical treatment (improvement 12/305, 4%:, deterioration 21/305, 7%) because patients with better performance status and early disease stages underwent radical treatment. For radical radiotherapy, patients with advanced disease (stages III and IV) showed more changes (improvement 4/108, 4%; deterioration 17/108, 16%) than those with early ones (stages I and II) (improvement 7/132, 5%; deterioration 3/132, 2%) (p<0.01). Better treatment results showed a higher treatment completion rate (CR 99%, PR 86%) than poor treatment results (NC 75%, PD 50%) (p<0.01). For palliative therapy, better performance status (PS 0-2) showed a better correlation with completion of treatment (403/451 or 89%) than did poor performance status (PS 3-4) (174/232, 75%) (p<0.01). Age is not a limiting factor for external radiation therapy. Poor performance status is a significant predisposing factor for interruption of palliative radiotherapy. (author)

  3. Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Elias, Elias G., E-mail: george.elias@medstar.net; Hasskamp, Joanne H.; Sharma, Bhuvnesh K. [Maryland Melanoma Center, Weinberg Cancer Institute, Franklin Square Hospital Center, Baltimore, MD (United States)

    2010-05-07

    Cytokines and growth factors have biologic effects that could stimulate tumor growth, invasion and angiogenesis. The incidence of 24 factors was investigated in 25 cultured human melanoma cell lines and in 62 fixed tissues at different stages of the disease. Over 80% of the human melanoma cell lines expressed TGF-β, IL-8, IL-6, VEGF, PDGF-AA and OPN. Significantly higher TGF-β, IGF-1 and IL-15 were determined in primary lesions compared to distant metastases by immunohistochemistry. Illustrating the complexity of the milieu of the tumor microenvironment, some of these factors may have to be considered in targeted therapy.

  4. Release of Growth Factors into Root Canal by Irrigations in Regenerative Endodontics.

    Science.gov (United States)

    Zeng, Qian; Nguyen, Sean; Zhang, Hongming; Chebrolu, Hari Priya; Alzebdeh, Dalia; Badi, Mustafa A; Kim, Jong Ryul; Ling, Junqi; Yang, Maobin

    2016-12-01

    The aim of this study was to investigate the release of growth factors into root canal space after the irrigation procedure of regenerative endodontic procedure. Sixty standardized root segments were prepared from extracted single-root teeth. Nail varnish was applied to all surfaces except the root canal surface. Root segments were irrigated with 1.5% NaOCl + 17% EDTA, 2.5% NaOCl + 17% EDTA, 17% EDTA, or deionized water. The profile of growth factors that were released after irrigation was studied by growth factor array. Enzyme-linked immunosorbent assay was used to validate the release of transforming growth factor (TGF)-β1 and basic fibroblast growth factor (bFGF) at 4 hours, 1 day, and 3 days after irrigation. The final concentrations were calculated on the basis of the root canal volume measured by cone-beam computed tomography. Dental pulp stem cell migration on growth factors released from root segments was measured by using Transwell assay. Total of 11 of 41 growth factors were detected by growth factors array. Enzyme-linked immunosorbent assay showed that TGF-β1 was released in all irrigation groups. Compared with the group with 17% EDTA (6.92 ± 4.49 ng/mL), the groups with 1.5% NaOCl + 17% EDTA and 2.5% NaOCl + 17% EDTA had significantly higher release of TGF-β1 (69.04 ± 30.41 ng/mL and 59.26 ± 3.37 ng/mL, respectively), with a peak release at day 1. The release of bFGF was detected at a low level in all groups (0 ng/mL to 0.43 ± 0.22 ng/mL). Migration assay showed the growth factors released from root segments induced dental pulp stem cell migration. The root segment model in present study simulated clinical scenario and indicated that the current irrigation protocol released a significant amount of TGF-β1 but not bFGF. The growth factors released into root canal space induced dental pulp stem cell migration. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Treatment of pituitary adenomas by fractionated stereotactic radiotherapy: A prospective study of 110 patients

    International Nuclear Information System (INIS)

    Colin, Philippe; Jovenin, Nicolas; Delemer, Brigitte; Caron, Jean; Grulet, Herve; Hecart, Annie-Claude; Lukas, Celine; Bazin, Arnaud; Bernard, Mary-Helene; Scherpereel, Bernard; Peruzzi, Philippe; Nakib, Iab; Redon, Charles; Rousseaux, Pascal

    2005-01-01

    Purpose: To optimize and reduce the toxicity of pituitary adenoma irradiation by assessing the feasibility and effectiveness of fractionated stereotactic radiotherapy (FSR). Methods and Materials: Between 1990 and 1999, 110 consecutive patients, 47 with a functioning adenoma, were treated according to a strategy of either early surgery and FSR (n = 89) or FSR only (n = 21). Of the 110 patients, 75 had persistent macroscopic tumor and 47 persistent hormonal secretions; 15 were treated in the prophylactic setting. The linear accelerator-delivered dose was 50.4 Gy (5 x 1.8 Gy weekly), with a 2-mm safety margin. Results: After a minimal follow-up of 48 months, only 1 patient had developed progression. Of the 110 patients, 27 (36%) had a complete tumor response, 67 (89.3%) had an objective tumor response, 20 (42%) had a hormonal complete response, and 47 (100%) had a hormonal objective tumor response. The proportion of patients without a complete tumor response, objective tumor response, complete hormonal response, and objective hormonal response was 85.1%, 62%, 83%, and 59.3% at 4 years and 49.3%, 9%, 59.3%, and 10.6% at 8 years, respectively. The sole unfavorable predictive factor was preoperative SSE >20 mm for tumor response (p = 0.01) and growth hormone adenoma for the hormonal response (p <0.001). No late complications, exc