Options and pitfalls of normal tissues complication probability models

International Nuclear Information System (INIS)

Dorr, Wolfgang

2011-01-01

Full text: Technological improvements in the physical administration of radiotherapy have led to increasing conformation of the treatment volume (TV) with the planning target volume (PTV) and of the irradiated volume (IV) with the TV. In this process of improvement of the physical quality of radiotherapy, the total volumes of organs at risk exposed to significant doses have significantly decreased, resulting in increased inhomogeneities in the dose distributions within these organs. This has resulted in a need to identify and quantify volume effects in different normal tissues. Today, irradiated volume today must be considered a 6t h 'R' of radiotherapy, in addition to the 5 'Rs' defined by Withers and Steel in the mid/end 1980 s. The current status of knowledge of these volume effects has recently been summarized for many organs and tissues by the QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) initiative [Int. J. Radiat. Oncol. BioI. Phys. 76 (3) Suppl., 2010]. However, the concept of using dose-volume histogram parameters as a basis for dose constraints, even without applying any models for normal tissue complication probabilities (NTCP), is based on (some) assumptions that are not met in clinical routine treatment planning. First, and most important, dose-volume histogram (DVH) parameters are usually derived from a single, 'snap-shot' CT-scan, without considering physiological (urinary bladder, intestine) or radiation induced (edema, patient weight loss) changes during radiotherapy. Also, individual variations, or different institutional strategies of delineating organs at risk are rarely considered. Moreover, the reduction of the 3-dimentional dose distribution into a '2dimensl' DVH parameter implies that the localization of the dose within an organ is irrelevant-there are ample examples that this assumption is not justified. Routinely used dose constraints also do not take into account that the residual function of an organ may be

Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models

NARCIS (Netherlands)

Xu, Cheng-Jian; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A.; van t Veld, Aart A.

2012-01-01

PURPOSE: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator

Calculation of normal tissue complication probability and dose-volume histogram reduction schemes for tissues with a critical element architecture

International Nuclear Information System (INIS)

Niemierko, Andrzej; Goitein, Michael

1991-01-01

The authors investigate a model of normal tissue complication probability for tissues that may be represented by a critical element architecture. They derive formulas for complication probability that apply to both a partial volume irradiation and to an arbitrary inhomogeneous dose distribution. The dose-volume isoeffect relationship which is a consequence of a critical element architecture is discussed and compared to the empirical power law relationship. A dose-volume histogram reduction scheme for a 'pure' critical element model is derived. In addition, a point-based algorithm which does not require precomputation of a dose-volume histogram is derived. The existing published dose-volume histogram reduction algorithms are analyzed. The authors show that the existing algorithms, developed empirically without an explicit biophysical model, have a close relationship to the critical element model at low levels of complication probability. However, it is also showed that they have aspects which are not compatible with a critical element model and the authors propose a modification to one of them to circumvent its restriction to low complication probabilities. (author). 26 refs.; 7 figs

Improving normal tissue complication probability models: the need to adopt a "data-pooling" culture.

Science.gov (United States)

Deasy, Joseph O; Bentzen, Søren M; Jackson, Andrew; Ten Haken, Randall K; Yorke, Ellen D; Constine, Louis S; Sharma, Ashish; Marks, Lawrence B

2010-03-01

Clinical studies of the dependence of normal tissue response on dose-volume factors are often confusingly inconsistent, as the QUANTEC reviews demonstrate. A key opportunity to accelerate progress is to begin storing high-quality datasets in repositories. Using available technology, multiple repositories could be conveniently queried, without divulging protected health information, to identify relevant sources of data for further analysis. After obtaining institutional approvals, data could then be pooled, greatly enhancing the capability to construct predictive models that are more widely applicable and better powered to accurately identify key predictive factors (whether dosimetric, image-based, clinical, socioeconomic, or biological). Data pooling has already been carried out effectively in a few normal tissue complication probability studies and should become a common strategy. Copyright 2010 Elsevier Inc. All rights reserved.

Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126

International Nuclear Information System (INIS)

Moore, Kevin L.; Schmidt, Rachel; Moiseenko, Vitali; Olsen, Lindsey A.; Tan, Jun; Xiao, Ying; Galvin, James; Pugh, Stephanie; Seider, Michael J.; Dicker, Adam P.; Bosch, Walter; Michalski, Jeff; Mutic, Sasa

2015-01-01

Purpose: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. Methods and Materials: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH 0126,top10% ). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed “high-quality,” “low-quality,” and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Results: Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH 0126,top10% to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP

Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126.

Science.gov (United States)

Moore, Kevin L; Schmidt, Rachel; Moiseenko, Vitali; Olsen, Lindsey A; Tan, Jun; Xiao, Ying; Galvin, James; Pugh, Stephanie; Seider, Michael J; Dicker, Adam P; Bosch, Walter; Michalski, Jeff; Mutic, Sasa

2015-06-01

The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH0126,top10%). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed "high-quality," "low-quality," and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH0126,top10% to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP reductions while maintaining the volume of the PTV

MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

International Nuclear Information System (INIS)

Constine, L; Hodgson, D; Bentzen, S

2014-01-01

With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-response data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for

MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

Energy Technology Data Exchange (ETDEWEB)

Constine, L; Hodgson, D; Bentzen, S [University of Maryland, Baltimore, MD (United States)

2014-06-15

With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-response data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for

The effect of customized beam shaping on normal tissue complications in radiation therapy of parotid gland tumors

International Nuclear Information System (INIS)

Keus, R.; Boer, R. de; Lebesque, J.; Noach, P.

1991-01-01

The impact of customized beam shaping was studied for 5 patients with parotid tumors treated with a paired wedged field technique. For each patient 2 plans were generated. The standard plan had unblocked portals with field sizes defined by the largest target contour found in any CT slice. In the 2nd plan customized beam's view (BEV) designed blocks were added to both beams. The differences in those distributions between the 2 types of plans were evaluated using dose-volume histograms (DVH). As expected, the dose distribution within the target volume showed no difference. However, a considerable sparing of normal tissue was observed for the plans with customized blocks. The volume of un-necessary exposed normal tissue that received more than 90 percent of the prescribed dose, was reduced by a factor of about 4: from 165 to 44 percent on an average, if the volume is expressed as a percentage of the target volume in each patient. In particular, the homolateral mandible showed a mean decrease of 21 percent of integral dose when blocks were used. Normal tissue complication probabilities (NTCP) were calculated. For a tumor dose of 70 Gy, the average bone necrosis probability was reduced from 8.4 percent (no blocks) to 4.1. percent (blocks). For other normal tissues such as nervous tissue, other soft tissues and bones a substantial reduction of integral dose was found for al patients when individual blocks were used. (author). 10 refs.; 4 figs.; 2 tabs

Normal tissue complication probability (NTCP), the clinician,s perspective

International Nuclear Information System (INIS)

Yeoh, E.K.

2011-01-01

Full text: 3D radiation treatment planning has enabled dose distributions to be related to the volume of normal tissues irradiated. The dose volume histograms thus derived have been utilized to set NTCP dose constraints to facilitate optimization of treatment planning. However, it is not widely appreciated that a number of important variables other than DYH's which determine NTCP in the individual patient. These variables will be discussed under the headings of patient and treatment related as well as tumour related factors. Patient related factors include age, co-morbidities such as connective tissue disease and diabetes mellitus, previous tissue/organ damage, tissue architectural organization (parallel or serial), regional tissue/organ and individual tissue/organ radiosensitivities as well as the development of severe acute toxicity. Treatment related variables which need to be considered include dose per fraction (if not the conventional 1.8012.00 Gy/fraction, particularly for IMRT), number of fractions and total dose, dose rate (particularly if combined with brachytherapy) and concurrent chemotherapy or other biological dose modifiers. Tumour related factors which impact on NTCP include infiltration of normal tissue/organ usually at presentation leading to compromised function but also with recurrent disease after radiation therapy as well as variable tumour radiosensitivities between and within tumour types. Whilst evaluation of DYH data is a useful guide in the choice of treatment plan, the current state of knowledge requires the clinician to make an educated judgement based on a consideration of the other factors.

Measurement of human normal tissue and tumour responses

International Nuclear Information System (INIS)

Ross, G.; Yarnold, J.R.

1988-01-01

The scarcity of quantitative measures of normal tissue damage and tumour response in patients undergoing radiotherapy is an obstacle to the clinical evaluation of new treatment strategies. Retrospective studies of complications in critical normal tissues taught important lessons in the past concerning the potential dangers of hypofractionation. However, it is unethical to use serious complications as planned end-points in prospective studies. This paper reviews the desirable characteristics of clinical end-points required to compare alternative treatments employing radiotherapy, with emphasis on simple scales applied by clinicians or even the patients themselves

A new plan-scoring method using normal tissue complication probability for personalized treatment plan decisions in prostate cancer

Science.gov (United States)

Kim, Kwang Hyeon; Lee, Suk; Shim, Jang Bo; Yang, Dae Sik; Yoon, Won Sup; Park, Young Je; Kim, Chul Yong; Cao, Yuan Jie; Chang, Kyung Hwan

2018-01-01

The aim of this study was to derive a new plan-scoring index using normal tissue complication probabilities to verify different plans in the selection of personalized treatment. Plans for 12 patients treated with tomotherapy were used to compare scoring for ranking. Dosimetric and biological indexes were analyzed for the plans for a clearly distinguishable group ( n = 7) and a similar group ( n = 12), using treatment plan verification software that we developed. The quality factor ( QF) of our support software for treatment decisions was consistent with the final treatment plan for the clearly distinguishable group (average QF = 1.202, 100% match rate, n = 7) and the similar group (average QF = 1.058, 33% match rate, n = 12). Therefore, we propose a normal tissue complication probability (NTCP) based on the plan scoring index for verification of different plans for personalized treatment-plan selection. Scoring using the new QF showed a 100% match rate (average NTCP QF = 1.0420). The NTCP-based new QF scoring method was adequate for obtaining biological verification quality and organ risk saving using the treatment-planning decision-support software we developed for prostate cancer.

The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

International Nuclear Information System (INIS)

Defraene, Gilles; Van den Bergh, Laura; Al-Mamgani, Abrahim; Haustermans, Karin; Heemsbergen, Wilma; Van den Heuvel, Frank; Lebesque, Joos V.

2012-01-01

Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011–0.013) clinical factor was “previous abdominal surgery.” As second significant (p = 0.012–0.016) factor, “cardiac history” was included in all three rectal bleeding fits, whereas including “diabetes” was significant (p = 0.039–0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003–0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D 50 . Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints. Conclusions

The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Defraene, Gilles, E-mail: gilles.defraene@uzleuven.be [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Van den Bergh, Laura [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Al-Mamgani, Abrahim [Department of Radiation Oncology, Erasmus Medical Center - Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Haustermans, Karin [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Heemsbergen, Wilma [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Van den Heuvel, Frank [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Lebesque, Joos V. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

2012-03-01

Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was 'previous abdominal surgery.' As second significant (p = 0.012-0.016) factor, 'cardiac history' was included in all three rectal bleeding fits, whereas including 'diabetes' was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D{sub 50}. Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints

Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

International Nuclear Information System (INIS)

Rose, Brent S.; Aydogan, Bulent; Liang, Yun; Yeginer, Mete; Hasselle, Michael D.; Dandekar, Virag; Bafana, Rounak; Yashar, Catheryn M.; Mundt, Arno J.; Roeske, John C.; Mell, Loren K.

2011-01-01

Purpose: To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. Methods and Materials: We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving ≥10 and 20 Gy (V 10 and V 20 ) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. Results: In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V 10 (regression coefficient (β) = -0.060, p = 0.009) and V 20 (β = -0.044, p = 0.010). In the combined cohort, the (adjusted) β estimates for log (white blood cell) vs. V 10 and V 20 were as follows: -0.022 (p = 0.025) and -0.021 (p = 0.002), respectively. Patients with V 10 ≥ 95% were more likely to experience Grade ≥3 leukopenia (68.8% vs. 24.6%, p 20 > 76% (57.7% vs. 21.8%, p = 0.001). Conclusions: These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V 10 20 < 76% may reduce HT.

Normal tissue complication models for clinically relevant acute esophagitis (≥ grade 2) in patients treated with dose differentiated accelerated radiotherapy (DART-bid)

International Nuclear Information System (INIS)

Zehentmayr, Franz; Söhn, Matthias; Exeli, Ann-Katrin; Wurstbauer, Karl; Tröller, Almut; Deutschmann, Heinz; Fastner, Gerd; Fussl, Christoph; Steininger, Philipp; Kranzinger, Manfred; Belka, Claus; Studnicka, Michael; Sedlmayer, Felix

2015-01-01

One of the primary dose-limiting toxicities during thoracic irradiation is acute esophagitis (AE). The aim of this study is to investigate dosimetric and clinical predictors for AE grade ≥ 2 in patients treated with accelerated radiotherapy for locally advanced non-small cell lung cancer (NSCLC). 66 NSCLC patients were included in the present analysis: 4 stage II, 44 stage IIIA and 18 stage IIIB. All patients received induction chemotherapy followed by dose differentiated accelerated radiotherapy (DART-bid). Depending on size (mean of three perpendicular diameters) tumors were binned in four dose groups: <2.5 cm 73.8 Gy, 2.5–4.5 cm 79.2 Gy, 4.5–6 cm 84.6 Gy, >6 cm 90 Gy. Patients were treated in 3D target splitting technique. In order to estimate the normal tissue complication probability (NTCP), two Lyman models and the cutoff-logistic regression model were fitted to the data with AE ≥ grade 2 as statistical endpoint. Inter-model comparison was performed with the corrected Akaike information criterion (AIC c ), which calculates the model’s quality of fit (likelihood value) in relation to its complexity (i.e. number of variables in the model) corrected by the number of patients in the dataset. Toxicity was documented prospectively according to RTOG. The median follow up was 686 days (range 84–2921 days), 23/66 patients (35 %) experienced AE ≥ grade 2. The actuarial local control rates were 72.6 % and 59.4 % at 2 and 3 years, regional control was 91 % at both time points. The Lyman-MED model (D50 = 32.8 Gy, m = 0.48) and the cutoff dose model (D c = 38 Gy) provide the most efficient fit to the current dataset. On multivariate analysis V38 (volume of the esophagus that receives 38 Gy or above, 95 %-CI 28.2–57.3) was the most significant predictor of AE ≥ grade 2 (HR = 1.05, CI 1.01–1.09, p = 0.007). Following high-dose accelerated radiotherapy the rate of AE ≥ grade 2 is slightly lower than reported for concomitant radio-chemotherapy with the

Normal tissue complication probability: Does simultaneous integrated boost intensity-modulated radiotherapy score over other techniques in treatment of prostate adenocarcinoma

Directory of Open Access Journals (Sweden)

Jothy Basu K

2009-01-01

Full Text Available Aim: The main objective of this study was to analyze the radiobiological effect of different treatment strategies on high-risk prostate adenocarcinoma. Materials and Methods: Ten cases of high-risk prostate adenocarcinoma were selected for this dosimetric study. Four different treatment strategies used for treating prostate cancer were compared. Conventional four-field box technique covering prostate and nodal volumes followed by three-field conformal boost (3D + 3DCRT, four-field box technique followed by intensity-modulated radiotherapy (IMRT boost (3D + IMRT, IMRT followed by IMRT boost (IMRT + IMRT, and simultaneous integrated boost IMRT (SIBIMRT were compared in terms of tumor control probability (TCP and normal tissue complication probability (NTCP. The dose prescription except for SIBIMRT was 45 Gy in 25 fractions for the prostate and nodal volumes in the initial phase and 27 Gy in 15 fractions for the prostate in the boost phase. For SIBIMRT, equivalent doses were calculated using biologically equivalent dose assuming the α/β ratio of 1.5 Gy with a dose prescription of 60.75 Gy for the gross tumor volume (GTV and 45 Gy for the clinical target volume in 25 fractions. IMRT plans were made with 15-MV equispaced seven coplanar fields. NTCP was calculated using the Lyman-Kutcher-Burman (LKB model. Results: An NTCP of 10.7 ± 0.99%, 8.36 ± 0.66%, 6.72 ± 0.85%, and 1.45 ± 0.11% for the bladder and 14.9 ± 0.99%, 14.04 ± 0.66%, 11.38 ± 0.85%, 5.12 ± 0.11% for the rectum was seen with 3D + 3DCRT, 3D + IMRT, IMRT + IMRT, and SIBIMRT respectively. Conclusions: SIBIMRT had the least NTCP over all other strategies with a reduced treatment time (3 weeks less. It should be the technique of choice for dose escalation in prostate carcinoma.

Normal tissue dose-effect models in biological dose optimisation

International Nuclear Information System (INIS)

Alber, M.

2008-01-01

Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

Radiobiology in clinical radiation therapy - Part III: Normal tissue damage

International Nuclear Information System (INIS)

Travis, Elizabeth L.

1996-01-01

relationship of tissue architecture to radiation-induced damage and the available clinical and experimental data which demonstrate volume effects as well as those factors which complicate efforts to estimate normal tissue complication probabilities

Lyman Alpha Control

CERN Document Server

Nielsen, Daniel Stefaniak

2015-01-01

This document gives an overview of how to operate the Lyman Alpha Control application written in LabVIEW along with things to watch out for. Overview of the LabVIEW code itself as well as the physical wiring of and connections from/to the NI PCI-6229 DAQ box is also included. The Lyman Alpha Control application is the interface between the ALPHA sequencer and the HighFinesse Wavelength Meter as well as the Lyman Alpha laser setup. The application measures the wavelength of the output light from the Lyman Alpha cavity through the Wavelength Meter. The application can use the Wavelength Meter’s PID capabilities to stabilize the Lyman Alpha laser output as well as switch between up to three frequencies.

Dosimetric precision requirements and quantities for characterizing the response of tumors and normal tissues

Energy Technology Data Exchange (ETDEWEB)

Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

1996-08-01

Based on simple radiobiological models the effect of the distribution of absorbed dose in therapy beams on the radiation response of tumor and normal tissue volumes are investigated. Under the assumption that the dose variation in the treated volume is small it is shown that the response of the tissue to radiation is determined mainly by the mean dose to the tumor or normal tissue volume in question. Quantitative expressions are also given for the increased probability of normal tissue complications and the decreased probability of tumor control as a function of increasing dose variations around the mean dose level to these tissues. When the dose variations are large the minimum tumor dose (to cm{sup 3} size volumes) will generally be better related to tumor control and the highest dose to significant portions of normal tissue correlates best to complications. In order not to lose more than one out of 20 curable patients (95% of highest possible treatment outcome) the required accuracy in the dose distribution delivered to the target volume should be 2.5% (1{sigma}) for a mean dose response gradient {gamma} in the range 2 - 3. For more steeply responding tumors and normal tissues even stricter requirements may be desirable. (author). 15 refs, 6 figs.

Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord

Energy Technology Data Exchange (ETDEWEB)

Adamus-Górka, Magdalena; Mavroidis, Panayiotis, E-mail: panayiotis.mavroidis@ki.se; Lind, Bengt K.; Brahme, Anders [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm S-17176 (Sweden)

2011-05-18

Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ{sup 2}-distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint.

Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord

International Nuclear Information System (INIS)

Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Lind, Bengt K.; Brahme, Anders

2011-01-01

Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ 2 -distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint

A method of analyzing rectal surface area irradiated and rectal complications in prostate conformal radiotherapy

International Nuclear Information System (INIS)

Lu Yong; Song, Paul Y.; Li Shidong; Spelbring, Danny R.; Vijayakumar, Srinivasan; Haraf, Daniel J.; Chen, George T.Y.

1995-01-01

Purpose: To develop a method of analyzing rectal surface area irradiated and rectal complications in prostate conformal radiotherapy. Methods and Materials: Dose-surface histograms of the rectum, which state the rectal surface area irradiated to any given dose, were calculated for a group of 27 patients treated with a four-field box technique to a total (tumor minimum) dose ranging from 68 to 70 Gy. Occurrences of rectal toxicities as defined by the Radiation Therapy Oncology Group (RTOG) were recorded and examined in terms of dose and rectal surface area irradiated. For a specified end point of rectal complication, the complication probability was analyzed as a function of dose irradiated to a fixed rectal area, and as a function of area receiving a fixed dose. Lyman's model of normal tissue complication probability (NTCP) was used to fit the data. Results: The observed occurrences of rectal complications appear to depend on the rectal surface area irradiated to a given dose level. The patient distribution of each toxicity grade exhibits a maximum as a function of percentage surface area irradiated, and the maximum moves to higher values of percentage surface area as the toxicity grade increases. The dependence of the NTCP for the specified end point on dose and percentage surface area irradiated was fitted to Lyman's NTCP model with a set of parameters. The curvature of the NTCP as a function of the surface area suggests that the rectum is a parallel structured organ. Conclusions: The described method of analyzing rectal surface area irradiated yields interesting insight into understanding rectal complications in prostate conformal radiotherapy. Application of the method to a larger patient data set has the potential to facilitate the construction of a full dose-surface-complication relationship, which would be most useful in guiding clinical practice

SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Lindsay, WD; Berlind, CG; Gee, JC; Simone, CB

2015-01-01

Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Lindsay, WD [University of Pennsylvania, Philadelphia, PA (United States); Oncora Medical, LLC, Philadelphia, PA (United States); Berlind, CG [Georgia Institute of Technology, Atlanta, GA (Georgia); Oncora Medical, LLC, Philadelphia, PA (United States); Gee, JC; Simone, CB [University of Pennsylvania, Philadelphia, PA (United States)

2015-06-15

Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models.

Science.gov (United States)

Xu, Cheng-Jian; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A; van't Veld, Aart A

2012-03-15

To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended. Copyright © 2012 Elsevier Inc. All rights reserved.

Impact of Statistical Learning Methods on the Predictive Power of Multivariate Normal Tissue Complication Probability Models

Energy Technology Data Exchange (ETDEWEB)

Xu Chengjian, E-mail: c.j.xu@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Schilstra, Cornelis; Langendijk, Johannes A.; Veld, Aart A. van' t [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

2012-03-15

Purpose: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. Methods and Materials: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. Results: It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. Conclusions: The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.

Impact of Statistical Learning Methods on the Predictive Power of Multivariate Normal Tissue Complication Probability Models

International Nuclear Information System (INIS)

Xu Chengjian; Schaaf, Arjen van der; Schilstra, Cornelis; Langendijk, Johannes A.; Veld, Aart A. van’t

2012-01-01

Purpose: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. Methods and Materials: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. Results: It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. Conclusions: The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.

Weighing the Low-Redshift Lyman-alpha Forest

Science.gov (United States)

Shull, Mike

2005-01-01

In 2003-2004, our FUSE research group prepared several major surveys of the amount of baryonic matter in the intergalactic medium (IGM), using the Far Ultraviolet Spectroscopic Explorer (FUSE) satellite. These surveys include measurements of the Lyman-alpha absorption line of neutral hydrogen (H I), the far-ultraviolet (1032,1038 Angstrom) doublet of highly ionized oxygen ( O VI), the higher Lyman-series lines (Ly-beta, Ly-gamma, etc) of H I, and the 977 Angstrom line of c III. As an overview, our FUSE spectroscopic studies, taken together with data from the Hubble Space Telescope, show that approximately 30% of the normal matter is contained in intergalactic hydrogen gas clouds (the Lyman-alpha forest). Another 5-10% resides in hotter gas at temperatures of 10(exp 5) to 10(exp 6) K, visible in 0 VI and C III absorption. Along with the matter attributed to galaxies, we have now accounted for approximately HALF of all the baryonic matter in the universe. Where is the other half? That matter my exist in even hotter gas, invisible through the ultraviolet absorption lines, but perhaps detectable through X-ray absorption lines of more highly ionized oxygen and neon.

Incorporating Single-nucleotide Polymorphisms Into the Lyman Model to Improve Prediction of Radiation Pneumonitis

Energy Technology Data Exchange (ETDEWEB)

Tucker, Susan L., E-mail: sltucker@mdanderson.org [Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li Minghuan [Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong (China); Xu Ting; Gomez, Daniel [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Yuan Xianglin [Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Yu Jinming [Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong (China); Liu Zhensheng; Yin Ming; Guan Xiaoxiang; Wang Lie; Wei Qingyi [Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Vinogradskiy, Yevgeniy [University of Colorado School of Medicine, Aurora, Colorado (United States); Martel, Mary [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2013-01-01

Purpose: To determine whether single-nucleotide polymorphisms (SNPs) in genes associated with DNA repair, cell cycle, transforming growth factor-{beta}, tumor necrosis factor and receptor, folic acid metabolism, and angiogenesis can significantly improve the fit of the Lyman-Kutcher-Burman (LKB) normal-tissue complication probability (NTCP) model of radiation pneumonitis (RP) risk among patients with non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen SNPs from 10 different genes (XRCC1, XRCC3, APEX1, MDM2, TGF{beta}, TNF{alpha}, TNFR, MTHFR, MTRR, and VEGF) were genotyped in 141 NSCLC patients treated with definitive radiation therapy, with or without chemotherapy. The LKB model was used to estimate the risk of severe (grade {>=}3) RP as a function of mean lung dose (MLD), with SNPs and patient smoking status incorporated into the model as dose-modifying factors. Multivariate analyses were performed by adding significant factors to the MLD model in a forward stepwise procedure, with significance assessed using the likelihood-ratio test. Bootstrap analyses were used to assess the reproducibility of results under variations in the data. Results: Five SNPs were selected for inclusion in the multivariate NTCP model based on MLD alone. SNPs associated with an increased risk of severe RP were in genes for TGF{beta}, VEGF, TNF{alpha}, XRCC1 and APEX1. With smoking status included in the multivariate model, the SNPs significantly associated with increased risk of RP were in genes for TGF{beta}, VEGF, and XRCC3. Bootstrap analyses selected a median of 4 SNPs per model fit, with the 6 genes listed above selected most often. Conclusions: This study provides evidence that SNPs can significantly improve the predictive ability of the Lyman MLD model. With a small number of SNPs, it was possible to distinguish cohorts with >50% risk vs <10% risk of RP when they were exposed to high MLDs.

Local stem cell depletion model for normal tissue damage

International Nuclear Information System (INIS)

Yaes, R.J.; Keland, A.

1987-01-01

The hypothesis that radiation causes normal tissue damage by completely depleting local regions of tissue of viable stem cells leads to a simple mathematical model for such damage. In organs like skin and spinal cord where destruction of a small volume of tissue leads to a clinically apparent complication, the complication probability is expressed as a function of dose, volume and stem cell number by a simple triple negative exponential function analogous to the double exponential function of Munro and Gilbert for tumor control. The steep dose response curves for radiation myelitis that are obtained with our model are compared with the experimental data for radiation myelitis in laboratory rats. The model can be generalized to include other types or organs, high LET radiation, fractionated courses of radiation, and cases where an organ with a heterogeneous stem cell population receives an inhomogeneous dose of radiation. In principle it would thus be possible to determine the probability of tumor control and of damage to any organ within the radiation field if the dose distribution in three dimensional space within a patient is known

Radiobiology of normal tissue. Scientific advances and perspectives; Strahlenbiologie der Normalgewebe. Wissenschaftliche Fortschritte und Perspektiven

Energy Technology Data Exchange (ETDEWEB)

Doerr, W. [Medizinische Univ. Wien (Austria). Universitaetsklinik fuer Strahlentherapie; Medizinische Univ. Wien (Austria). Universitaetsklinik fuer Radioonkologie; Medizinische Univ. Wien (Austria). Christian Doppler Labor fuer Medizinische Strahlenforschung fuer die Radioonkologie; Herskind, C. [Universitaetsmedizin Mannheim, Heidelberg Univ., Mannheim (Germany). Labor fuer Zellulaere und Molekulare Radioonkologie

2012-11-15

Radiotherapy involves always the exposure of normal tissue, resulting in an excepted risk of complications. The side effect rate is therefore the compromise between optimized tumor doses and the side effect minimization. The report covers the issues target cell hypothesis and the consequences, new aspect of the pathogenesis of normal issue reactions and strategies of targeted reduction of normal tissue effects. The complexity of the radiobiological processes, the specificity and action mechanisms, the mutual interactions of chemical and radiological processes require further coordinated radiobiological research in the future.

Method for Automatic Selection of Parameters in Normal Tissue Complication Probability Modeling.

Science.gov (United States)

Christophides, Damianos; Appelt, Ane L; Gusnanto, Arief; Lilley, John; Sebag-Montefiore, David

2018-07-01

To present a fully automatic method to generate multiparameter normal tissue complication probability (NTCP) models and compare its results with those of a published model, using the same patient cohort. Data were analyzed from 345 rectal cancer patients treated with external radiation therapy to predict the risk of patients developing grade 1 or ≥2 cystitis. In total, 23 clinical factors were included in the analysis as candidate predictors of cystitis. Principal component analysis was used to decompose the bladder dose-volume histogram into 8 principal components, explaining more than 95% of the variance. The data set of clinical factors and principal components was divided into training (70%) and test (30%) data sets, with the training data set used by the algorithm to compute an NTCP model. The first step of the algorithm was to obtain a bootstrap sample, followed by multicollinearity reduction using the variance inflation factor and genetic algorithm optimization to determine an ordinal logistic regression model that minimizes the Bayesian information criterion. The process was repeated 100 times, and the model with the minimum Bayesian information criterion was recorded on each iteration. The most frequent model was selected as the final "automatically generated model" (AGM). The published model and AGM were fitted on the training data sets, and the risk of cystitis was calculated. The 2 models had no significant differences in predictive performance, both for the training and test data sets (P value > .05) and found similar clinical and dosimetric factors as predictors. Both models exhibited good explanatory performance on the training data set (P values > .44), which was reduced on the test data sets (P values < .05). The predictive value of the AGM is equivalent to that of the expert-derived published model. It demonstrates potential in saving time, tackling problems with a large number of parameters, and standardizing variable selection in NTCP

Lyman NTCP model analysis of radiation-induced liver disease in hypofractionated conformal radiotherapy for primary liver carcinoma

International Nuclear Information System (INIS)

Xu Zhiyong; Zhu Yi; Zhao Jiaodong; Fu Xiaolong; Jiang Guoliang; Liang Shixiong; Zhu Xiaodong

2006-01-01

Objective: To identify the factors associated with radiation-induced liver disease (RILD) and to describe the probability of RILD using the Lyman normal tissue complication(NTCP) model for primary liver carcinoma(PLC) treated with hypofractionated conformal therapy (CRT). Methods: A total of 109 PLC patients treated with hypofractionated CRT were prospectively followed according to the Child-Pugh classification for liver cirrhosis, 93 patients in class A and 16 in class B. The mean dose of radiation to the isocenter was (53.5±5.5) Gy, fractions of (4.8±0.5) Gy, with interfraction interval of 48 hours and irradiation 3 times per week. Maximal likelihood analysis yielded the best estimates of parameters of the Lyman NTCP model for all patients; Child-Pugh A and Child-Pugh B patients, respectively. Results: Of all the patients, 17 developed RILD (17/109), 8 in Child-Pugh A (8/93) and 9 in Child-Pugh B (9/16). By multivariate analysis, only the Child-Pugh Grade of liver cirrhosis was the independent factor (P=0.000) associated with the developing of BILD. The best estimates of the NTCP parameters for all 109 patients were n=1.1, m=0.35 and TD 50 (1)=38.5 Gy. The n, m, TD 50 (1) estimated from patients with Child-Pugh A was 1.1, 0.28, 40.5 Gy, respectively, compared with 0.7, 0.43, 23 Gy respectively, for patients with Child-Pugh B. Conclusions: Primary liver cancer patients who possess Child-Pugh B cirrhosis would present a significantly greater susceptibility to RILD after hypofractionated CRT than patients with Child-Pugh A cirrhosis. The predominant risk factor for developing RILD is the severity of hepatic cirrhosis in the liver of PLC patients. (authors)

The Lyman alpha reference sample

DEFF Research Database (Denmark)

Hayes, M.; Östlin, G.; Schaerer, D.

2013-01-01

We report on new imaging observations of the Lyman alpha emission line (Lyα), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028

Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

International Nuclear Information System (INIS)

Bentzen, Soeren M.

1997-01-01

assays may be as a guide for the prescription of treatment schedules that are costly or involves a high risk of complications. Examples of this are certain strategies attempting to widen the therapeutic window, the use of very high doses or re-irradiation of a previously irradiated region, or the selection of patients for experimental strategies like the use of biological response modifiers to reduce normal-tissue toxicity. Finally, published data are summarized on the possible correlation between the radiosensitivities of tumor and normal tissues or between the sensitivities of various normal tissues

Multivariate Normal Tissue Complication Probability Modeling of Heart Valve Dysfunction in Hodgkin Lymphoma Survivors

International Nuclear Information System (INIS)

Cella, Laura; Liuzzi, Raffaele; Conson, Manuel; D’Avino, Vittoria; Salvatore, Marco; Pacelli, Roberto

2013-01-01

Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD). Methods and Materials: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger. Conclusions: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity

Multivariate normal tissue complication probability modeling of gastrointestinal toxicity after external beam radiotherapy for localized prostate cancer

International Nuclear Information System (INIS)

Cella, Laura; D’Avino, Vittoria; Liuzzi, Raffaele; Conson, Manuel; Doria, Francesca; Faiella, Adriana; Loffredo, Filomena; Salvatore, Marco; Pacelli, Roberto

2013-01-01

The risk of radio-induced gastrointestinal (GI) complications is affected by several factors other than the dose to the rectum such as patient characteristics, hormonal or antihypertensive therapy, and acute rectal toxicity. Purpose of this work is to study clinical and dosimetric parameters impacting on late GI toxicity after prostate external beam radiotherapy (RT) and to establish multivariate normal tissue complication probability (NTCP) model for radiation-induced GI complications. A total of 57 men who had undergone definitive RT for prostate cancer were evaluated for GI events classified using the RTOG/EORTC scoring system. Their median age was 73 years (range 53–85). The patients were assessed for GI toxicity before, during, and periodically after RT completion. Several clinical variables along with rectum dose-volume parameters (Vx) were collected and their correlation to GI toxicity was analyzed by Spearman’s rank correlation coefficient (Rs). Multivariate logistic regression method using resampling techniques was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC). At a median follow-up of 30 months, 37% (21/57) patients developed G1-2 acute GI events while 33% (19/57) were diagnosed with G1-2 late GI events. An NTCP model for late mild/moderate GI toxicity based on three variables including V65 (OR = 1.03), antihypertensive and/or anticoagulant (AH/AC) drugs (OR = 0.24), and acute GI toxicity (OR = 4.3) was selected as the most predictive model (Rs = 0.47, p < 0.001; AUC = 0.79). This three-variable model outperforms the logistic model based on V65 only (Rs = 0.28, p < 0.001; AUC = 0.69). We propose a logistic NTCP model for late GI toxicity considering not only rectal irradiation dose but also clinical patient-specific factors. Accordingly, the risk of G1-2 late GI increases as V65 increases, it is higher for patients experiencing

LYMAN : a new window on the universe

International Nuclear Information System (INIS)

Dopita, M.A.; Tuohy, I.R.; Mathewson, D.S.; Hunstead, R.W.; Waterworth, M.D.

1988-01-01

This document is the final Phase A Science Report of the Australian LYMAN Science Working Group, and describes in detail the scientific objectives, technical feasibility, and engineering implementation of the LYMAN mission as developed in the Australian studies. LYMAN represents the next generation, high-orbit, UV space observatory, and is designed to operate over the wavelength range λ 100 - 1900 Angstrom. The prime spectral range is λ 900 - 1250 Angstrom, which will be covered at a resolution of λ/Δ λ = 30000, and the sensitivity of the instrumentation will be orders of magnitude better than previous missions. In this region we find the Lyman series of molecular and atomic hydrogen, as well as a whole host of atomic and ionic lines of great diagnostic power. LYMAN will be able to accomplish uniquely valuable astrophysics as a result, and will be applied to the study of all types of astronomical targets in the fields of cosmology, galactic research, the interstellar medium, stars in all stages of their evolution, and to particular solar system objects. The LYMAN Mission was the subject of a $1M study contract awarded by the Australian Space Office, a section of DITAC, to Auspace Pty. Ltd. The Phase A study was conduced in parallel with the ESA Phase A Study, and with a strong scientific and technical liaison between the two groups. LYMAN is now likely to be launched as a joint ESA/NASA project, but the future Australian role in the mission, as determined by current policy, would be minimal. Australia would therefore be effectively locked out of the very exciting front-line science described in this document, and the valuable university - industry liaison that has been developed over the last eight years will be lost

Variability of the Lyman alpha flux with solar activity

International Nuclear Information System (INIS)

Lean, J.L.; Skumanich, A.

1983-01-01

A three-component model of the solar chromosphere, developed from ground based observations of the Ca II K chromospheric emission, is used to calculate the variability of the Lyman alpha flux between 1969 and 1980. The Lyman alpha flux at solar minimum is required in the model and is taken as 2.32 x 10 11 photons/cm 2 /s. This value occurred during 1975 as well as in 1976 near the commencement of solar cycle 21. The model predicts that the Lyman alpha flux increases to as much as 5 x 10 11 photons/cm 2 /s at the maximum of the solar cycle. The ratio of the average fluxes for December 1979 (cycle maximum) and July 1976 (cycle minimum) is 1.9. During solar maximum the 27-day solar rotation is shown to cause the Lyman alpha flux to vary by as much as 40% or as little as 5%. The model also shows that the Lyman alpha flux varies over intermediate time periods of 2 to 3 years, as well as over the 11-year sunspot cycle. We conclude that, unlike the sunspot number and the 10.7-cm radio flux, the Lyman alpha flux had a variability that was approximately the same during each of the past three cycles. Lyman alpha fluxes calculated by the model are consistent with measurements of the Lyman alpha flux made by 11 of a total of 14 rocket experiments conducted during the period 1969--1980. The model explains satisfactorily the absolute magnitude, long-term trends, and the cycle variability seen in the Lyman alpha irradiances by the OSO 5 satellite experiment. The 27-day variability observed by the AE-E satellite experiment is well reproduced. However, the magntidue of the AE-E 1 Lyman alpha irradiances are higher than the model calculations by between 40% and 80%. We suggest that the assumed calibration of the AE-E irradiances is in error

Neutron RBE for normal tissues

International Nuclear Information System (INIS)

Field, S.B.; Hornsey, S.

1979-01-01

RBE for various normal tissues is considered as a function of neutron dose per fraction. Results from a variety of centres are reviewed. It is shown that RBE is dependent on neutron energy and is tissue dependent, but is not specially high for the more critical tissues or for damage occurring late after irradiation. (author)

Normal tissue complication probability model parameter estimation for xerostomia in head and neck cancer patients based on scintigraphy and quality of life assessments

International Nuclear Information System (INIS)

Lee, Tsair-Fwu; Chao, Pei-Ju; Wang, Hung-Yu; Hsu, Hsuan-Chih; Chang, PaoShu; Chen, Wen-Cheng

2012-01-01

With advances in modern radiotherapy (RT), many patients with head and neck (HN) cancer can be effectively cured. However, xerostomia is a common complication in patients after RT for HN cancer. The purpose of this study was to use the Lyman–Kutcher–Burman (LKB) model to derive parameters for the normal tissue complication probability (NTCP) for xerostomia based on scintigraphy assessments and quality of life (QoL) questionnaires. We performed validation tests of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines against prospectively collected QoL and salivary scintigraphic data. Thirty-one patients with HN cancer were enrolled. Salivary excretion factors (SEFs) measured by scintigraphy and QoL data from self-reported questionnaires were used for NTCP modeling to describe the incidence of grade 3 + xerostomia. The NTCP parameters estimated from the QoL and SEF datasets were compared. Model performance was assessed using Pearson’s chi-squared test, Nagelkerke’s R 2 , the area under the receiver operating characteristic curve, and the Hosmer–Lemeshow test. The negative predictive value (NPV) was checked for the rate of correctly predicting the lack of incidence. Pearson’s chi-squared test was used to test the goodness of fit and association. Using the LKB NTCP model and assuming n=1, the dose for uniform irradiation of the whole or partial volume of the parotid gland that results in 50% probability of a complication (TD 50 ) and the slope of the dose–response curve (m) were determined from the QoL and SEF datasets, respectively. The NTCP-fitted parameters for local disease were TD 50 =43.6 Gy and m=0.18 with the SEF data, and TD 50 =44.1 Gy and m=0.11 with the QoL data. The rate of grade 3 + xerostomia for treatment plans meeting the QUANTEC guidelines was specifically predicted, with a NPV of 100%, using either the QoL or SEF dataset. Our study shows the agreement between the NTCP parameter modeling based on SEF and

Normal tissue complication probability model parameter estimation for xerostomia in head and neck cancer patients based on scintigraphy and quality of life assessments

Science.gov (United States)

2012-01-01

Background With advances in modern radiotherapy (RT), many patients with head and neck (HN) cancer can be effectively cured. However, xerostomia is a common complication in patients after RT for HN cancer. The purpose of this study was to use the Lyman–Kutcher–Burman (LKB) model to derive parameters for the normal tissue complication probability (NTCP) for xerostomia based on scintigraphy assessments and quality of life (QoL) questionnaires. We performed validation tests of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines against prospectively collected QoL and salivary scintigraphic data. Methods Thirty-one patients with HN cancer were enrolled. Salivary excretion factors (SEFs) measured by scintigraphy and QoL data from self-reported questionnaires were used for NTCP modeling to describe the incidence of grade 3+ xerostomia. The NTCP parameters estimated from the QoL and SEF datasets were compared. Model performance was assessed using Pearson’s chi-squared test, Nagelkerke’s R2, the area under the receiver operating characteristic curve, and the Hosmer–Lemeshow test. The negative predictive value (NPV) was checked for the rate of correctly predicting the lack of incidence. Pearson’s chi-squared test was used to test the goodness of fit and association. Results Using the LKB NTCP model and assuming n=1, the dose for uniform irradiation of the whole or partial volume of the parotid gland that results in 50% probability of a complication (TD50) and the slope of the dose–response curve (m) were determined from the QoL and SEF datasets, respectively. The NTCP-fitted parameters for local disease were TD50=43.6 Gy and m=0.18 with the SEF data, and TD50=44.1 Gy and m=0.11 with the QoL data. The rate of grade 3+ xerostomia for treatment plans meeting the QUANTEC guidelines was specifically predicted, with a NPV of 100%, using either the QoL or SEF dataset. Conclusions Our study shows the agreement between the NTCP

Normal tissue complication probability model parameter estimation for xerostomia in head and neck cancer patients based on scintigraphy and quality of life assessments

Directory of Open Access Journals (Sweden)

Lee Tsair-Fwu

2012-12-01

Full Text Available Abstract Background With advances in modern radiotherapy (RT, many patients with head and neck (HN cancer can be effectively cured. However, xerostomia is a common complication in patients after RT for HN cancer. The purpose of this study was to use the Lyman–Kutcher–Burman (LKB model to derive parameters for the normal tissue complication probability (NTCP for xerostomia based on scintigraphy assessments and quality of life (QoL questionnaires. We performed validation tests of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC guidelines against prospectively collected QoL and salivary scintigraphic data. Methods Thirty-one patients with HN cancer were enrolled. Salivary excretion factors (SEFs measured by scintigraphy and QoL data from self-reported questionnaires were used for NTCP modeling to describe the incidence of grade 3+ xerostomia. The NTCP parameters estimated from the QoL and SEF datasets were compared. Model performance was assessed using Pearson’s chi-squared test, Nagelkerke’s R2, the area under the receiver operating characteristic curve, and the Hosmer–Lemeshow test. The negative predictive value (NPV was checked for the rate of correctly predicting the lack of incidence. Pearson’s chi-squared test was used to test the goodness of fit and association. Results Using the LKB NTCP model and assuming n=1, the dose for uniform irradiation of the whole or partial volume of the parotid gland that results in 50% probability of a complication (TD50 and the slope of the dose–response curve (m were determined from the QoL and SEF datasets, respectively. The NTCP-fitted parameters for local disease were TD50=43.6 Gy and m=0.18 with the SEF data, and TD50=44.1 Gy and m=0.11 with the QoL data. The rate of grade 3+ xerostomia for treatment plans meeting the QUANTEC guidelines was specifically predicted, with a NPV of 100%, using either the QoL or SEF dataset. Conclusions Our study shows the agreement

Bariatric surgery: A review of normal postoperative anatomy and complications

International Nuclear Information System (INIS)

Quigley, S.; Colledge, J.; Mukherjee, S.; Patel, K.

2011-01-01

The number of bariatric surgery procedures performed is increasing every year. Patients may be referred for radiological investigations to exclude complications not only in the early postoperative period but many months later. Radiologists who do not work in bariatric centres are therefore required to have an understanding of the complex normal anatomy and complications associated with bariatric surgery to interpret imaging studies correctly. The purpose of this article is to describe the surgical techniques and normal anatomy of the four bariatric operations performed today, review the most common problems encountered in this patient group, and to describe the imaging findings that allow the accurate diagnosis of complications. In particular, we focus on identification of the internal hernia, a grave complication of bariatric surgery often missed by radiologists.

Bariatric surgery: A review of normal postoperative anatomy and complications

Energy Technology Data Exchange (ETDEWEB)

Quigley, S., E-mail: shaun.quigley@bartsandthelondon.nhs.uk [Radiology Department, Homerton University Hospital NHS Foundation Trust, London (United Kingdom); Colledge, J. [Radiology Department, Homerton University Hospital NHS Foundation Trust, London (United Kingdom); Mukherjee, S. [Bariatric Surgery Unit, Homerton University Hospital NHS Foundation Trust, London (United Kingdom); Patel, K. [Radiology Department, Homerton University Hospital NHS Foundation Trust, London (United Kingdom)

2011-10-15

The number of bariatric surgery procedures performed is increasing every year. Patients may be referred for radiological investigations to exclude complications not only in the early postoperative period but many months later. Radiologists who do not work in bariatric centres are therefore required to have an understanding of the complex normal anatomy and complications associated with bariatric surgery to interpret imaging studies correctly. The purpose of this article is to describe the surgical techniques and normal anatomy of the four bariatric operations performed today, review the most common problems encountered in this patient group, and to describe the imaging findings that allow the accurate diagnosis of complications. In particular, we focus on identification of the internal hernia, a grave complication of bariatric surgery often missed by radiologists.

Fragmentation inside atomic cooling haloes exposed to Lyman-Werner radiation

Science.gov (United States)

Regan, John A.; Downes, Turlough P.

2018-04-01

Supermassive stars born in pristine environments in the early Universe hold the promise of being the seeds for the supermassive black holes observed as high redshift quasars shortly after the epoch of reionisation. H2 suppression is thought to be crucial in order to negate normal Population III star formation and allow high accretion rates to drive the formation of supermassive stars. Only in the cases where vigorous fragmentation is avoided will a monolithic collapse be successful, giving rise to a single massive central object. We investigate the number of fragmentation sites formed in collapsing atomic cooling haloes subject to various levels of background Lyman-Werner flux. The background Lyman-Werner flux manipulates the chemical properties of the gas in the collapsing halo by destroying H2. We find that only when the collapsing gas cloud shifts from the molecular to the atomic cooling regime is the degree of fragmentation suppressed. In our particular case, we find that this occurs above a critical Lyman-Werner background of J ˜ 10 J21. The important criterion being the transition to the atomic cooling regime rather than the actual value of J, which will vary locally. Once the temperature of the gas exceeds T ≳ 104 K and the gas transitions to atomic line cooling, then vigorous fragmentation is strongly suppressed.

Wound Complications in Preoperatively Irradiated Soft-Tissue Sarcomas of the Extremities

Energy Technology Data Exchange (ETDEWEB)

Rosenberg, Lewis A. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Esther, Robert J. [Department of Orthopedics, University of North Carolina, Chapel Hill, North Carolina (United States); Erfanian, Kamil [Department of Surgery, University of North Carolina, Chapel Hill, North Carolina (United States); Green, Rebecca [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Kim, Hong Jin; Sweeting, Raeshell [Department of Surgery, University of North Carolina, Chapel Hill, North Carolina (United States); Tepper, Joel E., E-mail: tepper@med.unc.edu [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States)

2013-02-01

Purpose: To determine whether the involvement of plastic surgery and the use of vascularized tissue flaps reduces the frequency of major wound complications after radiation therapy for soft-tissue sarcomas (STS) of the extremities. Methods and Materials: This retrospective study evaluated patients with STS of the extremities who underwent radiation therapy before surgery. Major complications were defined as secondary operations with anesthesia, seroma/hematoma aspirations, readmission for wound complications, or persistent deep packing. Results: Between 1996 and 2010, 73 patients with extremity STS were preoperatively irradiated. Major wound complications occurred in 32% and secondary operations in 16% of patients. Plastic surgery closed 63% of the wounds, and vascularized tissue flaps were used in 22% of closures. When plastic surgery performed closure the frequency of secondary operations trended lower (11% vs 26%; P=.093), but the frequency of major wound complications was not different (28% vs 38%; P=.43). The use of a vascularized tissue flap seemed to have no effect on the frequency of complications. The occurrence of a major wound complication did not affect disease recurrence or survival. For all patients, 3-year local control was 94%, and overall survival was 72%. Conclusions: The rates of wound complications and secondary operations in this study were very similar to previously published results. We were not able to demonstrate a significant relationship between the involvement of plastic surgery and the rate of wound complications, although there was a trend toward reduced secondary operations when plastic surgery was involved in the initial operation. Wound complications were manageable and did not compromise outcomes.

Wound Complications in Preoperatively Irradiated Soft-Tissue Sarcomas of the Extremities

International Nuclear Information System (INIS)

Rosenberg, Lewis A.; Esther, Robert J.; Erfanian, Kamil; Green, Rebecca; Kim, Hong Jin; Sweeting, Raeshell; Tepper, Joel E.

2013-01-01

Purpose: To determine whether the involvement of plastic surgery and the use of vascularized tissue flaps reduces the frequency of major wound complications after radiation therapy for soft-tissue sarcomas (STS) of the extremities. Methods and Materials: This retrospective study evaluated patients with STS of the extremities who underwent radiation therapy before surgery. Major complications were defined as secondary operations with anesthesia, seroma/hematoma aspirations, readmission for wound complications, or persistent deep packing. Results: Between 1996 and 2010, 73 patients with extremity STS were preoperatively irradiated. Major wound complications occurred in 32% and secondary operations in 16% of patients. Plastic surgery closed 63% of the wounds, and vascularized tissue flaps were used in 22% of closures. When plastic surgery performed closure the frequency of secondary operations trended lower (11% vs 26%; P=.093), but the frequency of major wound complications was not different (28% vs 38%; P=.43). The use of a vascularized tissue flap seemed to have no effect on the frequency of complications. The occurrence of a major wound complication did not affect disease recurrence or survival. For all patients, 3-year local control was 94%, and overall survival was 72%. Conclusions: The rates of wound complications and secondary operations in this study were very similar to previously published results. We were not able to demonstrate a significant relationship between the involvement of plastic surgery and the rate of wound complications, although there was a trend toward reduced secondary operations when plastic surgery was involved in the initial operation. Wound complications were manageable and did not compromise outcomes.

Lyman-alpha clouds as a relic of primordial density fluctuations

International Nuclear Information System (INIS)

Bond, J.R.; Szalay, A.S.; Silk, J.

1988-01-01

Primordial density fluctuations are studied using a CDM model and primordial clouds some of which are expanding, driven by pressure gradients created when the medium is photionized, and some of which are massive enough to continue collapsing in spite of the pressure. Normalization of CDM models to the clustering properties on large scales are used to predict the parameters of collapsing clouds of subgalactic mass at early epochs. It is shown that the abundance and dimensions of these clouds are comparable to those of the Lyman-alpha systems. The evolutionary history of the clouds is computed, utilizing a spherically symmetric hydrodynamics code with the dark matter treated as a collisionless fluid, and the H I column density distribution is evaluated as a function of N(H I) and redshift. The observed cloud parameters come out naturally in the CDM model and suggest that Lyman-alpha clouds are the missing link between primordial density fluctuations and the formation of galaxies. 31 references

Comparison of incidences of normal tissue complications with tumor response in a phase III trial comparing heat plus radiation to radiation alone

International Nuclear Information System (INIS)

Dewhirst, M.W.; Sim, D.A.; Grochowski, K.J.

1984-01-01

The success of hyperthermia (/sup Δ/) as an adjuvant to radiation (XRT) will depend on whether the increase in tumor control is greater than that for normal tissue reactions. One hundred and thirty dogs and cats were stratified by histology and randomized to receive XRT (460 rads per fraction, two fractions per week, for eight fractions) or /sup Δ/ + XRT (30 min. at 44 +-2 0 C; one fraction per week, four fractions; immediately prior to XRT). Heat induced changes in tumor and normal tissue responses were made by comparing ratios of incidence for /sup Δ/ + XRT and XRT alone (TRR; Thermal Relative Risk). Change in tumor response duration was calculated from statistical analysis of response duration curves (RRR; Relative Relapse Rate). Heat increased early normal tissue reactions (moist desquamation and mucositis by a factor of 1.08. Tumor complete response, by comparison, was significantly improved (TRR = 2.12, p < .001). Late skin fibrosis was also increased (TRR = 1.51), but the prolongation in tumor response was greater (RRR 1.85). The degree of thermal enhancement for all tissues was dependent on the minimum temperature achieved on the first treatment, but the values for tumor were consistently greater than those achieved for normal tissues

Hard and soft tissue surgical complications in dental implantology.

Science.gov (United States)

Aziz, Shahid R

2015-05-01

This article discusses surgical complications associated with the placement of dental implants, specifically focusing on how they occur (etiology), as well as their management and prevention. Dental implant surgical complications can be classified into those of hard and soft tissues. In general, complications can be avoided with thorough preoperative treatment planning and proper surgical technique. Copyright © 2015 Elsevier Inc. All rights reserved.

Predicting Lung Radiotherapy-Induced Pneumonitis Using a Model Combining Parametric Lyman Probit With Nonparametric Decision Trees

International Nuclear Information System (INIS)

Das, Shiva K.; Zhou Sumin; Zhang, Junan; Yin, F.-F.; Dewhirst, Mark W.; Marks, Lawrence B.

2007-01-01

Purpose: To develop and test a model to predict for lung radiation-induced Grade 2+ pneumonitis. Methods and Materials: The model was built from a database of 234 lung cancer patients treated with radiotherapy (RT), of whom 43 were diagnosed with pneumonitis. The model augmented the predictive capability of the parametric dose-based Lyman normal tissue complication probability (LNTCP) metric by combining it with weighted nonparametric decision trees that use dose and nondose inputs. The decision trees were sequentially added to the model using a 'boosting' process that enhances the accuracy of prediction. The model's predictive capability was estimated by 10-fold cross-validation. To facilitate dissemination, the cross-validation result was used to extract a simplified approximation to the complicated model architecture created by boosting. Application of the simplified model is demonstrated in two example cases. Results: The area under the model receiver operating characteristics curve for cross-validation was 0.72, a significant improvement over the LNTCP area of 0.63 (p = 0.005). The simplified model used the following variables to output a measure of injury: LNTCP, gender, histologic type, chemotherapy schedule, and treatment schedule. For a given patient RT plan, injury prediction was highest for the combination of pre-RT chemotherapy, once-daily treatment, female gender and lowest for the combination of no pre-RT chemotherapy and nonsquamous cell histologic type. Application of the simplified model to the example cases revealed that injury prediction for a given treatment plan can range from very low to very high, depending on the settings of the nondose variables. Conclusions: Radiation pneumonitis prediction was significantly enhanced by decision trees that added the influence of nondose factors to the LNTCP formulation

Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: Normal tissue complication probability modeling with latent time correction

International Nuclear Information System (INIS)

Rønjom, Marianne Feen; Brink, Carsten; Bentzen, Søren M.; Hegedüs, Laszlo; Overgaard, Jens; Johansen, Jørgen

2013-01-01

Background and purpose: To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors. Patients and methods: Patients with HNSCC receiving definitive radiotherapy with 66–68 Gy without surgery were followed up with serial post-treatment thyrotropin (TSH) assessment. HT was defined as TSH >4.0 mU/l. Data were analyzed with both a logistic and a mixture model (correcting for latency) to determine risk factors for HT and develop an NTCP model based on mean thyroid dose (MTD) and thyroid volume. Results: 203 patients were included. Median follow-up: 25.1 months. Five-year estimated risk of HT was 25.6%. In the mixture model, the only independent risk factors for HT were thyroid volume (cm 3 ) (OR = 0.75 [95% CI: 0.64–0.85], p 3 , respectively. Conclusions: Comparing the logistic and mixture models demonstrates the importance of latent-time correction in NTCP-modeling. Thyroid dose constraints in treatment planning should be individualized based on thyroid volume

Oxygen delivery in irradiated normal tissue

Energy Technology Data Exchange (ETDEWEB)

Kiani, M.F.; Ansari, R. [Univ. of Tennessee Health Science Center, Memphis, TN (United States). School of Biomedical Engineering; Gaber, M.W. [St. Jude Children' s Research Hospital, Memphis, TN (United States)

2003-03-01

Ionizing radiation exposure significantly alters the structure and function of microvascular networks, which regulate delivery of oxygen to tissue. In this study we use a hamster cremaster muscle model to study changes in microvascular network parameters and use a mathematical model to study the effects of these observed structural and microhemodynamic changes in microvascular networks on oxygen delivery to the tissue. Our experimental observations indicate that in microvascular networks while some parameters are significantly affected by irradiation (e.g. red blood cell (RBC) transit time), others remain at the control level (e.g. RBC path length) up to 180 days post-irradiation. The results from our mathematical model indicate that tissue oxygenation patterns are significantly different in irradiated normal tissue as compared to age-matched controls and the differences are apparent as early as 3 days post irradiation. However, oxygen delivery to irradiated tissue was not found to be significantly different from age matched controls at any time between 7 days to 6 months post-irradiation. These findings indicate that microvascular late effects in irradiated normal tissue may be due to factors other than compromised tissue oxygenation. (author)

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

Energy Technology Data Exchange (ETDEWEB)

Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Washington University School of Medicine, St Louis, MO (United States); Barthold, H. Joseph [Commonwealth Hematology and Oncology, Weymouth, MA (United States); Beth Israel Deaconess Medical Center, Boston, MA (Israel); O' Meara, Elizabeth [Radiation Therapy Oncology Group, Philadelphia, PA (United States); Bosch, Walter R. [Washington University School of Medicine, St Louis, MO (United States); El Naqa, Issam [Department of Radiation Oncology, McGill University Health Center, Montreal, Quebec (Canada); Al-Lozi, Rawan [Washington University School of Medicine, St Louis, MO (United States); Rosenthal, Seth A. [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); Lawton, Colleen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Lee, W. Robert [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Sandler, Howard [Cedars-Sinai Medical Center, Los Angeles, CA (United States); Zietman, Anthony [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Myerson, Robert [Washington University School of Medicine, St Louis, MO (United States); Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Willett, Christopher [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Kachnic, Lisa A. [Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA (United States); Jhingran, Anuja [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Portelance, Lorraine [University of Miami, Miami, FL (United States); Ryu, Janice [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); and others

2012-07-01

Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa{sub R}, Adnexa{sub L}, Prostate, SeminalVesc, PenileBulb, Femur{sub R}, and Femur{sub L}. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.

Radiogenomics: predicting clinical normal tissue radiosensitivity

DEFF Research Database (Denmark)

Alsner, Jan

2006-01-01

Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on risk...

Continuous coherent Lyman-alpha excitation of atomic hydrogen.

NARCIS (Netherlands)

Eikema, K.S.E.; Waltz, J.; Hänsch, T.

2001-01-01

The first near natural linewidth of the 1S-2P transition in atomic hydrogen was reported with a high degree of accuracy. A high yield of continuous Lyman-α radiation based on four wave mixing in mercury was employed. It was shown that laser cooloing and detection with Lyman-α radiation has excellent

Probabilities of Pulmonary and Cardiac Complications and Radiographic Parameters in Breast Cancer Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Noh, O Kyu; Paek, Sung Ho; Ahn, Seung Do; Choi, Eun Kyung; Lee, Sang Wook; Song, Si Yeol; Yoon, Sang Min; Kim, Jong Hoon [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2010-11-15

To evaluate the relationship between the normal tissue complication probability (NTCP) of 3- dimensional (3-D) radiotherapy and the radiographic parameters of 2-dimensional (2-D) radiotherapy such as central lung distance (CLD) and maximal heart distance (MHD). We analyzed 110 patients who were treated with postoperative radiotherapy for breast cancer. A two-field tangential technique, a three-field technique, and the reverse hockey stick method were used. The radiation dose administered to whole breast or the chest wall was 50.4 Gy, whereas a 45 Gy was administered to the supraclavicular field. The NTCPs of the heart and lung were calculated by the modified Lyman model and the relative seriality model. For all patients, the NTCPs of radiation-induced pneumonitis and cardiac mortality were 0.5% and 0.7%, respectively. The NTCP of radiation-induced pneumonitis was higher in patients treated with the reverse hockey stick method than in those treated by other two techniques (0.0%, 0.0%, 3.1%, p<0.001). The NTCP of radiation-induced pneumonitis increased with CLD. The NTCP of cardiac mortality increased with MHD (R2=0.808). We found a close correlation between the NTCP of 3-D radiotherapy and 2-D radiographic parameters. Our results are useful to reanalyze the previous 2-D based clinical reports about breast radiation therapy complications as a viewpoint of NTCP.

Probabilities of Pulmonary and Cardiac Complications and Radiographic Parameters in Breast Cancer Radiotherapy

International Nuclear Information System (INIS)

Noh, O Kyu; Paek, Sung Ho; Ahn, Seung Do; Choi, Eun Kyung; Lee, Sang Wook; Song, Si Yeol; Yoon, Sang Min; Kim, Jong Hoon

2010-01-01

To evaluate the relationship between the normal tissue complication probability (NTCP) of 3- dimensional (3-D) radiotherapy and the radiographic parameters of 2-dimensional (2-D) radiotherapy such as central lung distance (CLD) and maximal heart distance (MHD). We analyzed 110 patients who were treated with postoperative radiotherapy for breast cancer. A two-field tangential technique, a three-field technique, and the reverse hockey stick method were used. The radiation dose administered to whole breast or the chest wall was 50.4 Gy, whereas a 45 Gy was administered to the supraclavicular field. The NTCPs of the heart and lung were calculated by the modified Lyman model and the relative seriality model. For all patients, the NTCPs of radiation-induced pneumonitis and cardiac mortality were 0.5% and 0.7%, respectively. The NTCP of radiation-induced pneumonitis was higher in patients treated with the reverse hockey stick method than in those treated by other two techniques (0.0%, 0.0%, 3.1%, p<0.001). The NTCP of radiation-induced pneumonitis increased with CLD. The NTCP of cardiac mortality increased with MHD (R2=0.808). We found a close correlation between the NTCP of 3-D radiotherapy and 2-D radiographic parameters. Our results are useful to reanalyze the previous 2-D based clinical reports about breast radiation therapy complications as a viewpoint of NTCP.

Lyman alpha SMM/UVSP absolute calibration and geocoronal correction

Science.gov (United States)

Fontenla, Juan M.; Reichmann, Edwin J.

1987-01-01

Lyman alpha observations from the Ultraviolet Spectrometer Polarimeter (UVSP) instrument of the Solar Maximum Mission (SMM) spacecraft were analyzed and provide instrumental calibration details. Specific values of the instrument quantum efficiency, Lyman alpha absolute intensity, and correction for geocoronal absorption are presented.

Lyman continuum observations of solar flares

Science.gov (United States)

Machado, M. E.; Noyes, R. W.

1978-01-01

A study is made of Lyman continuum observations of solar flares, using data obtained by the EUV spectroheliometer on the Apollo Telescope Mount. It is found that there are two main types of flare regions: an overall 'mean' flare coincident with the H-alpha flare region, and transient Lyman continuum kernels which can be identified with the H-alpha and X-ray kernels observed by other authors. It is found that the ground level hydrogen population in flares is closer to LTE than in the quiet sun and active regions, and that the level of Lyman continuum formation is lowered in the atmosphere from a mass column density .000005 g/sq cm in the quiet sun to .0003 g/sq cm in the mean flare, and to .001 g/sq cm in kernels. From these results the amount of chromospheric material 'evaporated' into the high temperature region is derived, which is found to be approximately 10 to the 15th g, in agreement with observations of X-ray emission measures.

A compendium of canine normal tissue gene expression.

Directory of Open Access Journals (Sweden)

Joseph Briggs

Full Text Available BACKGROUND: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. METHODOLOGY/PRINCIPAL FINDINGS: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. CONCLUSIONS/SIGNIFICANCE: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

DNA-repair, cell killing and normal tissue damage

International Nuclear Information System (INIS)

Dahm-Daphi, J.; Dikomey, E.; Brammer, I.

1998-01-01

Background: Side effects of radiotherapy in normal tissue is determined by a variety of factors of which cellular and genetic contributions are described here. Material and methods: Review. Results: Normal tissue damage after irradiation is largely due to loss of cellular proliferative capacity. This can be due to mitotic cell death, apoptosis, or terminal differentiation. Dead or differentiated cells release cytokines which additionally modulate the tissue response. DNA damage, in particular non-reparable or misrepaired double-strand breaks are considered the basic lesion leading to G1-arrest and ultimately to cell inactivation. Conclusion: Evidence for genetic bases of normal tissue response, cell killing and DNA-repair capacity is presented. However, a direct link of all 3 endpoints has not yet been proved directly. (orig.) [de

Radiation therapy and late reactions in normal tissues

International Nuclear Information System (INIS)

Aoyama, Takashi; Kuroda, Yasumasa

1998-01-01

Recent developments in cancer therapy have made us increasingly aware that the quality of life of a patient is as valuable as other benefits received from therapy. This awareness leads to an emphasis on organ and/or function preservation in the course of therapy. In line with this new thinking, greater consideration is placed on radiation therapy as an appropriate modality of cancer therapy. Possible complications in normal tissues, especially those of late reaction type after the therapy must be overcome. This review, therefore, focuses on recent progress of studies on mechanisms of the complications of the late reaction type. An observation of a clinical case concerning a late reaction of spinal cord (radiation myelopathy) and surveys of experimental studies on the mechanisms of late reactions (including radiation pneumonitis and lung fibrosis, and radiation response of vascular endothelial cells) provide a hypothesis that apoptosis through the pathway starting with radiation-induced sphingomyelin hydrolysis may play an important role in causing a variety of late reactions. This insight is based on the fact that radiation also activates protein kinase C which appears to block apoptosis. The mechanisms of late reactions, therefore, may involve a balance between radiation-induced apoptotic death and its down regulation by suppressor mechanisms through protein kinase C. (author)

Radiation-induced normal tissue damage: implications for radiotherapy

International Nuclear Information System (INIS)

Prasanna, Pataje G.

2014-01-01

Radiotherapy is an important treatment modality for many malignancies, either alone or as a part of combined modality treatment. However, despite technological advances in physical treatment delivery, patients suffer adverse effects from radiation therapy due to normal tissue damage. These side effects may be acute, occurring during or within weeks after therapy, or intermediate to late, occurring months to years after therapy. Minimizing normal tissue damage from radiotherapy will allow enhancement of tumor killing and improve tumor control and patients quality of life. Understanding mechanisms through which radiation toxicity develops in normal tissue will facilitate the development of next generation radiation effect modulators. Translation of these agents to the clinic will also require an understanding of the impact of these protectors and mitigators on tumor radiation response. In addition, normal tissues vary in radiobiologically important ways, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response. Therefore, successful development of radiation modulators may require multiple approaches to address organ/site-specific needs. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects. Further, an understanding of mechanisms of normal tissue damage will allow development of predictive biomarkers; however harmonization of such assays is critical. This is a necessary step towards patient-specific treatment customization. Examples of important adverse effects of radiotherapy either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors for improving therapeutic outcome will be highlighted. (author)

Acute and late effects of multimodal therapy on normal tissues

International Nuclear Information System (INIS)

Phillips, T.L.; Fu, K.K.

1977-01-01

The increasing use of combined radiation, chemotherapy, and surgery has led to an increased incidence of acute and late complications. The complications are, in general, similar to those seen with each modality alone, but occur with increased incidence. Enhanced effects of combined radiation and surgery are modest in number and consist primarily of problems with wound healing and fibrosis, as well as late gastrointestinal damage. Combinations of radiotherapy and chemotherapy have shown a greater degree of enhanced acute and late reactions. Drugs, such as actinomycin-D and Adriamycin, are particularly dangerous if the marked enhancement of radiation effects caused by the drugs in almost all organs is not appreciated and the radiation dose not adjusted accordingly. Proper selection of drugs can lead to enhanced local control by radiotherapy and/or surgery, as well as eradication of microscopic distant metastases, without increased normal tissue injury. Late induction of malignancy can occur with either radiation or chemotherapy alone and, in some cases, this appears to be enhanced when they are combined

Telomere length in normal and neoplastic canine tissues.

Science.gov (United States)

Cadile, Casey D; Kitchell, Barbara E; Newman, Rebecca G; Biller, Barbara J; Hetler, Elizabeth R

2007-12-01

To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues. 57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs. Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois. Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length. Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human anti-telomerase strategies.

Pathologic evaluation of normal and perfused term placental tissue

DEFF Research Database (Denmark)

Maroun, Lisa Leth; Mathiesen, Line; Hedegaard, Morten

2014-01-01

This study reports for the 1st time the incidence and interobserver variation of morphologic findings in a series of 34 term placentas from pregnancies with normal outcome used for perfusion studies. Histologic evaluation of placental tissue is challenging, especially when it comes to defining...... "normal tissue" versus "pathologic lesions." A scoring system for registration of abnormal morphologic findings was developed. Light microscopic examination was performed independently by 2 pathologists, and interobserver variation was analyzed. Findings in normal and perfused tissue were compared...... and selected findings were tested against success parameters from the perfusions. Finally, the criteria for frequent lesions with fair to poor interobserver variation in the nonperfused tissue were revised and reanalyzed. In the perfused tissue, the perfusion artefact "trophoblastic vacuolization," which...

Expression of von Willebrand factor and caldesmon in the placental tissues of pregnancies complicated with intrauterine growth restriction.

Science.gov (United States)

Göksever Çelik, Hale; Uhri, Mehmet; Yildirim, Gökhan

2017-11-02

The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues. A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits. The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction.

SU-D-18A-04: Quantifying the Ability of Tumor Tracking to Spare Normal Tissue

Energy Technology Data Exchange (ETDEWEB)

Burger, A; Buzurovic, I; Hurwitz, M; Williams, C; Lewis, J [Brigham and Women' s Hospital, Dana-Farber Cancer Center, Harvard Medical Sc, Boston, MA (United States); Mishra, P [Varian Medical Systems, Palo Alto, CA (United States); Seco, J [Mass General Hospital, Harvard Medical, Boston, MA (United States)

2014-06-01

Purpose: Tumor tracking allows for smaller tissue volumes to be treated, potentially reducing normal tissue damage. However, tumor tracking is a more complex treatment and has little benefit in some scenarios. Here we quantify the benefit of tumor tracking for a range of patients by estimating the dose of radiation to organs at risk and the normal tissue complication probability (NTCP) for both standard and tracking treatment plans. This comparison is performed using both patient 4DCT data and extended Cardiac-Torso (XCAT) digital phantoms. Methods: We use 4DCT data for 10 patients. Additionally, we generate digital phantoms with motion derived from measured patient long tumor trajectories to compare standard and tracking treatment plans. The standard treatment is based on the average intensity projection (AIP) of 4DCT images taken over a breath cycle. The tracking treatment is based on doses calculated on images representing the anatomy at each time point. It is assumed that there are no errors in tracking the target. The NTCP values are calculated based on RTOG guidelines. Results: The mean reduction in the mean dose delivered was 5.5% to the lungs (from 7.3 Gy to 6.9 Gy) and 4.0% to the heart (from 12.5 Gy to 12.0 Gy). The mean reduction in the max dose delivered was 13% to the spinal cord (from 27.6 Gy to 24.0 Gy), 2.5% to the carina (from 31.7 Gy to 30.9 Gy), and 15% to the esophagus (from 69.6 Gy to 58.9 Gy). The mean reduction in the probability of 2nd degree radiation pneumonitis (RP) was 8.7% (3.1% to 2.8%) and the mean reduction in the effective volume was 6.8% (10.8% to 10.2%). Conclusions: Tumor tracking has the potential to reduce irradiation of organs at risk, and consequentially reduce the normal tissue complication probability. The benefits vary based on the clinical scenario. This study is supported by Varian Medical Systems, Inc.

Galex Lyman-alpha Emitters: Physical Properties, Luminosity Bimodality, And Morphologies.

Science.gov (United States)

Mallery, Ryan P.

2010-01-01

The Galaxy Evolution Explorer spectroscopic survey has uncovered a large statistically significant sample of Lyman-alpha emitters at z sim0.3. ACS imaging of these sources in the COSMOS and AEGIS deep fields reveals that these Lyman-alpha emitters consist of two distinct galaxy morphologies, face on spiral galaxies and compact starburst/merging systems. The morphology bimodality also results in a bimodal distribution of optical luminosity. A comparison between the UV photometry and MIPS 24 micron detections of these sources indicates that they are bluer, and have less dust extinction than similar star forming galaxies that lack Lyman-alpha detection. Our findings show how the global gas and dust distribution of star forming galaxies inhibits Lyman-alpha emission in star forming galaxies. GALEX is a NASA Small Explorer, launched in April 2003. We gratefully acknowledge NASA's support for construction, operation, and science analysis for the GALEX mission, developed in cooperation with the CNES of France and the Korean Ministry of Science and Technology.

WE-AB-204-02: Molecular-Imaging Based Assessment of Liver Complications for Yttrium-90 Microsphere Treatments: Can Existing NTCP Models Explain Clinical Outcomes?

Energy Technology Data Exchange (ETDEWEB)

Lin, M; Choi, E; Chuong, M; Saboury, B; Moeslein, F; D’Souza, W; Guerrero, M [University of Maryland School of Medicine, Baltimore, MD (United States)

2015-06-15

Purpose: To evaluate weather the current radiobiological models can predict the normal liver complications of radioactive Yttrium-90 ({sup 90}Y) selective-internal-radiation-treatment (SIRT) for metastatic liver lesions based on the post-infusion {sup 90}Y PET images. Methods: A total of 20 patients with metastatic liver tumors treated with SIRT that received a post-infusion {sup 90}Y-PET/CT scan were analyzed in this work. The 3D activity distribution of the PET images was converted into a 3D dose distribution via a kernel convolution process. The physical dose distribution was converted into the equivalent dose (EQ2) delivered at 2 Gy based on the linear-quadratic (LQ) model considering the dose rate effect. The biological endpoint of this work was radiation-induce liver disease (RILD). The NTCPs were calculated with four different repair-times (T1/2-Liver-Repair= 0,0.5,1.0,2.0 hr) and three published NTCP models (Lyman-external-RT, Lyman 90Y-HCC-SIRT, parallel model) were compared to the incidence of RILD of the recruited patients to evaluate their ability of outcome prediction. Results: The mean normal liver physical dose (avg. 51.9 Gy, range 31.9–69.8 Gy) is higher than the suggested liver dose constraint for external beam treatment (∼30 Gy). However, none of the patients in our study developed RILD after the SIRT. The estimated probability of ‘no patient developing RILD’ obtained from the two Lyman models are 46.3% to 48.3% (T1/2-Liver-Repair= 0hr) and <1% for all other repair times. For the parallel model, the estimated probability is 97.3% (0hr), 51.7% (0.5hr), 2.0% (1.0hr) and <1% (2.0hr). Conclusion: Molecular-images providing the distribution of {sup 90}Y enable the dose-volume based dose/outcome analysis for SIRT. Current NTCP models fail to predict RILD complications in our patient population, unless a very short repair-time for the liver is assumed. The discrepancy between the Lyman {sup 90}Y-HCC-SIRT model predicted and the clinically

Lyman series profiles: From laser-plasmas to white dwarf stars

Energy Technology Data Exchange (ETDEWEB)

Kielkopf, J.F. [University of Louisville, Louisville, Kentucky 40292 (United States); Allard, N.F. [Observatoire de Paris-Meudon, France and Institut d Astrophysique, Paris (France)

1999-04-01

The low energy interactions of neutral and ionized hydrogen atoms are fundamental processes which also have important applications to the diagnostics of laboratory and astrophysical plasmas. Satellites in the far wings of Lyman {alpha} and Lyman {beta} have been identified as ultraviolet absorption features in the spectra of white dwarf and {lambda} Bootis stars, and they are seen in the emission spectra of plasmas produced when a pulsed laser excites a target H{sub 2} gas. The observed Lyman series profiles agree with unified line shape theory which includes variation of the dipole transition moment during the radiative collision. {copyright} {ital 1999 American Institute of Physics.}

SU-F-T-103: Analysis of Hepatitis B Virus Reactivation After Conformal Radiotherapy in Patients with Hepatocellular Carcinoma Using the Lyman NTCP Model

International Nuclear Information System (INIS)

Li, Z; Li, B; Huang, W; Li, H

2016-01-01

Purpose: The aim of this research was to investigate the feasibility of Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model in analyzing hepatitis B virus (HBV) reactivation in patients receiving conformal radiotherapy for patients with hepatocellular carcinoma (HCC). Methods: Between June 2009 and June 2012, 108 HBV-related HCC patients (90 were specifically selected and 18 patients were excluded) treated with conformal RT at three centers were enrolled in this retrospective study. They were all diagnosed as HCC by pathology or cytology. All 90 patients were followed up to September 2013 with a median follow-up time of 25.2 months. The parameters (TD50 (1), n, and m) of the modified LKB NTCP model were derived using maximum likelihood estimation. Bootstrap and leave-one-out were employed to test the generalizability of the results for use in a general population. Results: The incidences of complications in the study population were as follows: radiation-induced liver diseases (RILD) were 17.6%, HBV reactivation was 24.8%, and HBV reactivation-induced hepatitis was 22.7%, respectively. In multivariate analysis, the NTCP (p<0.001), and V20 were associated with HBV reactivation. TD50 (1), m and n were 42.9Gy (95% CI) (38.2–46.8), 0.14 (0.12–0.15) and 0.30 (0.2–0.33), respectively, for HBV reactivation. Bootstrap and leave-one-out results showed that the HBV parameter fits were extremely robust. Conclusion: A modified LKB NTCP model has been established to predict HBV reactivation for patients with HCC receiving conformal RT. The finding derives parameters set to predict potential endpoints of HBV reactivation.

SU-F-T-103: Analysis of Hepatitis B Virus Reactivation After Conformal Radiotherapy in Patients with Hepatocellular Carcinoma Using the Lyman NTCP Model

Energy Technology Data Exchange (ETDEWEB)

Li, Z; Li, B [Laboratory of Image Science and Technology, Southeast University (China); Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences (China); Huang, W; Li, H [Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences (China)

2016-06-15

Purpose: The aim of this research was to investigate the feasibility of Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model in analyzing hepatitis B virus (HBV) reactivation in patients receiving conformal radiotherapy for patients with hepatocellular carcinoma (HCC). Methods: Between June 2009 and June 2012, 108 HBV-related HCC patients (90 were specifically selected and 18 patients were excluded) treated with conformal RT at three centers were enrolled in this retrospective study. They were all diagnosed as HCC by pathology or cytology. All 90 patients were followed up to September 2013 with a median follow-up time of 25.2 months. The parameters (TD50 (1), n, and m) of the modified LKB NTCP model were derived using maximum likelihood estimation. Bootstrap and leave-one-out were employed to test the generalizability of the results for use in a general population. Results: The incidences of complications in the study population were as follows: radiation-induced liver diseases (RILD) were 17.6%, HBV reactivation was 24.8%, and HBV reactivation-induced hepatitis was 22.7%, respectively. In multivariate analysis, the NTCP (p<0.001), and V20 were associated with HBV reactivation. TD50 (1), m and n were 42.9Gy (95% CI) (38.2–46.8), 0.14 (0.12–0.15) and 0.30 (0.2–0.33), respectively, for HBV reactivation. Bootstrap and leave-one-out results showed that the HBV parameter fits were extremely robust. Conclusion: A modified LKB NTCP model has been established to predict HBV reactivation for patients with HCC receiving conformal RT. The finding derives parameters set to predict potential endpoints of HBV reactivation.

Chromospheric Lyman-alpha spectro-polarimeter (CLASP)

Science.gov (United States)

Kano, Ryouhei; Bando, Takamasa; Narukage, Noriyuki; Ishikawa, Ryoko; Tsuneta, Saku; Katsukawa, Yukio; Kubo, Masahito; Ishikawa, Shin-nosuke; Hara, Hirohisa; Shimizu, Toshifumi; Suematsu, Yoshinori; Ichimoto, Kiyoshi; Sakao, Taro; Goto, Motoshi; Kato, Yoshiaki; Imada, Shinsuke; Kobayashi, Ken; Holloway, Todd; Winebarger, Amy; Cirtain, Jonathan; De Pontieu, Bart; Casini, Roberto; Trujillo Bueno, Javier; Štepán, Jiří; Manso Sainz, Rafael; Belluzzi, Luca; Asensio Ramos, Andres; Auchère, Frédéric; Carlsson, Mats

2012-09-01

One of the biggest challenges in heliophysics is to decipher the magnetic structure of the solar chromosphere. The importance of measuring the chromospheric magnetic field is due to both the key role the chromosphere plays in energizing and structuring the outer solar atmosphere and the inability of extrapolation of photospheric fields to adequately describe this key boundary region. Over the last few years, significant progress has been made in the spectral line formation of UV lines as well as the MHD modeling of the solar atmosphere. It is found that the Hanle effect in the Lyman-alpha line (121.567 nm) is a most promising diagnostic tool for weaker magnetic fields in the chromosphere and transition region. Based on this groundbreaking research, we propose the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) to NASA as a sounding rocket experiment, for making the first measurement of the linear polarization produced by scattering processes and the Hanle effect in the Lyman-alpha line (121.567 nm), and making the first exploration of the magnetic field in the upper chromosphere and transition region of the Sun. The CLASP instrument consists of a Cassegrain telescope, a rotating 1/2-wave plate, a dual-beam spectrograph assembly with a grating working as a beam splitter, and an identical pair of reflective polarization analyzers each equipped with a CCD camera. We propose to launch CLASP in December 2014.

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications.

Science.gov (United States)

Vernochet, Cecile; Damilano, Federico; Mourier, Arnaud; Bezy, Olivier; Mori, Marcelo A; Smyth, Graham; Rosenzweig, Anthony; Larsson, Nils-Göran; Kahn, C Ronald

2014-10-01

Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75-81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications. © FASEB.

Normal tissue complications after radiation therapy Las complicaciones de la radioterapia en los tejidos sanos

Directory of Open Access Journals (Sweden)

Jolyon H. Hendry

2006-09-01

Full Text Available This paper describes the biological mechanisms of normal tissue reactions after radiation therapy, with reference to conventional treatments, new treatments, and treatments in developing countries. It also describes biological reasons for the latency period before tissue complications arise, the relationship of dose to incidence, the effect of increasing the size of the irradiated volume, early and late tissue reactions, effects of changes in dose fractionation and dose rate, and combined chemotherapy and radiotherapy responses. Examples are given of increases in knowledge of clinical radiobiology from trials of new protocols. Potential modification to treatments include the use of biological response modifiers. The introduction of "response prediction" modifications to treatments might also be available in the near future. Finally, the paper points out that in some radiotherapy centers, the biologically-effective doses prescribed for combined brachytherapy and teletherapy treatment of cervix cancer are lower than those prescribed in other centers. This issue needs to be addressed further. The wealth of preclinical and clinical data has led to a much greater understanding of the biological basis to radiotherapy. This understanding has underpinned a variety of new approaches in radiotherapy, including both physical and biological strategies. There is also the important issue of treatment of a large number of cancers in developing countries, for which efficacious resource-sparing protocols are being continuously developed. A unified scoring system should be widely accepted as the new standard in reporting the adverse effects of radiation therapy. Likewise, late toxicity should be reported on an actuarial basis as a mandatory endpoint.En este artículo se describen los mecanismos biológicos que intervienen en las reacciones provocadas por la radioterapia, tanto con tratamientos convencionales como con los más nuevos, y los aplicados en países en

THE LYMAN ALPHA REFERENCE SAMPLE: EXTENDED LYMAN ALPHA HALOS PRODUCED AT LOW DUST CONTENT

International Nuclear Information System (INIS)

Hayes, Matthew; Östlin, Göran; Duval, Florent; Guaita, Lucia; Melinder, Jens; Sandberg, Andreas; Schaerer, Daniel; Verhamme, Anne; Orlitová, Ivana; Mas-Hesse, J. Miguel; Otí-Floranes, Héctor; Adamo, Angela; Atek, Hakim; Cannon, John M.; Herenz, E. Christian; Kunth, Daniel; Laursen, Peter

2013-01-01

We report on new imaging observations of the Lyman alpha emission line (Lyα), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 P20 , Lyα radii are larger than those of Hα by factors ranging from 1 to 3.6, with an average of 2.4. The average ratio of Lyα-to-FUV radii is 2.9. This suggests that much of the Lyα light is pushed to large radii by resonance scattering. Defining the Relative Petrosian Extension of Lyα compared to Hα, ξ Lyα = R Lyα P20 /R Hα P20 , we find ξ Lyα to be uncorrelated with total Lyα luminosity. However, ξ Lyα is strongly correlated with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Lyα photons throughout the interstellar medium and drive a large extended Lyα halo.

Development of Flight Slit-Jaw Optics for Chromospheric Lyman-Alpha SpectroPolarimeter

Science.gov (United States)

Kubo, Masahito; Suematsu, Yoshinori; Kano, Ryohei; Bando, Takamasa; Hara, Hirohisa; Narukage, Noriyuki; Katsukawa, Yukio; Ishikawa, Ryoko; Ishikawa, Shin-nosuke; Kobiki, Toshihiko;

Immunolocalization of transforming growth factor alpha in normal human tissues

DEFF Research Database (Denmark)

Christensen, M E; Poulsen, Steen Seier

1996-01-01

anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

Extravascular transport in normal and tumor tissues.

Science.gov (United States)

Jain, R K; Gerlowski, L E

1986-01-01

The transport characteristics of the normal and tumor tissue extravascular space provide the basis for the determination of the optimal dosage and schedule regimes of various pharmacological agents in detection and treatment of cancer. In order for the drug to reach the cellular space where most therapeutic action takes place, several transport steps must first occur: (1) tissue perfusion; (2) permeation across the capillary wall; (3) transport through interstitial space; and (4) transport across the cell membrane. Any of these steps including intracellular events such as metabolism can be the rate-limiting step to uptake of the drug, and these rate-limiting steps may be different in normal and tumor tissues. This review examines these transport limitations, first from an experimental point of view and then from a modeling point of view. Various types of experimental tumor models which have been used in animals to represent human tumors are discussed. Then, mathematical models of extravascular transport are discussed from the prespective of two approaches: compartmental and distributed. Compartmental models lump one or more sections of a tissue or body into a "compartment" to describe the time course of disposition of a substance. These models contain "effective" parameters which represent the entire compartment. Distributed models consider the structural and morphological aspects of the tissue to determine the transport properties of that tissue. These distributed models describe both the temporal and spatial distribution of a substance in tissues. Each of these modeling techniques is described in detail with applications for cancer detection and treatment in mind.

Discovery of a very Lyman-α-luminous quasar at z = 6.62.

Science.gov (United States)

Koptelova, Ekaterina; Hwang, Chorng-Yuan; Yu, Po-Chieh; Chen, Wen-Ping; Guo, Jhen-Kuei

2017-02-02

Distant luminous quasars provide important information on the growth of the first supermassive black holes, their host galaxies and the epoch of reionization. The identification of quasars is usually performed through detection of their Lyman-α line redshifted to 0.9 microns at z > 6.5. Here, we report the discovery of a very Lyman-α luminous quasar, PSO J006.1240 + 39.2219 at redshift z = 6.618, selected based on its red colour and multi-epoch detection of the Lyman-α emission in a single near-infrared band. The Lyman-α line luminosity of PSO J006.1240 + 39.2219 is unusually high and estimated to be 0.8 × 10 12 Solar luminosities (about 3% of the total quasar luminosity). The Lyman-α emission of PSO J006.1240 + 39.2219 shows fast variability on timescales of days in the quasar rest frame, which has never been detected in any of the known high-redshift quasars. The high luminosity of the Lyman-α line, its narrow width and fast variability resemble properties of local Narrow-Line Seyfert 1 galaxies which suggests that the quasar is likely at the active phase of the black hole growth accreting close or even beyond the Eddington limit.

Computer modeling the boron compound factor in normal brain tissue

International Nuclear Information System (INIS)

Gavin, P.R.; Huiskamp, R.; Wheeler, F.J.; Griebenow, M.L.

1993-01-01

The macroscopic distribution of borocaptate sodium (Na 2 B 12 H 11 SH or BSH) in normal tissues has been determined and can be accurately predicted from the blood concentration. The compound para-borono-phenylalanine (p-BPA) has also been studied in dogs and normal tissue distribution has been determined. The total physical dose required to reach a biological isoeffect appears to increase directly as the proportion of boron capture dose increases. This effect, together with knowledge of the macrodistribution, led to estimates of the influence of the microdistribution of the BSH compound. This paper reports a computer model that was used to predict the compound factor for BSH and p-BPA and, hence, the equivalent radiation in normal tissues. The compound factor would need to be calculated for other compounds with different distributions. This information is needed to design appropriate normal tissue tolerance studies for different organ systems and/or different boron compounds

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

Directory of Open Access Journals (Sweden)

Thorsten Schlomm

2013-03-01

Full Text Available We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA levels (14 and 17 individuals, respectively were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs. Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b, which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.

Differentiating cancerous from normal breast tissue by redox imaging

Science.gov (United States)

Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

2015-02-01

Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (pcancerous tissues than in the normal ones (pcancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

T lymphocytes and normal tissue responses to radiation

International Nuclear Information System (INIS)

Schaue, Dörthe; McBride, William H.

2012-01-01

There is compelling evidence that lymphocytes are a recurring feature in radiation damaged normal tissues, but assessing their functional significance has proven difficult. Contradictory roles have been postulated in both tissue pathogenesis and protection, although these are not necessarily mutually exclusive as the immune system can display what may seem to be opposing faces at any one time. While the exact role of T lymphocytes in irradiated normal tissue responses may still be obscure, their accumulation after tissue damage suggests they may be critical targets for radiotherapeutic intervention and worthy of further study. This is accentuated by recent findings that pathologically damaged “self,” such as occurs after exposure to ionizing radiation, can generate danger signals with the ability to activate pathways similar to those that activate adoptive immunity to pathogens. In addition, the demonstration of T cell subsets with their recognition radars tuned to “self” moieties has revolutionized our ideas on how all immune responses are controlled and regulated. New concepts of autoimmunity have resulted based on the dissociation of immune functions between different subsets of immune cells. It is becoming axiomatic that the immune system has the power to regulate radiation-induced tissue damage, from failure of regeneration to fibrosis, to acute and chronic late effects, and even to carcinogenesis. Our understanding of the interplay between T lymphocytes and radiation-damaged tissue may still be rudimentary but this is a good time to re-examine their potential roles, their radiobiological and microenvironmental influences, and the possibilities for therapeutic manipulation. This review will discuss the yin and yang of T cell responses within the context of radiation exposures, how they might drive or protect against normal tissue side effects and what we may be able do about it.

Role of endothelium in radiation-induced normal tissue damages

International Nuclear Information System (INIS)

Milliat, F.

2007-05-01

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

Lyman-alpha detector designed for rocket measurements of the direct solar radiation at 121.5 nm

International Nuclear Information System (INIS)

Guineva, V.; Tashev, V.; Witt, G.; Gumbel, J.; Khaplanov, M.

2007-01-01

Rocket measurements of the direct Lyman-alpha radiation penetrating in the atmosphere were planned during the HotPay I rocket experiment, June 2006, Project ASLAF (Attenuation of the Solar Lyman-Alpha Flux), Andoya Rocket Range (ARR), Norway. The basic goal of ASLAF project was the study of the processes in the summer mesosphere and thermosphere (up to 110 km), at high latitudes using the Lyman-alpha measurements. The resonance transition 2 P- 2 S of the atomic hydrogen (Lyman-alpha emission) is the strongest and most conspicuous feature in the solar EUV spectrum. Due to the favourable circumstance, that the Lyman-alpha wavelength (121.5 nm) coincides with a minimum of the O 2 absorption spectrum, the direct Lyman-alpha radiation penetrates well in the mesosphere. The Lyman-alpha radiation is the basic agent of the NO molecules ionization, thus generating the ionospheric D-layer, and of the water vapour photolysis, being one of the main H 2 O loss processes. The Lyman-alpha radiation transfer depends on the resonance scattering from the hydrogen atoms in the atmosphere and on the O 2 absorption. Since the Lyman-alpha extinction in the atmosphere is a measure for the column density of the oxygen molecules, the atmospheric temperature profile can be calculated thereof. The detector of solar Lyman-alpha radiation was manufactured in the Stara Zagora Department of the Solar-Terrestrial Influences Laboratory (STIL). Its basic part is an ionization chamber, filled in with NO. A 60 V power supply is applied to the chamber. The produced photoelectric current from the sensor is fed to a 2-channels amplifier, providing an analogue signal. The characteristics of the Lyman-alpha detector were studied. It passed successfully all tests and the results showed that the instrument could be used in rocket experiments to measure the Lyman-alpha flux. From the measurements of the detector, the Lyman-alpha vertical profile can be obtained. The forthcoming scientific data analysis will

Human normal tissue reactions in radiotherapy

International Nuclear Information System (INIS)

Taniike, Keiko

1990-01-01

Acute and late normal tissue reactions in radiotherapy have not been considered to be major problems with conventional fractionation. But they may cause certain problems when newer schedules such as hyperfractionation or accelerated fractionation are used. In opposing parallel radiotherapy, the dose fractionation of skin or subcutaneous connective tissue are different between in one portal and two portals daily. So we examined acute skin erythema and late connective tissue fibrosis in the two groups (one and two portals) of the patients with uterus cancer. Acute skin erythema and late connective tissue fibrosis were slightly stronger in case of one portal daily. In relation to the anatomical site of skin, acute skin erythema was stronger at the buttocks than the lower abdomen, but late fibrosis was reverse to that. So the degree of acute skin erythema did not predict the degree of late connective tissue fibrosis. The number of Time Dose Fractionation Factor could roughly estimate the degree of erythema and fibrosis. Late fibrosis in 36 fractions increased with an increase of abdominal thickness, but acute erythema did not. (author)

Surveying the rate of tissue expander complications among reconstructive patients in Hazrat Fatima hospital between 1389-1391

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Amirasadola Khajerahimi

2016-05-01

Full Text Available Background: Tissue expansion is a common reconstructive surgery especially in burned patients. This study has been designed to evaluate the rate of complications of this method in Hazrat Fatima Hospital between 1389-1391. Materials & Methods: In this cross sectional and retrospective study, 150 patients' records have been studied between 1389-1391 years, frequency rate and types of complications related to tissue expander have been surveyed in these patients. Results: Complications have been observed in about 7% of the patients included in this study. Exposure of tissue expander was the most common complication (81.8%. Other complications which are resulted from this issue are capsular contracture and infection. Age was the only factor which had significant relation with increasing complication among the other surveyed factors including age, sex, indication of operation, wound location and duration of anaesthesia.(p=0.033 Conclusion: The incidence of complication in patients that required tissue expander was not high and it was less than 10%. It should be noted that patient selection should be carefully in paediatric group and also strict observance of surgical principles is necessary to avoid complication.

Analytical formulae in fractionated irradiation of normal tissue

International Nuclear Information System (INIS)

Kozubek, S.

1982-01-01

The new conception of the modeling of the cell tissue kinetics after fractionated irradiation is proposed. The formulae given earlier are compared with experimental data on various normal tissues and further adjustments are considered. The tissues are shown to exhibit several general patterns of behaviour. The repopulation, if it takes place, seems to start after some time, independently of fractionation in first approximation and can be treated as simple autogenesis. The results are compared with the commonly used NSD conception and the well-known Cohen cell tissue kinetic model

Comparative study of radiosensitivity of normal and regenerating tissues

International Nuclear Information System (INIS)

Samokhvalova, H.S.; Popova, M.F.

1983-01-01

A comparative study of radiosensitivity of cells of normal and regenerating tissues of bone marrow and spleen has demonstrated that single exposure to X-rays produces a lesser damaging effect on regenerating tissues than on normal ones. The data obtained indicate that the increase in radioresistance of the organism during active regeneration of the haemopoietic organs is due not merely to the increase in the dividing cell pool of these organs but also to qualitative changes in their functional state

Are the brightest Lyman Alpha Emitters at z=5.7 primeval galaxies?

Science.gov (United States)

Lidman, Christopher; Jones, Heath; Meisenheimer, Klaus; Pompei, Emanuela; Tapken, Christian; Vanzi, Leonardo; Westra, Eduard

2008-03-01

Wide-field, narrow-band surveys have proven to be effective at finding very high redshift galaxies that emit brightly in the Lyman alpha line, the so-called Lyman alpha emitters (LAEs). It was through this technique that the most distant spectroscopically confirmed galaxy, a galaxy at z=6.96, was discovered. Considerable effort is currently being spent on discovering these galaxies at ever higher redshifts by extending this technique into the near-IR. In contrast to this effort, there has been relatively little work on understanding these galaxies. In particular, how do LAEs relate to other high redshift galaxies, such as the galaxies discovered through broad band drop out techniques, and, perhaps, more importantly, what role do LAEs play in re-ionising the universe. We recently discovered two extremely luminous LAEs at z=5.7. These LAEs are among the brightest LAEs ever discovered at this redshift. In a recent paper by Mao et al. the brightest LAEs are associated to the most massive halos. We propose to use the IRAC 3.6 micron imager on Spitzer to measure the rest-frame optical flux of the these LAEs. With additional data from the near-IR (rest-frame UV) and very deep optical spectra around the Lyman alpha line, we propose to make a detailed study of the spectral energy distribution from the Lyman alpha line to the rest frame optical of these exceptional LAEs. These data will enable us to estimate the age and mass of the stellar burst that produces the Lyman alpha line, to estimate the contribution from an older stellar population, if any, and to estimate the fraction of Lyman continuum photons that can escape the galaxy and are thus available to reionise the universe.

Effects of pions on normal tissues

International Nuclear Information System (INIS)

Tokita, N.

1981-01-01

Verification of the uniform biological effectiveness of pion beams of various dimensions produced at LAMPF has been made using cultured mammalian cells and mouse jejunum. Normal tissue radiobiology studies at LAMPF are reviewed with regard to biological beam characterization for the therapy program and the current status of acute and late effect studies on rodents

A reliable cw Lyman-{alpha} laser source for future cooling of antihydrogen

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Kolbe, Daniel, E-mail: kolbed@uni-mainz.de; Beczkowiak, Anna; Diehl, Thomas; Koglbauer, Andreas; Sattler, Matthias; Stappel, Matthias; Steinborn, Ruth; Walz, Jochen [Johannes Gutenberg-Universitaet, Institut fuer Physik (Germany)

2012-12-15

We demonstrate a reliable continuous-wave (cw) laser source at the 1 S-2 P transition in (anti)hydrogen at 121.56 nm (Lyman-{alpha}) based on four-wave sum-frequency mixing in mercury. A two-photon resonance in the four-wave mixing scheme is essential for a powerful cw Lyman-{alpha} source and is well investigated.

A reliable cw Lyman-α laser source for future cooling of antihydrogen

International Nuclear Information System (INIS)

Kolbe, Daniel; Beczkowiak, Anna; Diehl, Thomas; Koglbauer, Andreas; Sattler, Matthias; Stappel, Matthias; Steinborn, Ruth; Walz, Jochen

2012-01-01

We demonstrate a reliable continuous-wave (cw) laser source at the 1 S–2 P transition in (anti)hydrogen at 121.56 nm (Lyman-α) based on four-wave sum-frequency mixing in mercury. A two-photon resonance in the four-wave mixing scheme is essential for a powerful cw Lyman-α source and is well investigated.

Normal tissue damage in radiotherapy development of a clinical audit tool

International Nuclear Information System (INIS)

Barrett, A.

2001-01-01

Radiotherapy treatments are evaluated by two main outcomes, rates of cure or local tumour control and normal tissue complication rates. Many excellent schemes have been devised for recording the late effects of radiotherapy treatments including the RTOG and LENT SOMA Scales. These have proved invaluable in documenting the outcome of clinical trials, but have proved too complex and time consuming for routine daily use in busy departments. A group in Eindhoven led by Professor Lybeert undertook a pilot study of a potential way of auditing late radiation complications. Using a simplified form derived from the LENT SOMA scales, they collected data on grade 3 and 4 complications in a total of 675 patients and were able to correlate a number of particular complications with specific protocols, ICD codes and physician practice. Further review of the case records made it possible to identify specific factors which may have led to toxicity and could be taken into account to modify treatment protocols. From September 1999 clinicians in participating centres undertaking normal follow-up procedures were asked to identify patients who showed evidence of grade 3 or 4 toxicity as defined in the pro-forma. Date of radiotherapy was recorded so that a temporal correlation of complication with treatment could be made, but this study did not attempt to assess the incidence of complications, but to provide a cross-sectional study of prevalence. Centres participating in the study have been Eindhoven, Koeln, Gent, Brussels, Glasgow, Mount Vernon, Madrid, Geneva and Lyon. In Eindhoven 651 reports were collected between January 1995 and December 1999. 89 reports had to be discarded because complications were not validated by the reviewing radiotherapists. Dr Lybeert noticed that individual radiotherapists appeared to have different thresholds for reporting specific complications. 13 patients deaths appeared to be related to radiation problems. An overall level of detection of morbidity was

DNA double strand break repair pathway plays a significant role in determining the radiotherapy induced normal tissue toxicity among head-and-neck and breast cancer

International Nuclear Information System (INIS)

Sadashiva, Satish Rao Bola; Mumbrekar, Kamalesh Dattaram; Venkatesh, Goutham Hassan; Fernandes, Donald Jerard; Bejadi, Vadhiraja Manjunath; Kapaettu, Satyamoorthy

2014-01-01

The ability to predict individual risk of radiotherapy induced normal tissue complications prior to the therapy may give an opportunity to personalize the treatment aiming improved therapeutic effect and quality of life. Therefore, predicting the risk of developing acute reactions before the initiation of radiation therapy may serve as a potential biomarker. DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of Head-and-Neck (n = 183) and Breast cancer (n = 132) patients undergoing chemoradiation or radiation therapy alone were analyzed by performing γ-H2AX foci, neutral comet and a modified neutral filter elution assay. Candidate radioresponsive genes like DNA repair, antioxidant pathway, profibrotic cytokine genes were screened for the common variants for their association with normal tissue toxicity outcome. Patients were stratified as non-over responders (NOR) and over responders (OR) based on their Radiation Therapy Oncology Group grading for normal tissue adverse reactions. Our results suggest that DSB repair plays a major role in the development of normal tissue adverse reactions in H and N and Breast cancer patients. The cellular (γ-H2AX analysis) and SNP analysis may have the potential to be developed into a clinically useful predictive assay for identifying the normal tissue over reactors

DNA Double-Strand Break Rejoining in Complex Normal Tissues

International Nuclear Information System (INIS)

Ruebe, Claudia E.; Dong, Xiaorong; Kuehne, Martin; Fricke, Andreas; Kaestner, Lars; Lipp, Peter; Ruebe, Christian

2008-01-01

Purpose: The clinical radiation responses of different organs vary widely and likely depend on the intrinsic radiosensitivities of their different cell populations. Double-strand breaks (DSBs) are the most deleterious form of DNA damage induced by ionizing radiation, and the cells' capacity to rejoin radiation-induced DSBs is known to affect their intrinsic radiosensitivity. To date, only little is known about the induction and processing of radiation-induced DSBs in complex normal tissues. Using an in vivo model with repair-proficient mice, the highly sensitive γH2AX immunofluorescence was established to investigate whether differences in DSB rejoining could account for the substantial differences in clinical radiosensitivity observed among normal tissues. Methods and Materials: After whole body irradiation of C57BL/6 mice (0.1, 0.5, 1.0, and 2.0 Gy), the formation and rejoining of DSBs was analyzed by enumerating γH2AX foci in various organs representative of both early-responding (small intestine) and late-responding (lung, brain, heart, kidney) tissues. Results: The linear dose correlation observed in all analyzed tissues indicated that γH2AX immunofluorescence allows for the accurate quantification of DSBs in complex organs. Strikingly, the various normal tissues exhibited identical kinetics for γH2AX foci loss, despite their clearly different clinical radiation responses. Conclusion: The identical kinetics of DSB rejoining measured in different organs suggest that tissue-specific differences in radiation responses are independent of DSB rejoining. This finding emphasizes the fundamental role of DSB repair in maintaining genomic integrity, thereby contributing to cellular viability and functionality and, thus, tissue homeostasis

Role of plasminogen activator inhibitor type-1 in radiation-induced normal tissues injury

International Nuclear Information System (INIS)

Abderrahmani, R.

2010-01-01

Radiotherapy is an essential tool for cancer treatment, but there is a balance between benefits and risks related to the use of ionizing radiation: the objective is to deliver a maximum dose to the tumour to destroy or to sterilize it while protecting surrounding normal tissues. Radio-induced damages to normal tissues are therefore a limiting factor when increasing the dose delivered to the tumour. One of the objectives of this research thesis is to bring to the fore a relationship between the initiation of lesions and the development of late damages, more particularly in the intestine, and to identify the involved molecular actors and their inter-connectivity. After a first part presenting ionizing radiation, describing biological effects of ionizing radiation and their use in radiotherapy, presenting the intestine and the endothelium and discussing the intestine radio-sensitivity, discussing the radio-induced intestine damages and radiotherapy-induced complications, and presenting the plasminogen activator inhibitor (PAI-1) and its behaviour in presence of ionizing radiation, two articles are reproduced. The first one addresses the effect of a pharmacological inhibition and of genetic deficiency in PAI-1 on the evolution of radio-induced intestine lesions. The second one discusses the fact that radio-induced PAI-1-related death of endothelial cells determines the severity of early radio-induced intestine lesions

β class II tubulin predominates in normal and tumor breast tissues

International Nuclear Information System (INIS)

Dozier, James H; Hiser, Laree; Davis, Jennifer A; Thomas, Nancy Stubbs; Tucci, Michelle A; Benghuzzi, Hamed A; Frankfurter, Anthony; Correia, John J; Lobert, Sharon

2003-01-01

Antimitotic chemotherapeutic agents target tubulin, the major protein in mitotic spindles. Tubulin isotype composition is thought to be both diagnostic of tumor progression and a determinant of the cellular response to chemotherapy. This implies that there is a difference in isotype composition between normal and tumor tissues. To determine whether such a difference occurs in breast tissues, total tubulin was fractionated from lysates of paired normal and tumor breast tissues, and the amounts of β-tubulin classes I + IV, II, and III were measured by competitive enzyme-linked immunosorbent assay (ELISA). Only primary tumor tissues, before chemotherapy, were examined. Her2/neu protein amplification occurs in about 30% of breast tumors and is considered a marker for poor prognosis. To gain insight into whether tubulin isotype levels might be correlated with prognosis, ELISAs were used to quantify Her2/neu protein levels in these tissues. β-Tubulin isotype distributions in normal and tumor breast tissues were similar. The most abundant β-tubulin isotypes in these tissues were β-tubulin classes II and I + IV. Her2/neu levels in tumor tissues were 5–30-fold those in normal tissues, although there was no correlation between the Her2/neu biomarker and tubulin isotype levels. These results suggest that tubulin isotype levels, alone or in combination with Her2/neu protein levels, might not be diagnostic of tumorigenesis in breast cancer. However, the presence of a broad distribution of these tubulin isotypes (for example, 40–75% β-tubulin class II) in breast tissue, in conjunction with other factors, might still be relevant to disease progression and cellular response to antimitotic drugs

Development of a multivariable normal tissue complication probability (NTCP) model for tube feeding dependence after curative radiotherapy/chemo-radiotherapy in head and neck cancer

International Nuclear Information System (INIS)

Wopken, Kim; Bijl, Hendrik P.; Schaaf, Arjen van der; Laan, Hans Paul van der; Chouvalova, Olga; Steenbakkers, Roel J.H.M.; Doornaert, Patricia; Slotman, Ben J.; Oosting, Sjoukje F.; Christianen, Miranda E.M.C.; Laan, Bernard F.A.M. van der; Roodenburg, Jan L.N.; René Leemans, C.; Verdonck-de Leeuw, Irma M.; Langendijk, Johannes A.

2014-01-01

Background and purpose: Curative radiotherapy/chemo-radiotherapy for head and neck cancer (HNC) may result in severe acute and late side effects, including tube feeding dependence. The purpose of this prospective cohort study was to develop a multivariable normal tissue complication probability (NTCP) model for tube feeding dependence 6 months (TUBE M6 ) after definitive radiotherapy, radiotherapy plus cetuximab or concurrent chemoradiation based on pre-treatment and treatment characteristics. Materials and methods: The study included 355 patients with HNC. TUBE M6 was scored prospectively in a standard follow-up program. To design the prediction model, the penalized learning method LASSO was used, with TUBE M6 as the endpoint. Results: The prevalence of TUBE M6 was 10.7%. The multivariable model with the best performance consisted of the variables: advanced T-stage, moderate to severe weight loss at baseline, accelerated radiotherapy, chemoradiation, radiotherapy plus cetuximab, the mean dose to the superior and inferior pharyngeal constrictor muscle, to the contralateral parotid gland and to the cricopharyngeal muscle. Conclusions: We developed a multivariable NTCP model for TUBE M6 to identify patients at risk for tube feeding dependence. The dosimetric variables can be used to optimize radiotherapy treatment planning aiming at prevention of tube feeding dependence and to estimate the benefit of new radiation technologies

Complications of anterior cruciate ligament reconstruction: MR imaging

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Papakonstantinou, Olympia; Chung, Christine B.; Chanchairujira, Kullanuch; Resnick, Donald L. [Department of Radiology, Veterans Affairs Medical Center, University of California, 3350 La Jolla Village Dr., San Diego, CA 92161 (United States)

2003-05-01

Arthroscopic reconstruction of the anterior cruciate ligament (ACL) using autografts or allografts is being performed with increasing frequency, particularly in young athletes. Although the procedure is generally well tolerated, with good success rates, early and late complications have been documented. As clinical manifestations of graft complications are often non-specific and plain radiographs cannot directly visualize the graft and the adjacent soft tissues, MR imaging has a definite role in the diagnosis of complications after ACL reconstruction and may direct subsequent therapeutic management. Our purpose is to review the normal MR imaging of the ACL graft and present the MR imaging findings of a wide spectrum of complications after ACL reconstruction, such as graft impingement, graft rupture, cystic degeneration of the graft, postoperative infection of the knee, diffuse and localized (i.e., cyclops lesion) arthrofibrosis, and associated donor site abnormalities. Awareness of the MR imaging findings of complications as well as the normal appearances of the normal ACL graft is essential for correct interpretation. (orig.)

Complications of anterior cruciate ligament reconstruction: MR imaging

International Nuclear Information System (INIS)

Papakonstantinou, Olympia; Chung, Christine B.; Chanchairujira, Kullanuch; Resnick, Donald L.

2003-01-01

Arthroscopic reconstruction of the anterior cruciate ligament (ACL) using autografts or allografts is being performed with increasing frequency, particularly in young athletes. Although the procedure is generally well tolerated, with good success rates, early and late complications have been documented. As clinical manifestations of graft complications are often non-specific and plain radiographs cannot directly visualize the graft and the adjacent soft tissues, MR imaging has a definite role in the diagnosis of complications after ACL reconstruction and may direct subsequent therapeutic management. Our purpose is to review the normal MR imaging of the ACL graft and present the MR imaging findings of a wide spectrum of complications after ACL reconstruction, such as graft impingement, graft rupture, cystic degeneration of the graft, postoperative infection of the knee, diffuse and localized (i.e., cyclops lesion) arthrofibrosis, and associated donor site abnormalities. Awareness of the MR imaging findings of complications as well as the normal appearances of the normal ACL graft is essential for correct interpretation. (orig.)

Late effects of normal tissues (lent) scoring system: the soma scale

International Nuclear Information System (INIS)

Mornex, F.; Pavy, J.J.; Denekamp, J.

1997-01-01

Radiation tolerance of normal tissues remains the limiting factor for delivering tumoricidal dose. The late toxicity of normal tissues is the most critical element of an irradiation: somatic, functional and structural alterations occur during the actual treatment itself, but late effects manifest months to years after acute effects heal, and may progress with time. The optimal therapeutic ratio ultimately requires not only complete tumor clearance, but also minimal residual injury to surrounding vital normal tissues. The disparity between the intensity of acute and late effects and the inability to predict the eventual manifestation of late normal tissue injury has made radiation oncologists recognize the importance of careful patient follow-up. There is so far no uniform toxicity scoring system to compare several clinical studies in the absence of a 'common toxicity language'. This justifies the need to establish a precise evaluation system for the analysis of late effects of radiation on normal tissues. The SOMA/LENT scoring system results from an international collaboration. European Organization Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) have created subcommittees with the aim of addressing the question of standardized toxic effects criteria. This effort appeared as a necessity to standardize and improve the data recording, to then describe and evaluate uniform toxicity at regular time intervals. The current proposed scale is not yet validated, and should be used cautiously. (authors)

Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

Directory of Open Access Journals (Sweden)

Tozeren Aydin

2006-11-01

Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

Comparison of hypo-fractional irradiation protocols used in the treatment of prostate cancer by external radiotherapy; Porovnanie hypofrakcionacnych ozarovacich protokolov pouzivanych v liecbe karcinomu prostaty pomocou externej radioterapie

Energy Technology Data Exchange (ETDEWEB)

Petruskova, B. [Univerzita Pavla Jozefa Safarika, Ustav fyzikalnych vied, Katedra jadrovej a subjadrovej fyziky, 04001 Kosice (Slovakia); Matula, P.; Koncik, J.; Jasencak, M. [Vychodoslovensky onkologicky ustav, a.s., 04001 Kosice (Slovakia)

2013-04-16

The main aim of this study is to compare two hypo-fractionated protocols used in the radiotherapy of prostate cancer in terms of late complications in normal tissue. 50 patients in first protocol were irradiated with the dose of 52,8 Gy in 16 fractions. 52 patients included in the second protocol were irradiated with the dose of 62 Gy in 20 fractions. Protocols were compared through dose-volume histograms (DVH) of rectum and bladder and radiobiological calculations with the use of Lyman-Kutcher-Burman model for Normal Tissue Complication Probability (NTCP). Results of NTCP were compared with real incidence of late toxicity for normal tissue. DVH of rectum and bladder for patients from second protocol have a better behavior then DVHs for patients from first protocol. NTCPs for first protocol are (12,5{+-}3,3)% and (1,6{+-}1,3)% for rectum and bladder, respectively. NTCPs for second protocol are (6,8{+-}3,0)% and (0,53{+-}0,9)% for rectum and bladder, respectively. From comparison of results of radiobiological calculations and real incidence had arisen a need of refinement of parameters of LKB model. (authors)

Comparison of effective atomic numbers of the cancerous and normal kidney tissue

International Nuclear Information System (INIS)

Manjunatha, H.C.

2015-01-01

The effective atomic number (Z eff ) and electron density (N e ) of normal kidney and cancerous kidney have been computed for total and partial photon interactions by computing the molecular, atomic, and electronic cross section in the wide energy range of 1 keV-100 GeV using WinXCOM. The mean Z eff and N e of normal kidney and cancerous kidney in the various energy ranges and for total and partial photon interactions are tabulated. The variation of effective N e with energy is shown graphically for all photon interactions. In addition to this computer tomography (CT), numbers of normal kidney and cancerous kidney for photon interaction and energy absorption is also computed. The role of Z eff in the dual-energy dividing radiography is also discussed. The values of Z eff and N e for cancerous kidney are higher than normal kidney. This is due to the levels of elements K, Ca, Fe, Ni, and Se are lower and those of the elements Ti, Co, Zn, As, and Cd are higher in the cancer tissue of kidney than those observed in the normal tissue. The soft tissue and cancerous tissue are very similar, but their atomic number differs. The cancerous tissue exhibits a higher Z eff than the normal tissue. This fact helps in the dual-energy dividing radiography which enables to improve the diagnosis of the kidney cancer. Hence, the computed values may be useful in the diagnosis of the kidney cancer. CT numbers for normal kidney are higher than cancerous kidney. (author)

Development of a Lyman-α Imaging Solar Telescope for the Satellite

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M. Jang

2005-09-01

Full Text Available Long term observations of full-disk Lyman-α irradiance have been made by the instruments on various satellites. In addition, several sounding rockets dating back to the 1950s and up through the present have measured the Lyman-α irradiance. Previous full disk Lyman-α images of the sun have been very interesting and useful scientifically, but have been only five-minute ``snapshots" obtained on sounding rocket flights. All of these observations to date have been snapshots, with no time resolution to observe changes in the chromospheric structure as a result of the evolving magnetic field, and its effect on the Lyman-α intensity. The Lyman-α Imaging Solar Telescope(LIST can provide a unique opportunity for the study of the sun in the Lyman-α region with the high time and spatial resolution for the first time. Up to the 2nd year development, the preliminary design of the optics, mechanical structure and electronics system has been completed. Also the mechanical structure analysis, thermal analysis were performed and the material for the structure was chosen as a result of these analyses. And the test plan and the verification matrix were decided. The operation systems, technical and scientific operation, were studied and finally decided. Those are the technical operation, mechanical working modes for the observation and safety, the scientific operation and the process of the acquired data. The basic techniques acquired through the development of satellite based solar telescope are essential for the construction of space environment forecast system in the future. The techniques which we developed through this study, like mechanical, optical and data processing techniques, could be applied extensively not only to the process of the future production of flight models of this kind, but also to the related industries. Also, we can utilize the scientific achievements which are obtained throughout the project. And these can be utilized to build a high

MRI characterization of brown adipose tissue in obese and normal-weight children

Energy Technology Data Exchange (ETDEWEB)

Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Schoeneman, Samantha E. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Zhang, Huiyuan [John H. Stroger, Jr. Hospital of Cook County, Collaborative Research Unit, Chicago, IL (United States); Kwon, Soyang [Ann and Robert H. Lurie Children' s Hospital of Chicago, Stanley Manne Children' s Research Institute, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States); Josefson, Jami L. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Endocrinology, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States)

2015-10-15

Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

MRI characterization of brown adipose tissue in obese and normal-weight children

International Nuclear Information System (INIS)

Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M.; Schoeneman, Samantha E.; Zhang, Huiyuan; Kwon, Soyang; Josefson, Jami L.

2015-01-01

Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

Radiosensitization effects of nicotinamide on malignant and normal mouse tissue

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Jonsson, G.G.; Kjellen, E.; Pero, R.W.; Cameron, R.

1985-01-01

Inhibitors of the chromatin-associated enzyme adenosine diphosphate ribosyltransferase have been found to inhibit DNA strand rejoining and to potentiate lethality of DNA-damaging agents both in vivo and in vitro. The authors have in this work examined the radiosensitizing potential of one such inhibitor, nicotinamide, on tumor tissue by using transplanted C3H mouse mammary adenocarcinomas and on normal tissue in a tail-stunting experiment using BALB/cA mice. The data indicate a radiosensitizing effect of nicotinamide on tumor cells as well as on normal tissue. The data indicate a possible role of adenosine diphosphate ribosyltransferase inhibitors as a sensitizing agent in the radiotherapy of malignant tumors

Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post Radioembolization 90Y PET

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Shyam Mohan Srinivas

2014-10-01

Full Text Available Background: Radioembolization with Yttrium-90 (90Y microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC. Using post-treatment 90Y PET/CT scans,the distribution of microspheres within the liver can be determined and quantitatively assessesed . We studied the radiation dose of 90Y delivered to liver and treated tumors.Methods: This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres® to the frequency of complications with mRECIST. 90Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL to an absorbed dose (Gy.Results: The 98 studied tumors received a mean dose of 169 Gy (mode 90-120 Gy;range 0-570 Gy. Tumor response by mRECIST criteria was performed for 48 tumors that had follow up scans. There were 21 responders (mean dose 215 Gy and 27 nonresponders (mean dose 167 Gy. The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p=0.099. Normal liver tissue received a mean dose of 67 Gy (mode 60-70 Gy; range 10-120 Gy. There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p=0.036.Conclusion: Our cohort of patients showed a possible dose response trend for the tumors. Collateral dose to normal liver is nontrivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the dose which the tumor or normal liver received.

Methods for Reducing Normal Tissue Complication Probabilities in Oropharyngeal Cancer: Dose Reduction or Planning Target Volume Elimination

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Samuels, Stuart E.; Eisbruch, Avraham; Vineberg, Karen; Lee, Jae; Lee, Choonik; Matuszak, Martha M.; Ten Haken, Randall K.; Brock, Kristy K., E-mail: kbrock@med.umich.edu

2016-11-01

Purpose: Strategies to reduce the toxicities of head and neck radiation (ie, dysphagia [difficulty swallowing] and xerostomia [dry mouth]) are currently underway. However, the predicted benefit of dose and planning target volume (PTV) reduction strategies is unknown. The purpose of the present study was to compare the normal tissue complication probabilities (NTCP) for swallowing and salivary structures in standard plans (70 Gy [P70]), dose-reduced plans (60 Gy [P60]), and plans eliminating the PTV margin. Methods and Materials: A total of 38 oropharyngeal cancer (OPC) plans were analyzed. Standard organ-sparing volumetric modulated arc therapy plans (P70) were created and then modified by eliminating the PTVs and treating the clinical tumor volumes (CTVs) only (C70) or maintaining the PTV but reducing the dose to 60 Gy (P60). NTCP dose models for the pharyngeal constrictors, glottis/supraglottic larynx, parotid glands (PGs), and submandibular glands (SMGs) were analyzed. The minimal clinically important benefit was defined as a mean change in NTCP of >5%. The P70 NTCP thresholds and overlap percentages of the organs at risk with the PTVs (56-59 Gy, vPTV{sub 56}) were evaluated to identify the predictors for NTCP improvement. Results: With the P60 plans, only the ipsilateral PG (iPG) benefited (23.9% vs 16.2%; P<.01). With the C70 plans, only the iPG (23.9% vs 17.5%; P<.01) and contralateral SMG (cSMG) (NTCP 32.1% vs 22.9%; P<.01) benefited. An iPG NTCP threshold of 20% and 30% predicted NTCP benefits for the P60 and C70 plans, respectively (P<.001). A cSMG NTCP threshold of 30% predicted for an NTCP benefit with the C70 plans (P<.001). Furthermore, for the iPG, a vPTV{sub 56} >13% predicted benefit with P60 (P<.001) and C70 (P=.002). For the cSMG, a vPTV{sub 56} >22% predicted benefit with C70 (P<.01). Conclusions: PTV elimination and dose-reduction lowered the NTCP of the iPG, and PTV elimination lowered the NTCP of the cSMG. NTCP thresholds and the

Mechanistic simulation of normal-tissue damage in radiotherapy-implications for dose-volume analyses

International Nuclear Information System (INIS)

Rutkowska, Eva; Baker, Colin; Nahum, Alan

2010-01-01

A radiobiologically based 3D model of normal tissue has been developed in which complications are generated when 'irradiated'. The aim is to provide insight into the connection between dose-distribution characteristics, different organ architectures and complication rates beyond that obtainable with simple DVH-based analytical NTCP models. In this model the organ consists of a large number of functional subunits (FSUs), populated by stem cells which are killed according to the LQ model. A complication is triggered if the density of FSUs in any 'critical functioning volume' (CFV) falls below some threshold. The (fractional) CFV determines the organ architecture and can be varied continuously from small (series-like behaviour) to large (parallel-like). A key feature of the model is its ability to account for the spatial dependence of dose distributions. Simulations were carried out to investigate correlations between dose-volume parameters and the incidence of 'complications' using different pseudo-clinical dose distributions. Correlations between dose-volume parameters and outcome depended on characteristics of the dose distributions and on organ architecture. As anticipated, the mean dose and V 20 correlated most strongly with outcome for a parallel organ, and the maximum dose for a serial organ. Interestingly better correlation was obtained between the 3D computer model and the LKB model with dose distributions typical for serial organs than with those typical for parallel organs. This work links the results of dose-volume analyses to dataset characteristics typical for serial and parallel organs and it may help investigators interpret the results from clinical studies.

Design and Selection of Machine Learning Methods Using Radiomics and Dosiomics for Normal Tissue Complication Probability Modeling of Xerostomia.

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Gabryś, Hubert S; Buettner, Florian; Sterzing, Florian; Hauswald, Henrik; Bangert, Mark

2018-01-01

The purpose of this study is to investigate whether machine learning with dosiomic, radiomic, and demographic features allows for xerostomia risk assessment more precise than normal tissue complication probability (NTCP) models based on the mean radiation dose to parotid glands. A cohort of 153 head-and-neck cancer patients was used to model xerostomia at 0-6 months (early), 6-15 months (late), 15-24 months (long-term), and at any time (a longitudinal model) after radiotherapy. Predictive power of the features was evaluated by the area under the receiver operating characteristic curve (AUC) of univariate logistic regression models. The multivariate NTCP models were tuned and tested with single and nested cross-validation, respectively. We compared predictive performance of seven classification algorithms, six feature selection methods, and ten data cleaning/class balancing techniques using the Friedman test and the Nemenyi post hoc analysis. NTCP models based on the parotid mean dose failed to predict xerostomia (AUCs  0.85), dose gradients in the right-left (AUCs > 0.78), and the anterior-posterior (AUCs > 0.72) direction. Multivariate models of long-term xerostomia were typically based on the parotid volume, the parotid eccentricity, and the dose-volume histogram (DVH) spread with the generalization AUCs ranging from 0.74 to 0.88. On average, support vector machines and extra-trees were the top performing classifiers, whereas the algorithms based on logistic regression were the best choice for feature selection. We found no advantage in using data cleaning or class balancing methods. We demonstrated that incorporation of organ- and dose-shape descriptors is beneficial for xerostomia prediction in highly conformal radiotherapy treatments. Due to strong reliance on patient-specific, dose-independent factors, our results underscore the need for development of personalized data-driven risk profiles for NTCP models of xerostomia. The facilitated

The normal tissue sparing obtained with simultaneous treatment of pelvic lymph nodes and bladder using intensity-modulated radiotherapy

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Soendergaard, Jimmi; Hoeyer, Morten; Wright, Pauliina; Grau, Cai; Muren, Ludvig Paul; Petersen, Joergen B.

2009-01-01

We have implemented an intensity-modulated radiotherapy (IMRT) protocol for simultaneous irradiation of bladder and lymph nodes. In this report, doses to normal tissue from IMRT and our previous conformal sequential boost technique are compared. Material and methods. Sixteen patients with urinary bladder cancer were treated using a six-field dynamic IMRT beam arrangement delivering 60 Gy to the bladder and 48 Gy to the pelvic lymph nodes. Dose-volume histogram (DVH) parameters for relevant normal tissues (bowel, bowel cavity, rectum and femoral heads) for the IMRT plans were compared with corresponding DVHs from our previous conformal sequential boost technique. Calculations of the generalized Equivalent Uniform Dose (gEUD) were performed for the bowel, with a reference volume of 200 cm 3 and a volume effect parameter k = 4, as well as for the rectum, using k = 12. Acute gastrointestinal (GI) and genitourinary (GU) RTOG toxicity was recorded. Results. Statistical significant normal tissue sparing was obtained by IMRT. For the bowel, a significant reduction was obtained at all dose levels between 20 and 50 Gy (p 3 at 50 Gy, while the gEUD was reduced from 58 to 53 Gy (p 3 at 50 Gy. The rectum gEUD was reduced from 55 to 53 Gy (p < 0.05). For the femoral heads, IMRT reduced the maximum dose as well as the volumes above all dose levels. The rate of acute peak Grade 2 GI RTOG complications was 38% after IMRT. Conclusion. IMRT to the urinary bladder and elective lymph nodes result in considerable normal tissue sparing compared to conformal sequential boost technique. This has paved the way for further studies combining IMRT with image-guided radiotherapy (IGRT) in bladder cancer

Effect of Cisplatin on Parotid Gland Function in Concomitant Radiochemotherapy

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Hey, Jeremias; Setz, Juergen; Gerlach, Reinhard; Vordermark, Dirk; Gernhardt, Christian R.; Kuhnt, Thomas

2009-01-01

Purpose: To determine the influence of concomitant radiochemotherapy with cisplatin on parotid gland tissue complication probability. Methods and Materials: Patients treated with either radiotherapy (n = 61) or concomitant radiochemotherapy with cisplatin (n = 36) for head-and-neck cancer were prospectively evaluated. The dose and volume distributions of the parotid glands were noted in dose-volume histograms. Stimulated salivary flow rates were measured before, during the 2nd and 6th weeks and at 4 weeks and 6 months after the treatment. The data were fit using the normal tissue complication probability model of Lyman. Complication was defined as a reduction of the salivary flow rate to less than 25% of the pretreatment flow rate. Results: The normal tissue complication probability model parameter TD 50 (the dose leading to a complication probability of 50%) was found to be 32.2 Gy at 4 weeks and 32.1 Gy at 6 months for concomitant radiochemotherapy and 41.1 Gy at 4 weeks and 39.6 Gy at 6 months for radiotherapy. The tolerated dose for concomitant radiochemotherapy was at least 7 to 8 Gy lower than for radiotherapy alone at TD 50 . Conclusions: In this study, the concomitant radiochemotherapy tended to cause a higher probability of parotid gland tissue damage. Advanced radiotherapy planning approaches such as intensity-modulated radiotherapy may be partiticularly important for parotid sparing in radiochemotherapy because of cisplatin-related increased radiosensitivity of glands.

Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

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Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

2014-04-16

The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women.

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Therése Andersson

Full Text Available With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1 which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05, indicating an increased whole-body 11betaHSD1 activity. Postmenopausal women had higher 11betaHSD1 gene expression in subcutaneous fat (P<0.05. Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion, suggesting higher hepatic 11betaHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11betaHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

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Li, Li; Xie, Wengming; Li, Hui

2012-12-01

The thyroid is one of the main endocrine glands of human body, which plays a crucial role in the body's metabolism. Thyroid cancer mortality ranks only second to ovarian cancer in endocrine cancer. Routine diagnostic methods of thyroid diseases in present clinic exist misdiagnosis and missed diagnosis to varying degrees. Those lead to miss the best period of cancer treatment--early. Photoacoustic spectroscopy technology is a new tool, which provides an effective and noninvasive way for biomedical materials research, being highly sensitive and without sample pretreatment. In this paper, we use photoacoustic spectroscopy technology (PAST) to detect the absorption spectrum between normal and malignant thyroid tissues. The result shows that the photoacoustic spectroscopy technology (PAST) could differentiate malignant thyroid tissue from normal thyroid tissue very well. This technique combined with routine diagnostic methods has the potential to increase the diagnostic accuracy in clinical thyroid cancer diagnosis.

Iso-effect tables and therapeutic ratios for epidermoid cancer and normal tissue stroma

International Nuclear Information System (INIS)

Cohen, L.; Creditor, M.

1983-01-01

Available literature on radiation injury to normal tissue stroma and ablation of epidermoid carcinoma was surveyed. Computer programs (RAD3 and RAD1) were then used to derive cell kinetic parameters and generate iso-effect tables for the relevant tissues. The two tables provide a set of limiting doses for tolerance of normal connective tissue (16% risk of injury) and for ablation of epidermoid cancer (16% risk of recurrence) covering a wide range of treatment schedules. Calculating the ratios of normal tissue tolerance to tumor control doses for each treatment scheme provides an array of therapeutic ratios, from which appropriate treatment schemes can be selected

The effect of setup uncertainty on normal tissue sparing with IMRT for head-and-neck cancer

International Nuclear Information System (INIS)

Manning, Matthew A.; Wu Quiwen; Cardinale, Robert M.; Mohan, Radhe; Lauve, Andrew D.; Kavanagh, Brian D.; Morris, Monica M.; Schmidt-Ullrich, Rupert K.

2001-01-01

coverage of the nodal region adjacent to the parotid gland. As expected, when the plans were shifted, the greatest increase in contralateral parotid irradiation was noted with shifts toward the contralateral parotid gland. With these shifts, the average volume of contralateral parotid receiving greater than 30 Gy was reduced from 22% to 4% when a PRV was used. This correlated with a reduction in the average normal-tissue complication probability (NTCP) from 22% to 7%. Conclusions: The use of PRV may limit the volume of normal tissue structures, such as the parotid gland, exceeding tolerance dose as a result of setup errors. Consequently, it will be important to incorporate the nomenclature of ICRU-62 into the design of future IMRT studies, if the clinical gains of increased normal-tissue sparing are to be realized

Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

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Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

1998-01-01

The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

Evaluation of normal tissue responses to high-LET radiations

International Nuclear Information System (INIS)

Halnan, K.E.

1979-01-01

Clinical results presented have been analysed to evaluate normal tissue responses to high-LET radiations. Damage to brain, spinal cord, gut, skin, connective tissue and bone has occurred. A high RBE is probable for brain and possible for spinal cord and gut but other reasons for damage are also discussed. A net gain seems likely. Random controlled trials are advocated. (author)

The significance of the choice of radiobiological (NTCP) models in treatment plan objective functions

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Miller, J.; Fuller, M.; Vinod, S.; Holloway, L.

2009-01-01

Full text: A Clinician's discrimination between radiation therapy treatment plans is traditionally a subjective process, based on experience and existing protocols. A more objective and quantitative approach to distinguish between treatment plans is to use radiobiological or dosimetric objective functions, based on radiobiological or dosimetric models. The efficacy of models is not well understood, nor is the correlation of the rank of plans resulting from the use of models compared to the traditional subjective approach. One such radiobiological model is the Normal Tissue Complication Probability (NTCP). Dosimetric models or indicators are more accepted in clinical practice. In this study, three radiobiological models, Lyman NTCP, critical volume NTCP and relative seriality NTCP, and three dosimetric models, Mean Lung Dose (MLD) and the Lung volumes irradiated at lOGy (V|0) and 20 G y (V20), were used to rank a series of treatment plans using, harm to normal (Lung) tissue as the objective criterion. None of the models considered in this study showed consistent correlation with the Radiation Oncologists plan ranking. If radiobiological or dosimetric models are to be used in objective functions for lung treatments, based on this study it is recommended that the Lyman NTCP model be used because it will provide most consistency with traditional clinician ranking.

Imaging of posterior cruciate ligament (PCL) reconstruction: normal postsurgical appearance and complications

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Alcala-Galiano, Andrea; Baeva, Maria; Jose Argueeso, Maria [Hospital ASEPEYO Coslada, Department of Radiology, Madrid (Spain); Ismael, Maryem [Hospital ASEPEYO Coslada, Department of Traumatology and Orthopaedic Surgery, Madrid (Spain)

2014-12-15

This article reviews the normal postsurgical anatomy and appearance of PCL reconstructions on MDCT and MRI with the different operative techniques considering the type of tibial fixation, use of a single or double bundle, type of tendon graft and the fixation material. Tunnel positioning, appearance of the ligament graft and findings at the donor site are considered. Imaging signs of PCL graft failure and its possible causes are discussed. Imaging manifestations of other potential complications of both the PCL graft and donor sites are described, such as laxity, impingement, arthrofibrosis, ganglion cyst formation or complications related to the fixation material. (orig.)

Lyman alpha emission in nearby star-forming galaxies with the lowest metallicities and the highest [OIII]/[OII] ratios

Science.gov (United States)

Izotov, Yuri

2017-08-01

The Lyman alpha line of hydrogen is the strongest emission line in galaxies and the tool of predilection for identifying and studying star-forming galaxies over a wide range of redshifts, especially in the early universe. However, it has become clear over the years that not all of the Lyman alpha radiation escapes, due to its resonant scattering on the interstellar and intergalactic medium, and absorption by dust. Although our knowledge of the high-z universe depends crucially on that line, we still do not have a complete understanding of the mechanisms behind the production, radiative transfer and escape of Lyman alpha in galaxies. We wish here to investigate these mechanisms by studying the properties of the ISM in a unique sample of 8 extreme star-forming galaxies (SFGs) that have the highest excitation in the SDSS spectral data base. These dwarf SFGs have considerably lower stellar masses and metallicities, and higher equivalent widths and [OIII]5007/[OII]3727 ratios compared to all nearby SFGs with Lyman alpha emission studied so far with COS. They are, however, very similar to the dwarf Lyman alpha emitters at redshifts 3-6, which are thought to be the main sources of reionization in the early Universe. By combining the HST/COS UV data with data in the optical range, and using photoionization and radiative transfer codes, we will be able to study the properties of the Lyman alpha in these unique objects, derive column densities of the neutral hydrogen N(HI) and compare them with N(HI) obtained from the HeI emission-line ratios in the optical spectra. We will derive Lyman alpha escape fractions and indirectly Lyman continuum escape fractions.

MRI appearance of radiation-induced changes of normal cervical tissues

International Nuclear Information System (INIS)

Noemayr, A.; Lell, M.; Bautz, W.; Sweeney, R.; Lukas, P.

2001-01-01

Irradiation causes specific MRI changes in anatomic morphology and signal intensity. To avoid misinterpretation, it is important to consider the potential radiation changes of normal tissue in MRI. The aim of this study was to describe the detected radiation effects on normal cervical tissues in MRI. Pretreatment and posttreatment MRI of 52 patients with primary neck tumors were evaluated retrospectively. The MR imaging was performed before initiating radiotherapy and at the end of the treatment period. Patients underwent follow-up studies within 24 months after the end of irradiation. Edema was the main radiation-induced effect. It was detected in the epiglottis, larynx, pharynx wall, retro- and parapharyngeal space, salivary glands, muscles, and subcutaneous tissue. In some cases the bone marrow of the mandible showed edema, due to osteonecrosis. We additionally detected fluid accumulation in the mastoid cells. Radiation caused volume reduction of the parotid gland, thickening of the pharynx wall, and fatty degeneration of bone marrow. Magnetic resonance imaging is an excellent method of depicting radiation-induced changes of normal tissue. Especially T2-weighted sequences allow the detection of even slight edema. It is important to be aware of the most common radiation-induced changes in MRI and to take them into account when assessing an examination. (orig.)

THE LYMAN ALPHA REFERENCE SAMPLE: EXTENDED LYMAN ALPHA HALOS PRODUCED AT LOW DUST CONTENT

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Hayes, Matthew [Universite de Toulouse, UPS-OMP, IRAP, Toulouse (France); Oestlin, Goeran; Duval, Florent; Guaita, Lucia; Melinder, Jens; Sandberg, Andreas [Department of Astronomy, Oskar Klein Centre, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden); Schaerer, Daniel [CNRS, IRAP, 14, avenue Edouard Belin, F-31400 Toulouse (France); Verhamme, Anne; Orlitova, Ivana [Geneva Observatory, University of Geneva, 51 Chemin des Maillettes, CH-1290 Versoix (Switzerland); Mas-Hesse, J. Miguel; Oti-Floranes, Hector [Centro de Astrobiologia (CSIC-INTA), Departamento de Astrofisica, POB 78, 28691 Villanueva de la Canada (Spain); Adamo, Angela [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany); Atek, Hakim [Laboratoire d' Astrophysique, Ecole Polytechnique Federale de Lausanne (EPFL), Observatoire, CH-1290 Sauverny (Switzerland); Cannon, John M. [Department of Physics and Astronomy, Macalester College, 1600 Grand Avenue, Saint Paul, MN 55105 (United States); Herenz, E. Christian [Leibniz-Institut fuer Astrophysik (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany); Kunth, Daniel [Institut d' Astrophysique de Paris, UMR 7095 CNRS and UPMC, 98 bis Bd Arago, F-75014 Paris (France); Laursen, Peter, E-mail: matthew@astro.su.se [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen (Denmark)

2013-03-10

We report on new imaging observations of the Lyman alpha emission line (Ly{alpha}), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 < z < 0.18 in continuum-subtracted Ly{alpha}, H{alpha}, and the far ultraviolet continuum. We show that Ly{alpha} is emitted on scales that systematically exceed those of the massive stellar population and recombination nebulae: as measured by the Petrosian 20% radius, R{sub P20}, Ly{alpha} radii are larger than those of H{alpha} by factors ranging from 1 to 3.6, with an average of 2.4. The average ratio of Ly{alpha}-to-FUV radii is 2.9. This suggests that much of the Ly{alpha} light is pushed to large radii by resonance scattering. Defining the Relative Petrosian Extension of Ly{alpha} compared to H{alpha}, {xi}{sub Ly{alpha}} = R {sup Ly{alpha}}{sub P20}/R {sup H{alpha}}{sub P20}, we find {xi}{sub Ly{alpha}} to be uncorrelated with total Ly{alpha} luminosity. However, {xi}{sub Ly{alpha}} is strongly correlated with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Ly{alpha} photons throughout the interstellar medium and drive a large extended Ly{alpha} halo.

Raman spectroscopy of normal oral buccal mucosa tissues: study on intact and incised biopsies

Science.gov (United States)

Deshmukh, Atul; Singh, S. P.; Chaturvedi, Pankaj; Krishna, C. Murali

2011-12-01

Oral squamous cell carcinoma is one of among the top 10 malignancies. Optical spectroscopy, including Raman, is being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex vivo tissues. Spectral features showed predominance of lipids and proteins in normal and cancer conditions, respectively, which were attributed to membrane lipids and surface proteins. In view of recent developments in deep tissue Raman spectroscopy, we have recorded Raman spectra from superior and inferior surfaces of 10 normal oral tissues on intact, as well as incised, biopsies after separation of epithelium from connective tissue. Spectral variations and similarities among different groups were explored by unsupervised (principal component analysis) and supervised (linear discriminant analysis, factorial discriminant analysis) methodologies. Clusters of spectra from superior and inferior surfaces of intact tissues show a high overlap; whereas spectra from separated epithelium and connective tissue sections yielded clear clusters, though they also overlap on clusters of intact tissues. Spectra of all four groups of normal tissues gave exclusive clusters when tested against malignant spectra. Thus, this study demonstrates that spectra recorded from the superior surface of an intact tissue may have contributions from deeper layers but has no bearing from the classification of a malignant tissues point of view.

Tumor and normal tissue responses to fractioned non-uniform dose delivery

Energy Technology Data Exchange (ETDEWEB)

Kaellman, P; Aegren, A; Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

1996-08-01

The volume dependence of the radiation response of a tumor is straight forward to quantify because it depends primarily on the eradication of all its clonogenic cells. A tumor therefore has a parallel organization as any surviving clonogen in principle can repopulate the tumor. The difficulty with the response of the tumor is instead to know the density and sensitivity distribution of the most resistant clonogenic cells. The increase in the 50% tumor control dose and the decrease in the maximum normalized slope of the dose response relation, {gamma}, in presence of small compartments of resistant tumor cells have therefore been quantified to describe their influence on the dose response relation. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of the differentiated and clonogenic cells that in addition may have a complex structural and functional organization. The volume dependence of the dose response relation of normal tissues is therefore described here by the relative seriality, s, of the infrastructure of the organ. The model can also be generalized to describe the response of heterogeneous tissues to non uniform dose distributions. The new model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose response relation and the volume dependence of the isoeffect dose. The response of tumors and normal tissues are quantified for arbitrary dose fractionations using the linear quadratic cell survival parameters {alpha} and {beta}. The parameters of the dose response relation are derived both for a constant dose per fraction and a constant number of dose fractions, thus in the latter case accounting also for non uniform dose delivery. (author). 26 refs, 4 figs.

High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

International Nuclear Information System (INIS)

Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

2012-01-01

Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

Identification of molecular mechanisms of radiation-induced vascular damage in normal tissues using microarray analyses

International Nuclear Information System (INIS)

Kruse, J.J.C.M.; Te Poele, J.A.M.; Russell, N.S.; Boersma, L.J.; Stewart, F.A.

2003-01-01

Radiation-induced telangiectasia, characterized by thin-walled dilated blood vessels, can be a serious late complication in patients that have been previously treated for cancer. It might cause cosmetic problems when occurring in the skin, and excessive bleeding requiring surgery when occurring in rectal mucosa. The mechanisms underlying the development of radiation-induced telangiectasia are unclear. The aim of the present study is to determine whether microarrays are useful for studying mechanisms of radiation-induced telangiectasia. The second aim is to test the hypotheses that telangiectasia is characterized by a final common pathway in different tissues. Microarray experiments were performed using amplified RNA from (sham)irradiated mouse tissues (kidney, rectum) at different intervals (1-30 weeks) after irradiation. After normalization procedures, the differentially expressed genes were identified. Control/repeat experiments were done to confirm that the observations were not artifacts of the array procedure. The mouse kidney experiments showed significant upregulation of 31 and 42 genes and downregulation of 9 and 4 genes at 10 and 20 weeks after irradiation, respectively. Irradiated mouse rectum has 278 upregulated and 537 downregulated genes at 10 weeks and 86 upregulated and 29 downregulated genes at 20 weeks. During the development of telangiectasia, 19 upregulated genes and 5 downregulated genes were common to both tissues. Upregulation of Jagged-1, known to play a role in angiogenesis, is particularly interesting in the context of radiation-induced telangiectasia. Microarrays are affective discovery tools to identify novel genes of interest, which may be involved in radiation-induced normal tissue injury. Using information from control arrays (particularly straight color, color reverse and self-self experiments) allowed for a more accurate and reproducible identification of differentially expressed genes than the selection of an arbitrary 2-fold change

Reconstruction of soft tissue after complicated calcaneal fractures.

Science.gov (United States)

Koski, E Antti; Kuokkanen, Hannu O M; Koskinen, Seppo K; Tukiainen, Erkki J

2004-01-01

A total of 35 flap reconstructions were done to cover exposed calcaneal bones in 31 patients. All patients had calcaneal fractures, 19 of which were primarily open. Soft tissue reconstruction for the closed fractures was indicated by a postoperative wound complication. A microvascular flap was used for reconstruction in 21 operations (gracilis, n = 11; anterolateral thigh, n = 5; rectus abdominis, n = 3; and latissimus dorsi, n = 2). A suralis neurocutaneous flap was used in eight, local muscle flaps in three, and local skin flaps in three cases. The mean follow-up time was 14 months (range 3 months-4 years). One suralis flap failed and was replaced by a latissimus dorsi flap. Necrosis of the edges that required revision affected three flaps. Deep infection developed in two patients and delayed wound healing in another four. During the follow-up the soft tissues healed in all patients and there were no signs of calcaneal osteitis. Flaps were considered too bulky in five patients. Soft tissues heal most rapidly with microvascular flaps. In the long term, gracilis muscle covered with free skin grafts gives a good contour to the foot. The suralis flap is reliable and gives a good final aesthetic outcome. Local muscles can be transposed for reconstruction in small defects.

Sonographic findings after total hip arthroplasty: normal and complications

International Nuclear Information System (INIS)

Lee, Kyoung Rok; Seon, Young Seok; Choi, Ji He; Kim, Sun Su; Kim, Se Jong; Park, Byong Lan; Kim, Byoung Geun

2002-01-01

The purpose of this study was to determine the efficacy of sonography in the evaluation of normal pseudocapsular morphology and the detection of complications after total hip arthroplasty. Between Janvary 1997 and June 2000, 47 patients (35 men and 12 women aged 24 to 84 (mean, 61) years) using real-time linear-array, convex US units with 3.5-MHz and 10-MHz transducers. Normal capsular morphology in 30 with total hip replacements, who had been asymptomatic for at least one year, was studied, and the prosthetic joint infection demonstrated in six of 17 who had experienced was confirmed at surgery or by US-guided aspiration. Sonograms indicated that a normal pseudocapsule lay straight over the neck of the prosthesis or was slightly convex toward the neck , and that the mean bone-to-pseudocapsule distance was 2.9 mm. However, in the 11 symptomatic patients in whom no evidence of infection was revealed by cultures, th mean distance was 4.7 mm; in the remaining six patients, whose joints were infected (a condition strongly suggested by the presence of extracapsular fluid), the mean distance was 5.5 mm, with no significant difference between the two groups. Sonography can be used to evaluate normal caspular morphology after total hip replacement and to diagnose infection around hip prostheses. In all patients in whom sonography revealed the presence of extra-articular fluid, infection had occurred

Sonographic findings after total hip arthroplasty: normal and complications

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyoung Rok; Seon, Young Seok; Choi, Ji He; Kim, Sun Su; Kim, Se Jong; Park, Byong Lan; Kim, Byoung Geun [Kwangju Christian Hospital, Kwangju (Korea, Republic of)

2002-04-01

The purpose of this study was to determine the efficacy of sonography in the evaluation of normal pseudocapsular morphology and the detection of complications after total hip arthroplasty. Between Janvary 1997 and June 2000, 47 patients (35 men and 12 women aged 24 to 84 (mean, 61) years) using real-time linear-array, convex US units with 3.5-MHz and 10-MHz transducers. Normal capsular morphology in 30 with total hip replacements, who had been asymptomatic for at least one year, was studied, and the prosthetic joint infection demonstrated in six of 17 who had experienced was confirmed at surgery or by US-guided aspiration. Sonograms indicated that a normal pseudocapsule lay straight over the neck of the prosthesis or was slightly convex toward the neck , and that the mean bone-to-pseudocapsule distance was 2.9 mm. However, in the 11 symptomatic patients in whom no evidence of infection was revealed by cultures, th mean distance was 4.7 mm; in the remaining six patients, whose joints were infected (a condition strongly suggested by the presence of extracapsular fluid), the mean distance was 5.5 mm, with no significant difference between the two groups. Sonography can be used to evaluate normal caspular morphology after total hip replacement and to diagnose infection around hip prostheses. In all patients in whom sonography revealed the presence of extra-articular fluid, infection had occurred.

Does Acellular Dermal Matrix Thickness Affect Complication Rate in Tissue Expander Based Breast Reconstruction?

Directory of Open Access Journals (Sweden)

Jessica F. Rose

2016-01-01

Full Text Available Background. While the benefits of using acellular dermal matrices (ADMs in breast reconstruction are well described, their use has been associated with additional complications. The purpose of this study was to determine if ADM thickness affects complications in breast reconstruction. Methods. A retrospective chart review was performed including all tissue expander based breast reconstructions with AlloDerm (LifeCell, Branchburg, NJ over 4 years. We evaluated preoperative characteristics and assessed postoperative complications including seroma, hematoma, infection, skin necrosis, and need for reintervention. We reviewed ADM thickness and time to Jackson-Pratt (JP drain removal. Results. Fifty-five patients underwent 77 ADM-associated tissue expander based breast reconstructions, with average age of 48.1 years and average BMI of 25.9. Average ADM thickness was 1.21 mm. We found higher complication rates in the thick ADM group. Significant associations were found between smokers and skin necrosis (p<0.0001 and seroma and prolonged JP drainage (p=0.0004; radiated reconstructed breasts were more likely to suffer infections (p=0.0085, and elevated BMI is a significant predictor for increased infection rate (p=0.0037. Conclusion. We found a trend toward increased complication rates with thicker ADMs. In the future, larger prospective studies evaluating thickness may provide more information.

Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

International Nuclear Information System (INIS)

Jakobi, Annika; Bandurska-Luque, Anna; Stützer, Kristin; Haase, Robert; Löck, Steffen; Wack, Linda-Jacqueline; Mönnich, David; Thorwarth, Daniela

2015-01-01

Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons

Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

Energy Technology Data Exchange (ETDEWEB)

Jakobi, Annika, E-mail: Annika.Jakobi@OncoRay.de [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Bandurska-Luque, Anna [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Stützer, Kristin; Haase, Robert; Löck, Steffen [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Wack, Linda-Jacqueline [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); Mönnich, David [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); German Cancer Research Center, Heidelberg (Germany); German Cancer Consortium, Tübingen (Germany); Thorwarth, Daniela [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); and others

2015-08-01

Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.

Therapy-induced effects in normal tissue; Therapieinduzierte Effekte am Normalgewebe

Energy Technology Data Exchange (ETDEWEB)

Kaick, G. van; Delorme, S. [Deutsches Krebsforschungszentrum (DKFZ), Abteilung E010 - Radiologie, Heidelberg (Germany)

2008-09-15

More than 50% of cancer patients survive for more than 5 years, owing to modern and effective treatment. Therefore, long-term sequelae of treatment are more frequently seen than in the past. Such effects on normal tissue may both mimic and obscure tumor recurrences. Besides the direct consequences of surgery, tissue damage due to radiation or chemotherapy frequently cause problems in differential diagnosis. Among the numerous sequelae of radiotherapy, the most prominent are disturbance of the blood-brain barrier, radiation pneumonitis, osteodystrophy and osteoradionecrosis, fatty changes of bone marrow, or increased radiodensity of breast parenchyma. Chemotherapy may cause, e.g., diffuse abnormalities of white matter, pneumonitis and lung fibrosis, cardiomyopathy, or diffuse and patchy changes in bone marrow signals in MRI. The most devastating long-term complications are secondary cancers and leukemia induced by both radiotherapy and chemotherapy. (orig.) [German] Mehr als 50% der Tumorpatienten ueberleben dank moderner Therapie laenger als 5 Jahre, sodass die Spaetfolgen am gesunden Gewebe haeufiger und genauer erfasst werden. Diese koennen Tumorrezidive sowohl verschleiern als auch vortaeuschen. Neben den unmittelbaren Folgen operativer Eingriffe sind Auswirkungen der Chemo- und Strahlentherapie ein haeufiges differenzialdiagnostisches Problem. Wichtige Folgen einer Strahlentherapie sind z. B. Blut-Hirn-Schranken-Stoerungen, Strahlenpneumonitis, Osteodystrophie und -radionekrose, Verfettung des blutbildenden Knochenmarks oder Parenchymverdichtungen der Brust. Chemotherapie kann u. a. zur Leukenzephalopathie, Pneumonitis und Lungenfibrose, Kardiomyopathie sowie zu diffusen und fleckfoermigen Signalaenderungen des Knochenmarks in der MRT fuehren. Die schwerstwiegende Spaetkomplikation ist die Induktion solider Zweittumoren und Leukaemien sowohl nach Strahlen- als auch Chemotherapie. (orig.)

Oxygen sensitivity of krypton and Lyman-alpha hygrometers

NARCIS (Netherlands)

Dijk, van A.; Kohsiek, W.; Bruin, de H.A.R.

2003-01-01

The oxygen sensitivity of krypton and Lyman-¿ hygrometers is studied. Using a dewpoint generator and a controlled nitrogen/oxygen flow the extinction coefficients of five hygrometers associated with the third-order Taylor expansion of the Lambert¿Beer law around reference conditions for oxygen and

Optical redox imaging indices discriminate human breast cancer from normal tissues

Science.gov (United States)

Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

2016-01-01

Abstract. Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (predox ratio Fp/(NADH + Fp) was ∼27% higher in the cancerous tissues (predox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. PMID:27896360

Iatrogenic Pneumothorax as a Complication to Delayed Breast Reconstruction With Tissue Expander—A Case Report

DEFF Research Database (Denmark)

Willert, Cecilie Balslev; Bredgaard, Rikke

2017-01-01

Breast reconstruction with expander implant is the most common breast reconstructive procedure. Irradiated patients are seldom reconstructed this way because the tissue expansion is difficult and the complication rates are higher. Pneumothorax is a serious condition and can be seen as a complicat......Breast reconstruction with expander implant is the most common breast reconstructive procedure. Irradiated patients are seldom reconstructed this way because the tissue expansion is difficult and the complication rates are higher. Pneumothorax is a serious condition and can be seen...... as a complication to the operation. Literature is sparse; hence, the only study is by Schneider et al who found an incidence of 0.55%. The study focused on immediate reconstruction only and did not report the percentage of irradiated patients. We present a unique case of iatrogenic pneumothorax in a previously...

Morphologic alterations in normal and neoplastic tissues following hyperthermia treatment

International Nuclear Information System (INIS)

Badylak, S.F.; Babbs, C.F.

1984-01-01

The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 0 C and 45 0 for 20 minutes) were studied by light and electron microscopy. Normal muscle and Walker 256 tumors showed vascular damage at 5 minutes post-heating (PH), followed by suppuration and thrombosis at 6 and 48 hours PH, and by regeneration and repair at 7 days PH. Endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive ischemic injury occurred for at least 48 hours PH. Two hyperthermia treatments, separated by a 30 or 60 minute cooling interval, were applied to rats implanted with Walker 256 tumors. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results characterized the sequential morphologic alterations following hyperthermia treatment and showed that: 1) vascular damage contributed to the immediate and latent cytotoxic effects of hyperthermia, 2) selective heating occurred in the neoplastic tissue disrupted by prior heat treatment, and 3) not all neoplasms are responsive to hyperthermia treatment

Increase in tumor control and normal tissue complication probabilities in advanced head-and-neck cancer for dose-escalated intensity-modulated photon and proton therapy

Directory of Open Access Journals (Sweden)

Annika eJakobi

2015-11-01

Full Text Available Introduction:Presently used radio-chemotherapy regimens result in moderate local control rates for patients with advanced head and neck squamous cell carcinoma (HNSCC. Dose escalation (DE may be an option to improve patient outcome, but may also increase the risk of toxicities in healthy tissue. The presented treatment planning study evaluated the feasibility of two DE levels for advanced HNSCC patients, planned with either intensity-modulated photon therapy (IMXT or proton therapy (IMPT.Materials and Methods:For 45 HNSCC patients, IMXT and IMPT treatment plans were created including DE via a simultaneous integrated boost (SIB in the high-risk volume, while maintaining standard fractionation with 2 Gy per fraction in the remaining target volume. Two DE levels for the SIB were compared: 2.3 Gy and 2.6 Gy. Treatment plan evaluation included assessment of tumor control probabilities (TCP and normal tissue complication probabilities (NTCP.Results:An increase of approximately 10% in TCP was estimated between the DE levels. A pronounced high-dose rim surrounding the SIB volume was identified in IMXT treatment. Compared to IMPT, this extra dose slightly increased the TCP values and to a larger extent the NTCP values. For both modalities, the higher DE level led only to a small increase in NTCP values (mean differences < 2% in all models, except for the risk of aspiration, which increased on average by 8% and 6% with IMXT and IMPT, respectively, but showed a considerable patient dependence. Conclusions:Both DE levels appear applicable to patients with IMXT and IMPT since all calculated NTCP values, except for one, increased only little for the higher DE level. The estimated TCP increase is of relevant magnitude. The higher DE schedule needs to be investigated carefully in the setting of a prospective clinical trial, especially regarding toxicities caused by high local doses that lack a sound dose response description, e.g., ulcers.

Avoiding Complications in Bone and Soft Tissue Ablation

International Nuclear Information System (INIS)

Kurup, A. Nicholas; Schmit, Grant D.; Morris, Jonathan M.; Atwell, Thomas D.; Schmitz, John J.; Weisbrod, Adam J.; Woodrum, David A.; Eiken, Patrick W.; Callstrom, Matthew R.

2017-01-01

As with percutaneous ablation of tumors in the liver, lungs, and kidneys, ablation of bone and non-visceral soft tissue tumors carries risk, primarily from collateral damage to vital structures in proximity to the target tumor. Certain risks are of particular interest when ablating bone and non-visceral soft tissue tumors, namely neural or skin injury, bowel injury, fracture, and gas embolism from damaged applicators. Ablation of large volume tumors also carries special risk. Many techniques may be employed by the interventional radiologist to minimize complications when treating tumors in the musculoskeletal system. These methods include those to depict, displace, or monitor critical structures. Thus, measures to provide thermoprotection may be active, such as careful ablation applicator placement and use of various displacement techniques, as well as passive, including employment of direct temperature, radiographic, or neurophysiologic monitoring techniques. Cementoplasty should be considered in certain skeletal locations at risk of fracture. Patients treated with large volume tumors should be monitored for renal dysfunction and properly hydrated. Finally, ablation applicators should be cautiously placed in the constrained environment of intact bone.

Avoiding Complications in Bone and Soft Tissue Ablation

Energy Technology Data Exchange (ETDEWEB)

Kurup, A. Nicholas, E-mail: kurup.anil@mayo.edu; Schmit, Grant D., E-mail: schmit.grant@mayo.edu; Morris, Jonathan M., E-mail: morris.jonathan@mayo.edu; Atwell, Thomas D., E-mail: atwell.thomas@mayo.edu; Schmitz, John J., E-mail: schmitz.john@mayo.edu; Weisbrod, Adam J., E-mail: weisbrod.adam@mayo.edu; Woodrum, David A., E-mail: woodrum.david@mayo.edu; Eiken, Patrick W., E-mail: eiken.patrick@mayo.edu; Callstrom, Matthew R., E-mail: callstrom.matthew@mayo.edu [Mayo Clinic, Department of Radiology (United States)

2017-02-15

As with percutaneous ablation of tumors in the liver, lungs, and kidneys, ablation of bone and non-visceral soft tissue tumors carries risk, primarily from collateral damage to vital structures in proximity to the target tumor. Certain risks are of particular interest when ablating bone and non-visceral soft tissue tumors, namely neural or skin injury, bowel injury, fracture, and gas embolism from damaged applicators. Ablation of large volume tumors also carries special risk. Many techniques may be employed by the interventional radiologist to minimize complications when treating tumors in the musculoskeletal system. These methods include those to depict, displace, or monitor critical structures. Thus, measures to provide thermoprotection may be active, such as careful ablation applicator placement and use of various displacement techniques, as well as passive, including employment of direct temperature, radiographic, or neurophysiologic monitoring techniques. Cementoplasty should be considered in certain skeletal locations at risk of fracture. Patients treated with large volume tumors should be monitored for renal dysfunction and properly hydrated. Finally, ablation applicators should be cautiously placed in the constrained environment of intact bone.

Risk Factors for Complications Differ Between Stages of Tissue-Expander Breast Reconstruction.

Science.gov (United States)

Lovecchio, Francis; Jordan, Sumanas W; Lim, Seokchun; Fine, Neil A; Kim, John Y S

2015-09-01

Tissue-expander (TE) placement followed by implant exchange is currently the most popular method of breast reconstruction. There is a relative paucity of data demonstrating patient factors that predict complications specifically by stage of surgery. The present study attempts to determine what complications are most likely to occur at each stage and how the risk factors for complications vary by stage of reconstruction. A retrospective chart review was performed on all 1275 patients who had TEs placed by the 2 senior authors between 2004 and 2013. Complication rates were determined at each stage of reconstruction, and these rates were further compared between patients who had pre-stage I radiation, post-stage I radiation, and no radiation exposure. Multivariate logistic regression was used to identify independent predictors of complications at each stage of reconstruction. A total of 1639 consecutive TEs were placed by the senior authors during the study period. The overall rate for experiencing a complication at any stage of surgery was 17%. Complications occurred at uniformly higher rates during stage I for all complications (92% stage I vs 7% stage II vs 1% stage III, P higher intraoperative percent fill (OR, 3.3; 95% CI, 1.7-6.3). Post-stage I radiation was the only independent risk factor for a stage II complication (OR, 4.5; 95% CI, 1.4-15.2). Complications occur at higher rates after stage I than after stage II, and as expected, stage III complications are exceedingly rare. Risk factors for stage I complications are different from risk factors for stage II complications. Body mass index and smoking are associated with complications at stage I, but do not predict complications at stage II surgery. The stratification of risk factors by stage of surgery will help surgeons and patients better manage both risk and expectations.

Reconstruction of complicated skull base defects utilizing free tissue transfer.

Science.gov (United States)

Djalilian, Hamid R; Gapany, Markus; Levine, Samuel C

2002-11-01

We managed five patients with large skull base defects complicated by complex infections with microvascular free tissue transfer. The first patient developed an infection, cerebrospinal fluid (CSF) leak, and meningitis after undergoing a translabyrinthine resection of an acoustic neuroma. The second patient had a history of a gunshot wound to the temporal bone, with a large defect and an infected cholesteatoma that caused several episodes of meningitis. The third through the fifth patients had persistent CSF leakage and infection refractory to conventional therapy. In all cases prior attempts of closure with fat grafts or regional flaps had failed. Rectus abdominis myofascial free flap, radial forearm free flap or a gracilis muscle free flap was used after debridement of the infected cavities. The CSF leaks, local infections, and meningitis were controlled within a week. In our experience, microvascular free tissue provides the necessary bulk of viable, well-vascularized tissue, which not only assures a mechanical seal but also helps clear the local infection.

Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo

International Nuclear Information System (INIS)

Ostrau, Christian; Huelsenbeck, Johannes; Herzog, Melanie; Schad, Arno; Torzewski, Michael; Lackner, Karl J.; Fritz, Gerhard

2009-01-01

Background and purpose: HMG-CoA-reductase inhibitors (statins) are widely used lipid-lowering drugs. Moreover, they have pleiotropic effects on cellular stress responses, proliferation and apoptosis in vitro. Here, we investigated whether lovastatin attenuates acute and subchronic ionizing radiation-induced normal tissue toxicity in vivo. Materials and methods: Four hours to 24 h after total body irradiation (6 Gy) of Balb/c mice, acute pro-inflammatory and pro-fibrotic responses were analyzed. To comprise subchronic radiation toxicity, mice were irradiated twice with 2.5 Gy and analyses were performed 3 weeks after the first radiation treatment. Molecular markers of inflammation and fibrosis as well as organ toxicities were measured. Results: Lovastatin attenuated IR-induced activation of NF-κB, mRNA expression of cell adhesion molecules and mRNA expression of pro-inflammatory and pro-fibrotic marker genes (i.e. TNFα, IL-6, TGFβ, CTGF, and type I and type III collagen) in a tissue- and time-dependent manner. γH2AX phosphorylation stimulated by IR was not affected by lovastatin, indicating that the statin has no major impact on the induction of DNA damage in vivo. Radiation-induced thrombopenia was significantly alleviated by lovastatin. Conclusions: Lovastatin inhibits both acute and subchronic IR-induced pro-inflammatory and pro-fibrotic responses and cell death in normal tissue in vivo. Therefore, lovastatin might be useful for selectively attenuating acute and subchronic normal tissue damage caused by radiotherapy.

Modification of the biologic dose to normal tissue by daily fraction

Energy Technology Data Exchange (ETDEWEB)

Wollin, M; Kagan, A R [Southern California Permanente Medical Group, Los Angeles Calif. (USA). Dep. of Radiation Therapy

1976-12-01

A method to predict normal tissue injury is proposed that includes high daily doses and unusual times successfully by calculating a new value called BIR (Biologic Index of Reaction). BIR and NSD were calculated for various normal tissue reactions. With the aid of statistical correlation techniques it is found that the BIR model is better than the NSD model in predicting radiation myelopathy and vocal edema and as good as NSD IN PREDICTING RIB FRACTURE/ Neither model predicts pericardial effusion. In no case were the results of BIR inferior to those of NSD.

Differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance

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Ben-Zhou Feng

2016-04-01

Full Text Available Objective: To study the differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance. Methods: Preeclampsia placenta tissue and normal placenta tissue were collected and GPR30 expression levels were detected; human umbilical vein endothelial cells were cultured and processed with GRP30 inhibitor and GRP30 agonist combined with hypoxia-reoxygenation respectively, and cell apoptosis as well as pro-angiogenesis molecule and apoptosis molecule contents were detected. Results: mRNA content and protein content of GRP30 in preeclampsia placenta tissue were significantly lower than those in normal placenta tissue; apoptosis rate of G15 group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of H/R group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of G1 group was significantly lower than that of H/R group, VEGF and bFGF contents in supernatant were significantly higher than those of H/R group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly lower than those of H/R group. Conclusions: Low expression of GPR30 in placenta tissue is closely associated with the occurrence of preeclampsia, enhancing GPR function can reduce endothelial cell apoptosis and increase the contents of pro-angiogenesis factors, and it has endothelial protection effect.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L. [Dept.of Radiation Oncology, Henry Ford Health System, Detroit (United States)

2014-09-15

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

International Nuclear Information System (INIS)

Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L.

2014-01-01

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

Minimizing complications of ultrasound-assisted lipoplasty: an initial experience with no related complications.

Science.gov (United States)

Tebbetts, J B

1998-10-01

Numerous complications and increased operating times were reported with ultrasonically assisted lipoplasty in the first several months after introduction of the technology in the United States. The purpose of this study was to review early reported complications and management regimens, evaluate possible causes of problems, and apply indications and techniques to attempt to minimize complications during an initial experience with this technique beginning in January of 1997. Seven specific indications and modifications of existing techniques were developed and applied to an initial clinical series of 70 consecutive patients who underwent ultrasound-assisted suction lipoplasty between January 10, 1997, and August 1, 1997. Follow-up ranged from 1 to 7 months. No perioperative or postoperative complication occurred in any patient in this series. In this series of ultrasound-assisted lipoplasty cases, application of the following criteria resulted in a series of 70 patients with 1 to 7-month follow-up without complications: (1) selecting patients with well localized fat deposits who were no more than 20 percent above their ideal body weight; (2) infusing a solution of Ringer's Lactate containing 1 cc of 1:1000 epinephrine per 1000 cc into the area of fat removal, stopping infusion when the tissues first become firm, not infusing to marked tissue turgor or skin induration; (3) restricting the level of energy application to a minimum of 1 cm from the undersurface of the dermis; (4) limiting ultrasonic energy application in each area to approximately 1 minute per estimated 100 cc of total aspirate in a wet to superwet environment; (5) not performing ultrasound-assisted lipoplasty in the same area as another procedure that could potentially compromise tissue vascularity; (6) using a Lysonix 2000 generator and 5-mm golf tee tip probe at a power setting of 8 to apply ultrasonic energy to the area of fat removal, ceasing energy application when tissue resistance to the passage

Comparison of Tissue Stiffness Using Shear Wave Elastography in Men with Normal Testicular Tissue, Testicular Microlithiasis and Testicular Cancer

DEFF Research Database (Denmark)

Pedersen, Malene Roland; Møller, Henrik; Osther, Palle Jørn Sloth

2017-01-01

Objectives: To compare elastography measurements in men with normal testicular tissue, testicular microlithiasis and testicular cancer. Methods: A total of 248 consecutive patients were included. All men provided written informed consent. Testicular stiffness was assessed using shear wave...... elastography (SWE). Three SWE velocity measurements were assessed in each testicle. The patients were divided into three groups; men with normal testicular tissue (n=130), men with testicular microlithiasis (n=99) and men with testicular cancer (n=19). Results: We found a higher mean velocity in the group...... of patients with testicular cancer (1.92 m/s (95% CI 1.82-2.03)) compared to both the group with normal tissue (0.76 m/s (95% CI: 0.75-0.78)) (ptesticular microlithiasis 0.79 m/s (95% CI: 0.77-0.81) (ptesticular microlithiasis increased stiffness...

Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

International Nuclear Information System (INIS)

Simpson, Daniel R.; Song, William Y.; Moiseenko, Vitali; Rose, Brent S.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

2012-01-01

Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I–III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade ≥2 GI toxicity and the volume of bowel receiving ≥45 Gy (V 45 ) using the logistic model. Results: Twenty-three patients (46%) had Grade ≥2 GI toxicity. The mean (SD) V 45 was 143 mL (99). The mean V 45 values for patients with and without Grade ≥2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V 45 >150 mL. The proportion of patients with Grade ≥2 GI toxicity with and without V 45 >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and γ were 161 mL (95% confidence interval [CI] 60–399) and 0.31 (95% CI 0.04–0.63), respectively. On multivariable logistic regression, increased V 45 was associated with an increased odds of Grade ≥2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04–4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V 45 is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V 45 could reduce the risk of Grade ≥2 GI toxicity by approximately 50% per 100 mL of bowel spared.

Proteinase-activated receptors - mediators of early and delayed normal tissue radiation responses

International Nuclear Information System (INIS)

Hauer-Jensen, M.

2003-01-01

Proteinase-activated receptors (PARs) are G-protein coupled receptors that are activated by proteolytic exposure of a receptor-tethered ligand. The discovery of this receptor family represents one of the most intriguing recent developments in signal transduction. PARs are involved in the regulation of many normal and pathophysiological processes, notably inflammatory and fibroproliferative responses to injury. Preclinical studies performed in our laboratory suggest that proteinase-activated receptor-1 (PAR-1) plays a critical role in the mechanism of chronicity of radiation fibrosis, while proteinase-activated receptor-2 (PAR-2) may mediate important fibroproliferative responses in irradiated intestine. Specifically, activation of PAR-1 by thrombin, and PAR-2 by pancreatic trypsin and mast cell proteinases, appears to be involved in acute radiation-induced inflammation, as well as in subsequent extracellular matrix deposition, leading to the development of intestinal wall fibrosis and clinical complications. Pharmacological modulators of PAR-1 or PAR-2 expression or activation would be potentially useful as preventive or therapeutic agents in patients who receive radiation therapy, especially if blockade could be targeted to specific tissues or cellular compartments

Trace elemental correlation study in malignant and normal breast tissue by PIXE technique

International Nuclear Information System (INIS)

Raju, G.J. Naga; Sarita, P.; Kumar, M. Ravi; Murty, G.A.V. Ramana; Reddy, B. Seetharami; Lakshminarayana, S.; Vijayan, V.; Lakshmi, P.V.B. Rama; Gavarasana, Satyanarayana; Reddy, S. Bhuloka

2006-01-01

Particle induced X-ray emission technique was used to study the variations in trace elemental concentrations between normal and malignant human breast tissue specimens and to understand the effects of altered homeostasis of these elements in the etiology of breast cancer. A 3 MeV proton beam was used to excite the biological samples of normal and malignant breast tissues. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb and Sr were identified and their relative concentrations were estimated. Almost all the elements were found to be elevated (p < 0.05, Wilcoxon signed-ranks test) in the cancerous tissues when compared with normal tissues. The excess levels of trace elements observed in the cancerous breast tissues could either be a cause or a consequence of breast cancer. Regarding their role in the initiation or promotion of breast cancer, one possible interpretation is that the elevated levels of Cu, Fe and Cr could have led to the formation of free radicals or other reactive oxygen species (ROS) that adversely affect DNA thereby causing breast cancer, which is mainly attributed to genetic abnormalities. Moreover, since Cu and Fe are required for angiogenesis, elevated concentrations of these elements are likely to promote breast cancer by increasing the blood supply for tumor growth. On the other hand elevated concentrations of elements in breast cancer tissues might also be a consequence of the cancer. This can be understood in terms of the biochemical and histological differences between normal and cancerous breast tissues. Tumors, characterized by unregulated multiplication of cells, need an ever-increasing supply of essential nutrients including trace elements. This probably results in an increased vascularity of malignant tissues, which in turn leads to enhancement of elemental concentrations in tumors

The expression of Egfl7 in human normal tissues and epithelial tumors.

Science.gov (United States)

Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

2013-04-23

To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

Dosimetric Analysis of Radiation-induced Gastric Bleeding

Energy Technology Data Exchange (ETDEWEB)

Feng, Mary, E-mail: maryfeng@umich.edu [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Normolle, Daniel [Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Pan, Charlie C. [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Amarnath, Sudha [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Ensminger, William D. [Department of Internal Medicine, Division of Hematology Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Lawrence, Theodore S.; Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States)

2012-09-01

Purpose: Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. Methods and Materials: The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of {>=}grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. Results: Sixteen of 116 evaluable patients (14%) developed gastric bleeds at a median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD{sub 50} (normal) = 56 Gy and TD{sub 50} (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD{sub 50} value for the cirrhosis patients points out their greater sensitivity. Conclusions: This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.

Dosimetric Analysis of Radiation-induced Gastric Bleeding

International Nuclear Information System (INIS)

Feng, Mary; Normolle, Daniel; Pan, Charlie C.; Dawson, Laura A.; Amarnath, Sudha; Ensminger, William D.; Lawrence, Theodore S.; Ten Haken, Randall K.

2012-01-01

Purpose: Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. Methods and Materials: The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of ≥grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. Results: Sixteen of 116 evaluable patients (14%) developed gastric bleeds at a median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD 50 (normal) = 56 Gy and TD 50 (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD 50 value for the cirrhosis patients points out their greater sensitivity. Conclusions: This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.

Design and Selection of Machine Learning Methods Using Radiomics and Dosiomics for Normal Tissue Complication Probability Modeling of Xerostomia

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Hubert S. Gabryś

2018-03-01

Full Text Available PurposeThe purpose of this study is to investigate whether machine learning with dosiomic, radiomic, and demographic features allows for xerostomia risk assessment more precise than normal tissue complication probability (NTCP models based on the mean radiation dose to parotid glands.Material and methodsA cohort of 153 head-and-neck cancer patients was used to model xerostomia at 0–6 months (early, 6–15 months (late, 15–24 months (long-term, and at any time (a longitudinal model after radiotherapy. Predictive power of the features was evaluated by the area under the receiver operating characteristic curve (AUC of univariate logistic regression models. The multivariate NTCP models were tuned and tested with single and nested cross-validation, respectively. We compared predictive performance of seven classification algorithms, six feature selection methods, and ten data cleaning/class balancing techniques using the Friedman test and the Nemenyi post hoc analysis.ResultsNTCP models based on the parotid mean dose failed to predict xerostomia (AUCs < 0.60. The most informative predictors were found for late and long-term xerostomia. Late xerostomia correlated with the contralateral dose gradient in the anterior–posterior (AUC = 0.72 and the right–left (AUC = 0.68 direction, whereas long-term xerostomia was associated with parotid volumes (AUCs > 0.85, dose gradients in the right–left (AUCs > 0.78, and the anterior–posterior (AUCs > 0.72 direction. Multivariate models of long-term xerostomia were typically based on the parotid volume, the parotid eccentricity, and the dose–volume histogram (DVH spread with the generalization AUCs ranging from 0.74 to 0.88. On average, support vector machines and extra-trees were the top performing classifiers, whereas the algorithms based on logistic regression were the best choice for feature selection. We found no advantage in using data cleaning or class balancing

Small-scale structure and the Lyman-α forest baryon acoustic oscillation feature

Science.gov (United States)

Hirata, Christopher M.

2018-02-01

The baryon-acoustic oscillation (BAO) feature in the Lyman-α forest is a key probe of the cosmic expansion rate at redshifts z ˜ 2.5, well before dark energy is believed to have become significant. A key advantage of the BAO as a standard ruler is that it is a sharp feature and hence is more robust against broad-band systematic effects than other cosmological probes. However, if the Lyman-α forest transmission is sensitive to the initial streaming velocity of the baryons relative to the dark matter, then the BAO peak position can be shifted. Here we investigate this sensitivity using a suite of hydrodynamic simulations of small regions of the intergalactic medium with a range of box sizes and physics assumptions; each simulation starts from initial conditions at the kinematic decoupling era (z ˜ 1059), undergoes a discrete change from neutral gas to ionized gas thermal evolution at reionization (z ˜ 8), and is finally processed into a Lyman-α forest transmitted flux cube. Streaming velocities suppress small-scale structure, leading to less violent relaxation after reionization. The changes in the gas distribution and temperature-density relation at low redshift are more subtle, due to the convergent temperature evolution in the ionized phase. The change in the BAO scale is estimated to be of the order of 0.12 per cent at z = 2.5; some of the major uncertainties and avenues for future improvement are discussed. The predicted streaming velocity shift would be a subdominant but not negligible effect (of order 0.26σ) for the upcoming DESI Lyman-α forest survey, and exceeds the cosmic variance floor.

Lyman-alpha transit observations of the warm rocky exoplanet GJ1132b

Science.gov (United States)

Waalkes, William; Berta-Thompson, Zachory K.; Charbonneau, David; Irwin, Jonathan; Newton, Elisabeth; Dittmann, Jason; Bourrier, Vincent; Ehrenreich, David; Kempton, Eliza; Will

2018-06-01

GJ1132b is one of the few known Earth-sized planets, and at 12pc away it is also one of the closest known transiting planets. With an equilibrium temperature of 500 K, this planet is too hot to be habitable but we can use it to learn about the presence and volatile content of rocky planet atmospheres around M dwarf stars. Using Hubble STIS spectra obtained during primary transit, we search for a Lyman-α transit. If we were to observe a deep Lyman-α transit, that would indicate the presence of a neutral hydrogen envelope flowing from GJ1132b. On the other hand, ruling out deep absorption from neutral hydrogen may indicate that this planet has either retained its volatiles or lost them very early in the star’s life. We carry out this analysis by extracting 1D spectra from the STIS pipeline, splitting the time-tagged spectra into higher resolution samples, and producing light curves of the red and blue wings of the Lyman-α line. We fit for the baseline stellar flux and transit depths in order to constrain the characteristics of the cloud of neutral hydrogen gas that may surround the planet. We do not conclusively detect a transit but the results provide an upper limit for the transit depth. We also analyze the stellar variability and Lyman-α spectrum of GJ1132, a slowly-rotating 0.18 solar mass M dwarf with previously uncharacterized UV activity. Understanding the role that UV variability plays in planetary atmospheres and volatile retention is crucial to assess atmospheric evolution and the habitability of cooler rocky planets.

SU-E-T-168: Evaluation of Normal Tissue Damage in Head and Neck Cancer Treatments

International Nuclear Information System (INIS)

Ai, H; Zhang, H

2014-01-01

Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant that represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients

Adipose Tissues Characteristics of Normal, Obesity, and Type 2 Diabetes in Uygurs Population

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Jun Zhang

2015-01-01

Full Text Available Our results showed that, at the same BMI level, Uygurs have greater WHR values, abdominal visceral fat content, and diabetes risks than Kazaks. In addition, values of HDL-C in Uygur subjects were lower than those in Kazak subjects, and values of creatinine, uric acid, diastolic blood pressure, blood glucose, and fructosamine in Uygur male subjects were lower than those in Kazak male subjects. In contrast, systolic blood pressure values in Uygur subjects were greater than those in Kazak subjects, and blood glucose values were greater in Uygur female subjects than in Kazak female subjects. Additionally, in Uygurs, visceral adipose tissue expression levels of TBX1 and TCF21 were greater in obesity group than in normal and T2DM groups and lower in T2DM group than in normal group (P<0.01. The visceral adipose tissue expression levels of APN in normal group was greater than those in obesity and T2DM groups, and visceral adipose tissue expression levels of TNF-α and MCP-1 in normal group were lower than those in obesity and T2DM groups (P<0.01. In conclusion, T2DM in Uygurs was mainly associated with not only distribution of adipose tissue in body, but also change in metabolic activity and adipocytokines secretion of adipose tissue.

Radioprotection of normal tissues in tumor-bearing mice by troxerutin

International Nuclear Information System (INIS)

Maurya, D.K.; Salvi, V.P.; Krishnan Nair, C.K.

2004-01-01

The flavanoid derivative troxerutin, used clinically for treating venous disorders, protected biomembranes and cellular DNA against the deleterious effects of γ-radiation. The peroxidation of lipids (measured as thiobarbituric acid-reacting substances, or TBARS) in rat liver microsomal and mitochondrial membranes resulting from γ-irradiation up to doses of 500 Gy in vitro was prevented by 0.2 mM troxerutin. The administration of troxerutin (175 mg/kg body weight) to tumor-bearing mice by intraperitoneal (ip) one hour prior to 4 Gy whole-body γ-irradiation significantly decreased the radiation-induced peroxidation of lipids in tissues such as liver and spleen, but there was no reduction of lipid peroxidation in tumor. The effect of troxerutin in γ-radiation-induced DNA strand breaks in different tissues of tumor-bearing mice was studied by comet assay. The administration of troxerutin to tumor-bearing animals protected cellular DNA against radiation-induced strand breaks. This was evidenced from decreases in comet tail length, tail moment, and percent of DNA in the tails in cells of normal tissues such as blood leukocytes and bone marrow, and these parameters were not altered in cells of fibrosarcoma tumor. The results revealed that troxerutin could preferentially protect normal tissues against radiation-induced damages in tumor-bearing animals. (author)

Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

Science.gov (United States)

Hoffmann, Aswin L; Nahum, Alan E

2013-10-07

The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

Complications of minimally invasive cosmetic procedures: Prevention and management

Directory of Open Access Journals (Sweden)

Lauren L Levy

2012-01-01

Full Text Available Over the past decade, facial rejuvenation procedures to circumvent traditional surgery have become increasingly popular. Office-based, minimally invasive procedures can promote a youthful appearance with minimal downtime and low risk of complications. Injectable botulinum toxin (BoNT, soft-tissue fillers, and chemical peels are among the most popular non-invasive rejuvenation procedures, and each has unique applications for improving facial aesthetics. Despite the simplicity and reliability of office-based procedures, complications can occur even with an astute and experienced injector. The goal of any procedure is to perform it properly and safely; thus, early recognition of complications when they do occur is paramount in dictating prevention of long-term sequelae. The most common complications from BoNT and soft-tissue filler injection are bruising, erythema and pain. With chemical peels, it is not uncommon to have erythema, irritation and burning. Fortunately, these side effects are normally transient and have simple remedies. More serious complications include muscle paralysis from BoNT, granuloma formation from soft-tissue filler placement and scarring from chemical peels. Thankfully, these complications are rare and can be avoided with excellent procedure technique, knowledge of facial anatomy, proper patient selection, and appropriate pre- and post-skin care. This article reviews complications of office-based, minimally invasive procedures, with emphasis on prevention and management. Practitioners providing these treatments should be well versed in this subject matter in order to deliver the highest quality care.

Compton scattering spectrum as a source of information of normal and neoplastic breast tissues' composition

Energy Technology Data Exchange (ETDEWEB)

Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil)

2012-07-15

In this work we measured X-ray scatter spectra from normal and neoplastic breast tissues using photon energy of 17.44 keV and a scattering angle of 90 Degree-Sign , in order to study the shape (FWHM) of the Compton peaks. The obtained results for FWHM were discussed in terms of composition and histological characteristics of each tissue type. The statistical analysis shows that the distribution of FWHM of normal adipose breast tissue clearly differs from all other investigated tissues. Comparison between experimental values of FWHM and effective atomic number revealed a strong correlation between them, showing that the FWHM values can be used to provide information about elemental composition of the tissues. - Highlights: Black-Right-Pointing-Pointer X-ray scatter spectra from normal and neoplastic breast tissues were measured. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak was related with elemental composition and characteristics of each tissue type. Black-Right-Pointing-Pointer A statistical hypothesis test showed clear differences between normal and neoplastic breast tissues. Black-Right-Pointing-Pointer There is a strong correlation between experimental values of FWHM and effective atomic number. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak can be used to provide information about elemental composition of the tissues.

Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer

International Nuclear Information System (INIS)

Ananthanarayanan, Vijayalakshmi; Deaton, Ryan J; Yang, Ximing J; Pins, Michael R; Gann, Peter H

2006-01-01

Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant. The aforementioned markers were studied in 13 radical prostatectomy (RP) and 6 cystoprostatectomy (CP) specimens. Tissue compartments representing normal, low grade prostatic intraepithelial neoplasia (LGPIN), high grade prostatic intraepithelial neoplasia (HGPIN), as well as different grades of cancer were mapped on H&E slides and adjacent sections were analyzed using immunohistochemistry. Normal glands within 1 mm distance of a tumor focus and glands beyond 5 mm were considered 'near' and 'far', respectively. Randomly selected nuclei and 40 × fields were scored by a single observer; basal and luminal epithelial layers were scored separately. Both Ki-67 and Mcm-2 showed an upward trend from normal tissue through HGPIN and cancer with a shift in proliferation from basal to luminal compartment. Activated caspase-3 showed a significant decrease in HGPIN and cancer compartments. Supernormal glands had significantly lower proliferation indices and higher a-casp3 expression compared to normal glands. 'Near' normal glands had higher Mcm-2 indices compared to 'far' glands; however, they also had higher a-casp3 expression. Bcl-2, which varied minimally in normal tissue, did not show any trend

Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples.

Science.gov (United States)

Karavitakis, Markos; Msaouel, Pavlos; Michalopoulos, Vassilis; Koutsilieris, Michael

2014-06-01

Known risks factors for bladder cancer progression and recurrence are limited regarding their prognostic ability. Therefore identification of molecular determinants of disease progression could provide with more specific prognostic information and could be translated into new approaches for biomarker development. In the present study we evaluated, the expression patterns of somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. The expression of SSTR1-5 was characterized in 45 normal and bladder cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT-PCR). SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4 in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed lower levels of SSTR3. Co-expression of SSTRs was associated with superficial disease. Our results demonstrate, for the first time, that there is expression of SSTR in normal and bladder cancer urothelium. Further studies are required to evaluate the prognostic and therapeutic significance of these findings. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Radioprotection of normal tissues of the mouse by hypoxic breathing

International Nuclear Information System (INIS)

Stevens, G.N.; Joiner, B.; Denekamp, J.

1989-01-01

Hypoxic breathing during irradiation has been advocated as a therapeutic modality, to increase the efficacy of radiotherapy. In this form of treatment, the total and daily X-ray dose is increased by a factor of 1.25, on the assumption that all normal tissues in the beam will be protected to a similar extent by breathing gas containing a reduced oxygen concentration (usually 10%). To test this concept, we have determined the effect of varying the inspired oxygen tension on the radiosensitivity of 3 normal tissues in the mouse (kidney, jejunum and skin), and have compared these results with data from the literature for mouse lung. Reduction of the inspired oxygen tension from 21% (air) to 7-8% led to much greater radioprotection of skin (protection factor 1.37) than of lung (1.09). Protection factors for jejunum and kidney were 1.16 and 1.36 respectively. The results show that the extent of radioprotection afforded by hypoxic breathing is tissue dependent, and that great care must be taken clinically in choosing the increased radiation dose to be used in conjunction with hypoxic breathing

Quantifying glucose permeability and enhanced light penetration in ex vivo human normal and cancerous esophagus tissues with optical coherence tomography

International Nuclear Information System (INIS)

Zhao, Q L; Guo, Z Y; Wei, H J; Guo, X; Zhong, H Q; Li, L Q; Si, J L; Yang, H Q; Xie, S S; Wu, G Y; Li, X Y

2011-01-01

We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10 -5 cm/s in normal esophagus and (2.45±0.06)×10 -5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G

Quantifying glucose permeability and enhanced light penetration in ex vivo human normal and cancerous esophagus tissues with optical coherence tomography

Science.gov (United States)

Zhao, Q. L.; Si, J. L.; Guo, Z. Y.; Wei, H. J.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Li, X. Y.; Guo, X.; Zhong, H. Q.; Li, L. Q.

2011-01-01

We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10-5 cm/s in normal esophagus and (2.45±0.06)×10-5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G.

Radiotherapy- and chemotherapy-induced normal tissue damage. The role of cytokines and adhesion molecules

International Nuclear Information System (INIS)

Plevova, P.

2002-01-01

Background. Ionising radiation and cytostatic agents used in cancer therapy exert damaging effects on normal tissues and induce a complex response at the cellular and molecular levels. Cytokines and adhesion molecules are involved in this response. Methods. Published data on the given topic have been reviewed. Results and conclusions. Various cytokines and adhesion molecules, including tumor necrosis factor α, interleukins- 1,-2,-4, and -6, interferon γ, granulocyte macrophage- and macrophage- colony stimulating factors, transforming growth factor β, platelet-derived growth factor, insulin-like growth factor I, fibroblast and epidermal growth factors, platelet-activating factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E- and P-selectins are involved in the response of normal tissues to ionizing radiation- and chemotherapy- induced normal tissues damage and are co-responsible for some side effects of these treatment modalities, including fever, anorexia and fatigue, suppression of hematopoiesis, both acute and late local tissue response. (author)

Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells

International Nuclear Information System (INIS)

Rettig, W.F.; Garin-Chesa, P.; Beresford, H.R.; Oettgen, H.F.; Melamed, M.R.; Old, L.J.

1988-01-01

Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, the authors have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and > 200 tumor specimens. Differential patterns of F19, F24, G171, G253, S5, and Thy-1 antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes

The Lyman Alpha Imaging-Monitor Experiment (LAIME) for TESIS/CORONAS-PHOTON

Science.gov (United States)

Damé, L.; Koutchmy, S.; Kuzin, S.; Lamy, P.; Malherbe, J.-M.; Noëns, J.-C.

LAIME the Lyman Alpha Imaging-Monitor Experiment is a remarkably simple no mechanisms and compact 100x100x400 mm full Sun imager to be flown with TESIS on the CORONAS-PHOTON mission launch expected before mid-2008 As such it will be the only true chromospheric imager to be flown in the next years supporting TESIS EUV-XUV imaging SDO and the Belgian LYRA Lyman Alpha flux monitor on the ESA PROBA-2 microsatellite launch expected in September 2007 We will give a short description of this unique O60 mm aperture imaging telescope dedicated to the investigating of the magnetic sources of solar variability in the UV and chromospheric and coronal disruptive events rapid waves Moreton waves disparitions brusques of prominences filaments eruptions and CMEs onset The resolution pixel is 2 7 arcsec the field of view 1 4 solar radius and the acquisition cadence could be as high as 1 image minute The back thinned E2V CCD in the focal plane is using frame transfer to avoid shutter and mechanisms Further more the double Lyman Alpha filtering allows a 40 AA FWHM bandwidth and excellent rejection yet providing a vacuum seal design of the telescope MgF2 entrance window Structural stability of the telescope focal length 1 m is preserved by a 4-INVAR bars design with Aluminium compensation in a large pm 10 o around 20 o

SU-E-J-264: Using Magnetic Resonance Imaging-Derived Features to Quantify Radiotherapy-Induced Normal Tissue Morbidity

Energy Technology Data Exchange (ETDEWEB)

Thor, M; Tyagi, N; Deasy, J [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

2015-06-15

Purpose: The aim of this study was to explore the use of Magnetic Resonance Imaging (MRI)-derived features as indicators of Radiotherapy (RT)-induced normal tissue morbidity. We also investigate the relationship between these features and RT dose in four critical structures. Methods: We demonstrate our approach for four patients treated with RT for base of tongue cancer in 2005–2007. For each patient, two MRI scans (T1-weighted pre (T1pre) and post (T1post) gadolinium contrast-enhancement) were acquired within the first six months after RT. The assessed morbidity endpoint observed in 2/4 patients was Grade 2+ CTCAEv.3 trismus. Four ipsilateral masticatory-related structures (masseter, lateral and medial pterygoid, and the temporal muscles) were delineated on both T1pre and T1post and these scans were co-registered to the treatment planning CT using a deformable demons algorithm. For each structure, the maximum and mean RT dose, and six MRI-derived features (the second order texture features entropy and homogeneity, and the first order mean, median, kurtosis, and skewness) were extracted and compared structure-wise between patients with and without trismus. All MRI-derived features were calculated as the difference between T1pre and T1post, ΔS. Results: For 5/6 features and all structures, ΔS diverged between trismus and non-trismus patients particularly for the masseter, lateral pterygoid, and temporal muscles using the kurtosis feature (−0.2 vs. 6.4 for lateral pterygoid). Both the maximum and mean RT dose in all four muscles were higher amongst the trismus patients (with the maximum dose being up to 25 Gy higher). Conclusion: Using MRI-derived features to quantify RT-induced normal tissue complications is feasible. We showed that several features are different between patients with and without morbidity and that the RT dose in all investigated structures are higher amongst patients with morbidity. MRI-derived features, therefore, has the potential to

Correlation study of trace metals in malignant and normal breast tissues by AAS technique

International Nuclear Information System (INIS)

Rahman, S.

2012-01-01

The study reports the application of atomic absorption spectrophotometry (AAS) for quantification of Fe, Cu and Zn in forty one formalin-fixed biopsy breast carcinoma tissue and adjoining fifteen normal tissue samples. These tissues samples were of category two breast carcinoma patients and of normal subjects. The qualitative comparison between the elements levels measured in the two types of specimens suggests significant elevation of these metals in the histopathological samples of carcinoma tissue. The samples were collected from women aged 19-51 years. Most of the patients belong to urban areas of Pakistan and middle to high socioeconomic status with the exception of few. Findings of study depicts that these elements have an important role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu and Zn was observed. The results showed the excessive accumulation of Fe (166.9 mg/L) in tissue samples of breast carcinoma patients (p < 0.01) than that in normal tissues samples (23.5 mg/L). In order to validate our method of analysis certified reference material Muscle Tissue Lyophilised (IAEA) MA-M-2/TM was analyzed for Fe, Cu and Zn. Determined concentrations were in good agreement with certified levels. The concentration distribution of trace elements Cu, Zn and Fe measured in the malignant tissues were found to be higher when compared to benign tissues, indicating the involvement of these metals in the breast malignancy. Results also indicate that excess iron may play a role in breast carcinogenesis. (Orig./A.B.)

Utility of Normal Tissue-to-Tumor {alpha}/{beta} Ratio When Evaluating Isodoses of Isoeffective Radiation Therapy Treatment Plans

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Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Jin Jianyue [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Chang, Albert J. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

2013-01-01

Purpose: To achieve a better understanding of the effect of the number of fractions on normal tissue sparing for equivalent tumor control in radiation therapy plans by using equivalent biologically effective dose (BED) isoeffect calculations. Methods and Materials: The simple linear quadratic (LQ) model was assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a well-known mathematical equality for the tumor prescription dose and probed and solved a second mathematical problem for normal tissue isoeffect. That is, for a given arbitrary relative isodose distribution (treatment plan in percentages), 2 isoeffective tumor treatment regimens (N fractions of the dose D and n fractions of the dose d) were denoted, which resulted in the same BED (corresponding to 100% prescription isodose). Given these situations, the LQ model was further exploited to mathematically establish a unique relative isodose level, z (%), for the same arbitrary treatment plan, where the BED to normal tissues was also isoeffective for both fractionation regimens. Results: For the previously stated problem, the relative isodose level z (%), where the BEDs to the normal tissue were also equal, was defined by the normal tissue {alpha}/{beta} ratio divided by the tumor {alpha}/{beta} times 100%. Fewer fractions offers a therapeutic advantage for those portions of the normal tissue located outside the isodose surface, z, whereas more fractions offer a therapeutic advantage for those portions of the normal tissue within the isodose surface, z. Conclusions: Relative isodose-based treatment plan evaluations may be useful for comparing isoeffective tumor regimens in terms of normal tissue effects. Regions of tissues that would benefit from hypofractionation or standard fractionation can be identified.

Genetic markers for prediction of normal tissue toxicity after radiotherapy

DEFF Research Database (Denmark)

Alsner, Jan; Andreassen, Christian Nicolaj; Overgaard, Jens

2008-01-01

During the last decade, a number of studies have supported the hypothesis that there is an important genetic component to the observed interpatient variability in normal tissue toxicity after radiotherapy. This review summarizes the candidate gene association studies published so far on the risk...

EPR study of the reactions of tumour and normal tissues under ionizing radiation

International Nuclear Information System (INIS)

Rikhireva, G.T.; Pulatova, M.K.; Turganov, M.M.; Pal'mina, N.P.; Burlakova, E.B.

1978-01-01

Data on the EPR spectrum characteristics of irradiated tissues of tumour-free animals and animals with tumour are presented. Mice of the Csub(3)Hsub(A) line were used in the experiments. Hepatoma was subcutaneously transplanted with the suspension of tumour tissue reduced to fragments. Animals were killed in 6-8 days after transplantation and in the case of tumour-free animals liver was immediately isolated while in the case of animals with tumour isolated were liver and tumour. Tissues cut with scissors were frozen in liquid nitrogen. Tissue samples were exposed to 60 Co at 1 Mrad dose and -196 deg C. On the base of the data it has been concluded: firstly, there are differences between the EPR spectra of normal and tumour tissue samples irradiated at -196 deg C. Asymmetryc signal with Δ H=Ge and g=2.0005 (''tumour signal'') is typical only for the EPR spectra of tumour and liver tissues of the animal with tumour. Thus, in the -author's opinion, irradiation use turns out to be useful for detecting the difference between the normal and tumour tissues. Secondly, ''tumour signal'' intensity changes after ionol incorporation into animal organism, used as a modificator of tissue sensitivity to the irradiation effect

Impact of margin on tumour and normal tissue dosimetry in patients treated with IMRT using an endorectal balloon for prostate immobilization

International Nuclear Information System (INIS)

Ahmad, S.

2004-01-01

Full text: In treatment of prostate cancer with IMRT (Intensity Modulated Radiation Therapy), clinical target volume margin is determined by organ motion and set-up error. However, the margin width that achieves the desired dose escalation while minimizing normal tissue exposure is dependent upon the patient immobilization and/or organ localization techniques. In this study, we compare the impact of margin width on the dosimetry of tumour and normal tissues using the endorectal balloon for prostate immobilization. IMRT plans were generated for ten patients using margin widths of 0, 3, 5, 8 and 10 mm. Patients had a planning CT scan in the prone position with an endorectal balloon filled with 100 cc of air for prostate immobilization. The Corvus version 3.0.11 was used for treatment planning. The dose for the prostate and seminal vesicles was 70 Gy in 2 Gy per fractions, prescribed at the 83% isodose line. Dose restrictions to normal tissues were as follows: 33% of bladder was allowed to receive above 65 Gy, 15% of rectum above 68 Gy and 10% of femurs above 45 Gy. Analysis of Variance was used to compare the target and normal tissue doses. Tumour control probability and normal tissue complication probability calculations are currently being performed and will be presented. The mean doses ranged from 73.93 to 75.31 Gy for the prostate and from 73.71 to 75.31 Gy for the seminal vesicles. A 10 mm margin produced significantly lower mean doses compared to 0 or 5 mm for both targets (prostate p 0.062). For bladder and rectum the mean doses ranged from 18.49 to 22.30 Gy (p=0.605) and from 29.34 to 31.33 Gy (p=0.135), respectively, while the percent rectal volumes above 68 Gy were significantly higher for margins of 5, 8 and 10 mm (p<0.006) ranging from 10.72% to 15.81%. Mean doses to the femurs and pelvis were significantly higher for 8 and 10 mm margins, ranging from 20.9 to 29.39 Gy for femurs (p<0.015) and from 15.05 to 19.98 Gy for pelvis (p<0.0005). Also the percent

Aqueous Leaf Extract of Heliotropium Indicum Ameliorates Hyperglycaemia-Induced Tissue Complications in Albino Rats

Directory of Open Access Journals (Sweden)

Rasheed Bolaji Ibrahim

2018-01-01

Full Text Available Background: Heliotropium indicum is used by traditional medical practitioners in North Central Nigeria for the management of ailments including diabetes. However, the folkloric use of H. indicum as antidiabetic has been asserted, but its roles on the hyperglycemia-induced organ-specific complications are not yet scientifically proven. Thus, ameliorative effect of aqueous leaf extract of H. indicum on selected toxicological parameters in hyperglycaemic rats was investigated in this study. Methods: Twenty-five rats were randomized into five groups. The study was carried out at the Animal Holding Unit, Biochemistry Department, University of Ilorin in 2013. Four groups were intraperitoneally administered singly with 150 mg/kg b.wt of alloxan to induce hyperglycemia. The normal control (NC and hyperglycaemic control (HC groups were administered 1 ml distilled water, while the reference group (HR were administered 14.2 mg/kg b.wt of metformin and the test groups, H30 and H75 were administered 30 and 75 mg/kg b.wt, the extract respectively for fourteen days. Results: The significantly increased (P<0.05 serum concentrations of tissue membrane bound enzymes (ALT, AST, ACP and ALP, direct and total bilirubin, urea and creatinine in HC indicating compromised tissue structures and functions in HC were attenuated. The significantly (P<0.05 reduced serum total protein, globulin and albumin in HC were significantly increased by both doses of the extract. The ameliorative role of the extract at the test doses was supported by the histological assessment of liver and kidney of the animals. Conclusion: Aqueous leaf extract of H. indicum can be explored at the ethnobotanical dose of 30 and 75 mg/kg b.wt on the management of some of the tissue-specific disarrays associated with diabetes.

Accumulation of DNA Double-Strand Breaks in Normal Tissues After Fractionated Irradiation

International Nuclear Information System (INIS)

Ruebe, Claudia E.; Fricke, Andreas; Wendorf, Juliane; Stuetzel, Annika; Kuehne, Martin; Ong, Mei Fang; Lipp, Peter; Ruebe, Christian

2010-01-01

Purpose: There is increasing evidence that genetic factors regulating the recognition and/or repair of DNA double-strand breaks (DSBs) are responsible for differences in radiosensitivity among patients. Genetically defined DSB repair capacities are supposed to determine patients' individual susceptibility to develop adverse normal tissue reactions after radiotherapy. In a preclinical murine model, we analyzed the impact of different DSB repair capacities on the cumulative DNA damage in normal tissues during the course of fractionated irradiation. Material and Methods: Different strains of mice with defined genetic backgrounds (SCID -/- homozygous, ATM -/- homozygous, ATM +/- heterozygous, and ATM +/+ wild-type mice) were subjected to single (2 Gy) or fractionated irradiation (5 x 2 Gy). By enumerating γH2AX foci, the formation and rejoining of DSBs were analyzed in organs representative of both early-responding (small intestine) and late-responding tissues (lung, kidney, and heart). Results: In repair-deficient SCID -/- and ATM -/- homozygous mice, large proportions of radiation-induced DSBs remained unrepaired after each fraction, leading to the pronounced accumulation of residual DNA damage after fractionated irradiation, similarly visible in early- and late-responding tissues. The slight DSB repair impairment of ATM +/- heterozygous mice was not detectable after single-dose irradiation but resulted in a significant increase in unrepaired DSBs during the fractionated irradiation scheme. Conclusions: Radiation-induced DSBs accumulate similarly in acute- and late-responding tissues during fractionated irradiation, whereas the whole extent of residual DNA damage depends decisively on the underlying genetically defined DSB repair capacity. Moreover, our data indicate that even minor impairments in DSB repair lead to exceeding DNA damage accumulation during fractionated irradiation and thus may have a significant impact on normal tissue responses in clinical

The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation

International Nuclear Information System (INIS)

Wheldon, T.E.; Michalowski, A.S.

1982-01-01

The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as ''hierarchical'' (like haemopoietic tissues) or as ''flexible'' (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the ''flexible'' or ''F-type'' category display a variety of novel radiobiological properties, different from those of the more familiar ''hierarchical'' or ''H-type'' tissues. The ''F-type'' responses are strongly influenced by radiation-sterilised (''doomed'') cells, and is is suggested that the role of ''doomed'' cells has been undervalued relative to that of clonogenic survivors. Since ''F-type'' tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy. (author)

ORO dental complications of radiotherapy

International Nuclear Information System (INIS)

Kaumuri, Sunil

2014-01-01

Radiation and radioactivity were discovered more than 100 years ago. Since then, radiation has become important in cancer treatment. Approximately one million people will develop invasive cancer each year. Of these, 40% will receive curative benefit from surgery, radiation, chemotherapy, or a combination modality. Normal body tissues vary in their response to radiation. As with tumors, normal tissues in which cells are quickly dividing may be affected. This causes some of the side effects of radiation treatment. Since radiation is a local treatment, side effects depend on the area of the body being treated. The early effects of radiation may be seen a few days or weeks after treatments have started and may go on for several weeks after treatments have ended. Other effects may not show up until months, or even years, later. As radiotherapy is a viable treatment modality for head and neck cancer, however a wide range of potentially debilitating dental complications may accompany this treatment. The orofacial tissues of dental significance that may be affected by head and neck radiotherapy are the salivary glands, mucous membranes, taste buds, bone and teeth. (author)

Prodrugs designed to discriminate pathological (tumour) and physiological (normal tissue) hypoxia

International Nuclear Information System (INIS)

Wilson, W.R.; Patterson, A.V.

2003-01-01

There is now abundant evidence that hypoxic contributes to treatment failure in radiation therapy. As a target for therapeutic intervention, hypoxia is especially attractive because it is a common feature of most human tumours and therefore a potential 'pan target' across many tumour types. However, attempts to exploit hypoxia face the problem that oxygen concentrations in some normal tissues are also heterogeneous and that O 2 distributions in tumours and normal tissues overlap. Simply adjusting the K value (O 2 concentration for 50% inhibition of activation) does not provide a satisfactory solution. Bioreductive drugs like tirapazamine with high K values are activated significantly in several normal tissues, while nitro compounds and quinones with low K values spare the hypoxic tumour cells at 'intermediate' O 2 tensions (1-10 mM O 2 ) which are considered to be major contributors to tumour radioresistance. A potential strategy for overcoming this dilemma is to design prodrugs that are activated only at very low K values, but give relatively stable cytotoxic metabolites capable of diffusing to cells at higher O 2 concentrations. This approach redefines the therapeutic target as cells adjacent to zones of pathological hypoxia ( 2 ), providing discrimination from physiological hypoxia in normal tissues. Detecting bioreductive prodrugs capable of providing bystander killing of this kind is not straightforward. We have adapted a multicellular layer (MCL) co-culture model for quantifying bystander effects in GDEPT (Wilson et al., Cancer Res., 62: 1425-1432, 2002), and have used this to measure bystander effects of hypoxia-activated prodrugs. This model uses differences in metabolic activation of bioreductive drugs between A459 cell lines with low and high cytochrome P450 reductase activity, rather than O 2 gradients, to effect localised prodrug activation. It shows that TPZ and the nitroimidazole RSU-1069 have little or no bystander effect, but that dinitrobenzamide

Proteolytic processing of connective tissue growth factor in normal ocular tissues and during corneal wound healing.

Science.gov (United States)

Robinson, Paulette M; Smith, Tyler S; Patel, Dilan; Dave, Meera; Lewin, Alfred S; Pi, Liya; Scott, Edward W; Tuli, Sonal S; Schultz, Gregory S

2012-12-13

Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is up-regulated by TGF-β and mediates most key fibrotic actions of TGF-β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. This study addresses the role of proteolytic processing of CTGF in human corneal fibroblasts (HCF) stimulated with TGF-β, normal ocular tissues and wounded corneas. Proteolytic processing of CTGF in HCF cultures, normal animal eyes, and excimer laser wounded rat corneas were examined by Western blot. The identity of a 21-kDa band was determined by tandem mass spectrometry, and possible alternative splice variants of CTGF were assessed by 5' Rapid Amplification of cDNA Ends (RACE). HCF stimulated by TGF-β contained full length 38-kDa CTGF and fragments of 25, 21, 18, and 13 kDa, while conditioned medium contained full length 38- and a 21-kDa fragment of CTGF that contained the middle "hinge" region of CTGF. Fragmentation of recombinant CTGF incubated in HCF extracts was blocked by the aspartate protease inhibitor, pepstatin. Normal mouse, rat, and rabbit whole eyes and rabbit ocular tissues contained abundant amounts of C-terminal 25- and 21-kDa fragments and trace amounts of 38-kDa CTGF, although no alternative transcripts were detected. All forms of CTGF (38, 25, and 21 kDa) were detected during healing of excimer ablated rat corneas, peaking on day 11. Proteolytic processing of 38-kDa CTGF occurs during corneal wound healing, which may have important implications in regulation of corneal scar formation.

Are the brightest Lyman Alpha Emitters at zD5.7 primeval galaxies?

Science.gov (United States)

Lidman, Christopher; Hayes, Matthew; Jones, Heath; Meisenheimer, Klaus; Tapken, Christian; Westra, Eduard

2009-04-01

Wide-field, narrow-band surveys have proven to be effective at finding very high redshift galaxies that emit brightly in the Lyman alpha line - the so-called Lyman alpha emitters (LAEs). It was through this technique that the most distant spectroscopically confirmed galaxy, a galaxy at zD6.96 (Iye et al. 2006), was discovered. Considerable effort is currently being spent on discovering these galaxies at ever higher redshifts by extending this technique into the near-IR. In contrast to this effort, there has been relatively little work on understanding these galaxies. In particular, how do LAEs relate to other high redshift galaxies, such as those discovered through drop out techniques, and, more importantly, what role LAEs play in re-ionising the universe, if any. We recently discovered two extremely luminous LAEs at zD5.7. These LAEs are among the brightest LAEs ever discovered at this redshift. In a recent paper by Mao et al. (2007), the brightest LAEs are associated to the most massive halos. One of these targets was successfully observed with the IRAC 3.6 micron imager on Spitzer during cycle 5. These data, when combined with constraints that we derive from our deep ground-based spectroscopic data, indicate that the bulk of the flux at 3.6 microns comes from a stellar population that is considserably older than the stars that dominate the flux in the UV. We propose to complete the project and image the second target. These data will enable us to estimate the age and mass of the stellar burst that produces the Lyman alpha line, to estimate the contribution from an older stellar population and to estimate the fraction of Lyman continuum photons that escape the galaxy and are thus available to re-ionise the universe.

Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

NARCIS (Netherlands)

Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

Science.gov (United States)

Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

2014-04-01

The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

Science.gov (United States)

Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

2014-01-01

Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional

Comparison of Lyman-alpha and LI-COR infrared hygrometers for airborne measurement of turbulent fluctuations of water vapour

Science.gov (United States)

Lampert, Astrid; Hartmann, Jörg; Pätzold, Falk; Lobitz, Lennart; Hecker, Peter; Kohnert, Katrin; Larmanou, Eric; Serafimovich, Andrei; Sachs, Torsten

2018-05-01

To investigate if the LI-COR humidity sensor can be used as a replacement of the Lyman-alpha sensor for airborne applications, the measurement data of the Lyman-alpha and several LI-COR sensors are analysed in direct intercomparison flights on different airborne platforms. One vibration isolated closed-path and two non-isolated open-path LI-COR sensors were installed on a Dornier 128 twin engine turbo-prop aircraft. The closed-path sensor provided absolute values and fluctuations of the water vapour mixing ratio in good agreement with the Lyman-alpha. The signals of the two open-path sensors showed considerable high-frequency noise, and the absolute value of the mixing ratio was observed to drift with time in this vibrational environment. On the helicopter-towed sensor system Helipod, with very low vibration levels, the open-path LI-COR sensor agreed very well with the Lyman-alpha sensor over the entire frequency range up to 3 Hz. The results show that the LI-COR sensors are well suited for airborne measurements of humidity fluctuations, provided that a vibrationless environment is given, and this turns out to be more important than close sensor spacing.

Responses of some normal tissues to low doses of γ-radiation

International Nuclear Information System (INIS)

Withers, H.R.

1975-01-01

The response of four normal tissues to low doses of γ-radiation was measured in mice using three indirect methods. The survival curves for cells of the tissues studied (colon, jejunum, testis and haemoleucopoietic system) may be exponential over an uncertain dose range (from zero to between 100 to 230 rad), the slope being about one third of that in the high-dose region. Some of the uncertainties in the data probably reflect variations in age-density distribution. (author)

Discriminant analysis of normal and malignant breast tissue based upon INAA investigation of elemental concentration

International Nuclear Information System (INIS)

Kwanhoong Ng; Senghuat Ong; Bradley, D.A.; Laimeng Looi

1997-01-01

Discriminant analysis of six trace element concentrations measured by instrumental neutron activation analysis (INAA) in 26 paired-samples of malignant and histologically normal human breast tissues shows the technique to be a potentially valuable clinical tool for making malignant-normal classification. Nonparametric discriminant analysis is performed for the data obtained. Linear and quadratic discriminant analyses are also carried out for comparison. For this data set a formal analysis shows that the elements which may be useful in distinguishing between malignant and normal tissues are Ca, Rb and Br, providing correct classification for 24 out of 26 normal samples and 22 out of 26 malignant samples. (Author)

Review of RBE values of 15 MeV neutrons for effects on normal tissues

NARCIS (Netherlands)

Broerse, J.J.

1974-01-01

Values of the relative biological effectiveness (RBE) of fast neutrons for effect on normal tissue depend not only on the neutron energy and the dose, but also on the type of tissue irradiated. Values of the RBE of 15 MeV neutrons are reviewed for rapidly proliferating rodent tissue, such as mouse

Mathematical model of normal tissue injury in telegammatherapy

International Nuclear Information System (INIS)

Belov, S.A.; Lyass, F.M.; Mamin, R.G.; Minakova, E.I.; Raevskaya, S.A.

1983-01-01

A model of normal tissue injury as a result of exposure to ionizing radiation is based on an assumption that the degree of tissue injury is determined by the degree of destruction by certain critical cells. The dependence of the number of lethal injuriies on a single dose is expressed by a trinomial - linear and quadratic parts and a constant, obtained as a result of the processing of experimental data. Quantitative correlations have been obtained for the skin and brain. They have been tested using clinical and experimental material. The results of the testing point out to the absence of time dependence on a single up to 6-week irradiation cources. Correlation with an irradiation field has been obtained for the skin. A conclusion has been made that the concept of isoefficacy of irradiation cources is conditional. Spatial-time fractionation is a promising direction in the development of radiation therapy

Therapeutic options and postoperative wound complications after extremity soft tissue sarcoma resection and postoperative external beam radiotherapy.

Science.gov (United States)

Abouarab, Mohamed H; Salem, Iman L; Degheidy, Magdy M; Henn, Dominic; Hirche, Christoph; Eweida, Ahmad; Uhl, Matthias; Kneser, Ulrich; Kremer, Thomas

2018-02-01

Soft tissue sarcomas occur most commonly in the lower and upper extremities. The standard treatment is limb salvage surgery combined with radiotherapy. Postoperative radiotherapy is associated with wound complications. This systematic review aims to summarise the available evidence and review the literature of the last 10 years regarding postoperative wound complications in patients who had limb salvage surgical excision followed by direct closure vs flap coverage together with postoperative radiotherapy and to define the optimal timeframe for adjuvant radiotherapy after soft tissue sarcomas resection and flap reconstruction. A literature search was performed using PubMed. The following keywords were searched: limb salvage, limb-sparing, flaps, radiation therapy, radiation, irradiation, adjuvant radiotherapy, postoperative radiotherapy, radiation effects, wound healing, surgical wound infection, surgical wound dehiscence, wound healing, soft tissue sarcoma and neoplasms. In total, 1045 papers were retrieved. Thirty-seven articles were finally selected after screening of abstracts and applying dates and language filters and inclusion and exclusion criteria. Plastic surgery provides a vast number of reconstructive flap procedures that are directly linked to decreasing wound complications, especially with the expectant postoperative radiotherapy. This adjuvant radiotherapy is better administered in the first 3-6 weeks after reconstruction to allow timely wound healing and avoid local recurrence. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Variation in normal and tumor tissue sensitivity of mice to ionizing radiation-induced DNA strand breaks in vivo

International Nuclear Information System (INIS)

Meyn, R.E.; Jenkins, W.T.

1983-01-01

The efficiency of DNA strand break formation in normal and tumor tissues of mice was measured using the technique of alkaline elution coupled with a microfluorometric determination of DNA. This methodology allowed measurement of the DNA strand breaks produced in tissues irradiated in vivo with doses of radiation comparable to those used in radiotherapy (i.e., 1.0 gray) without the necessity for the cells to be dividing and incorporating radioactive precursors to label the DNA. The results showed that substantial differences existed among various tissues in terms of the amount of DNA strand break damage produced for a given dose of radiation. Of the normal tissues, the most breaks were produced in bone marrow and the least were produced in gut. Furthermore, strand break production was relatively inefficient in the tumor compared to the normal tissues. The efficiency of DNA strand break formation measured in the cells from the tissues irradiated in vitro was much more uniform and considerably greater than that measured in vivo, suggesting that the normal tissues in the animal may be radiobiologically hypoxic

Mathematical models of tumour and normal tissue response

International Nuclear Information System (INIS)

Jones, B.; Dale, R.G.; Charing Cross Group of Hospitals, London

1999-01-01

The historical application of mathematics in the natural sciences and in radiotherapy is compared. The various forms of mathematical models and their limitations are discussed. The Linear Quadratic (LQ) model can be modified to include (i) radiobiological parameter changes that occur during fractionated radiotherapy, (ii) situations such as focal forms of radiotherapy, (iii) normal tissue responses, and (iv) to allow for the process of optimization. The inclusion of a variable cell loss factor in the LQ model repopulation term produces a more flexible clonogenic doubling time, which can simulate the phenomenon of 'accelerated repopulation'. Differential calculus can be applied to the LQ model after elimination of the fraction number integers. The optimum dose per fraction (maximum cell kill relative to a given normal tissue fractionation sensitivity) is then estimated from the clonogen doubling times and the radiosensitivity parameters (or α/β ratios). Economic treatment optimization is described. Tumour volume studies during or following teletherapy are used to optimize brachytherapy. The radiation responses of both individual tumours and tumour populations (by random sampling 'Monte-Carlo' techniques from statistical ranges of radiobiological and physical parameters) can be estimated. Computerized preclinical trials can be used to guide choice of dose fractionation scheduling in clinical trials. The potential impact of gene and other biological therapies on the results of radical radiotherapy are testable. New and experimentally testable hypotheses are generated from limited clinical data by exploratory modelling exercises. (orig.)

Endometrial ablation: normal appearance and complications.

Science.gov (United States)

Drylewicz, Monica R; Robinson, Kathryn; Siegel, Cary Lynn

2018-03-14

Global endometrial ablation is a commonly performed, minimally invasive technique aimed at improving/resolving abnormal uterine bleeding and menorrhagia in women. As non-resectoscopic techniques have come into existence, endometrial ablation performance continues to increase due to accessibility and decreased requirements for operating room time and advanced technical training. The increased utilization of this method translates into increased imaging of patients who have undergone the procedure. An understanding of the expected imaging appearances of endometrial ablation using different modalities is important for the abdominal radiologist. In addition, the frequent usage of the technique naturally comes with complications requiring appropriate imaging work-up. We review the expected appearance of the post-endometrial ablated uterus on multiple imaging modalities and demonstrate the more common and rare complications seen in the immediate post-procedural time period and remotely.

Experimental studies on interactions of radiation and cancer chemotherapeutic drugs in normal tissues and a solid tumour

International Nuclear Information System (INIS)

Maase, H. van der

1986-01-01

The interactions of radiation and seven cancer chemotherapeutic drugs have been investigated in four normal tissues and in a solid C 3 H mouse mammary carcinoma in vivo. The investigated drugs were adriamycin (ADM), bleomycin (BLM), cyclophosphamide (CTX), 5-fluorouracil (5-FU), methotrexate (MTX), mitomycin C (MM-C) and cis-diamminedichloroplatinum(II) (cis-DDP). The drugs enhanced the radiation response in most cases. However, signs of radioprotection was observed for CTX in skin and for MTX in haemopoietic tissue. The interval and the sequence of the two treatment modalities were of utmost importance for the normal tissue reactions. In general, the most serious interactions occurred when drugs were administered simultaneously with or a few hours before radiation. The radiation-modifying effect of the drugs deviated from this pattern in the haemopoietic tissue as the radiation response was most enhanced on drug administration 1-3 days after radiation. Enhancement of the radiation response was generally less pronounced in the tumour model than in the normal tissues. The combined drug-radiation effect was apparently less time-dependent in the tumour than in the normal tissues. (Auth.)

Elemental concentration analysis in PCa, BPH and normal prostate tissues using SR-TXRF

International Nuclear Information System (INIS)

Leitao, Roberta G.; Anjos, Marcelino J.; Canellas, Catarine G.L.; Lopes, Ricardo T.

2009-01-01

Prostate cancer (PCa) is one of the main causes of illness and death all over the world. In Brazil, prostate cancer currently represents the second most prevalent malignant neoplasia in men, representing 21% of all cancer cases. Benign Prostate Hyperplasia (BPH) is an illness prevailing in men above the age of 50, close to 90% after the age of 80. The prostate presents a high zinc concentration, about 10-fold higher than any other body tissue. In this work, samples of human prostate tissues with cancer (PCa), BPH and normal tissue were analyzed utilizing the total reflection X-ray fluorescence spectroscopy using synchrotron radiation technique (SRTXRF) to investigate the differences in the elemental concentrations in these tissues. SR-TXRF analyses were performed at the X-Ray fluorescence beamline at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, Sao Paulo. It was possible to determine the concentrations of the following elements: P, S, K, Ca, Fe, Cu, Zn, Br and Rb. By using Mann-Whitney U test it was observed that almost all elements presented concentrations with significant differences α = 0.05) between the groups studied. The elements and groups were: S, K, Ca, Fe, Zn, Br and Rb (PCa X Normal); S, Fe, Zn and Br (PCa X BPH); K, Ca, Fe, Zn, Br and Rb (BPH X Normal). (author)

Trace element determinations in brain tissues from normal and clinically demented individuals

International Nuclear Information System (INIS)

Saiki, Mitiko; Genezini, Frederico A.; Leite, Renata E.P.; Grinberg, Lea T.; Ferretti, Renata E.L.; Suemoto, Claudia; Pasqualucci, Carlos A.; Jacob-Filho, Wilson

2013-01-01

Studies on trace element levels in human brains under normal and pathological conditions have indicated a possible correlation between some trace element concentrations and neurodegenerative diseases. In this study, analysis of brain tissues was carried out to investigate if there are any differences in elemental concentrations between brain tissues from a normal population above 50 years of age presenting Clinical Dementia Rating (CDR) equal to zero (CDR=0) and that cognitively affected population ( CDR=3). The tissues were dissected, ground, freeze-dried and then analyzed by instrumental neutron activation analysis. Samples and elemental standards were irradiated in a neutron flux at the IEA-R1 nuclear research reactor for Br, Fe, K, Na, Rb, Se and Zn determinations. The induced gamma ray activities were measured using a hyperpure Ge detector coupled to a gamma ray spectrometer. The one-way ANOVA test (p< 0.05) was used to compare the results. All the elements determined in the hippocampus brain region presented differences between the groups presenting CDR=0 and CDR=3. In the case of frontal region only the elements Na, Rb and Zn showed differences between these two groups. These findings proved the correlation between elemental levels present in brain tissues neurodegenerative diseases. Biological standard reference materials SRM 1566b Oyster Tissue and SRM 1577b Bovine Liver analyzed for quality control indicated good accuracy and precision of the results. (author)

Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

Science.gov (United States)

Samani, Abbas; Zubovits, Judit; Plewes, Donald

2007-03-01

Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

International Nuclear Information System (INIS)

Samani, Abbas; Zubovits, Judit; Plewes, Donald

2007-01-01

Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed

Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

Energy Technology Data Exchange (ETDEWEB)

Samani, Abbas [Department of Medical Biophysics/Electrical and Computer Engineering, University of Western Ontario, Medical Sciences Building, London, Ontario, N6A 5C1 (Canada); Zubovits, Judit [Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 (Canada); Plewes, Donald [Department of Medical Biophysics, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 (Canada)

2007-03-21

Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

Safety and Efficacy of Intrapleural Tissue Plasminogen Activator and DNase during Extended Use in Complicated Pleural Space Infections

Directory of Open Access Journals (Sweden)

Jason R. McClune

2016-01-01

Full Text Available The use of intrapleural therapy with tissue plasminogen activator and DNase improves outcomes in patients with complicated pleural space infections. However, little data exists for the use of combination intrapleural therapy after the initial dosing period of six doses. We sought to describe the safety profile and outcomes of intrapleural therapy beyond this standard dosing. A retrospective review of patients receiving intrapleural therapy with tissue plasminogen activator and DNase was performed at two institutions. We identified 101 patients from January 2013 to August 2015 receiving intrapleural therapy for complicated pleural space infection. The extended use of intrapleural tissue plasminogen activator and DNase therapy beyond six doses was utilized in 20% (20/101 of patients. The mean number of doses in those undergoing extended dosing was 9.8 (range of 7–16. Within the population studied there appears to be no statistically significant increased risk of complications, need for surgical referral, or outcome differences when comparing those receiving standard or extended dosing intrapleural therapy. Future prospective study of intrapleural therapy as an alternative option for patients who fail initial pleural drainage and are unable to tolerate/accept a surgical intervention appears a potential area of study.

A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries.

Science.gov (United States)

Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

2007-05-21

The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at the University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties.

A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries

International Nuclear Information System (INIS)

Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

2007-01-01

The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties

Enhancer of the rudimentary gene homologue (ERH expression pattern in sporadic human breast cancer and normal breast tissue

Directory of Open Access Journals (Sweden)

Knüchel Ruth

2008-05-01

Full Text Available Abstract Background The human gene ERH (Enhancer of the Rudimentary gene Homologue has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1 via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule. Methods The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH. Results Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test; the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1. These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue. Conclusion ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian

Performance Characterization of UV Science Cameras Developed for the Chromospheric Lyman-Alpha Spectro-Polarimeter

Science.gov (United States)

Champey, P.; Kobayashi, K.; Winebarger, A.; Cirtain, J.; Hyde, D.; Robertson, B.; Beabout, D.; Beabout, B.; Stewart, M.

2014-01-01

The NASA Marshall Space Flight Center (MSFC) has developed a science camera suitable for sub-orbital missions for observations in the UV, EUV and soft X-ray. Six cameras will be built and tested for flight with the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP), a joint National Astronomical Observatory of Japan (NAOJ) and MSFC sounding rocket mission. The goal of the CLASP mission is to observe the scattering polarization in Lyman-alpha and to detect the Hanle effect in the line core. Due to the nature of Lyman-alpha polarization in the chromosphere, strict measurement sensitivity requirements are imposed on the CLASP polarimeter and spectrograph systems; science requirements for polarization measurements of Q/I and U/I are 0.1 percent in the line core. CLASP is a dual-beam spectro-polarimeter, which uses a continuously rotating waveplate as a polarization modulator, while the waveplate motor driver outputs trigger pulses to synchronize the exposures. The CCDs are operated in frame-transfer mode; the trigger pulse initiates the frame transfer, effectively ending the ongoing exposure and starting the next. The strict requirement of 0.1 percent polarization accuracy is met by using frame-transfer cameras to maximize the duty cycle in order to minimize photon noise. Coating the e2v CCD57-10 512x512 detectors with Lumogen-E coating allows for a relatively high (30 percent) quantum efficiency at the Lyman-alpha line. The CLASP cameras were designed to operate with 10 e-/pixel/second dark current, 25 e- read noise, a gain of 2.0 +/- 0.5 and 1.0 percent residual non-linearity. We present the results of the performance characterization study performed on the CLASP prototype camera; dark current, read noise, camera gain and residual non-linearity.

Comparative study of rabbit VX2 hepatic implantation tumor and normal liver tissue on magnetic resonance perfusion weighted imaging

International Nuclear Information System (INIS)

Jiao Zimei; Wang Xizhen; Wang Bin; Liu Feng; Li Haiqing; Sun Yequan; Dong Peng

2012-01-01

Objective: To investigate the value of magnetic resonance (MR) perfusion weighted imaging (PWI) in evaluating the blood perfusion of tumor by analyzing the features and indexes of PWI on rabbit VX2 hepatic implantation tumor and normal liver tissue. Methods: Twenty-four New Zealand White rabbits with VX2 carcinoma were established under direct surgical vision embedding tumor tissue. MR examination was performed at 21 days after the tumor implantation. The signal intensity -time curve of hepatic tumor and normal liver tissue were obtained. Mean time to enhance (MTE), negative enhancement integral (NEI), time to minimum (TM), maximum slope of decrease (MSD) and maximum slope of increase (MSI) were measured. Results: MTE, NEI, TM, MSD, and MSI of the normal liver tissue were 208.341±2.226 ms, 78.334±8.152, 24.059±1.927 ms, 38.221±2.443, and 15.389±2.526, respectively. MTE, NEI, TM, MSD, and MSI of the tumor tissue were 175.437±4.182 ms, 123.203±19.455, 17.061±1.834 ms, 125.740±4.842, and 67.832±2.882, respectively. The MTE and TM of tumor were shorter than those of normal hepatic tissue (P<0.05). NEI, MSD, and MSI of tumor were higher than those of normal hepatic tissue (P<0.05). Conclusion: PWI can distinguish the normal liver tissue from the tumor tissue, which is helpful in evaluating blood perfusion of different hepatic tissues. (authors)

Unexpected complication associated with balneotherapy: Skin and soft tissue infection

Science.gov (United States)

Alım, Bülent; Bostancı, Fahrettin; Servi, M. Alperen; Ćetinel, Sinan; Bingöl, M. Ozan

2017-04-01

Balneotherapy cure is an ongoing process, but patients can benefit most when cure is complete. For these reason, patients should be closely monitored and necessary precautions should be taken in terms of the complications that may occur in order to prevent the interruption or discontinuation of balneotherapy. Here, we wanted to represent a case that developed left leg soft tissue infection during the application of balneotherapy and because of this reason we stopped the balneotherapy As a result, when balneotherapy is planned for patients with risk factors such as diabetes and obesity, frequent examination of the skin and the application of skin moisturizers will be beneficial to prevent itching and skin dryness.

YAP expression in normal and neoplastic breast tissue: an immunohistochemical study.

Science.gov (United States)

Jaramillo-Rodríguez, Yolanda; Cerda-Flores, Ricardo M; Ruiz-Ramos, Ruben; López-Márquez, Francisco C; Calderón-Garcidueñas, Ana Laura

2014-04-01

Yes-associated protein (YAP) is a transcriptional factor involved in normal cell proliferation, apoptosis and carcinogenesis; however, its contribution to breast cancer (BC) is still controversial. We undertook this study to compare the expression of YAP by immunohistochemistry (IHC) in normal breast tissue of women without breast cancer (BC) (controls), non-neoplastic breast tissue in women with cancer (internal controls) and in four different subtypes of invasive ductal carcinoma. There were 17 controls and 105 tumor cases (53 luminal A, 15 luminal B, 20 overexpression of HER2 and 17 triple negative cases) studied by IHC. Statistical analysis included χ(2) for linear trend (Extended Mantel-Haenszel). There were 40% of internal controls that showed expression of YAP in myoepithelial cells, whereas in controls expression was 100%. In controls, 3/17 (17.6%) showed cytoplasmic staining in luminal cells. There was a significant difference in nuclear expression between the ductal BC subtypes. Luminal A had 4% of positive cases with <10% of cells affected in each case; in contrast, there were 17-20% of positive cases in the other groups with 50% or more of stained cells. YAP expression in stromal cells was not observed in controls or in triple-negative cases, and luminal B pattern had the highest YAP nuclear expression (20%). YAP showed decreased expression in tumor cells compared with normal breast tissue. These findings are consistent with a role of YAP as a suppressor gene in BC and show differences in YAP expression in different patterns of ductal BC. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

Differential Expression of Cytochrome P450 Enzymes in Normal and Tumor Tissues from Childhood Rhabdomyosarcoma

Science.gov (United States)

Molina-Ortiz, Dora; Camacho-Carranza, Rafael; González-Zamora, José Francisco; Shalkow-Kalincovstein, Jaime; Cárdenas-Cardós, Rocío; Ností-Palacios, Rosario; Vences-Mejía, Araceli

2014-01-01

Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs. PMID:24699256

Relationship between acute and late normal tissue injury after postoperative radiotherapy in endometrial cancer

International Nuclear Information System (INIS)

Jereczek-Fossa, Barbara A.; Jassem, Jacek; Badzio, Andrzej

2002-01-01

Purpose: To evaluate the relationship between acute and late normal tissue reactions in 317 consecutive endometrial cancer patients treated with surgery and adjuvant radiotherapy (RT). Methods: The data of 317 patients (staging according to the International Federation of Gynecology and Obstetrics) treated with postoperative RT were analyzed. Both low-dose-rate brachytherapy and external beam RT were applied in 247 patients (78%); brachytherapy only in 49 (15%) and external beam irradiation only in 21 (7%). The median follow-up was 7.3 years (range 4-21). The European Organization for Research and Treatment of Cancer, Radiation Therapy Oncology Group system with elements of the late effects of normal tissue, subjective, objective, management, analytic (LENT/SOMA) scale was used to score the RT reactions. The correlation between the occurrence and severity of acute and late bowel and bladder toxicity, as well as the relationship between the severity of acute effects and time to occurrence of late reactions, were assessed using linear and logistic regression analyses. Results: Of the 317 patients, 268 (85%) experienced acute RT reactions of any grade. Severe acute bowel reactions were observed in 15 patients (5%), urinary bladder complications in 1 patient (0.5%), cutaneous in 1 patient (0.5%), and vaginal in 1 patient (0.5%). Severe acute hematologic toxicity was seen in 3 patients (1%). A total of 158 patients (51%) experienced late RT reactions of any grade. Severe late bowel reactions were observed in 19 patients (6%), urinary bladder in 5 (2%), vaginal in 3 (1%), and bone in 10 (4%). When all toxic events were considered, there was a highly significant correlation between the acute and late bowel reactions (p <0.001), but the acute and late urinary bladder reactions did not correlate (p=0.64). The grade of acute toxicity was found to predict the grade of late toxicity for the bowel but not for the bladder (p<0.001 and p=0.47, respectively). The severity of acute

Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues

Directory of Open Access Journals (Sweden)

Emara Marwan

2010-09-01

Full Text Available Abstract Background Cytoglobin (Cygb and neuroglobin (Ngb are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX, a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Results Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Conclusions Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human

Tumor control and normal tissue toxicity: The two faces of radiotherapy

NARCIS (Netherlands)

van Oorschot, B.

2016-01-01

This thesis discusses the two contrasting sides of radiotherapy: tumor control and normal tissue toxicity. On one hand, radiation treatment aims to target the tumor with the highest possible radiation dose, inducing as much lethal DNA damage as possible. On the other hand however, escalation of the

The influence of dose fractionation and dose rate on normal tissue responses

International Nuclear Information System (INIS)

Barendsen, G.W.

1982-01-01

An analysis of responses of a variety of normal tissues in animals to fractionated irradiations has been made with the aim of developing a formalism for the prediction of tolerance doses as a function of the dose per fraction and the overall treatment time. An important feature of the formalism is that it is directly based on radiological insights and therefore provides a logical concept to account for the diversity of tissue responses. (Auth.)

CURED I - LENT. Late effects of cancer treatment on normal tissues

International Nuclear Information System (INIS)

Rubin, P.; Okunieff, P.; Constine, L.S.; Rochester Univ. School of Medicine and Dentistry, Rochester, NY; Marks, L.B.

2008-01-01

The search for the most favorable therapeutic ratio - at which ablation of cancer is achieved while normal tissues are conserved - has been modern radiation oncology's equivalent of the quest for the Holy Grail. Our awareness of the late effects of radiation grew during the past century as new modalities were introduced. Heightened normal tissue reactions accompanied the higher rates of cancer ablation achieved by escalation of radiation doses, accelerated fractionated radiotherapy, and aggressive concurrent chemotherapy and radiation regimens. This volume is based on the LENT V NCI-sponsored meeting held in May 2004 and the CURED I conference held in 2006. Written by experts in the field, it addresses a number of critical topics relating to late effects, such as mechanisms of injury, the role of screening, options for interventions, second malignancies, and prevention. It is hoped that it will assist the reader in understanding how to prevent and treat the long-term side-effects of irradiation. (orig.)

New constraints on Lyman-α opacity using 92 quasar lines of sight

Science.gov (United States)

Bosman, Sarah E. I.; Fan, Xiaohui; Jiang, Linhua; Reed, Sophie; Matsuoka, Yoshiki; Becker, George; Rorai, Albert

2018-05-01

The large scatter in Lyman-α opacity at z > 5.3 has been an ongoing mystery, prompting a flurry of numerical models. A uniform ultra-violet background has been ruled out at those redshifts, but it is unclear whether any proposed models produce sufficient inhomogeneities. In this paper we provide an update on the measurement which first highlighted the issue: Lyman-α effective optical depth along high-z quasar lines of sight. We nearly triple on the previous sample size in such a study thanks to the cooperation of the DES-VHS, SHELLQs, and SDSS collaborations as well as new reductions and spectra. We find that a uniform UVB model is ruled out at 5.1 < z < 5.3, as well as higher redshifts, which is perplexing. We provide the first such measurements at z ~ 6. None of the numerical models we confronted to this data could reproduce the observed scatter.

Diagnostics of the Solar Wind and Global Heliosphere with Lyman-α Emission Measurements

Science.gov (United States)

Provornikova, E. P.; Izmodenov, V. V.; Laming, J. M.; Strachan, L.; Wood, B. E.; Katushkina, O. A.; Ko, Y.-K.; Tun Beltran, S.; Chakrabarti, S.

2018-02-01

We propose to develop an instrument measuring full sky intensity maps and spectra of interplanetary Lyman-α emission to reveal the global solar wind variability and the nature of the heliosphere and the local interstellar medium.

Complications of cancer therapy

International Nuclear Information System (INIS)

Moskowitz, P.S.; Parker, B.R.

1985-01-01

The purpose of this chapter is to review systematically the toxicity of contemporary chemotherapy and irradiation on normal tissues of growing children. Whenever possible, the separate toxicity of chemotherapy, irradiation, and combination therapy is addressed. However, it is not always possible to quantitate specifically such reactions in the face of multiple drug therapy, which may enhance radiation injury or reactivate prior radiation injury. Prior detailed reviews have provided important sources of information concerning radiation injury for this more general discussion. The information provided will assist both the clinician and the radiologist in the recognition of early and late complications of therapy in pediatric oncology

Effect of different BNCT protocols on DNA synthesis in precancerous and normal tissues in an experimental model of oral cancer

International Nuclear Information System (INIS)

Heber, Elisa M.; Aromando, Romina; Trivillin, Veronica A.; Itoiz, Maria E.; Kreimann, Erica L.; Schwint, Amanda E.; Nigg, David W.

2006-01-01

We previously reported the therapeutic success of different BNCT protocols in the treatment of oral cancer, employing the hamster cheek pouch model. The aim of the present study was to evaluate the effect of these BNCT protocols on DNA synthesis in precancerous and normal tissue in this model and assess the potential lag in the development of second primary tumors in precancerous tissue. The data are relevant to potential control of field cancerized tissue and tolerance of normal tissue. We evaluated DNA synthesis in precancerous and normal pouch tissue 1-30 days post-BNCT mediated by BPA, GB-10 or BPA + GB-10 employing incorporation of bromo-deoxyuridine as an end-point. The BNCT-induced potential lag in the development of second primary tumors in precancerous tissue was monitored. A drastic, statistically significant reduction in DNA synthesis occurred in pacancerous tissue as early as 1 day post-BNCT and was sustained at virtually all time points until 30 days post-BNCT for all protocols. The histological categories evaluated individually within precancerous tissue (dysplasia, hyperplasia and NUMF [no unusual microscopic features]) responded similarly. DNA synthesis in normal tissue treated with BNCT oscillated around the very low pre-treatment values. A BNCT-induced lag in the development of second primary tumors was observed. BNCT induced a drastic fall in DNA synthesis in precancerous tissue that would be associated to the observed lag in the development of second primary tumors. The minimum variations in DNA synthesis in BNCT-treated normal tissue would correlate with the absence of normal tissue radiotoxicity. The present data would contribute to optimize therapeutic efficacy in the treatment of field-cancerized areas. (author)

Lewis x is highly expressed in normal tissues: a comparative immunohistochemical study and literature revision.

Science.gov (United States)

Croce, María V; Isla-Larrain, Marina; Rabassa, Martín E; Demichelis, Sandra; Colussi, Andrea G; Crespo, Marina; Lacunza, Ezequiel; Segal-Eiras, Amada

2007-01-01

An immunohistochemical analysis was employed to determine the expression of carbohydrate antigens associated to mucins in normal epithelia. Tissue samples were obtained as biopsies from normal breast (18), colon (35) and oral cavity mucosa (8). The following carbohydrate epitopes were studied: sialyl-Lewis x, Lewis x, Lewis y, Tn hapten, sialyl-Tn and Thomsen-Friedenreich antigen. Mucins were also studied employing antibodies against MUC1, MUC2, MUC4, MUC5AC, MUC6 and also normal colonic glycolipid. Statistical analysis was performed and Kendall correlations were obtained. Lewis x showed an apical pattern mainly at plasma membrane, although cytoplasmic staining was also found in most samples. TF, Tn and sTn haptens were detected in few specimens, while sLewis x was found in oral mucosa and breast tissue. Also, normal breast expressed MUC1 at a high percentage, whereas MUC4 was observed in a small number of samples. Colon specimens mainly expressed MUC2 and MUC1, while most oral mucosa samples expressed MUC4 and MUC1. A positive correlation between MUC1VNTR and TF epitope (r=0.396) was found in breast samples, while in colon specimens MUC2 and colonic glycolipid versus Lewis x were statistically significantly correlated (r=0.28 and r=0.29, respectively). As a conclusion, a defined carbohydrate epitope expression is not exclusive of normal tissue or a determined localization, and it is possible to assume that different glycoproteins and glycolipids may be carriers of carbohydrate antigens depending on the tissue localization considered.

Effect of implanted radioactive 125I seeds on normal tissue structures of bronchus, esophagus, pulmonary artery, pulmonary vein and alveolus in dogs

International Nuclear Information System (INIS)

Qi Liangchen; Han Zhenguo; Yang Bin; Heersitai

2008-01-01

Objective: To investigate the effect of implanted radioactive 125 I seeds on normal tissue structures of bronchus, esophagus, pulmonary artery, pulmonary vein and alveolus in dogs. Methods: Nine healthy male dogs weighing 17-21 kg were randomly divided into three groups: 30 d, 60 d experimental groups and control group. Radioactive 125 I seeds (3.7 x 10 7 Bg, 1.0 mCi) were implanted into the sides of bronchus, esophagus, pulmonary artery, pulmonary vein respectively, the samples of bronchus, esophagus, pulmonary artery, pulmonary vein were taken 30 and 60 d after transplantation, HE staining was used to observe the pathologic changes of the tissues under light microscope. Results: The damages of normal bronchus, esophagus, pulmonary artery, pulmonary vein and alveolus after radioactive 125 I seeds implantation in 30 d group were weaker than those in control group and 60 d group, there were no complications such as perforation, hemorrhage, necrosis, etc. Histopathological score indicated that the scores of bronchus, esophagus and alveolar in 30 d group and 60 d group were higher than those in control group (P 0.05); there was no significant difference in histopathological score of pulmonary vein among all groups (P>0.05). Conclusion: The implanted radioactive 125 I seeds can damage all kinds of tissues at different degrees, but this kind of damage is reversible, the dog may repair the damage through its own repair ability, its clinical application is safe. (authors)

The Lyman Continuum Escape Fraction of Emission Line-selected z ∼ 2.5 Galaxies Is Less Than 15%

Energy Technology Data Exchange (ETDEWEB)

Rutkowski, Michael J.; Hayes, Matthew [Department of Astronomy, AlbaNova University Centre, Stockholm University, SE-10691 Stockholm (Sweden); Scarlata, Claudia; Mehta, Vihang [Minnesota Institute for Astrophysics, University of Minnesota, 116 Church Street SE, Minneapolis, MN 55455 (United States); Henry, Alaina; Hathi, Nimish; Koekemoer, Anton M. [Space Telescope Science Institute, Baltimore, MD 21218 (United States); Cohen, Seth; Windhorst, Rogier [School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85281 (United States); Teplitz, Harry I. [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); Haardt, Francesco [DiSAT, Università dellInsubria, via Valleggio 11, I-22100 Como (Italy); Siana, Brian [Department of Physics, University of California, Riverside, CA 92521 (United States)

2017-06-01

Recent work suggests that strong emission line, star-forming galaxies (SFGs) may be significant Lyman continuum leakers. We combine archival Hubble Space Telescope broadband ultraviolet and optical imaging (F275W and F606W, respectively) with emission line catalogs derived from WFC3 IR G141 grism spectroscopy to search for escaping Lyman continuum (LyC) emission from homogeneously selected z ∼ 2.5 SFGs. We detect no escaping Lyman continuum from SFGs selected on [O ii] nebular emission ( N = 208) and, within a narrow redshift range, on [O iii]/[O ii]. We measure 1 σ upper limits to the LyC escape fraction relative to the non-ionizing UV continuum from [O ii] emitters, f {sub esc} ≲ 5.6%, and strong [O iii]/[O ii] > 5 ELGs, f {sub esc} ≲ 14.0%. Our observations are not deep enough to detect f {sub esc} ∼ 10% typical of low-redshift Lyman continuum emitters. However, we find that this population represents a small fraction of the star-forming galaxy population at z ∼ 2. Thus, unless the number of extreme emission line galaxies grows substantially to z ≳ 6, such galaxies may be insufficient for reionization. Deeper survey data in the rest-frame ionizing UV will be necessary to determine whether strong line ratios could be useful for pre-selecting LyC leakers at high redshift.

The Lyman Continuum Escape Fraction of Emission Line-selected z ∼ 2.5 Galaxies Is Less Than 15%

International Nuclear Information System (INIS)

Rutkowski, Michael J.; Hayes, Matthew; Scarlata, Claudia; Mehta, Vihang; Henry, Alaina; Hathi, Nimish; Koekemoer, Anton M.; Cohen, Seth; Windhorst, Rogier; Teplitz, Harry I.; Haardt, Francesco; Siana, Brian

2017-01-01

Recent work suggests that strong emission line, star-forming galaxies (SFGs) may be significant Lyman continuum leakers. We combine archival Hubble Space Telescope broadband ultraviolet and optical imaging (F275W and F606W, respectively) with emission line catalogs derived from WFC3 IR G141 grism spectroscopy to search for escaping Lyman continuum (LyC) emission from homogeneously selected z ∼ 2.5 SFGs. We detect no escaping Lyman continuum from SFGs selected on [O ii] nebular emission ( N = 208) and, within a narrow redshift range, on [O iii]/[O ii]. We measure 1 σ upper limits to the LyC escape fraction relative to the non-ionizing UV continuum from [O ii] emitters, f _e_s_c ≲ 5.6%, and strong [O iii]/[O ii] > 5 ELGs, f _e_s_c ≲ 14.0%. Our observations are not deep enough to detect f _e_s_c ∼ 10% typical of low-redshift Lyman continuum emitters. However, we find that this population represents a small fraction of the star-forming galaxy population at z ∼ 2. Thus, unless the number of extreme emission line galaxies grows substantially to z ≳ 6, such galaxies may be insufficient for reionization. Deeper survey data in the rest-frame ionizing UV will be necessary to determine whether strong line ratios could be useful for pre-selecting LyC leakers at high redshift.

Performance Characterization of UV Science Cameras Developed for the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP)

Science.gov (United States)

Champey, Patrick; Kobayashi, Ken; Winebarger, Amy; Cirtin, Jonathan; Hyde, David; Robertson, Bryan; Beabout, Brent; Beabout, Dyana; Stewart, Mike

2014-01-01

The NASA Marshall Space Flight Center (MSFC) has developed a science camera suitable for sub-orbital missions for observations in the UV, EUV and soft X-ray. Six cameras will be built and tested for flight with the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP), a joint National Astronomical Observatory of Japan (NAOJ) and MSFC sounding rocket mission. The goal of the CLASP mission is to observe the scattering polarization in Lyman-alpha and to detect the Hanle effect in the line core. Due to the nature of Lyman-alpha polarization in the chromosphere, strict measurement sensitivity requirements are imposed on the CLASP polarimeter and spectrograph systems; science requirements for polarization measurements of Q/I and U/I are 0.1% in the line core. CLASP is a dual-beam spectro-polarimeter, which uses a continuously rotating waveplate as a polarization modulator, while the waveplate motor driver outputs trigger pulses to synchronize the exposures. The CCDs are operated in frame-transfer mode; the trigger pulse initiates the frame transfer, effectively ending the ongoing exposure and starting the next. The strict requirement of 0.1% polarization accuracy is met by using frame-transfer cameras to maximize the duty cycle in order to minimize photon noise. Coating the e2v CCD57-10 512x512 detectors with Lumogen-E coating allows for a relatively high (30%) quantum efficiency at the Lyman-$\\alpha$ line. The CLASP cameras were designed to operate with =10 e- /pixel/second dark current, = 25 e- read noise, a gain of 2.0 and =0.1% residual non-linearity. We present the results of the performance characterization study performed on the CLASP prototype camera; dark current, read noise, camera gain and residual non-linearity.

A Sounding Rocket Experiment for the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP)

Science.gov (United States)

Kubo, M.; Kano, R.; Kobayashi, K.; Bando, T.; Narukage, N.; Ishikawa, R.; Tsuneta, S.; Katsukawa, Y.; Ishikawa, S.; Suematsu, Y.; Hara, H.; Shimizu, T.; Sakao, T.; Ichimoto, K.; Goto, M.; Holloway, T.; Winebarger, A.; Cirtain, J.; De Pontieu, B.; Casini, R.; Auchère, F.; Trujillo Bueno, J.; Manso Sainz, R.; Belluzzi, L.; Asensio Ramos, A.; Štěpán, J.; Carlsson, M.

2014-10-01

A sounding-rocket experiment called the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) is presently under development to measure the linear polarization profiles in the hydrogen Lyman-alpha (Lyα) line at 121.567 nm. CLASP is a vacuum-UV (VUV) spectropolarimeter to aim for first detection of the linear polarizations caused by scattering processes and the Hanle effect in the Lyα line with high accuracy (0.1%). This is a fist step for exploration of magnetic fields in the upper chromosphere and transition region of the Sun. Accurate measurements of the linear polarization signals caused by scattering processes and the Hanle effect in strong UV lines like Lyα are essential to explore with future solar telescopes the strength and structures of the magnetic field in the upper chromosphere and transition region of the Sun. The CLASP proposal has been accepted by NASA in 2012, and the flight is planned in 2015.

Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

Energy Technology Data Exchange (ETDEWEB)

Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Partridge, Mike [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Carrington, Rhys [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hurt, Chris [Wales Cancer Trials Unit, School of Medicine, Heath Park, Cardiff (United Kingdom); Crosby, Thomas [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hawkins, Maria A. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

2014-10-01

Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

Reconstructive surgery for the complications of pelvic irradiation

International Nuclear Information System (INIS)

Bricker, E.M.; Johnston, W.D.; Kraybill, W.G.; Lopez, M.J.

1984-01-01

Severe damage to the pelvic viscera is a complication of irradiation therapy that, unfortunately, cannot always be avoided. Resulting rectal and rectocolonic strictures, rectovaginal fistulas, and shortening and stenosis of the vagina present very difficult problems that frequently require a colostomy for relief and may permanently impair sexual function. The authors present a new approach to correction of these unfortunate lesions based on the use of proximal nonirradiated colon which serves as a vascular pedicle graft to correct the defect without a complicated and massive resection. Twenty-two such operations have been done with 19 satisfactory to excellent results and two total failures (one death from small bowel complications). All patterns and combinations of irradiation injury have been found amenable to this technique of repair. These have included both web and linear strictures with and without fistulas. In half of the patients, it was possible to make use of normal colon bypassed by a prior colostomy. Normal nonirradiated colon with good blood supply will heal satisfactorily to irradiated colon or rectum, thus making excision of all the irradiated tissue unnecessary. The results of this surgical approach have thus far been gratifying and warrant further trials for these distressing injuries

Adverse event reporting and developments in radiation biology after normal tissue injury: International Atomic Energy Agency consultation

International Nuclear Information System (INIS)

Chen Yuhchyau; Trotti, Andy; Coleman, C. Norman; Machtay, Mitchell; Mirimanoff, Rene O.; Hay, John; O'Brien, Peter C.; El-Gueddari, Brahim; Salvajoli, Joao V.; Jeremic, Branislav

2006-01-01

Purpose: Recent research has enhanced our understanding of radiation injury at the molecular-cellular and tissue levels; significant strides have occurred in standardization of adverse event reporting in clinical trials. In response, the International Atomic Energy Agency, through its Division of Human Health and its section for Applied Radiation Biology and Radiotherapy, organized a consultation meeting in Atlanta (October 2, 2004) to discuss developments in radiobiology, normal tissue reactions, and adverse event reporting. Methods and Materials: Representatives from cooperative groups of African Radiation Oncology Group, Curriculo Radioterapeutica Ibero Latino Americana, European Organization for Research and Treatment of Cancer, National Cancer Institute of Canada Clinical Trials Group, Radiation Therapy Oncology Group, and Trans-Tasman Radiation Oncology Group held the meeting discussion. Results: Representatives of major radiotherapy groups/organizations and prominent leaders in radiotherapy discussed current understanding of normal tissue radiobiologic effects, the design and implementation of future clinical and translational projects for normal tissue injury, and the standardization of adverse-event reporting worldwide. Conclusions: The consensus was to adopt NCI comprehensive adverse event reporting terminology and grading system (CTCAE v3.0) as the new standard for all cooperative group trials. Future plans included the implementation of coordinated research projects focusing on normal tissue biomarkers and data collection methods

Investigating the Lyman photon escape in local starburst galaxies with the Cosmic Origins Spectrograph ★

Science.gov (United States)

Hernandez, Svea; Leitherer, Claus; Boquien, Médéric; Buat, Véronique; Burgarella, Denis; Calzetti, Daniela; Noll, Stefan

2018-04-01

We present a study of 7 star-forming galaxies from the Cosmic Evolution Survey (COSMOS) observed with the Cosmic Origins Spectrograph (COS) on board the Hubble Space Telescope (HST). The galaxies are located at relatively low redshifts, z ˜0.3, with morphologies ranging from extended and disturbed to compact and smooth. To complement the HST observations we also analyze observations taken with the VIMOS spectrograph on the Very Large Telescope (VLT). In our galaxy sample we identify three objects with double peak Lyman-α profiles similar to those seen in Green Pea compact galaxies and measure peak separations of 655, 374, and 275 km s-1. We measure Lyman-α escape fractions with values ranging between 5-13%. Given the low flux levels in the individual COS exposures we apply a weighted stacking approach to obtain a single spectrum. From this COS combined spectrum we infer upper limits for the absolute and relative Lyman continuum escape fractions of f_abs(LyC) = 0.4^{+10.1}_{-0.4}% and f_res(LyC) = 1.7^{+15.2}_{-1.7}%, respectively. Finally, we find that most of these galaxies have moderate UV and optical SFRs (SFRs ≲ 10 M⊙ yr-1).

Optimization of the dose level for a given treatment plan to maximize the complication-free tumor cure

International Nuclear Information System (INIS)

Lind, B.K.; Mavroidis, P.; Hyoedynmaa, S.; Kappas, C.

1999-01-01

During the past decade, tumor and normal tissue reactions after radiotherapy have been increasingly quantified in radiobiological terms. For this purpose, response models describing the dependence of tumor and normal tissue reactions on the irradiated volume, heterogeneity of the delivered dose distribution and cell sensitivity variations can be taken into account. The probability of achieving a good treatment outcome can be increased by using an objective function such as P + , the probability of complication-free tumor control. A new procedure is presented, which quantifies P + from the dose delivery on 2D surfaces and 3D volumes and helps the user of any treatment planning system (TPS) to select the best beam orientations, the best beam modalities and the most suitable beam energies. The final step of selecting the prescribed dose level is made by a renormalization of the entire dose plan until the value of P + is maximized. The index P + makes use of clinically established dose-response parameters, for tumors and normal tissues of interest, in order to improve its clinical relevance. The results, using P + , are compared against the assessments of experienced medical physicists and radiation oncologists for two clinical cases. It is observed that when the absorbed dose level for a given treatment plan is increased, the treatment outcome first improves rapidly. As the dose approaches the tolerance of normal tissues the complication-free curve begins to drop. The optimal dose level is often just below this point and it depends on the geometry of each patient and target volume. Furthermore, a more conformal dose delivery to the target results in a higher control rate for the same complication level. This effect can be quantified by the increased value of the P + parameter. (orig.)

Changes in regional blood flow of normal and tumor tissues following hyperthermia and combined X-ray irradiation

International Nuclear Information System (INIS)

Suga, Kazuyoshi

1986-01-01

Hyperthermia and X-ray irradiation were given to Ehrlich tumors, which were induced in the ventrum of the right hind foot of ICR mice, and to the normal tissues. Their effects on regional blood flow were examined using Xe-133 local clearance method. Blood flow of the normal tissues remained unchanged by heating at 41 deg C for 30 minutes, and increased by heating at 43 deg C and 45 deg C for 30 minutes. On the contrary, blood flow of the tumors decreased with an increase in temperature. When hypertermia (43 deg C for 30 minutes) was combined with irradiation of 30 Gy, decrease in blood flow of the tumors was greater than the normal tissues at 24 hours. Blood flow of the tumors depended on tumor size. The decreased amount of blood flow by hyperthermia was more for tumors > 250 mm 3 than tumors 3 . Blood flow ratios of tumor to normal tissues were also smaller in tumors > 250 mm 3 than tumors 3 . In the case of tumors 3 , blood flow tended to return to normal at 3 hr after heating at 43 deg C for 30 min. However, this was not seen in tumors > 250 mm 3 . (Namekawa, K.)

Lyman-continuum leakage as dominant source of diffuse ionized gas in the Antennae galaxy

Science.gov (United States)

Weilbacher, Peter M.; Monreal-Ibero, Ana; Verhamme, Anne; Sandin, Christer; Steinmetz, Matthias; Kollatschny, Wolfram; Krajnović, Davor; Kamann, Sebastian; Roth, Martin M.; Erroz-Ferrer, Santiago; Marino, Raffaella Anna; Maseda, Michael V.; Wendt, Martin; Bacon, Roland; Dreizler, Stefan; Richard, Johan; Wisotzki, Lutz

2018-04-01

The Antennae galaxy (NGC 4038/39) is the closest major interacting galaxy system and is therefore often studied as a merger prototype. We present the first comprehensive integral field spectroscopic dataset of this system, observed with the MUSE instrument at the ESO VLT. We cover the two regions in this system which exhibit recent star formation: the central galaxy interaction and a region near the tip of the southern tidal tail. In these fields, we detect HII regions and diffuse ionized gas to unprecedented depth. About 15% of the ionized gas was undetected by previous observing campaigns. This newly detected faint ionized gas is visible everywhere around the central merger, and shows filamentary structure. We estimate diffuse gas fractions of about 60% in the central field and 10% in the southern region. We are able to show that the southern region contains a significantly different population of HII regions, showing fainter luminosities. By comparing HII region luminosities with the HST catalog of young star clusters in the central field, we estimate that there is enough Lyman-continuum leakage in the merger to explain the amount of diffuse ionized gas that we detect. We compare the Lyman-continuum escape fraction of each HII region against emission line ratios that are sensitive to the ionization parameter. While we find no systematic trend between these properties, the most extreme line ratios seem to be strong indicators of density bounded ionization. Extrapolating the Lyman-continuum escape fractions to the southern region, we conclude that simply from the comparison of the young stellar populations to the ionized gas there is no need to invoke other ionization mechanisms than Lyman-continuum leaking HII regions for the diffuse ionized gas in the Antennae. FITS images and Table of HII regions are available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/611/A95 and at http://muse-vlt.eu/science/antennae/

Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

International Nuclear Information System (INIS)

Curtis, Carol D; Thorngren, Daniel L; Nardulli, Ann M

2010-01-01

During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells

Repair in normal tissues and the possible relevance to radiotherapy

International Nuclear Information System (INIS)

Field, S.B.; Hornsey, S.

1977-01-01

Between each fraction in radiotherapy, there is repair and recovery of both normal and neoplastic tissues. Several different types of repair have been identified. Some relate specifically to the effect of changing the number of fractions and others to the overall treatment time. Each will be discussed and particular attention will be paid to slow repair phenomena which have recently been the subject of much interest. (orig.) [de

Evaluation of cyclooxygenase protein expression in traumatized versus normal tissues from eastern box turtles (Terrapene carolina carolina).

Science.gov (United States)

Royal, Lillian W; Lascelles, B Duncan X; Lewbart, Gregory A; Correa, Maria T; Jones, Samuel L

2012-06-01

This pilot study was designed to determine whether cyclooxygenase (COX)-1, COX-2, or both are expressed in normal turtle tissues and whether level of expression changes when tissue becomes inflamed. Five eastern box turtles, Terrapene carolina carolina, that either died or were euthanatized due to disease or injuries were used for this work. Tissues were obtained from the five turtles. Western blot analysis was used to evaluate tissues for COX-1 and COX-2 proteins. Densiometric analysis was used to compare Western blot bands within each turtle. COX-1 and COX-2 were found in the liver, kidney, grossly normal muscle, and grossly traumatized (inflamed) muscle of all study turtles. In all cases, COX-1 and COX-2 proteins were increased in traumatized muscle over grossly normal nontraumatized muscle. The highest levels of COX-1 and COX-2 proteins were found in kidney and liver. There was no statistical difference between the amount of COX-1 protein in liver and kidney, but traumatized muscle compared with grossly normal muscle had significantly greater COX-1 but not COX 2 protein concentrations. There was no statistical difference between the amount of COX-2 protein in liver and kidney. Traumatized muscle expressed nonstatistically significant greater amounts of COX-2 compared with grossly normal muscle. COX-1 and COX-2 proteins are expressed in turtle tissues, and both isoforms are upregulated during inflammation of muscle tissue. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) that block both COX isoforms might be more efficacious than COX-2-selective drugs. This work suggests that NSAIDs should be evaluated for potential liver and kidney toxicity in turtles.

Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.

Science.gov (United States)

Johnson, Kevin C; Houseman, E Andres; King, Jessica E; Christensen, Brock C

2017-07-10

The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies. Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors, age, body mass index, parity, and family history of disease, with DNA methylation adjusting for potential variation in cell-type proportions. We identified 787 cytosine-guanine dinucleotide (CpG) sites that demonstrated significant associations (Q value breast cancer risk factors. Age-related DNA methylation changes are primarily increases in methylation enriched at breast epithelial cell enhancer regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF). We validated the age-related associations in two independent populations, using normal breast tissue samples (n = 18) and samples of normal tissue adjacent to tumor tissue (n = 97). The genomic regions classified as age-related were more likely to be regions altered in both pre-invasive (n = 40, P = 3.0E-03) and invasive breast tumors (n = 731, P = 1.1E-13). DNA methylation changes with age occur at regulatory regions, and are further exacerbated in cancer, suggesting that age influences breast cancer risk in part through its contribution to epigenetic dysregulation in normal breast tissue.

Metabolomic Evidence for a Field Effect in Histologically Normal and Metaplastic Tissues in Patients with Esophageal Adenocarcinoma

Directory of Open Access Journals (Sweden)

Michelle A.C. Reed

2017-03-01

Full Text Available Patients with Barrett's esophagus (BO are at increased risk of developing esophageal adenocarcinoma (EAC. Most Barrett's patients, however, do not develop EAC, and there is a need for markers that can identify those most at risk. This study aimed to see if a metabolic signature associated with the development of EAC existed. For this, tissue extracts from patients with EAC, BO, and normal esophagus were analyzed using 1H nuclear magnetic resonance. Where possible, adjacent histologically normal tissues were sampled in those with EAC and BO. The study included 46 patients with EAC, 7 patients with BO, and 68 controls who underwent endoscopy for dyspeptic symptoms with normal appearances. Within the cancer cohort, 9 patients had nonneoplastic Barrett's adjacent to the cancer suitable for biopsy. It was possible to distinguish between histologically normal, BO, and EAC tissue in EAC patients [area under the receiver operator curve (AUROC 1.00, 0.86, and 0.91] and between histologically benign BO in the presence and absence of EAC (AUROC 0.79. In both these cases, sample numbers limited the power of the models. Comparison of histologically normal tissue proximal to EAC versus that from controls (AUROC 1.00 suggests a strong field effect which may develop prior to overt EAC and hence be useful for identifying patients at high risk of developing EAC. Excellent sensitivity and specificity were found for this model to distinguish histologically normal squamous esophageal mucosa in EAC patients and healthy controls, with 8 metabolites being very significantly altered. This may have potential diagnostic value if a molecular signature can detect tissue from which neoplasms subsequently arise.

Response approach to the squeezed-limit bispectrum: application to the correlation of quasar and Lyman-α forest power spectrum

Energy Technology Data Exchange (ETDEWEB)

Chiang, Chi-Ting [C.N. Yang Institute for Theoretical Physics, Stony Brook University, Stony Brook, NY 11794 (United States); Cieplak, Agnieszka M.; Slosar, Anže [Brookhaven National Laboratory, Blgd 510, Upton, NY 11375 (United States); Schmidt, Fabian, E-mail: chi-ting.chiang@stonybrook.edu, E-mail: acieplak@bnl.gov, E-mail: fabians@mpa-garching.mpg.de, E-mail: anze@bnl.gov [Max-Planck-Institut für Astrophysik, Karl-Schwarzschild-Str. 1, 85741 Garching (Germany)

2017-06-01

The squeezed-limit bispectrum, which is generated by nonlinear gravitational evolution as well as inflationary physics, measures the correlation of three wavenumbers, in the configuration where one wavenumber is much smaller than the other two. Since the squeezed-limit bispectrum encodes the impact of a large-scale fluctuation on the small-scale power spectrum, it can be understood as how the small-scale power spectrum ''responds'' to the large-scale fluctuation. Viewed in this way, the squeezed-limit bispectrum can be calculated using the response approach even in the cases which do not submit to perturbative treatment. To illustrate this point, we apply this approach to the cross-correlation between the large-scale quasar density field and small-scale Lyman-α forest flux power spectrum. In particular, using separate universe simulations which implement changes in the large-scale density, velocity gradient, and primordial power spectrum amplitude, we measure how the Lyman-α forest flux power spectrum responds to the local, long-wavelength quasar overdensity, and equivalently their squeezed-limit bispectrum. We perform a Fisher forecast for the ability of future experiments to constrain local non-Gaussianity using the bispectrum of quasars and the Lyman-α forest. Combining with quasar and Lyman-α forest power spectra to constrain the biases, we find that for DESI the expected 1−σ constraint is err[ f {sub NL}]∼60. Ability for DESI to measure f {sub NL} through this channel is limited primarily by the aliasing and instrumental noise of the Lyman-α forest flux power spectrum. The combination of response approach and separate universe simulations provides a novel technique to explore the constraints from the squeezed-limit bispectrum between different observables.

Determination of magnetic field direction in tokamaks from laser-induced Lyman-α fluorescence

International Nuclear Information System (INIS)

Voslamber, D.

1988-04-01

Resonant laser scattering in the Lyman-α line of hydrogen is investigated as a possible tool for measuring the magnetic field direction in tokamak plasmas. The method is based on the depolarisation-dependence of the scattering process. Limitations arising from depolarising collisions are studied in detail by employing a previously developed theory for the collisional redistribution of light. An error analysis is performed to derive the expected experimental precision under various plasma conditions and for laser energies ranging between 1 micronJ and 10 mJ. This analysis also includes the measurement of neutral hydrogen densities. It is shown that with presently available laser powers application of the method would be restricted to the border regions of the plasma. Application to the central regions would require further developments in laser technology, especially with regard to higher powers at the wavelength of Lyman-α and (or) to fast repetition rates

A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

Energy Technology Data Exchange (ETDEWEB)

Lazebnik, Mariya [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Popovic, Dijana [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); McCartney, Leah [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); Watkins, Cynthia B [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Lindstrom, Mary J [Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI (United States); Harter, Josephine [Department of Pathology, University of Wisconsin, Madison, WI (United States); Sewall, Sarah [Department of Pathology, University of Wisconsin, Madison, WI (United States); Ogilvie, Travis [Department of Pathology, University of Calgary, Calgary, AB (Canada); Magliocco, Anthony [Department of Pathology, University of Calgary, Calgary, AB (Canada); Breslin, Tara M [Department of Surgery, University of Wisconsin, Madison, WI (United States); Temple, Walley [Department of Surgery and Oncology, University of Calgary, Calgary, AB (Canada); Mew, Daphne [Department of Surgery and Oncology, University of Calgary, Calgary, AB (Canada); Booske, John H [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Okoniewski, Michal [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); Hagness, Susan C [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States)

2007-10-21

The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

Science.gov (United States)

Lazebnik, Mariya; Popovic, Dijana; McCartney, Leah; Watkins, Cynthia B.; Lindstrom, Mary J.; Harter, Josephine; Sewall, Sarah; Ogilvie, Travis; Magliocco, Anthony; Breslin, Tara M.; Temple, Walley; Mew, Daphne; Booske, John H.; Okoniewski, Michal; Hagness, Susan C.

2007-10-01

The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

International Nuclear Information System (INIS)

Lazebnik, Mariya; Popovic, Dijana; McCartney, Leah; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Ogilvie, Travis; Magliocco, Anthony; Breslin, Tara M; Temple, Walley; Mew, Daphne; Booske, John H; Okoniewski, Michal; Hagness, Susan C

2007-01-01

The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%

Calculation of the uncertainty in complication probability for various dose-response models, applied to the parotid gland

International Nuclear Information System (INIS)

Schilstra, C.; Meertens, H.

2001-01-01

Purpose: Usually, models that predict normal tissue complication probability (NTCP) are fitted to clinical data with the maximum likelihood (ML) method. This method inevitably causes a loss of information contained in the data. In this study, an alternative method is investigated that calculates the parameter probability distribution (PD), and, thus, conserves all information. The PD method also allows the calculation of the uncertainty in the NTCP, which is an (often-neglected) prerequisite for the intercomparison of both treatment plans and NTCP models. The PD and ML methods are applied to parotid gland data, and the results are compared. Methods and Materials: The drop in salivary flow due to radiotherapy was measured in 25 parotid glands of 15 patients. Together with the parotid gland dose-volume histograms (DVH), this enabled the calculation of the parameter PDs for three different NTCP models (Lyman, relative seriality, and critical volume). From these PDs, the NTCP and its uncertainty could be calculated for arbitrary parotid gland DVHs. ML parameters and resulting NTCP values were calculated also. Results: All models fitted equally well. The parameter PDs turned out to have nonnormal shapes and long tails. The NTCP predictions of the ML and PD method usually differed considerably, depending on the NTCP model and the nature of irradiation. NTCP curves and ML parameters suggested a highly parallel organization of the parotid gland. Conclusions: Considering the substantial differences between the NTCP predictions of the ML and PD method, the use of the PD method is preferred, because this is the only method that takes all information contained in the clinical data into account. Furthermore, PD method gives a true measure of the uncertainty in the NTCP

Altered expression of estrogen receptor-α variant messenger RNAs between adjacent normal breast and breast tumor tissues

International Nuclear Information System (INIS)

Leygue, Etienne; Dotzlaw, Helmut; Watson, Peter H; Murphy, Leigh C

2000-01-01

Using semiquantitative reverse transcription-polymerase chain reaction assays, we investigated the expression of variant messenger RNAs relative to wild-type estrogen receptor (ER)-α messenger RNA in normal breast tissues and their adjacent matched breast tumor tissues. Higher ER variant truncated after sequences encoding exon 2 of the wild-type ER-α (ERC4) messenger RNA and a lower exon 3 deleted ER-α variant (ERD3) messenger RNA relative expression in the tumor compartment were observed in the ER-positive/PR-positive and the ER-positive subsets, respectively. A significantly higher relative expression of exon 5 deleted ER-α varient (ERD5) messenger RNA was observed in tumor components overall. These data demonstrate that changes in the relative expression of ER-α variant messenger RNAs occur between adjacent normal and neoplastic breast tissues. We suggest that these changes might be involved in the mechanisms that underlie breast tumorigenesis. Estrogen receptor (ER)-α and ER-β are believed to mediate the action of estradiol in target tissues. Several ER-α and ER-β variant messenger RNAs have been identified in both normal and neoplastic human tissues. Most of these variants contain a deletion of one or more exons of the wild-type (WT) ER messenger RNAs. The putative proteins that are encoded by these variant messenger RNAs would therefore be missing some functional domains of the WT receptors, and might interfere with WT-ER signaling pathways. The detection of ER-α variants in both normal and neoplastic human breast tissues raised the question of their possible role in breast tumorigenesis. We have previously reported an increased relative expression of exon 5 deleted ER-α variant (ERD5) messenger RNA and of another ER-α variant truncated of all sequences following the exon 2 of the WT ER-α (ERC4) messenger RNA in breast tumor samples versus independent normal breast tissues. In contrast, a decreased relative expression of exon 3 deleted ER

THE BIVARIATE SIZE-LUMINOSITY RELATIONS FOR LYMAN BREAK GALAXIES AT z {approx} 4-5

Energy Technology Data Exchange (ETDEWEB)

Huang, Kuang-Han; Su, Jian [Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States); Ferguson, Henry C. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Ravindranath, Swara, E-mail: kuanghan@pha.jhu.edu [The Inter-University Center for Astronomy and Astrophysics, Pune University Campus, Pune 411007, Maharashtra (India)

2013-03-01

We study the bivariate size-luminosity distribution of Lyman break galaxies (LBGs) selected at redshifts around 4 and 5 in GOODS and the HUDF fields. We model the size-luminosity distribution as a combination of log-normal distribution (in size) and Schechter function (in luminosity), therefore it enables a more detailed study of the selection effects. We perform extensive simulations to quantify the dropout-selection completenesses and measurement biases and uncertainties in two-dimensional size and magnitude bins, and transform the theoretical size-luminosity distribution to the expected distribution for the observed data. Using maximum-likelihood estimator, we find that the Schechter function parameters for B {sub 435}-dropouts and are consistent with the values in the literature, but the size distributions are wider than expected from the angular momentum distribution of the underlying dark matter halos. The slope of the size-luminosity (RL) relation is similar to those found for local disk galaxies, but considerably shallower than local early-type galaxies.

THE BIVARIATE SIZE-LUMINOSITY RELATIONS FOR LYMAN BREAK GALAXIES AT z ∼ 4-5

International Nuclear Information System (INIS)

Huang, Kuang-Han; Su, Jian; Ferguson, Henry C.; Ravindranath, Swara

2013-01-01

We study the bivariate size-luminosity distribution of Lyman break galaxies (LBGs) selected at redshifts around 4 and 5 in GOODS and the HUDF fields. We model the size-luminosity distribution as a combination of log-normal distribution (in size) and Schechter function (in luminosity), therefore it enables a more detailed study of the selection effects. We perform extensive simulations to quantify the dropout-selection completenesses and measurement biases and uncertainties in two-dimensional size and magnitude bins, and transform the theoretical size-luminosity distribution to the expected distribution for the observed data. Using maximum-likelihood estimator, we find that the Schechter function parameters for B 435 -dropouts and are consistent with the values in the literature, but the size distributions are wider than expected from the angular momentum distribution of the underlying dark matter halos. The slope of the size-luminosity (RL) relation is similar to those found for local disk galaxies, but considerably shallower than local early-type galaxies.

Radiosensitization In Vivo by Histone Deacetylase Inhibition with No Increase in Early Normal Tissue Radiation Toxicity.

Science.gov (United States)

Groselj, Blaz; Ruan, Jia-Ling; Scott, Helen; Gorrill, Jessica; Nicholson, Judith; Kelly, Jacqueline; Anbalagan, Selvakumar; Thompson, James; Stratford, Michael R L; Jevons, Sarah J; Hammond, Ester M; Scudamore, Cheryl L; Kerr, Martin; Kiltie, Anne E

2018-02-01

As the population ages, more elderly patients require radiotherapy-based treatment for their pelvic malignancies, including muscle-invasive bladder cancer, as they are unfit for major surgery. Therefore, there is an urgent need to find radiosensitizing agents minimally toxic to normal tissues, including bowel and bladder, for such patients. We developed methods to determine normal tissue toxicity severity in intestine and bladder in vivo , using novel radiotherapy techniques on a small animal radiation research platform (SARRP). The effects of panobinostat on in vivo tumor growth delay were evaluated using subcutaneous xenografts in athymic nude mice. Panobinostat concentration levels in xenografts, plasma, and normal tissues were measured in CD1-nude mice. CD1-nude mice were treated with drug/irradiation combinations to assess acute normal tissue effects in small intestine using the intestinal crypt assay, and later effects in small and large intestine at 11 weeks by stool assessment and at 12 weeks by histologic examination. In vitro effects of panobinostat were assessed by qPCR and of panobinostat, TMP195, and mocetinostat by clonogenic assay, and Western blot analysis. Panobinostat resulted in growth delay in RT112 bladder cancer xenografts but did not significantly increase acute (3.75 days) or 12 weeks' normal tissue radiation toxicity. Radiosensitization by panobinostat was effective in hypoxic bladder cancer cells and associated with class I HDAC inhibition, and protein downregulation of HDAC2 and MRE11. Pan-HDAC inhibition is a promising strategy for radiosensitization, but more selective agents may be more useful radiosensitizers clinically, resulting in fewer systemic side effects. Mol Cancer Ther; 17(2); 381-92. ©2017 AACR See all articles in this MCT Focus section, "Developmental Therapeutics in Radiation Oncology." ©2017 American Association for Cancer Research.

Simulation study of pO2 distribution in induced tumour masses and normal tissues within a microcirculation environment.

Science.gov (United States)

Li, Mao; Li, Yan; Wen, Peng Paul

2014-01-01

The biological microenvironment is interrupted when tumour masses are introduced because of the strong competition for oxygen. During the period of avascular growth of tumours, capillaries that existed play a crucial role in supplying oxygen to both tumourous and healthy cells. Due to limitations of oxygen supply from capillaries, healthy cells have to compete for oxygen with tumourous cells. In this study, an improved Krogh's cylinder model which is more realistic than the previously reported assumption that oxygen is homogeneously distributed in a microenvironment, is proposed to describe the process of the oxygen diffusion from a capillary to its surrounding environment. The capillary wall permeability is also taken into account. The simulation study is conducted and the results show that when tumour masses are implanted at the upstream part of a capillary and followed by normal tissues, the whole normal tissues suffer from hypoxia. In contrast, when normal tissues are ahead of tumour masses, their pO2 is sufficient. In both situations, the pO2 in the whole normal tissues drops significantly due to the axial diffusion at the interface of normal tissues and tumourous cells. As the existence of the axial oxygen diffusion cannot supply the whole tumour masses, only these tumourous cells that are near the interface can be partially supplied, and have a small chance to survive.

Influence of nanoparticles accumulation on optical properties of human normal and cancerous liver tissue in vitro estimated by OCT

International Nuclear Information System (INIS)

Zhou, Fang; Wei, Huajiang; Guo, Zhouyi; Ye, Xiangping; Hu, Kun; Wu, Guoyong; Yang, Hongqin; Xie, Shusen; He, Yonghong

2015-01-01

In this work, the potential use of nanoparticles as contrast agents by using spectral domain optical coherence tomography (SD-OCT) in liver tissue was demonstrated. Gold nanoparticles (average size of 25 and 70 nm), were studied in human normal and cancerous liver tissues in vitro, respectively. Each sample was monitored with SD-OCT functional imaging for 240 min. Continuous OCT monitoring showed that, after application of gold nanoparticles, the OCT signal intensities of normal liver and cancerous liver tissue both increase with time, and the larger nanoparticles tend to produce a greater signal enhancement in the same type of tissue. The results show that the values of attenuation coefficients have significant differences between normal liver tissue and cancerous liver tissue. In addition, 25 nm gold nanoparticles allow higher penetration depth than 70 nm gold nanoparticles in liver tissues. (paper)

Chemical modification of conventional cancer radiotherapy. Tumor sensitization combined with normal tissue protection

International Nuclear Information System (INIS)

Kagiya, Tsutomu

2006-01-01

Nitrotriazole radiosensitizer, Sanazole (AK-2123, N-(2'-methoxyethyl)-2-(3''-nitro-1''-triazolyl) acetamide) developed by Kyoto University group was studied by 18 groups of 7 countries on fundamental aspects and clinical studies by 30 groups of 12 countries, and reported its effects on tumor sensitization of conventional cancer radiotherapy. On the other hand, the glucosides of vitamin C (Ascorbic acid glucoside, (AsAG) and water soluble derivative of vitamin-E (α-tocopherol glucoside, TMG) developed by Kyoto University group were studied fundamentally by 4 groups of 4 countries and clinically by 2 groups of 2 countries, and reported their effects on normal tissue protection in cancer treatments. These two studies of tumor sensitization and normal tissue protection were proposed as an advanced strategy of conventional cancer radiotherapy. (author)

Hole Burning Imaging Studies of Cancerous and Analogous Normal Ovarian Tissues Utilizing Organelle Specific Dyes

Energy Technology Data Exchange (ETDEWEB)

Matsuzaki, Satoshi [Iowa State Univ., Ames, IA (United States)

2004-01-01

Presented in this dissertation is the successful demonstration that nonphotochemical hole burning (NPWB) imaging can be used to study in vitro tissue cellular systems for discerning differences in cellular ultrastructures due to cancer development. This has been accomplished with the surgically removed cancerous ovarian and analogous normal peritoneal tissues from the same patient and the application of a fluorescent mitochondrion specific dye, Molecular Probe MitoFluor Far Red 680 (MF680), commonly known as rhodamine 800, that has been proven to exhibit efficient NPHB. From the results presented in Chapters 4 and 5 , and Appendix B, the following conclusions were made: (1) fluorescence excitation spectra of MF680 and confocal microscopy images of thin sliced tissues incubated with MF680 confirm the site-specificity of the probe molecules in the cellular systems. (2) Tunneling parameters, {lambda}{sub 0} and σ_Λ, as well as the standard hole burning parameters (namely, γ and S), have been determined for the tissue samples by hole growth kinetics (HGK) analyses. Unlike the preliminary cultured cell studies, these parameters have not shown the ability to distinguish tissue cellular matrices surrounding the chromophores. (3) Effects of an external electric (Stark) field on the nonphotochemical holes have been used to determine the changes in permanent dipole moment (fΔμ) for MF680 in tissue samples when burn laser polarization is parallel to the Stark field. Differences are detected between fΔμs in the two tissue samples, with the cancerous tissue exhibiting a more pronounced change (1.35-fold increase) in permanent dipole moment change relative to the normal analogs. It is speculated that the difference may be related to differences in mitochondrial membrane potentials in these tissue samples. (4) In the HGK mode, hole burning imaging (HBI) of cells adhered to coverslips and cooled to liquid helium temperatures in the complete absence of

Soft-tissue Necrosis Complicating Bone-cement Filling in a Patient with Proximal Tibia Giant cell Tumour and Co-morbid Depressive Illness

Directory of Open Access Journals (Sweden)

Sagar Narang

2013-12-01

Full Text Available Giant-cell tumors are common around the knee. Proximal tibia is a challenging location for limb-salvage due to paucity of soft-tissue cover. Bone cement has been used in treatment of giant-cell tumors after curettage. Tissue irritant properties of its monomer and exothermic reaction involved in polymerization may compromise surgical outcome to varying degrees. Preoperative planning and intra-operative positioning during cementing process are of importance to avoid complications. Co-occurrence of psychiatric illness in tumor patients should be managed by psychiatric counselling and drug therapy. This case has been presented to suggest measures for preventing soft-tissue complications during cement filling in proximal tibia, and for dealing with concomitant psychiatric problems for a holistic improvement in tumor patients.

Detection of 3-Minute Oscillations in Full-Disk Lyman-alpha Emission During A Solar Flare

Science.gov (United States)

Milligan, R. O.; Ireland, J.; Fleck, B.; Hudson, H. S.; Fletcher, L.; Dennis, B. R.

2017-12-01

We report the detection of chromospheric 3-minute oscillations in disk-integrated EUV irradiance observations during a solar flare. A wavelet analysis of detrended Lyman-alpha (from GOES/EUVS) and Lyman continuum (from SDO/EVE) emission from the 2011 February 15 X-class flare revealed a 3-minute period present during the flare's main phase. The formation temperature of this emission locates this radiation to the flare's chromospheric footpoints, and similar behaviour is found in the SDO/AIA 1600A and 1700A channels, which are dominated by chromospheric continuum. The implication is that the chromosphere responds dynamically at its acoustic cutoff frequency to an impulsive injection of energy. Since the 3-minute period was not found at hard X-ray energies (50-100 keV) in RHESSI data we can state that this 3-minute oscillation does not depend on the rate of energization of, or energy deposition by, non-thermal electrons. However, a second period of 120 s found in both hard X-ray and chromospheric emission is consistent with episodic electron energization on 2-minute timescales. Our finding on the 3-minute oscillation suggests that chromospheric mechanical energy should be included in the flare energy budget, and the fluctuations in the Lyman-alpha line may influence the composition and dynamics of planetary atmospheres during periods of high activity.

Fatty acid and lipidomic data in normal and tumor colon tissues of rats fed diets with and without fish oil

Directory of Open Access Journals (Sweden)

Zora Djuric

2017-08-01

Full Text Available Data is provided to show the detailed fatty acid and lipidomic composition of normal and tumor rat colon tissues. Rats were fed either a Western fat diet or a fish oil diet, and half the rats from each diet group were treated with chemical carcinogens that induce colon cancer (azoxymethane and dextran sodium sulfate. The data show total fatty acid profiles of sera and of all the colon tissues, namely normal tissue from control rats and both normal and tumor tissues from carcinogen-treated rats, as obtained by gas chromatography with mass spectral detection. Data from lipidomic analyses of a representative subset of the colon tissue samples is also shown in heat maps generated from hierarchical cluster analysis. These data display the utility lipidomic analyses to enhance the interpretation of dietary feeding studies aimed at cancer prevention and support the findings published in the companion paper (Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors, Djuric et al., 2017 [1].

Bias of damped Lyman-α systems from their cross-correlation with CMB lensing

Science.gov (United States)

Alonso, D.; Colosimo, J.; Font-Ribera, A.; Slosar, A.

2018-04-01

We cross-correlate the positions of damped Lyman-α systems (DLAs) and their parent quasar catalog with a convergence map derived from the Planck cosmic microwave background (CMB) temperature data. We make consistent measurements of the lensing signal of both samples in both Fourier and configuration space. By interpreting the excess signal present in the DLA catalog with respect to the parent quasar catalog as caused by the large scale structure traced by DLAs, we are able to infer the bias of these objects: bDLA=2.6±0.9. These results are consistent with previous measurements made in cross-correlation with the Lyman-α forest, although the current noise in the lensing data and the low number density of DLAs limits the constraining power of this measurement. We discuss the robustness of the analysis with respect to a number different systematic effects and forecast prospects of carrying out this measurement with data from future experiments.

N-isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Eiko; Mishima, Michiaki; Kawakami, Kenzo; Sakai, Naoki; Sugiura, Naoharu; Kuno, Kenshi [Kyoto Univ. (Japan). Dept. of Clinical Physiology; Taniguchi, Takashi [Kyoto Pharmaceutical Univ. (Japan). Dept. of Neurobiology

1993-04-01

N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (K[sub d]) values of 53[+-]2 and 4687[+-]124 nM and maximum binding capacity (Bmax) values of 7[+-]1 and 133[+-]27 pmol/mg protein (n=5) respectively. The IC[sub 50] values of various amines were as follows: IMP, 9x10[sup -5] M; propranolol, 5x10[sup -4] M; haloperidol, 6x10[sup -4] M; ketamine, 9x10[sup -3] M; dopamine, 1x10[sup -2] M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with K[sub d] values of 54[+-]2 and 5277[+-]652 nM and Bmax values of 7[+-]1 and 103[+-]21 pmol/mg protein (n=3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue. (orig.).

[FTIR study on the normal and cancerous stomach tissues].

Science.gov (United States)

Tong, Y; Lin, Y

2001-06-01

Tissues of cancerous and corresponding normal stomach were studied by FTIR technique. The results showed that there are obvious differences between FTIR spectra of them in spectral parameters such as frequency, intensity and band shape etc. The changes involving the phosphate symmetric stretching nu s, PO2- and asymmetric stretching nu as, PO2- modes, the CH3 and CH2 groups stretching (nu s, CH2, nu as, CH3) and bending (delta CH2) modes and the C-O stretching nu C-O mode were discussed. In addition, the changes of structure of hydrogen-bonding of nucleic acid and cell proteins and the packing and the conformational structure of the membrance lipids were analysed further. The average wavenumber of band of nu s, PO2- shifted from 1,080.92 cm-1 to 1,085.93 cm-1 and that of nu as, PO2- shifted from 1,239.64 cm-1 to 1,238.73 cm-1 which indicated that the degree of hydrogen-bonding formed by oxygen atom of the phosphodiester groups of nucleic acids was increased. The average wavenumber of band of delta CH2 of membrance lipids shifted from 1,455.23 cm-1 to 1,457.37 cm-1 that suggested that the conformational structure of the methylene chains of membrance lipids is more disordered than in normal tissues. The shift of band of nu C-O of cell proteins from 1,166.08 cm-1 to 1,166.58 cm-1 indicated that the hydrogen-bond of cell proteins become weaker.

Hyaluronic Acid in Normal and Neoplastic Colorectal Tissue: Electrospray Ionization Mass Spectrometric and Fluor Metric Analysis

Directory of Open Access Journals (Sweden)

Ana Paula Cleto Marolla

2016-01-01

Conclusions: The expression of HA was found to be slightly lower in tumor tissue than in colorectal non-neoplastic mucosa, although this difference was not statistically significant. This finding probably influenced the lower expression of HA in tumor tissue than in colorectal non-neoplastic mucosa. Compared to normal tissues, HA levels are significantly increased in the tumor tissues unless they exhibit lymph node metastasis. Otherwise, the expression of HA in tumor tissue did not correlated with the other clinicopathological parameters.

Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

Energy Technology Data Exchange (ETDEWEB)

Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil)

2012-07-15

Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: Black-Right-Pointing-Pointer Electron density of normal and neoplastic breast tissues was measured using Compton scattering. Black-Right-Pointing-Pointer Monochromatic synchrotron radiation was used to obtain the Compton scattering data. Black-Right-Pointing-Pointer The area of Compton peaks was used to determine the electron densities of samples. Black-Right-Pointing-Pointer Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. Black-Right-Pointing-Pointer Comparison with previous results showed differences smaller than 4%.

Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

International Nuclear Information System (INIS)

Antoniassi, M.; Conceição, A.L.C.; Poletti, M.E.

2012-01-01

Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: ► Electron density of normal and neoplastic breast tissues was measured using Compton scattering. ► Monochromatic synchrotron radiation was used to obtain the Compton scattering data. ► The area of Compton peaks was used to determine the electron densities of samples. ► Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. ► Comparison with previous results showed differences smaller than 4%.

Calculation of complication probability of pion treatment at PSI using dose-volume histograms

International Nuclear Information System (INIS)

Nakagawa, Keiichi; Akanuma, Atsuo; Aoki, Yukimasa

1991-01-01

In the conformation technique a target volume is irradiated uniformly as in conventional radiations, whereas surrounding tissue and organs are nonuniformly irradiated. Clinical data on radiation injuries that accumulate with conventional radiation are not applicable without appropriate compensation. Recently a putative solution of this problem was proposed by Lyman using dose-volume histograms. This histogram reduction method reduces a given dose-volume histogram of an organ to a single step which corresponds to the equivalent complication probability by interpolation. As a result it converts nonuniform radiation into a unique dose to the whole organ which has the equivalent likelihood of radiation injury. This method is based on low LET radiation with conventional fractionation schedules. When it is applied to high LET radiation such as negative pion treatment, a high LET dose should be converted to an equivalent photon dose using an appropriate value of RBE. In the present study the histogram reduction method was applied to actual patients treated by the negative pion conformation technique at the Paul Scherrer Institute. Out of evaluable 90 cases of pelvic tumors, 16 developed grade III-IV bladder injury, and 7 developed grade III-IV rectal injury. The 90 cases were divided into roughly equal groups according to the equivalent doses to the entire bladder and rectum. Complication rates and equivalent doses to the full organs in these groups could be represented by a sigmoid dose-effect relation. When RBE from a pion dose to a photon dose is assumed to be 2.1 for bladder injury, the rates of bladder complications fit best to the theoretical complication curve. When the RBE value was 2.3, the rates of rectal injury fit the theoretical curve best. These values are close to the conversion factor of 2.0 that is used in clinical practice at PSI. This agreement suggests the clinical feasibility of the histogram reduction method in conformation radiotherapy. (author)

Mineral density volume gradients in normal and diseased human tissues.

Directory of Open Access Journals (Sweden)

Sabra I Djomehri

Full Text Available Clinical computed tomography provides a single mineral density (MD value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca to phosphorus (P and Ca to zinc (Zn elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males contained significant mineral density variations (enamel: 2820-3095 mg/cc, bone: 570-1415 mg/cc, cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc, hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770 mg/cc. A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49, hypomineralized dentin (0.32-0.46, cementum (1.51, and bone (1.68 were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765 and in cementum (595-990, highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

Mineral Density Volume Gradients in Normal and Diseased Human Tissues

Science.gov (United States)

Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.

2015-01-01

Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations. PMID:25856386

Validation of putative reference genes for normalization of Q-RT-PCR data from paraffin-embedded lymphoid tissue

DEFF Research Database (Denmark)

Green, Tina Marie; de Stricker, Karin; Møller, Michael Boe

2009-01-01

Normalization of quantitative reverse transcription-PCR (Q-RT-PCR) data to appropriate tissue-specific reference genes is an essential part of interpreting the results. This study aimed to determine the most appropriate reference genes for normalizing gene expressions in lymphatic tissue...... was 0.93 (Pnormalization with the appropriate reference genes. Thus, we show that formalin-fixed, paraffin-embedded lymphoid samples are suitable for Q-RT-PCR when using thoroughly validated reference genes....

SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

International Nuclear Information System (INIS)

Zhang, Q; Lei, Y; Zheng, D; Zhu, X; Wahl, A; Lin, C; Zhou, S; Zhen, W

2015-01-01

Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness were created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing

Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series.

Science.gov (United States)

Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia; Norrild, Bodil; Prause, Jan Ulrik; Vinding, Troels; Heegaard, Steffen

2007-08-01

To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV). Archival paraffin wax-embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type-specific HPV probes, were analysed with DNA sequencing. HPV was present in 86 of 106 (81%) beta-globin-positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.

An automatic method to discriminate malignant masses from normal tissue in digital mammograms

International Nuclear Information System (INIS)

Brake, Guido M. te; Karssemeijer, Nico; Hendriks, Jan H.C.L.

2000-01-01

Specificity levels of automatic mass detection methods in mammography are generally rather low, because suspicious looking normal tissue is often hard to discriminate from real malignant masses. In this work a number of features were defined that are related to image characteristics that radiologists use to discriminate real lesions from normal tissue. An artificial neural network was used to map the computed features to a measure of suspiciousness for each region that was found suspicious by a mass detection method. Two data sets were used to test the method. The first set of 72 malignant cases (132 films) was a consecutive series taken from the Nijmegen screening programme, 208 normal films were added to improve the estimation of the specificity of the method. The second set was part of the new DDSM data set from the University of South Florida. A total of 193 cases (772 films) with 372 annotated malignancies was used. The measure of suspiciousness that was computed using the image characteristics was successful in discriminating tumours from false positive detections. Approximately 75% of all cancers were detected in at least one view at a specificity level of 0.1 false positive per image. (author)

Dark energy and curvature from a future baryonic acoustic oscillation survey using the Lyman-α forest

International Nuclear Information System (INIS)

McDonald, Patrick; Eisenstein, Daniel J.

2007-01-01

We explore the requirements for a Lyman-α forest survey designed to measure the angular diameter distance and Hubble parameter at 2 or approx. 250 spectrograph is sufficient to measure both the radial and transverse oscillation scales to 1.4% from the Lyα forest (or better, if fainter magnitudes and possibly Lyman-break galaxies can be used). At fixed integration time and in the sky-noise-dominated limit, a wider, noisier survey is generally more efficient; the only fundamental upper limit on noise being the need to identify a quasar and find a redshift. Because the Lyα forest is much closer to linear and generally better understood than galaxies, systematic errors are even less likely to be a problem

Reversal of Type 1 Diabetes in Mice by Brown Adipose Tissue Transplant

OpenAIRE

Gunawardana, Subhadra C.; Piston, David W.

2012-01-01

Current therapies for type 1 diabetes (T1D) involve insulin replacement or transplantation of insulin-secreting tissue, both of which suffer from numerous limitations and complications. Here, we show that subcutaneous transplants of embryonic brown adipose tissue (BAT) can correct T1D in streptozotocin-treated mice (both immune competent and immune deficient) with severely impaired glucose tolerance and significant loss of adipose tissue. BAT transplants result in euglycemia, normalized gluco...

Characteristics and intraoperative treatments associated with head and neck free tissue transfer complications and failures.

Science.gov (United States)

Hand, William R; McSwain, Julie R; McEvoy, Matthew D; Wolf, Bethany; Algendy, Abdalrahman A; Parks, Matthew D; Murray, John L; Reeves, Scott T

2015-03-01

To investigate the association between perioperative patient characteristics and treatment modalities (eg, vasopressor use and volume of fluid administration) with complications and failure rates in patients undergoing head and neck free tissue transfer (FTT). A retrospective review of medical records. Perioperative hospitalization for head and neck FTT at 1 tertiary care medical center between January 1, 2009, and October 31, 2011. Consecutive patients (N=235) who underwent head and neck FTT. Demographic, patient characteristic, and intraoperative data were extracted from medical records. Complication and failure rates within the first 30 days were collected In a multivariate analysis controlling for age, sex, ethnicity, reason for receiving flap, and type and volume of fluid given, perioperative complication was significantly associated with surgical blood loss (P=.019; 95% confidence interval [CI], 1.01-1.16), while the rate of intraoperative fluid administration did not reach statistical significance (P=.06; 95% CI, 0.99-1.28). In a univariate analysis, FTT failure was significantly associated with reason for surgery (odds ratio, 5.40; P=.03; 95% CI, 1.69-17.3) and preoperative diagnosis of coronary artery disease (odds ratio, 3.60; P=.03; 95% CI, 1.16-11.2). Intraoperative vasopressor administration was not associated with either FTT complication or failure rate. FTT complications were associated with surgical blood loss but not the use of vasoactive drugs. For patients undergoing FTT, judicious monitoring of blood loss may help stratify the risk of complication and failure. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

On radiation damage to normal tissues and its treatment. Pt. 2

International Nuclear Information System (INIS)

Michalowski, A.S.

1994-01-01

In addition to transiently inhibiting cell cycle progression and sterilizing those cells capable of proliferation, irradiation disturbs the homeostasis effected by endogenous mediators of intercellular communication (humoral component of tissue response to radiation). Changes in the mediator levels may modulate radiation effects either by a assisting a return to normality (e.g., through a rise in H-type cell lineage-specific growth factors) or by aggravating the damage. The latter mode is illustrated with reports on changes in eicosanoid levels after irradiation and on results of empirical treatment of radiation injuries with anti-inflammatory drugs. Prodromal, acute and chronic effects of radiation are accompanied by excessive production of eicosanoids (prostaglandins, prostacyclin, thromboxanes and leukotrienes). These endogenous mediators of inflammatory reactions may be responsible for the vasodilatation, vasoconstriction, increased microvascular permeability, thrombosis and chemotaxis observed after radiation exposure. Glucocorticoids inhibit eicosanoid synthesis primarily by interfering with phospholipase A 2 whilst non-steroidal anti-inflammatory drugs prevent prostaglandin/thromboxane synthesis by inhibiting cycloxygenase. When administered after irradiation on empirical grounds, drugs belonging to both groups tend to attenuate a range of prodomal, acute and chronic effects of radiation in man and animals. Taken together, these two sets of observations are highly suggestive of a contribution of humoral factors to the adverse responses of normal tissues and organs to radiation. A full account of radiation damage should therefore consist of complementary descriptions of cellular and humoral events. Further studies on anti-inflammatory drug treatment of radiation damage to normal organs are justified and desirable. (orig.)

Extracranial soft-tissue swelling: a normal postmortem radiographic finding or a sign of trauma?

International Nuclear Information System (INIS)

Strouse, P.J.; Caplan, M.; Owings, C.L.

1998-01-01

Objective. To determine if extracranial soft-tissue swelling is an expected postmortem finding or a sign of trauma. Materials and methods. Extracranial soft-tissue thickness was measured at 5 standardized locations on postmortem skull films obtained of 18 infants with no evidence of trauma on autopsy. The same measurements were performed on the skull films of 100 living children, all less than 3 years old and without clinical history of trauma. Results. Extracranial soft tissues measured only slightly greater in the postmortem group than on films of living children; however, the difference did achieve statistical significance. Conclusion. Minimal extracranial soft-tissue swelling is a normal finding on a postmortem skeletal survey. The presence of substantial or asymmetric extracranial soft-tissue swelling should be viewed with suspicion for trauma. (orig.)

Extracranial soft-tissue swelling: a normal postmortem radiographic finding or a sign of trauma?

Energy Technology Data Exchange (ETDEWEB)

Strouse, P.J. [Section of Pediatric Radiology, University of Michigan Medical Center, Ann Arbor (United States); Caplan, M. [Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan (United States); Owings, C.L. [Department of Pediatrics and Communicable Diseases, C. S. Mott Children`s Hospital, Ann Arbor, Michigan (United States)

1998-08-01

Objective. To determine if extracranial soft-tissue swelling is an expected postmortem finding or a sign of trauma. Materials and methods. Extracranial soft-tissue thickness was measured at 5 standardized locations on postmortem skull films obtained of 18 infants with no evidence of trauma on autopsy. The same measurements were performed on the skull films of 100 living children, all less than 3 years old and without clinical history of trauma. Results. Extracranial soft tissues measured only slightly greater in the postmortem group than on films of living children; however, the difference did achieve statistical significance. Conclusion. Minimal extracranial soft-tissue swelling is a normal finding on a postmortem skeletal survey. The presence of substantial or asymmetric extracranial soft-tissue swelling should be viewed with suspicion for trauma. (orig.) With 2 tabs., 5 refs.

Cerebral hemodynamics in normal and complicated pregnancy

NARCIS (Netherlands)

van Veen, Teelkien

2016-01-01

During pregnancy, approximately 6-25% of women are diagnosed with some form of hypertension. These disorders are among the leading causes of maternal mortality and severe morbidity. While multiple maternal organs can be affected, cerebral involvement is one of the most feared complications as it can

A general native-state method for determination of proliferation capacity of human normal and tumor tissues in vitro

International Nuclear Information System (INIS)

Hoffman, R.M.; Connors, K.M.; Meerson-Monosov, A.Z.; Herrera, H.; Price, J.H.

1989-01-01

An important need in cancer research and treatment is a physiological means in vitro by which to assess the proliferation capacity of human tumors and corresponding normal tissue for comparison. The authors have recently developed a native-state, three-dimensional, gel-supported primary culture system that allows every type of human cancer to grow in vitro at more than 90% frequency, with maintenance of tissue architecture, tumor-stromal interaction, and differentiated functions. Here they demonstrate that the native-state culture system allows proliferation indices to be determined for all solid cancer types explanted directly from surgery into long-term culture. Normal tissues also proliferate readily in this system. The degree of resolution of measurement of cell proliferation by histological autoradiography within the cultured tissues is greatly enhanced with the use of epi-illumination polarization microscopy. The histological status of the cultured tissues can be assessed simultaneously with the proliferation status. Carcinomas generally have areas of high epithelial proliferation with quiescent stromal cells. Sarcomas have high proliferation of cells of mesenchymal organ. Normal tissues can also proliferate at high rates. An image analysis system has been developed to automate proliferation determination. The high-resolution physiological means described here to measure the proliferation capacity of tissues will be important in further understanding of the deregulation of cell proliferation in cancer as well as in cancer prognosis and treatment

Silver nanoparticle based surface enhanced Raman scattering spectroscopy of diabetic and normal rat pancreatic tissue under near-infrared laser excitation

International Nuclear Information System (INIS)

Huang, H; Shi, H; Chen, W; Yu, Y; Lin, D; Xu, Q; Feng, S; Lin, J; Huang, Z; Li, Y; Chen, R

2013-01-01

This paper presents the use of high spatial resolution silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) from rat pancreatic tissue to obtain biochrmical information about the tissue. A high quality SERS signal from a mixture of pancreatic tissues and silver nanoparticles can be obtained within 10 s using a Renishaw micro-Raman system. Prominent SERS bands of pancreatic tissue were assigned to known molecular vibrations, such as the vibrations of DNA bases, RNA bases, proteins and lipids. Different tissue structures of diabetic and normal rat pancreatic tissues have characteristic features in SERS spectra. This exploratory study demonstrated great potential for using SERS imaging to distinguish diabetic and normal pancreatic tissues on frozen sections without using dye labeling of functionalized binding sites. (letter)

The Sunburst Arc: Direct Lyman α escape observed in the brightest known lensed galaxy

Science.gov (United States)

Rivera-Thorsen, T. E.; Dahle, H.; Gronke, M.; Bayliss, M.; Rigby, J. R.; Simcoe, R.; Bordoloi, R.; Turner, M.; Furesz, G.

2017-11-01

We present rest-frame ultraviolet and optical spectroscopy of the brightest lensed galaxy yet discovered, at redshift z = 2.4. The source reveals a characteristic triple-peaked Lyman α profile that has been predicted in various theoretical works, but to our knowledge has not been unambiguously observed previously. The feature is well fit by a superposition of two components: a double-peak profile emerging from substantial radiative transfer, and a narrow, central component resulting from directly escaping Lyman α photons, but it is poorly fit by either component alone. We demonstrate that the feature is unlikely to contain contamination from nearby sources, and that the central peak is unaffected by radiative transfer effects except for very slight absorption. The feature is detected at signal-to-noise ratios exceeding 80 per pixel at line center, and bears strong resemblance to synthetic profiles predicted by numerical models. Based on observations obtained at the Magellan-I (Baade) Telescope at Las Campanas Observatory, Chile.

Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

Science.gov (United States)

Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

2011-01-01

Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

Use of a gentamicin-impregnated collagen sheet (Collatamp(®)) in the management of major soft tissue complications in pediatric cochlear implants.

Science.gov (United States)

Benito-González, Fernando; Benito, Jose; Sánchez, Luis Alberto Guardado; Estevez Alonso, Santiago; Muñoz Herrera, Angel; Batuecas-Caletrio, Angel

2014-09-01

The objective was to report the effectiveness of salvage treatment in soft tissue infection around cochlear implants with an absorbable gentamicin collagen sheet and a periosteum and skin rotation flaps. Three patients with cochlear implant and persistent surrounding soft tissue infection are included. All of them underwent antibiotic treatment prior to surgery without any response. In this study preoperative and postoperative audiograms were practiced. Surgical excision of infectious skin and a periosteum and skin rotation flaps were performed. The cochlear implant was refixed in the temporal bone and a gentamicin-impregnated collagen sheet was located covering the cochlear implant. headings In all patients with soft tissue infection around the cochlear implant, infection was completely resolved. It was not necessary to remove the device in any case. The use of an absorbable gentamicin-impregnated collagen sheet is not described for the management of soft tissue complications in pediatric cochlear implant patients. The local application of high concentrations of antibiotic administered by this sheet may be effective against resistant bacteria and, in conjunction with surgery, may resolve this type of complications.

Expression of Apoptosis Inducing-Ligands, TRAIL and Fas-L in Hydatid Cyst Germinal Layer and Normal Tissue

Directory of Open Access Journals (Sweden)

Adel Spotin

2012-04-01

Full Text Available Background & objectives: Hydaticosis is a zoonotic helminthic disease of human and other intermediated hosts in which larval stages of the tapeworm Echinococcus granulosu transfect human. The liver and lung are the host tissues for the hydatid cyst . It is unknown which mechanisms are involved in infertility of the cyst and suppression of the fertile cyst. This study was aimed to evaluate the expression of the apoptosis inducing-ligands such as TRAIL and Fas-L in germinal layer of the cyst and human normal tissue surrounding the cyst that is one of the unknown host innate immunity mechanisms against the hydatid cyst.   Methods: In this study, four isolated hydatid cysts were used which had been diagnosed in patients by radiography and parasitological examination in Mashhad Ghaem hospital. Furthermore, the germinal layer of the cyst and accompanied normal peripheral tissues were separated by scalpel in sterile conditions. After homogenization, expression of TRAIL and Fas-L genes were studied by semi-quantitive RT-PCR method.   Results: The TRAIL and Fas-L showed significant higher level expression in germinal layer of infertile cyst than the fertile cyst and host normal tissues.   Conclusion: The host tissue-induced apoptosis of germinal layer of the fertile cysts is probably one of the infertility mechanism in patients with hydaticosis

Dose-volume complication analysis for visual pathway structures of patients with advanced paranasal sinus tumors

International Nuclear Information System (INIS)

Martel, Mary Kaye; Sandler, Howard M.; Cornblath, Wayne T.; Marsh, Lon H.; Hazuka, Mark B.; Roa, Wilson H.; Fraass, Benedict A.; Lichter, Allen S.

1997-01-01

Purpose: The purpose of the present work was to relate dose and volume information to complication data for visual pathway structures in patients with advanced paranasal sinus tumors. Methods and Materials: Three-dimensional (3D) dose distributions for chiasm, optic nerve, and retina were calculated and analyzed for 20 patients with advanced paranasal sinus malignant tumors. 3D treatment planning with beam's eye view capability was used to design beam and block arrangements, striving to spare the contralateral orbit (to lessen the chance of unilateral blindness) and frequently the ipsilateral orbit (to help prevent bilateral blindness). Point doses, dose-volume histogram analysis, and normal tissue complication probability (NTCP) calculations were performed. Published tolerance doses that indicate significant risk of complications were used as guidelines for analysis of the 3D dose distributions. Results: Point doses, percent volume exceeding a specified published tolerance dose, and NTCP calculations are given in detail for patients with complications versus patients without complications. Two optic nerves receiving maximum doses below the published tolerance dose sustained damage (mild vision loss). Three patients (of 13) without optic nerve sparing and/or chiasm sparing had moderate or severe vision loss. Complication data, including individual patient analysis to estimate overall risk for loss of vision, are given. Conclusion: 3D treatment planning techniques were used successfully to provide bilateral sparing of the globe for most patients. It was more difficult to spare the optic nerves, especially on the ipsilateral side, when prescription dose exceeded the normal tissue tolerance doses. NTCP calculations may be useful in assessing complication risk better than point dose tolerance criteria for the chiasm, optic nerve, and retina. It is important to assess the overall risk of blindness for the patient in addition to the risk for individual visual pathway

The effect of 6 and 15 MV on intensity-modulated radiation therapy prostate cancer treatment: plan evaluation, tumour control probability and normal tissue complication probability analysis, and the theoretical risk of secondary induced malignancies

Science.gov (United States)

Hussein, M; Aldridge, S; Guerrero Urbano, T; Nisbet, A

2012-01-01

Objective The aim of this study was to investigate the effect of 6 and 15-MV photon energies on intensity-modulated radiation therapy (IMRT) prostate cancer treatment plan outcome and to compare the theoretical risks of secondary induced malignancies. Methods Separate prostate cancer IMRT plans were prepared for 6 and 15-MV beams. Organ-equivalent doses were obtained through thermoluminescent dosemeter measurements in an anthropomorphic Aldersen radiation therapy human phantom. The neutron dose contribution at 15 MV was measured using polyallyl-diglycol-carbonate neutron track etch detectors. Risk coefficients from the International Commission on Radiological Protection Report 103 were used to compare the risk of fatal secondary induced malignancies in out-of-field organs and tissues for 6 and 15 MV. For the bladder and the rectum, a comparative evaluation of the risk using three separate models was carried out. Dose–volume parameters for the rectum, bladder and prostate planning target volume were evaluated, as well as normal tissue complication probability (NTCP) and tumour control probability calculations. Results There is a small increased theoretical risk of developing a fatal cancer from 6 MV compared with 15 MV, taking into account all the organs. Dose–volume parameters for the rectum and bladder show that 15 MV results in better volume sparing in the regions below 70 Gy, but the volume exposed increases slightly beyond this in comparison with 6 MV, resulting in a higher NTCP for the rectum of 3.6% vs 3.0% (p=0.166). Conclusion The choice to treat using IMRT at 15 MV should not be excluded, but should be based on risk vs benefit while considering the age and life expectancy of the patient together with the relative risk of radiation-induced cancer and NTCPs. PMID:22010028

Radionuclide investigation of the blood flow in tumor and normal rat tissues in induced hyperglycemia

International Nuclear Information System (INIS)

Istomin, Yu.P.; Shitikov, B.D.; Markova, L.V.

1991-01-01

Radionuclide angiography was performed in rats with transplantable tumors. Induced hyperglycemia was shown to result in blood flow inhibition in tumor and normal tissues of tumor-bearing rats. Some differences were revealed in a degree of reversibility of blood flow disorders in tissues of the above strains. The results obtained confirmed the advisability of radiation therapy at the height of a decrease in tumor blood

Thermal coagulation-induced changes of the optical properties of normal and adenomatous human colon tissues in vitro in the spectral range 400-1100 nm

International Nuclear Information System (INIS)

Ao Huilan; Xing Da; Wei Huajiang; Gu Huaimin; Wu Guoyong; Lu Jianjun

2008-01-01

The absorption coefficients, the reduced scattering coefficients and the optical penetration depths for native and coagulated human normal and adenomatous colon tissues in vitro were determined over the range of 400-1100 nm using a spectrophotometer with an internal integrating sphere system, and the inverse adding-doubling method was applied to calculate the tissue optical properties from diffuse reflectance and total transmittance measurements. The experimental results showed that in the range of 400-1100 nm there were larger absorption coefficients (P < 0.01) and smaller reduced scattering coefficients (P < 0.01) for adenomatous colon tissues than for normal colon tissues, and there were smaller optical penetration depths for adenomatous colon tissues than for normal colon tissues, especially in the near-infrared wavelength. Thermal coagulation induced significant increase of the absorption coefficients and reduced scattering coefficients for the normal and adenomatous colon tissues, and significantly reduced decrease of the optical penetration depths for the normal and adenomatous colon tissues. The smaller optical penetration depth for coagulated adenomatous colon tissues is a disadvantage for laser-induced thermotherapy (LITT) and photodynamic therapy (PDT). It is necessary to adjust the application parameters of lasers to achieve optimal therapy

Elemental analysis of the frontal lobe of 'normal' brain tissue and that affected by Alzheimer's disease

International Nuclear Information System (INIS)

Stedman, J.D.; Spyrou, N.M.

1997-01-01

'Normal' brain tissue and brain tissue affected by Alzheimer's disease has been taken from the frontal lobe of both hemispheres and their elemental compositions in terms of major, minor and trace elements compared. Brain samples were obtained from the MRC Alzheimer's Disease Brain Bank, London. 25 samples were taken from 18 individuals (5 males and 13 females) of mean age 79.9 ± 7.3 years with pathologically confirmed Alzheimer's disease and 26 samples from 15 individuals (8 males and 7 females) of mean age 71.8 ± 13.0 years with no pathological sings of Alzheimer's disease ('normals'). The elemental concentration of the samples were determined by the techniques of Rutherford backscattering (RBS) analysis, particle induced X-ray emission (PIXE) analysis and instrumental neutron activation analysis (INAA). Na, Mg, Al, Cl, K, Sc, Fe, Zn, Se, Br, Rb and Cs were detected by INAA and significant differences in concentrations were found between concentrations in normal and Alzheimer tissue for the elements. Na, Cl, K, Se, Br and Rb, P, S, Cl, K, Ca, Fe, Zn and Cd were detected by PIXE analysis and significant differences found for the elements P, S, Cl, K and Ca. (author)

Comparison of soft-tissue orbital morphometry in attractive and normal Italian subjects.

Science.gov (United States)

Sforza, Chiarella; Dolci, Claudia; Grandi, Gaia; Tartaglia, Gianluca M; Laino, Alberto; Ferrario, Virgilio F

2015-01-01

To identify esthetic characteristics of the orbital soft tissues of attractive Italian adult women and men. Three-dimensional computerized digitizers were used to collect the coordinates of facial landmarks in 199 healthy, normal subjects aged 18 to 30 years (71 women, 128 men; mean age, 22 years) and in 126 coetaneous attractive subjects (92 women, 34 men; mean age, 20 years) selected during beauty competitions. From the landmarks, six linear distances, two ratios, six angles, and two areas were calculated. Attractive subjects were compared with normal ones by computing z-scores. Intercanthal width was reduced while eye fissure lengths were increased in both genders. Orbital heights (os-or) were increased only in attractive women, with a significant gender-related difference. The inclinations of the eye fissure were increased in attractive subjects, while the inclinations of the orbit were reduced. For several of the analyzed measurements, similar patterns of z-scores were observed for attractive men and women (r  =  .883). Attractive women and men had several specific esthetic characteristics in their orbital soft tissues; esthetic reference values can be used to determine optimal goals in surgical treatment.

SU-E-T-214: Comparison of Treatment Techniques for Dupuytren’s Contracture and Risk Assessment of Normal Tissue Complications

International Nuclear Information System (INIS)

Arentsen, L; Lopater, Z; Dusenbery, K; Gerbi, B

2015-01-01

Purpose: Duputren’s contracture (DC) is a benign disease characterized by abnormal thickening of the fascial surfaces of the hands or feet causing curling of the surface, functional impairment, weakness, and pain. The purpose of the investigation is to describe the radiation treatment approaches, compare these techniques, and discuss the potential side effects and complications of these techniques. Methods: Early stage DC has been treated with 120 kVp X rays but also with high-energy electrons or photons. High-energy electrons have been the radiation of choice but severe contracture of the hand makes it difficult to produce a plan with acceptable dose uniformity. High-energy photons can overcome this difficulty either by directing a beam onto the palmer or back of the surface of the hand, including bolus to maximize the surface dose. We calculated the dose to the bone for the 120 kVp treatment using published %DD data and mass energy absorption coefficients for bone and muscle. Results: The dose to underlying bone from megavoltage photons and electrons is essentially the same, but dose to the bone for using 120 kVp can be 4–5 times greater due to the photoelectric effect. For the 30 Gy dose deliver using this technique, the dose to the bone could be 84–105 Gy after taking the penetration of the beam into account. After radiotherapy, there is often decreased osteoblastic activity and vascular fibrosis that leads to osteitis, atrophy, and decreased metabolic bone activity. Incidence of fractures occurs routinely above 60 Gy with higher doses potentially leading to higher incidences of bone complications. Conclusion: Radiation therapy for DC using low-energy X rays can deliver a prohibitively high dose to the underlying bone potentially leading to severe bone complications

Oral complications of radiation therapy

International Nuclear Information System (INIS)

Lockhart, P.B.

1986-01-01

Approximately 24,000 patients are diagnosed each year with malignant tumors of the head and neck. Many of these patients will be treated with radiotherapy, surgery, or chemotherapy, either singly or in combination. Certain predictable sequelae of radiotherapy exist that may be considered consequences of treatment rather than complications; these may be unavoidable consequences of curative radiotherapy to the head and neck. There are, however, additional problems that occur as a result of radiotherapy that are preventable in both incidence and severity, and are therefore avoidable complications. Cell kinetic factors, radiosensitivity of normal tissues, radiotherapeutic doses necessary for tumor control, and the complex anatomy of the maxillofacial region often predispose patients serious treatment morbidity. The potential for pain, infection, and long-term functional disability with decreased quality of life dictate conscientious management before, during, and after radiotherapy. This chapter discusses common problems that can arise, as well as current methods utilized both to improve patient tolerance to treatment and to decrease the risk of preventable and potentially dose-limiting morbidity

Pulse frequency in pulsed brachytherapy based on tissue repair kinetics

International Nuclear Information System (INIS)

Sminia, Peter; Schneider, Christoph J.; Koedooder, Kees; Tienhoven, Geertjan van; Blank, Leo E.C.M.; Gonzalez Gonzalez, Dionisio

1998-01-01

Purpose: Investigation of normal tissue sparing in pulsed brachytherapy (PB) relative to continuous low-dose rate irradiation (CLDR) by adjusting pulse frequency based on tissue repair characteristics. Method: Using the linear quadratic model, the relative effectiveness (RE) of a 20 Gy boost was calculated for tissue with an α/β ratio ranging from 2 to 10 Gy and a half-time of sublethal damage repair between 0.1 and 3 h. The boost dose was considered to be delivered either in a number of pulses varying from 2 to 25, or continuously at a dose rate of 0.50, 0.80, or 1.20 Gy/h. Results: The RE of 20 Gy was found to be identical for PB in 25 pulses of 0.80 Gy each h and CLDR delivered at 0.80 Gy/h for any α/β value and for a repair half-time > 0.75 h. When normal tissue repair half-times are assumed to be longer than tumor repair half-times, normal tissue sparing can be obtained, within the restriction of a fixed overall treatment time, with higher dose per pulse and longer period time (time elapsed between start of pulse n and start of pulse n + 1). An optimum relative normal tissue sparing larger than 10% was found with 4 pulses of 5 Gy every 8 h. Hence, a therapeutic gain might be obtained when changing from CLDR to PB by adjusting the physical dose in such a way that the biological dose on the tumor is maintained. The normal tissue-sparing phenomenon can be explained by an increase in RE with longer period time for tissue with high α/β ratio and fast or intermediate repair half-time, and the RE for tissue with low α/β ratio and long repair half-time remains almost constant. Conclusion: Within the benchmark of the LQ model, advantage in normal tissue-sparing is expected when matching the pulse frequency to the repair kinetics of the normal tissue exposed. A period time longer than 1 h may lead to a reduction of late normal tissue complications. This theoretical advantage emphasizes the need for better knowledge of human tissue-repair kinetics

Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

Science.gov (United States)

Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

2013-07-01

Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

Performance characterization of UV science cameras developed for the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP)

Science.gov (United States)

Champey, P.; Kobayashi, K.; Winebarger, A.; Cirtain, J.; Hyde, D.; Robertson, B.; Beabout, D.; Beabout, B.; Stewart, M.

2014-07-01

The NASA Marshall Space Flight Center (MSFC) has developed a science camera suitable for sub-orbital missions for observations in the UV, EUV and soft X-ray. Six cameras will be built and tested for flight with the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP), a joint National Astronomical Observatory of Japan (NAOJ) and MSFC sounding rocket mission. The goal of the CLASP mission is to observe the scattering polarization in Lyman-α and to detect the Hanle effect in the line core. Due to the nature of Lyman-α polarizationin the chromosphere, strict measurement sensitivity requirements are imposed on the CLASP polarimeter and spectrograph systems; science requirements for polarization measurements of Q/I and U/I are 0.1% in the line core. CLASP is a dual-beam spectro-polarimeter, which uses a continuously rotating waveplate as a polarization modulator, while the waveplate motor driver outputs trigger pulses to synchronize the exposures. The CCDs are operated in frame-transfer mode; the trigger pulse initiates the frame transfer, effectively ending the ongoing exposure and starting the next. The strict requirement of 0.1% polarization accuracy is met by using frame-transfer cameras to maximize the duty cycle in order to minimize photon noise. The CLASP cameras were designed to operate with ≤ 10 e-/pixel/second dark current, ≤ 25 e- read noise, a gain of 2.0 +- 0.5 and ≤ 1.0% residual non-linearity. We present the results of the performance characterization study performed on the CLASP prototype camera; dark current, read noise, camera gain and residual non-linearity.

The Lyman-α forest in three dimensions: measurements of large scale flux correlations from BOSS 1st-year data

Energy Technology Data Exchange (ETDEWEB)

Slosar, Anže [Brookhaven National Laboratory, Blgd 510, Upton NY 11375 (United States); Font-Ribera, Andreu [Institut de Ciències de l' Espai (CSIC-IEEC), Campus UAB, Fac. Ciències, torre C5 parell 2, Bellaterra, Catalonia (Spain); Pieri, Matthew M. [Center for Astrophysics and Space Astronomy, University of Colorado, 389 UCB, Boulder, Colorado 80309 (United States); Rich, James; Goff, Jean-Marc Le; Charlassier, Romain [CEA, Centre de Saclay, IRFU, 91191 Gif-sur-Yvette (France); Aubourg, Éric; Busca, Nicolas; Hamilton, Jean-Christophe [APC, Université Paris Diderot-Paris 7, CNRS/IN2P3, CEA, Observatoire de Paris, 10, rue A. Domon and L. Duquet, Paris (France); Brinkmann, Jon [Apache Point Observatory, P.O. Box 59, Sunspot, NM 88349 (United States); Carithers, Bill; Cortês, Marina; Ho, Shirley; McDonald, Patrick [Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720 (United States); Croft, Rupert [Bruce and Astrid McWilliams Center for Cosmology, Carnegie Mellon University, Pittsburgh, PA 15213 (United States); Dawson, Kyle S. [University of Utah, Dept. of Physics and Astronomy, 115 S 1400 E, Salt Lake City, UT 84112 (United States); Eisenstein, Daniel [Harvard College Observatory, 60 Garden St., Cambridge MA 02138 (United States); Lee, Khee-Gan; Lupton, Robert [Department of Astrophysical Sciences, Princeton University, Princeton, New Jersey 08544 (United States); Medolin, Bumbarija, E-mail: anze@bnl.gov [104-20 Queens Blvd 17A, Forest Hills, NY 11375 (United States); and others

2011-09-01

Using a sample of approximately 14,000 z > 2.1 quasars observed in the first year of the Baryon Oscillation Spectroscopic Survey (BOSS), we measure the three-dimensional correlation function of absorption in the Lyman-α forest. The angle-averaged correlation function of transmitted flux (F = e{sup −τ}) is securely detected out to comoving separations of 60 h{sup −1}Mpc, the first detection of flux correlations across widely separated sightlines. A quadrupole distortion of the redshift-space correlation function by peculiar velocities, the signature of the gravitational instability origin of structure in the Lyman-α forest, is also detected at high significance. We obtain a good fit to the data assuming linear theory redshift-space distortion and linear bias of the transmitted flux, relative to the matter fluctuations of a standard ΛCDM cosmological model (inflationary cold dark matter with a cosmological constant). At 95% confidence, we find a linear bias parameter 0.16 < b < 0.24 and redshift-distortion parameter 0.44 < β < 1.20, at central redshift z = 2.25, with a well constrained combination b(1+β) = 0.336±0.012. The errors on β are asymmetric, with β = 0 excluded at over 5σ confidence level. The value of β is somewhat low compared to theoretical predictions, and our tests on synthetic data suggest that it is depressed (relative to expectations for the Lyman-α forest alone) by the presence of high column density systems and metal line absorption. These results set the stage for cosmological parameter determinations from three-dimensional structure in the Lyman-α forest, including anticipated constraints on dark energy from baryon acoustic oscillations.

Morphological, clinical and radiological aspects in diagnostics of bronchopulmonary diseases and their complications in children with dysplasia of connective tissue

Directory of Open Access Journals (Sweden)

Palchik S.M.

2016-06-01

Full Text Available The article provides an overview of the literature devoted to study of radiological, morphological and clinical aspects of diagnostics of respiratory diseases and their complications in children with dysplasia of connective tissue nowadays. We made an analysis of the role of connective tissue disorders in pathogenesis of bronchopulmonary diseases. Theoretically was substantiated the importance of radiological methods in early diagnostics of this disease in children.

The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage

Directory of Open Access Journals (Sweden)

Arpita Chatterjee

2018-01-01

Full Text Available Radiation therapy is commonly used for prostate cancer treatment; however, normal tissues can be damaged from the reactive oxygen species (ROS produced by radiation. In separate reports, we and others have shown that manganese porphyrins (MnPs, ROS scavengers, protect normal cells from radiation-induced damage but inhibit prostate cancer cell growth. However, there have been no studies demonstrating that MnPs protect normal tissues, while inhibiting tumor growth in the same model. LNCaP or PC3 cells were orthotopically implanted into athymic mice and treated with radiation (2 Gy, for 5 consecutive days in the presence or absence of MnPs. With radiation, MnPs enhanced overall life expectancy and significantly decreased the average tumor volume, as compared to the radiated alone group. MnPs enhanced lipid oxidation in tumor cells but reduced oxidative damage to normal prostate tissue adjacent to the prostate tumor in combination with radiation. Mechanistically, MnPs behave as pro-oxidants or antioxidants depending on the level of oxidative stress inside the treated cell. We found that MnPs act as pro-oxidants in prostate cancer cells, while in normal cells and tissues the MnPs act as antioxidants. For the first time, in the same in vivo model, this study reveals that MnPs enhance the tumoricidal effect of radiation and reduce oxidative damage to normal prostate tissue adjacent to the prostate tumor in the presence of radiation. This study suggests that MnPs are effective radio-protectors for radiation-mediated prostate cancer treatment.

Pregnancy Complicated by Obesity Induces Global Transcript Expression Alterations in Visceral and Subcutaneous Fat

Science.gov (United States)

Bashiri, Asher; Heo, Hye J.; Ben-Avraham, Danny; Mazor, Moshe; Budagov, Temuri; Einstein, Francine H.; Atzmon, Gil

2014-01-01

Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet little is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n=4/group) at time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations lead to identification of indolethylamine N-methyltransferase (INMT), tissue factor pathway inhibitor-2 (TFPI-2), and ephrin type-B receptor 6 (EPHB6), not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity. PMID:24696292

Immunohistochemical Expression of FXR1 in Canine Normal Tissues and Melanomas.

Science.gov (United States)

Nordio, Laura; Marques, Andreia T; Lecchi, Cristina; Luciano, Alberto M; Stefanello, Damiano; Giudice, Chiara

2018-04-01

Fragile X mental retardation-related protein 1 (FXR1) is a cytoplasmic RNA-binding protein highly conserved among vertebrates. It has been studied for its role in muscle development, inflammation, and tumorigenesis, being related, for example, to metastasizing behavior in human and canine uveal melanoma. Anti-FXR1 antibodies have never been validated in the canine species. To investigate FXR1 expression in canine melanocytic tumors, the present study tested two commercially available polyclonal anti-human FXR1 antibodies, raised in goat and rabbit, respectively. The cross-reactivity of the anti-FXR1 antibodies was assessed by Western blot analysis, and the protein was localized by IHC in a set of normal canine tissues and in canine melanocytic tumors (10 uveal and 10 oral). Western blot results demonstrated that the antibody raised in rabbit specifically recognized the canine FXR1, while the antibody raised in goat did not cross-react with this canine protein. FXR1 protein was immunodetected using rabbit anti-FXR1 antibody, in canine normal tissues with different levels of intensity and distribution. It was also detected in 10/10 uveal and 9/10 oral melanocytic tumors. The present study validated for the first time the use of anti-FXR1 antibody in dogs and highlighted different FXR1 protein expression in canine melanocytic tumors, the significance of which is undergoing further investigations.

The use of biological isodoses ''IsobioGy 2'' for evaluation of tumour and normal tissues response for fractionated irradiation

International Nuclear Information System (INIS)

Maciejewski, B.; Skolyszewski, J.; Majewski, S.; Lobodziec, W.; Jedynak, T.; Slosarek, K.

1988-01-01

Divergences between physical and biological dose distributions were analysed using linear quadratic model. It was found that small variations in physical dose distribution and differences in normal tissue sensitivity for change in dose per fraction, expressed by a α/β value, can cause a high difference between physical and biological doses. This difference significantly increases when one field instead of two fields is daily treated. If there is no enough separation between treated fields, the biological dose may dramatically increase. The use of biological ''isobioGy 2'' isodoses, instead of physical isodoses, can provide an important information on biological effect in tumour or normal tissue and may diminish the risk of giving too high dose to normal tissue and too low dose to the tumour. 6 figs., 13 refs. (author)

Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours

Energy Technology Data Exchange (ETDEWEB)

Meyer, Carsten [University of Bonn, Department of Radiology, Bonn (Germany); Pieper, Claus Christian; Wilhelm, Kai E.; Schild, Hans Heinz [University of Bonn, Department of Radiology, Bonn (Germany); Ezziddin, Samer; Ahmadzadehfar, Hojjat [University of Bonn, Department of Nuclear Medicine, Bonn (Germany)

2014-02-15

To describe a new approach to protect nontarget healthy liver tissue using degradable starch microspheres (DSM) as a short-term embolizate during radioembolization of liver tumours with {sup 90}Y microspheres. Between December 2011 and July 2012 radioembolization was performed in 54 patients. Five of these patients (three women, two men; mean age 67 years) underwent protective temporary embolization using DSM (EmboCept {sup registered} S) of normal liver tissue that could not be excluded from the area treated by radioembolization through catheter repositioning. Clinical symptoms, laboratory findings, preinterventional imaging, and {sup 99m}Tc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with {sup 18}F-FDG PET/CT and MRI, were evaluated in relation to the technical and clinical success of the protective embolization. Temporary embolization of arteries supplying normal liver tissue using DSM was technically successful in all five patients. {sup 99m}Tc-MAA SPECT/CT performed in the first two patients after DSM injection showed no increased pulmonary shunting compared to the MAA test injection without DSM. Bremsstrahlung SPECT/CT after radioembolization demonstrated satisfactory irradiation of the tumour and successful protection of normal liver tissue. There were only mild hepatotoxic effects (grade 1) on laboratory follow-up examinations, and no adverse events associated with DSM embolization or radioembolization were recorded. Temporary embolization with DSM before radioembolization is feasible and can effectively protect areas of normal liver tissue from irradiation and avoid permanent embolization if other methods such as catheter repositioning are not possible due to the location of the metastases. (orig.)

Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours

International Nuclear Information System (INIS)

Meyer, Carsten; Pieper, Claus Christian; Wilhelm, Kai E.; Schild, Hans Heinz; Ezziddin, Samer; Ahmadzadehfar, Hojjat

2014-01-01

To describe a new approach to protect nontarget healthy liver tissue using degradable starch microspheres (DSM) as a short-term embolizate during radioembolization of liver tumours with 90 Y microspheres. Between December 2011 and July 2012 radioembolization was performed in 54 patients. Five of these patients (three women, two men; mean age 67 years) underwent protective temporary embolization using DSM (EmboCept registered S) of normal liver tissue that could not be excluded from the area treated by radioembolization through catheter repositioning. Clinical symptoms, laboratory findings, preinterventional imaging, and 99m Tc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with 18 F-FDG PET/CT and MRI, were evaluated in relation to the technical and clinical success of the protective embolization. Temporary embolization of arteries supplying normal liver tissue using DSM was technically successful in all five patients. 99m Tc-MAA SPECT/CT performed in the first two patients after DSM injection showed no increased pulmonary shunting compared to the MAA test injection without DSM. Bremsstrahlung SPECT/CT after radioembolization demonstrated satisfactory irradiation of the tumour and successful protection of normal liver tissue. There were only mild hepatotoxic effects (grade 1) on laboratory follow-up examinations, and no adverse events associated with DSM embolization or radioembolization were recorded. Temporary embolization with DSM before radioembolization is feasible and can effectively protect areas of normal liver tissue from irradiation and avoid permanent embolization if other methods such as catheter repositioning are not possible due to the location of the metastases. (orig.)

Variability of individual normal tissue radiation sensitivity. An international empirical evaluation of endogenous and exogenous

International Nuclear Information System (INIS)

Zimmermann, J.S.; Kumpf, L.; Kimmig, B.

1998-01-01

Background: The variability of normal-tissue response is of major concern for radiation therapy. Multiple endogenous and exogenous factors are qualitatively known to alter the acute and late tissue response. Which of them are regarded most important by the European radiation oncologists and what is, empirically, their quantitative influence on the acute or late tissue tolerance? Methods: In August 1997, we sent a questionnaire to 255 European radiation oncology departments. Among others, the questionnaire asked for endogenous and exogenous factors modifying the tissue response to radiation therapy and their quantitative influence on the acute and late radiation morbidity (TD5/5). Fifty-five questionnaires (21.5%) were answered. Results: Empirically, the most important endogenous factors to modify the acute tissue tolerance are (a) metabolic/other diseases with macro- or microangiopathia (17 answers [a]/32% mean decrease of tissue tolerance), (b) collagen diseases (9 a/37%) and (c) immune diseases (5 a/53%). As endogenous response modifiers for the TD5/5 are recognized (a) metabolic or other diseases leading to marcro- or microangiopathia (15 a/31%), (b) collagen diseases (11 a/38%) and (c) immune diseases (2 a/50%). Inflammations from any reason are assumed to alter the acute tissue tolerance by (6 a/26%) and the TD5/5 by (10 a/24%). Exogenous modifiers of the acute tissue response mentioned are (a) smoking (34 a/44%), (b) alcohol (23 a/45%), (c) nutrition/diets (16 a/45%), (d) hygiene (9 a/26%) and (e) medical therapies (10 a/37%). Exogenous factors assumed to influence the TD5/5 are (a) smoking (22 a/40%), (b) alcohol (15 a/38%), (c) nutrition/diets (9 a/48%), (d) hygiene (5 a/34%) and (e) medical therapies (10 a/30%). Conclusions: Exogenous factors are regarded more important by number and extent on the acute and late tissue response than endogenous modifiers. Both may have an important influence on the individual expression of normal tissue response. (orig

Treatment of Soft Tissue Filler Complications: Expert Consensus Recommendations.

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Urdiales-Gálvez, Fernando; Delgado, Nuria Escoda; Figueiredo, Vitor; Lajo-Plaza, José V; Mira, Mar; Moreno, Antonio; Ortíz-Martí, Francisco; Del Rio-Reyes, Rosa; Romero-Álvarez, Nazaret; Del Cueto, Sofía Ruiz; Segurado, María A; Rebenaque, Cristina Villanueva

2018-04-01

Dermal fillers have been increasingly used in minimally invasive facial esthetic procedures. This widespread use has led to a rise in reports of associated complications. The aim of this expert consensus report is to describe potential adverse events associated with dermal fillers and to provide guidance on their treatment and avoidance. A multidisciplinary group of experts in esthetic treatments convened to discuss the management of the complications associated with dermal fillers use. A search was performed for English, French, and Spanish language articles in MEDLINE, the Cochrane Database, and Google Scholar using the search terms "complications" OR "soft filler complications" OR "injectable complications" AND "dermal fillers" AND "Therapy". An initial document was drafted by the Coordinating Committee, and it was reviewed and modified by the experts, until a final text was agreed upon and validated. The panel addressed consensus recommendations about the classification of filler complications according to the time of onset and about the clinical management of different complications including bruising, swelling, edema, infections, lumps and bumps, skin discoloration, and biofilm formation. Special attention was paid to vascular compromise and retinal artery occlusion. Clinicians should be fully aware of the signs and symptoms related to complications and be prepared to confidently treat them. Establishing action protocols for emergencies, with agents readily available in the office, would reduce the severity of adverse outcomes associated with injection of hyaluronic acid fillers in the cosmetic setting. This document seeks to lay down a set of recommendations and to identify key issues that may be useful for clinicians who are starting to use dermal fillers. Additionally, this document provides a better understanding about the diagnoses and management of complications if they do occur. This journal requires that authors assign a level of evidence to each

Expression and relevant research of MGMT and XRCC1 gene in differentgrades of brain glioma and normal brain tissues

Institute of Scientific and Technical Information of China (English)

Ya-Fei Zhang

2015-01-01

Objective: To explore and analyze expression and relevant research of MGMT and XRCC1 gene in different grades of brain glioma and normal brain tissues. Methods: 52 cases of patients with brain glioma treated in our hospital from December 2013 to December 2014, and 50 cases of normal brain-tissue patients with intracranial hypertension were selected, and proceeding test to the surgical resection of brain tissue of the above patients to determine its MGMT and XRCC1 protein content, sequentially to record the expression of MGMT and XRCC1 of both groups. Grading of tumors to brain glioma after operation was carried out, and the expression of MGMT and XRCC1 gene in brain tissues of different patients was analyzed and compared;finally the contingency tables of X2 test was used to analyze the correlation of XRCC1and MGMT. Results:Positive rate of MGMT expression in normal brain tissue was 2%,while positive rate of MGMT expression in brain glioma was 46.2%,which was obviously higher than that in normal brain tissues (χ2=26.85, P0.05), which had no statistical significance. There were 12 cases of patients whose MGMT protein expression was positive and XRCC1 protein expression was positive; there were 18 cases of patients whose MGMT protein expression was negative and XRCC1 protein expression was negative. Contingency tables of X2 test was used to analyze the correlation of XRCC1 and MGMT, which indicated that the expression of XRCCI and MGMT in brain glioma had no correlation (r=0.9%, P=0.353), relevancy of both was r=0.9%. Conclusions: Positive rate of the expression of MGMT and XRCC1 in brain glioma was obviously higher than that in normal brain tissues, but the distribution of different grades of brain glioma had no obvious difference, and MGMT and XRCC1 expression had no obvious correlation, which needed further research.

Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

Science.gov (United States)

Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

2017-09-01

Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

Immunohistochemical Study of Expression of Sohlh1 and Sohlh2 in Normal Adult Human Tissues.

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Xiaoli Zhang

Full Text Available The expression pattern of Sohlh1 (spermatogenesis and oogenesis specific basic helix-loop-helix 1 and Sohlh2 in mice has been reported in previous studies. Sohlh1 and Sohlh2 are specifically expressed in spermatogonia, prespermatogonia in male mice and oocytes of primordial and primary follicles in female mice. In this report, we studied the expression pattern of Sohlh1 and Sohlh2 in human adult tissues. Immunohistochemical staining of Sohlh1 and Sohlh2 was performed in 5 samples of normal ovaries and testes, respectively. The results revealed that Sohlh genes are not only expressed in oocytes and spermatogonia, but also in granular cells, theca cells, Sertoli cells and Leydig cells, and in smooth muscles of blood vessel walls. To further investigate the expression of Sohlh genes in other adult human tissues, we collected representative normal adult tissues developed from three embryonic germ layers. Compared with the expression in mice, Sohlhs exhibited a much more extensive expression pattern in human tissues. Sohlhs were detected in testis, ovary and epithelia developed from embryonic endoderm, ectoderm and tissues developed from embryonic mesoderm. Sohlh signals were found in spermatogonia, Sertoli cells and also Leydig cells in testis, while in ovary, the expression was mainly in oocytes of primordial and primary follicles, granular cells and theca cells of secondary follicles. Compared with Sohlh2, the expression of Sohlh1 was stronger and more extensive. Our study explored the expression of Sohlh genes in human tissues and might provide insights for functional studies of Sohlh genes.

[Morphology of basement membrane and associated matrix proteins in normal and pathological tissues].

Science.gov (United States)

Nerlich, A

1995-01-01

Basement membranes (BM) are specialized structures of the extracellular matrix. Their composition is of particular importance for the maintenance of normal morphological and functional properties of a multitude of organs and tissue systems and it is thus required for regular homeostasis of body function. Generally, they possess three main functions, i.e. participation in the maintenance of tissue structure, control of fluid and substrate exchange, and regulation of cell growth and differentiation. BMs are made up by various components which are in part specifically localized within the BM zone, or which represent ubiquitous matrix constituents with specific quantitative and/or qualitative differences in their localization. On the basis of a thorough immunohistochemical analysis of normal and diseased tissues, we provide here a concept of "functional morphology/pathomorphology" of the different BM components analyzed: 1.) The ubiquitous BM-constituent collagen IV primarily stabilizes the BM-zone and thus represents the "backbone" of the BM providing mechanical strength. Its loss leads to cystic tissue transformation as it is evidenced from the analysis of polycystic nephropathies. Thus, in other cystic tissue transformations a similar formal pathogenesis may be present. 2.) The specific localization of collagen VII as the main structural component of anchoring fibrils underlines the mechanical anchoring function of this collagenous protein. Defects in this protein lead to hereditary epidermolysis. The rapid re-occurrence of epidermal collagen VII during normal human wound healing indicates a quick reconstitution of the mechanical tensile strength of healing wounds. 3.) The BM-specific heparan sulfate proteoglycan (HSPG, Perlecan) with its highly negative anionic charge can be assumed to exert filter control. This assumption is corroborated by the localizatory findings of a preferential deposition of HSPG in endothelial and particularly in glomerular BM. Similarly

Connective Tissue Disorders and Cardiovascular Complications: The indomitable role of Transforming Growth Factor-beta signaling

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Wheeler, Jason B.; Ikonomidis, John S.; Jones, Jeffrey A.

2015-01-01

Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-β) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-β signaling pathway, heritable connective tissue syndromes related to TGF-β receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-β to these syndromes with a primary focus on the cardiovascular system. PMID:24443024

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

Science.gov (United States)

Cooper, Colin S; Eeles, Rosalind; Wedge, David C; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, ZSofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; O'Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Warren, Anne Y; Foster, Christopher S; Stratton, Michael R; Whitaker, Hayley C; McDermott, Ultan; Brewer, Daniel S; Neal, David E

2015-04-01

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

Pharmacokinetics and tissue distribution of five active ingredients of Eucommiae cortex in normal and ovariectomized mice by UHPLC-MS/MS.

Science.gov (United States)

An, Jing; Hu, Fangdi; Wang, Changhong; Zhang, Zijia; Yang, Li; Wang, Zhengtao

2016-09-01

1. Pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA) are the representative active ingredients in Eucommiae cortex (EC), which may be estrogenic. 2. The ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the five ingredients showed good linearity, low limits of quantification and high extraction recoveries, as well as acceptable precision, accuracy and stability in mice plasma and tissue samples (liver, spleen, kidney and uterus). It was successfully applied to the comparative study on pharmacokinetics and tissue distribution of PDG, GE, GA, AN and CA between normal and ovariectomized (OVX) mice. 3. The results indicated that except CA, the plasma and tissue concentrations of PDG, GE, GA in OVX mice were all greater than those in normal mice. AN could only be detected in the plasma and liver homogenate of normal mice, which was poorly absorbed in OVX mice and low in other measured tissues. PDG, GE and GA seem to be better absorbed in OVX mice than in normal mice proved by the remarkable increased value of AUC0-∞ and Cmax. It is beneficial that PDG, GE, GA have better plasma absorption and tissue distribution in pathological state.

Quantitative radiation dose-response relationships for normal tissues in man - I. Gustatory tissues response during photon and neutron radiotherapy

International Nuclear Information System (INIS)

Mossman, K.L.

1982-01-01

Quantitative radiation dose-response curves for normal gustatory tissue in man were studied. Taste function, expressed as taste loss, was evaluated in 84 patients who were given either photon or neutron radiotherapy for tumors in the head and neck region. Patients were treated to average tumor doses of 6600 cGy (photon) or 2200 cGy intervals for photon patients and 320-cGy intervals for neutron patients during radiotherapy. The dose-response curves for photons and neutrons were analyzed by fitting a four-parameter logistic equation to the data. Photon and neutron curves differed principally in their relative position along the dose axis. Comparison of the dose-response curves were made by determination of RBE. At 320 cGy, the lowest neutron dose at which taste measurements were made, RBE = 5.7. If this RBE is correct, then the therapeutic gain factor may be equal to or less than 1, indicating no biological advantage in using neutrons over photons for this normal tissue. These studies suggest measurements of taste function and evaluation of dose-response relationships may also be useful in quantitatively evaluating the efficacy of chemical modifiers of radiation response such as hypoxic cell radiosensitizers and radioprotectors

Constraining Lyman continuum escape using Machine Learning

Science.gov (United States)

Giri, Sambit K.; Zackrisson, Erik; Binggeli, Christian; Pelckmans, Kristiaan; Cubo, Rubén; Mellema, Garrelt

2018-05-01

The James Webb Space Telescope (JWST) will observe the rest-frame ultraviolet/optical spectra of galaxies from the epoch of reionization (EoR) in unprecedented detail. While escaping into the intergalactic medium, hydrogen-ionizing (Lyman continuum; LyC) photons from the galaxies will contribute to the bluer end of the UV slope and make nebular emission lines less prominent. We present a method to constrain leakage of the LyC photons using the spectra of high redshift (z >~ 6) galaxies. We simulate JWST/NIRSpec observations of galaxies at z =6-9 by matching the fluxes of galaxies observed in the Frontier Fields observations of galaxy cluster MACS-J0416. Our method predicts the escape fraction fesc with a mean absolute error Δfesc ~ 0.14. The method also predicts the redshifts of the galaxies with an error .

Performance Characterization of the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) CCD Cameras

Science.gov (United States)

Joiner, R. K.; Kobayashi, K.; Winebarger, A. R.; Champey, P. R.

2014-12-01

The Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) is a sounding rocket instrument which is currently being developed by NASA's Marshall Space Flight Center (MSFC) and the National Astronomical Observatory of Japan (NAOJ). The goal of this instrument is to observe and detect the Hanle effect in the scattered Lyman-Alpha UV (121.6nm) light emitted by the Sun's Chromosphere to make measurements of the magnetic field in this region. In order to make accurate measurements of this effect, the performance characteristics of the three on-board charge-coupled devices (CCDs) must meet certain requirements. These characteristics include: quantum efficiency, gain, dark current, noise, and linearity. Each of these must meet predetermined requirements in order to achieve satisfactory performance for the mission. The cameras must be able to operate with a gain of no greater than 2 e-/DN, a noise level less than 25e-, a dark current level which is less than 10e-/pixel/s, and a residual non-linearity of less than 1%. Determining these characteristics involves performing a series of tests with each of the cameras in a high vacuum environment. Here we present the methods and results of each of these performance tests for the CLASP flight cameras.

Red cell 2, 3-diphosphoglycerate levels among diabetic patents with and without vascular complications.

Science.gov (United States)

Kanter, Y; Bessman, S P; Bessman, A

1975-08-01

There have been differences of opinion among authors concening in the levels of red cell 2,3-diphosphoglycerate (2,3-DPG) and nucleotides in nonacidotic diabetic patients. Our data suggest that abnormal levels of 2, 3-DPG in diabetic patients are related to the presence of vascular complications and not to the duration of the disease per sec. 2,3-DPG levels are normal in diabetic patients with no evidence of vascular complications (group A). In ambulatory patients with vascular complications (group B), significantly higher levels of 2,3-DPG are found than in normal subjects and patients in group A. In hospitalized diabetic patients with active peripheral vascular complications (group C), levels of 2,3-DPG are likewise significantly increased over those of normal subjects and patients of group A. 2,3-DPG was found to be significantly elevated in patients of group C as compared with group B. 2,3-DPG levels in venous blood from infected legs as compared with those of the peripheral venous blood were not significantly different, thereby ruling out local factors. There were no differences in the blood lactate levels in any of the group studied. The elevation of the 2,3-DPG levels may be a reflection of attempted red blood cell compensation for tissue hypoxia in the diabetic with vascular disease.

Correlations in the three-dimensional Lyman-alpha forest contaminated by high column density absorbers

Science.gov (United States)

Rogers, Keir K.; Bird, Simeon; Peiris, Hiranya V.; Pontzen, Andrew; Font-Ribera, Andreu; Leistedt, Boris

2018-05-01

Correlations measured in three dimensions in the Lyman-alpha forest are contaminated by the presence of the damping wings of high column density (HCD) absorbing systems of neutral hydrogen (H I; having column densities N(H I) > 1.6 × 10^{17} atoms cm^{-2}), which extend significantly beyond the redshift-space location of the absorber. We measure this effect as a function of the column density of the HCD absorbers and redshift by measuring three-dimensional (3D) flux power spectra in cosmological hydrodynamical simulations from the Illustris project. Survey pipelines exclude regions containing the largest damping wings. We find that, even after this procedure, there is a scale-dependent correction to the 3D Lyman-alpha forest flux power spectrum from residual contamination. We model this residual using a simple physical model of the HCD absorbers as linearly biased tracers of the matter density distribution, convolved with their Voigt profiles and integrated over the column density distribution function. We recommend the use of this model over existing models used in data analysis, which approximate the damping wings as top-hats and so miss shape information in the extended wings. The simple `linear Voigt model' is statistically consistent with our simulation results for a mock residual contamination up to small scales (|k| account for the effect of the highest column density absorbers on the smallest scales (e.g. |k| > 0.4 h Mpc^{-1} for small damped Lyman-alpha absorbers; HCD absorbers with N(H I) ˜ 10^{21} atoms cm^{-2}). However, these systems are in any case preferentially removed from survey data. Our model is appropriate for an accurate analysis of the baryon acoustic oscillations feature. It is additionally essential for reconstructing the full shape of the 3D flux power spectrum.

GALEX-SELECTED LYMAN BREAK GALAXIES AT z {approx} 2: COMPARISON WITH OTHER POPULATIONS

Energy Technology Data Exchange (ETDEWEB)

Haberzettl, L.; Williger, G. [Department of Physics and Astronomy, University of Louisville, Louisville KY 20492 (United States); Lehnert, M. D. [GEPI, Observatoire de Paris, UMR 8111 du CNRS, 5 Place Jules Janssen, 92195 Meudon (France); Nesvadba, N. [Institut d' Astrophysique Spatiale, CNRS, Universite Paris-Sud, Bat. 120-121, 91405 Orsay (France); Davies, L. [Department of Physics, H H Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol BS8 1TL (United Kingdom)

2012-01-20

We present results of a search for bright Lyman break galaxies (LBGs) at 1.5 {<=} z {<=} 2.5 in the GOODS-S field using an NUV-dropout technique in combination with color selection. We derived a sample of 73 LBG candidates. We compare our selection efficiencies to BM/BX and BzK methods (techniques solely based on ground-based data sets), and find the NUV data to provide greater efficiency for selecting star-forming galaxies. We estimate LBG candidate ages, masses, star formation rates, and extinction from fitting PEGASE synthesis evolution models. We find that about 20% of our LBG candidates are comparable to infrared-luminous LBGs or submillimeter galaxies which are thought to be precursors of massive elliptical galaxies today. Overall, we can show that although BM/BX and BzK methods do identify star-forming galaxies at z {approx} 2, the sample they provide biases against those star-forming galaxies which are more massive and contain sizeable red stellar populations. A true Lyman break criterion at z {approx} 2 is therefore more directly comparable to the populations found at z {approx} 3, which does contain a red fraction.

GALEX-SELECTED LYMAN BREAK GALAXIES AT z ∼ 2: COMPARISON WITH OTHER POPULATIONS

International Nuclear Information System (INIS)

Haberzettl, L.; Williger, G.; Lehnert, M. D.; Nesvadba, N.; Davies, L.

2012-01-01

We present results of a search for bright Lyman break galaxies (LBGs) at 1.5 ≤ z ≤ 2.5 in the GOODS-S field using an NUV-dropout technique in combination with color selection. We derived a sample of 73 LBG candidates. We compare our selection efficiencies to BM/BX and BzK methods (techniques solely based on ground-based data sets), and find the NUV data to provide greater efficiency for selecting star-forming galaxies. We estimate LBG candidate ages, masses, star formation rates, and extinction from fitting PEGASE synthesis evolution models. We find that about 20% of our LBG candidates are comparable to infrared-luminous LBGs or submillimeter galaxies which are thought to be precursors of massive elliptical galaxies today. Overall, we can show that although BM/BX and BzK methods do identify star-forming galaxies at z ∼ 2, the sample they provide biases against those star-forming galaxies which are more massive and contain sizeable red stellar populations. A true Lyman break criterion at z ∼ 2 is therefore more directly comparable to the populations found at z ∼ 3, which does contain a red fraction.

An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues.

Science.gov (United States)

Saraco, Nora; Nesi-Franca, Suzana; Sainz, Romina; Marino, Roxana; Marques-Pereira, Rosana; La Pastina, Julia; Perez Garrido, Natalia; Sandrini, Romolo; Rivarola, Marco Aurelio; de Lacerda, Luiz; Belgorosky, Alicia

2015-01-01

Splicing CYP19 gene variants causing aromatase deficiency in 46,XX disorder of sexual development (DSD) patients have been reported in a few cases. A misbalance between normal and aberrant splicing variants was proposed to explain spontaneous pubertal breast development but an incomplete sex maturation progress. The aim of this study was to functionally characterize a novel CYP19A1 intronic homozygote mutation (IVS9+5G>A) in a 46,XX DSD girl presenting spontaneous breast development and primary amenorrhea, and to evaluate similar splicing variant expression in normal steroidogenic tissues. Genomic DNA analysis, splicing prediction programs, splicing assays, and in vitro protein expression and enzyme activity analyses were carried out. CYP19A1 mRNA expression in human steroidogenic tissues was also studied. A novel IVS9+5G>A homozygote mutation was found. In silico analysis predicts the disappearance of the splicing donor site in intron 9, confirmed by patient peripheral leukocyte cP450arom and in vitro studies. Protein analysis showed a shorter and inactive protein. The intron 9 transcript variant was also found in human steroidogenic tissues. The mutation IVS9+5G>A generates a splicing variant that includes intron 9 which is also present in normal human steroidogenic tissues, suggesting that a misbalance between normal and aberrant splicing variants might occur in target tissues, explaining the clinical phenotype in the affected patient. © 2015 S. Karger AG, Basel.

Differentiation of prostate cancer from normal prostate tissue in an animal model: conventional MRI and dynamic contrast-enhanced MRI

International Nuclear Information System (INIS)

Gemeinhardt, O.; Prochnow, D.; Taupitz, M.; Hamm, B.; Beyersdorff, D.; Luedemann, L.; Abramjuk, C.

2005-01-01

Purpose: to differentiate orthotopically implanted prostate cancer from normal prostate tissue using magnetic resonance imaging (MRI) and Gd-DTPA-BMA-enhanced dynamic MRI in the rat model. Material and methods: tumors were induced in 15 rats by orthotopic implantation of G subline Dunning rat prostatic tumor cells. MRI was performed 56 to 60 days after tumor cell implantation using T1-weighted spin-echo, T2-weighted turbo SE sequences, and a 2D FLASH sequence for the contrast medium based dynamic study. The interstitial leakage volume, normalized permeability and the permeability surface area product of tumor and healthy prostate were determined quantitatively using a pharmacokinetic model. The results were confirmed by histologic examination. Results: axial T2-weighted TSE images depicted low-intensity areas suspicious for tumor in all 15 animals. The mean tumor volume was 46.5 mm3. In the dynamic study, the suspicious areas in all animals displayed faster and more pronounced signal enhancement than surrounding prostate tissue. The interstitial volume and the permeability surface area product of the tumors increased significantly by 420% (p<0.001) and 424% (p<0.001), respectively, compared to normal prostate tissue, while no significant difference was seen for normalized permeability alone. Conclusion: the results of the present study demonstrate that quantitative analysis of contrast-enhanced dynamic MRI data enables differentiation of small, slowly growing orthotopic prostate cancer from normal prostate tissue in the rat model. (orig.)

The claudin gene family: expression in normal and neoplastic tissues

International Nuclear Information System (INIS)

Hewitt, Kyle J; Agarwal, Rachana; Morin, Patrice J

2006-01-01

The claudin (CLDN) genes encode a family of proteins important in tight junction formation and function. Recently, it has become apparent that CLDN gene expression is frequently altered in several human cancers. However, the exact patterns of CLDN expression in various cancers is unknown, as only a limited number of CLDN genes have been investigated in a few tumors. We identified all the human CLDN genes from Genbank and we used the large public SAGE database to ascertain the gene expression of all 21 CLDN in 266 normal and neoplastic tissues. Using real-time RT-PCR, we also surveyed a subset of 13 CLDN genes in 24 normal and 24 neoplastic tissues. We show that claudins represent a family of highly related proteins, with claudin-16, and -23 being the most different from the others. From in silico analysis and RT-PCR data, we find that most claudin genes appear decreased in cancer, while CLDN3, CLDN4, and CLDN7 are elevated in several malignancies such as those originating from the pancreas, bladder, thyroid, fallopian tubes, ovary, stomach, colon, breast, uterus, and the prostate. Interestingly, CLDN5 is highly expressed in vascular endothelial cells, providing a possible target for antiangiogenic therapy. CLDN18 might represent a biomarker for gastric cancer. Our study confirms previously known CLDN gene expression patterns and identifies new ones, which may have applications in the detection, prognosis and therapy of several human cancers. In particular we identify several malignancies that express CLDN3 and CLDN4. These cancers may represent ideal candidates for a novel therapy being developed based on CPE, a toxin that specifically binds claudin-3 and claudin-4

The z~4 Lyman Break Galaxies: Colors and Theoretical Predictions

Science.gov (United States)

Idzi, Rafal; Somerville, Rachel; Papovich, Casey; Ferguson, Henry C.; Giavalisco, Mauro; Kretchmer, Claudia; Lotz, Jennifer

2004-01-01

We investigate several fundamental properties of z~4 Lyman break galaxies by comparing observations with the predictions of a semianalytic model based on the cold dark matter theory of hierarchical structure formation. We use a sample of B435-dropouts from the Great Observatories Origins Deep Survey and complement the Advanced Camera for Surveys optical B435, V606, i775, and z850 data with the Very Large Telescope Infrared Spectrometer and Array Camera J, H, and Ks observations. We extract B435-dropouts from our semianalytic mock catalog using the same color criteria and magnitude limits that were applied to the observed sample. We find that the i775-Ks colors of the model-derived and observed B435-dropouts are in good agreement. However, we find that the i775-z850 colors differ significantly, indicating perhaps that either too little dust or an incorrect extinction curve has been used. Motivated by the reasonably good agreement between the model and observed data, we present predictions for the stellar masses, star formation rates, and ages for the z~4 Lyman break sample. We find that according to our model, the color selection criteria used to select our z~4 sample surveys 67% of all galaxies at this epoch down to z850Universities for Research in Astronomy (AURA), Inc., under NASA contract NAS5-26555. Based on observations collected at the European Southern Observatory, Chile (ESO programmes 168.A-0485, 64.0-0643, 66.A-0572, and 68.A-0544).

ALERT. Adverse late effects of cancer treatment. Vol. 2. Normal tissue specific sites and systems

Energy Technology Data Exchange (ETDEWEB)

Rubin, Philip; Constine, Louis S. [Univ. Rochester Medical Center, NY (United States). Dept. of Radiation Oncology; Marks, Lawrence B. (ed.) [Univ. North Carolina and Lineberger, Comprehensive Cancer Center, Chapel Hill, NC (United States). Dept. of Radiation Oncology

2014-09-01

Comprehensively documents potential late effects in all the normal tissue sites in the human body. Considers in detail the detection, diagnosis, management and prevention of effects and discusses prognostic outcomes. Clearly presents radiation risk factors and interactions with chemotherapy effects. Provides the most current evidence-based medicine for cancer care survivorship guidelines. The literature on the late effects of cancer treatment is widely scattered in different journals since all major organ systems are affected and management is based on a variety of medical and surgical treatments. The aim of ALERT - Adverse Late Effects of Cancer Treatment is to offer a coherent multidisciplinary approach to the care of cancer survivors. The central paradigm is that cytotoxic multimodal therapy results in a perpetual cascade of events that affects each major organ system differently and is expressed continually over time. Essentially, radiation and chemotherapy are intense biologic modifiers that allow for cancer cure and cancer survivorship but accelerate senescence of normal tissues and increase the incidence of age-related diseases and second malignant tumors. Volume 2 of this two-volume work comprehensively documents potential late effects in all the normal tissue anatomic sites in the human body. The detection, diagnosis, management and prevention of effects are all considered in detail, and prognostic outcomes are discussed. Radiation risk factors and interactions with chemotherapy effects are clearly presented. The text is accompanied by numerous supportive illustrations and tables.

Normal tissue tolerance to external beam radiation therapy: Peripheral nerves

International Nuclear Information System (INIS)

Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G.; Huchet, A.; Mamou, N.; Loiseau, H.

2010-01-01

Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

Postanesthetic ulceration of palate: A rare complication

OpenAIRE

Gupta, Ramesh; Garg, Meenu; Pawah, Salil; Gupta, Ajay

2016-01-01

The routine dental practice involves various dental procedures which needs the application of local anesthetics. Generally, there are very few complications associated with these procedures. Complications such as tissue necrosis can occur following the rapid injection of local anesthetic solutions. Palate is a favorable site for soft tissue lesions, various factors such as direct effects of the drug, blanching of the tissues during injection, a relatively poor blood supply, and reactivation o...

Relative Contribution of the Hydrogen 2 s Two-Photon Decay and Lyman- α Escape Channels during the Epoch of Cosmological Recombination

Science.gov (United States)

Rubiño-Martin, J. A.; Sunyaev, R. A.

2018-01-01

We discuss the evolution of the ratio in number of recombinations due to 2 s two photon escape and due to the escape of Lyman- α photons from the resonance during the epoch of cosmological recombination, within the width of the last scattering surface and near its boundaries. We discuss how this ratio evolves in time, and how it defines the profile of the Lyman- α line in the spectrum of CMB. One of the key reasons for explaining its time dependence is the strong overpopulation of the 2 p level relative to the 2 s level at redshifts z ≲ 750.

Pulmonary infiltration with eosinophilia complicated with mucosa-associated lymphoid tissue lymphoma: A case report.

Science.gov (United States)

Liu, Yin; Tangsun, Yinyan; Xiao, Yonglong; Zhang, Deping; Cao, Min

2016-09-01

Tissue eosinophilia is rarely observed in cases of non-Hodgkin's lymphoma of B cell origin. The present study describes a rare case of mucosa-associated lymphoid tissue (MALT) lymphoma, which was initially misdiagnosed as eosinophilic pneumonia. The initial diagnosis was formed based on the results of chest radiography, peripheral eosinophilia tests and bronchoalveolar lavage, and the clinical course of the patient. Following administration of methylprednisolone (40 mg/day) for 4 days and oral administration of prednisolone (30 mg/day), the clinical course rapidly improved and the eosinophil count immediately decreased a to normal level. However, abnormal shadows observed on computed tomography (CT) scans of the chest did not diminish. At 6 months after the initiation of treatment, CT-guided percutaneous lung biopsy was performed, and a final diagnosis of primary pulmonary mucosa-associated lymphoid tissue lymphoma was made based on immunohistochemical examination. Primary lung MALT lymphoma remains a rare entity, with an indolent course and a reasonably favorable prognosis, whose diagnosis may be challenging.

Postanesthetic ulceration of palate: A rare complication.

Science.gov (United States)

Gupta, Ramesh; Garg, Meenu; Pawah, Salil; Gupta, Ajay

2016-01-01

The routine dental practice involves various dental procedures which needs the application of local anesthetics. Generally, there are very few complications associated with these procedures. Complications such as tissue necrosis can occur following the rapid injection of local anesthetic solutions. Palate is a favorable site for soft tissue lesions, various factors such as direct effects of the drug, blanching of the tissues during injection, a relatively poor blood supply, and reactivation of the latent forms of herpes can all promote to tissue ischemia and a lesion in the palate.

Analysis of clinical complication data for radiation hepatitis using a parallel architecture model

International Nuclear Information System (INIS)

Jackson, A.; Haken, R.K. ten; Robertson, J.M.; Kessler, M.L.; Kutcher, G.J.; Lawrence, T.S.

1995-01-01

Purpose: The detailed knowledge of dose volume distributions available from the three-dimensional (3D) conformal radiation treatment of tumors in the liver (reported elsewhere) offers new opportunities to quantify the effect of volume on the probability of producing radiation hepatitis. We aim to test a new parallel architecture model of normal tissue complication probability (NTCP) with these data. Methods and Materials: Complication data and dose volume histograms from a total of 93 patients with normal liver function, treated on a prospective protocol with 3D conformal radiation therapy and intraarterial hepatic fluorodeoxyuridine, were analyzed with a new parallel architecture model. Patient treatment fell into six categories differing in doses delivered and volumes irradiated. By modeling the radiosensitivity of liver subunits, we are able to use dose volume histograms to calculate the fraction of the liver damaged in each patient. A complication results if this fraction exceeds the patient's functional reserve. To determine the patient distribution of functional reserves and the subunit radiosensitivity, the maximum likelihood method was used to fit the observed complication data. Results: The parallel model fit the complication data well, although uncertainties on the functional reserve distribution and subunit radiosensitivy are highly correlated. Conclusion: The observed radiation hepatitis complications show a threshold effect that can be described well with a parallel architecture model. However, additional independent studies are required to better determine the parameters defining the functional reserve distribution and subunit radiosensitivity

The role of hormones of adipose tissue in the development pregnancy complications in obese women

Directory of Open Access Journals (Sweden)

2013-03-01

Full Text Available Obesity in pregnancy is a risk factor for complications for both the mother and of the fetus. Adipose tissue hormones (leptin, adiponectin, resistin are secreted by the human placenta and regulate the function of trophoblast.The review presents data from the literature on the role of adipocytokines in the development of gestational diabetes and preeclampsia in obesity women. The article considers the criteria and algorithms for the diagnosis of gestational diabetes recommended by the World Health Organization and the International Association of research groups for diabetes and pregnancy.

Apparent diffusion coefficient of breast cancer and normal fibroglandular tissue in diffusion-weighted imaging: the effects of menstrual cycle and menopausal status.

Science.gov (United States)

Kim, Jin You; Suh, Hie Bum; Kang, Hyun Jung; Shin, Jong Ki; Choo, Ki Seok; Nam, Kyung Jin; Lee, Seok Won; Jung, Young Lae; Bae, Young Tae

2016-05-01

The purpose of this study was to investigate prospectively whether the apparent diffusion coefficients (ADCs) of both breast cancer and normal fibroglandular tissue vary with the menstrual cycle and menopausal status. Institutional review board approval was obtained, and informed consent was obtained from each participant. Fifty-seven women (29 premenopausal, 28 postmenopausal) with newly diagnosed breast cancer underwent diffusion-weighted imaging twice (interval 12-20 days) before surgery. Two radiologists independently measured ADC of breast cancer and normal contralateral breast tissue, and we quantified the differences according to the phases of menstrual cycle and menopausal status. With normal fibroglandular tissue, ADC was significantly lower in postmenopausal than in premenopausal women (P = 0.035). In premenopausal women, ADC did not differ significantly between proliferative and secretory phases in either breast cancer or normal fibroglandular tissue (P = 0.969 and P = 0.519, respectively). In postmenopausal women, no significant differences were found between ADCs measured at different time intervals in either breast cancer or normal fibroglandular tissue (P = 0.948 and P = 0.961, respectively). The within-subject variability of the ADC measurements was quantified using the coefficient of variation (CV) and was small: the mean CVs of tumor ADC were 2.90 % (premenopausal) and 3.43 % (postmenopausal), and those of fibroglandular tissue ADC were 4.37 % (premenopausal) and 2.55 % (postmenopausal). Both intra- and interobserver agreements were excellent for ADC measurements, with intraclass correlation coefficients in the range of 0.834-0.974. In conclusion, the measured ADCs of breast cancer and normal fibroglandular tissue were not affected significantly by menstrual cycle, and the measurements were highly reproducible both within and between observers.

2-deoxyglucose tissue levels and insulin levels following tolazamide dosing in normal and obese mice

International Nuclear Information System (INIS)

Skillman, C.A.; Fletcher, H.P.

1986-01-01

The effect of tolazamide (TZ), a sulfonylurea, on 14 C-2-deoxyglucose ( 14 C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased 14 C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased 14 C-2DG levels in muscle and fat. The results demonstrate that the in vivo 14 C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated 14 C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing 14 C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on 14 C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable mice may be resistant to subchronic treatment with TZ. (author)

Human BLCAP transcript: new editing events in normal and cancerous tissues.

Science.gov (United States)

Galeano, Federica; Leroy, Anne; Rossetti, Claudia; Gromova, Irina; Gautier, Philippe; Keegan, Liam P; Massimi, Luca; Di Rocco, Concezio; O'Connell, Mary A; Gallo, Angela

2010-07-01

Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing events. Some of the new editing events alter the highly conserved amino terminus of the protein creating alternative protein isoforms by changing the genetically coded amino acids. We found that both ADAR1 and ADAR2-editing enzymes cooperate to edit this transcript and that different tissues displayed distinctive ratios of edited and unedited BLCAP transcripts. Moreover, we observed a general decrease in BLCAP-editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues. The newly identified editing events, found to be downregulated in cancers, could be useful for future studies as a diagnostic tool to distinguish malignancies or epigenetic changes in different tumors.

Identification of the boundary between normal breast tissue and invasive ductal carcinoma during breast-conserving surgery using multiphoton microscopy

Science.gov (United States)

Deng, Tongxin; Nie, Yuting; Lian, Yuane; Wu, Yan; Fu, Fangmeng; Wang, Chuan; Zhuo, Shuangmu; Chen, Jianxin

2014-11-01

Breast-conserving surgery has become an important way of surgical treatment for breast cancer worldwide nowadays. Multiphoton microscopy (MPM) has the ability to noninvasively visualize tissue architectures at the cellular level using intrinsic fluorescent molecules in biological tissues without the need for fluorescent dye. In this study, MPM is used to image the microstructures of terminal duct lobular unit (TDLU), invasive ductal carcinoma and the boundary region between normal and cancerous breast tissues. Our study demonstrates that MPM has the ability to not only reveal the morphological changes of the cuboidal epithelium, basement membrane and interlobular stroma but also identify the boundary between normal breast tissue and invasive ductal carcinoma, which correspond well to the Hematoxylin and Eosin (H and E) images. Predictably, MPM can monitor surgical margins in real time and provide considerable accuracy for resection of breast cancerous tissues intraoperatively. With the development of miniature, real-time MPM imaging technology, MPM should have great application prospects during breast-conserving surgery.

Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa.

Directory of Open Access Journals (Sweden)

Valeria Musella

Full Text Available BACKGROUND: Genome-wide gene expression analyses of tumors are a powerful tool to identify gene signatures associated with biologically and clinically relevant characteristics and for several tumor types are under clinical validation by prospective trials. However, handling and processing of clinical specimens may significantly affect the molecular data obtained from their analysis. We studied the effects of tissue handling time on gene expression in human normal and tumor colon tissues undergoing routine surgical procedures. METHODS: RNA extracted from specimens of 15 patients at four time points (for a total of 180 samples after surgery was analyzed for gene expression on high-density oligonucleotide microarrays. A mixed-effects model was used to identify probes with different expression means across the four different time points. The p-values of the model were adjusted with the Bonferroni method. RESULTS: Thirty-two probe sets associated with tissue handling time in the tumor specimens, and thirty-one in the normal tissues, were identified. Most genes exhibited moderate changes in expression over the time points analyzed; however four of them were oncogenes, and two confirmed the effect of tissue handling by independent validation. CONCLUSIONS: Our results suggest that a critical time point for tissue handling in colon seems to be 60 minutes at room temperature. Although the number of time-dependent genes we identified was low, the three genes that already showed changes at this time point in tumor samples were all oncogenes, hence recommending standardization of tissue-handling protocols and effort to reduce the time from specimen removal to snap freezing accounting for warm ischemia in this tumor type.

The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

International Nuclear Information System (INIS)

Lawton, P.A.

1995-01-01

Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author)

The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

Energy Technology Data Exchange (ETDEWEB)

Lawton, P.A.

1995-12-31

Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author).

Large animal normal tissue tolerance with boron neutron capture.

Science.gov (United States)

Gavin, P R; Kraft, S L; DeHaan, C E; Swartz, C D; Griebenow, M L

1994-03-30

Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA2B12H11SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood.

Large animal normal tissue tolerance with boron neutron capture

International Nuclear Information System (INIS)

Gavin, P.R.; Swartz, C.D.; Kraft, S.L.; Briebenow, M.L.; DeHaan, C.E.

1994-01-01

Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA 2 B 12 H 11 SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood. 23 refs., 6 figs., 2 tabs

Antiandrogenic actions of medroxyprogesterone acetate on epithelial cells within normal human breast tissues cultured ex vivo.

Science.gov (United States)

Ochnik, Aleksandra M; Moore, Nicole L; Jankovic-Karasoulos, Tanja; Bianco-Miotto, Tina; Ryan, Natalie K; Thomas, Mervyn R; Birrell, Stephen N; Butler, Lisa M; Tilley, Wayne D; Hickey, Theresa E

2014-01-01

Medroxyprogesterone acetate (MPA), a component of combined estrogen-progestin therapy (EPT), has been associated with increased breast cancer risk in EPT users. MPA can bind to the androgen receptor (AR), and AR signaling inhibits cell growth in breast tissues. Therefore, the aim of this study was to investigate the potential of MPA to disrupt AR signaling in an ex vivo culture model of normal human breast tissue. Histologically normal breast tissues from women undergoing breast surgical operation were cultured in the presence or in the absence of the native AR ligand 5α-dihydrotestosterone (DHT), MPA, or the AR antagonist bicalutamide. Ki67, bromodeoxyuridine, B-cell CLL/lymphoma 2 (BCL2), AR, estrogen receptor α, and progesterone receptor were detected by immunohistochemistry. DHT inhibited the proliferation of breast epithelial cells in an AR-dependent manner within tissues from postmenopausal women, and MPA significantly antagonized this androgenic effect. These hormonal responses were not commonly observed in cultured tissues from premenopausal women. In tissues from postmenopausal women, DHT either induced or repressed BCL2 expression, and the antiandrogenic effect of MPA on BCL2 was variable. MPA significantly opposed the positive effect of DHT on AR stabilization, but these hormones had no significant effect on estrogen receptor α or progesterone receptor levels. In a subset of postmenopausal women, MPA exerts an antiandrogenic effect on breast epithelial cells that is associated with increased proliferation and destabilization of AR protein. This activity may contribute mechanistically to the increased risk of breast cancer in women taking MPA-containing EPT.

Analysis of coronal H I Lyman alpha measurements from a rocket flight on 1979 April 13

Science.gov (United States)

Withbroe, G. L.; Kohl, J. L.; Weiser, H.; Noci, G.; Munro, R. H.

1982-01-01

It is noted that measurements of the profiles of resonantly scattered hydrogen Lyman-alpha coronal radiation have been used in determining hydrogen kinetic temperatures from 1.5 to 4 solar radii from sun center in a quiet region of the corona. Proton temperatures derived using the line widths decrease with height from 2.6 x 10 to the 6th K at 1.5 solar radii to 1.2 x 10 to the 6th K at 4 solar radii. These measurements, together with temperatures for lower heights determined from earlier Skylab and eclipse data, suggest that there is a maximum in the quiet coronal proton temperature at about 1.5 solar radii. Comparison of measured Lyman-alpha intensities with those calculated using a representative model for the radial variation of the coronal electron density yields information on the magnitude of the electron temperature gradient and suggests that the solar wind flow was subsonic for distances less than 4 solar radii.

Lenses in the forest: cross correlation of the Lyman-alpha flux with cosmic microwave background lensing.

Science.gov (United States)

Vallinotto, Alberto; Das, Sudeep; Spergel, David N; Viel, Matteo

2009-08-28

We present a theoretical estimate for a new observable: the cross correlation between the Lyman-alpha flux fluctuations in quasar spectra and the convergence of the cosmic microwave background as measured along the same line of sight. As a first step toward the assessment of its detectability, we estimate the signal-to-noise ratio using linear theory. Although the signal-to-noise is small for a single line of sight and peaks at somewhat smaller redshifts than those probed by the Lyman-alpha forest, we estimate a total signal-to-noise of 9 for cross correlating quasar spectra of SDSS-III with Planck and 20 for cross correlating with a future polarization based cosmic microwave background experiment. The detection of this effect would be a direct measure of the neutral hydrogen-matter cross correlation and could provide important information on the growth of structures at large scales in a redshift range which is still poorly probed.

Pesquisa da prevalência do papilomavírus humano em amostras de tecido endometrial normal e com carcinoma pela técnica de PCR Search for human papillomavirus in samples of normal endometrial tissue and tissue with carcinoma by the PCR technique

Directory of Open Access Journals (Sweden)

Edison Natal Fedrizzi

2004-05-01

tissue, and tissue with endometrial carcinoma of women submitted to surgical treatment (hysterectomy, or between endometrial carcinoma and benign disease, through the PCR technique. METHODS: this is an observational control-case study where 100 women (50 with endometrial carcinoma and 50 with normal endometrial tissue were analyzed for the detection of HPV DNA in samples of endometrial tissue kept in paraffin blocks by the PCR technique. The cases of endometrial carcinoma with uncertain primary site of the lesion as well as the cases with previous or current history of pre-neoplasic lesions or carcinoma of the lower genital tract were excluded. Variables as age, smoking habit, endometrial trophism, squamous differentiation and degree of tumor differentiation were also evaluated. RESULTS: the estimated relative risk of the presence of HPV in the endometrial carcinoma and in the normal endometrial tissue was the same. HPV was detected in 8% of the cases of carcinoma and 10% in the normal endometrial tissue. In spite of HPV having been 3.5 times more detected in women with smoking habit in the group without carcinoma, there was no statistical difference. The presence of HPV was also not correlated with the women's age, endometrial trophism, squamous differentiation and degree of tumor differentiation. The HPV types 16 (5 cases and 18 (4 cases were the viruses most frequently found both in the normal endometrial tissue or in the tissue with carcinoma. No oncogenic low risk virus was detected in the samples. CONCLUSION: The same proportion of HPV is present in the endometrial tissue of women with endometrial cancer and with normal endometrium. It could not be demonstrated a possible correlation of DNA of HPV with the development of endometrial carcinoma.

Hyperbaric oxygen therapy in the treatment of radio-induced lesions in normal tissues: a literature review

International Nuclear Information System (INIS)

Pasquier, David; Hoelscher, Tobias; Schmutz, Jorg; Dische, Stanley; Mathieu, Daniel; Baumann, Michael; Lartigau, Eric

2004-01-01

Late complications are one of the major factors limiting radiotherapy treatment, and their treatment is not codified. Hyperbaric oxygen (HBO) has been used in combination with radiotherapy for over half a century, either to maximise its effectiveness or in an attempt to treat late complications. In this latter case, retrospective trials and case reports are prevailing in literature. This prompted European Society for Therapeutic Radiotherapy and Oncology and European Committee for Hyperbaric Medicine to organise a consensus conference in October 2001, dealing with the HBO indications on radiotherapy for the treatment and prevention of late complications. This updated literature review is part of the documents the jury based its opinion on. A systematic search was done on literature from 1960 to 2004, by only taking into account the articles that appeared in peer review journals. Hyperbaric oxygen treatment involving complications to the head and neck, pelvis and nervous system, and the prevention of complications after surgery in irradiated tissues have been studied. Despite the small number of controlled trials, it may be indicated for the treatment of mandibular osteoradionecrosis in combination with surgery, haemorrhagic cystitis resistant to conventional treatments and the prevention of osteoradionecrosis after dental extraction, whose level of evidence seems to be the most significant though randomised trials are still necessary. The other treatment methods are also outlined for each location

Interpreting HST observations with simulations of reionization: the ionizing photon budget and the decline of Lyman-alpha emission in z>6 dropouts

Science.gov (United States)

D'Aloisio, Anson

2017-08-01

In recent years, HST surveys such as CANDELS, HUDF, BoRG/HIPPIES, ERS, and the Frontier Fields, have made possible the first robust measurements of the rest-frame UV luminosity function of z =6-10 galaxies, spanning much of the redshift range over which reionization likely occurred. These measurements provide an estimate of the galactic ionizing photon output, addressing the critical question of whether these galaxies could have reionized the Universe. In addition, follow-up spectroscopy has measured the fraction of these galaxies that show Lyman-alpha emission. Interestingly, a dramatic decrease in this fraction above z 6 has been observed, and this evolution has (controversially) been interpreted as evidence that much of reionization happened over z=6-8 (as intergalactic neutral gas leads to large damping wings that scatter the Lyman-alpha line). The clumpiness of the IGM and how it self shields to ionizing photons impacts whether the observed population of galaxies can reionize the Universe, as well as the interpretation of the evolving Lyman-alpha emitter fraction. We propose to run fully coupled radiative-hydrodynamics simulations that are the first to resolve the evaporation of small structures by passing ionization fronts and, hence, to accurately assess the level of clumpiness and self-shielding from the IGM. Our study will nail down the clumping factor used to assess whether the observed population of galaxies can drive reionization, and it will address whether neutral self-shielding clumps in recently reionized regions can scatter galaxies' Lyman-alpha lines.

The Faint End of the Lyman Alpha Luminosity Function at 2 < z < 3.8

Science.gov (United States)

Devarakonda, Yaswant; Livermore, Rachael; Indahl, Briana; Wold, Isak; Davis, Dustin; Finkelstein, Steven

2018-01-01

Most current models predict that our universe is mostly composed of small, dim galaxies. Due to these galaxies being so faint, it is very difficult to study these types of galaxies outside of our local universe. This is particularly an issue for studying how these small galaxies evolved over their lifetimes. With the benefit of gravitational lensing, however, we are able to observe galaxies that are farther and fainter than ever before possible. In this particular study, we focus on Lyman-Alpha emitting galaxies between the redshifts of 2-3.8, so that we may study these galaxies during the epoch of peak star formation in the universe. We use the McDonald Observatory 2.7, Harlan Smith telescope with the VIRUS-P IFU spectrograph to observe several Hubble Frontier Field lensing clusters to spectroscopically discover faint galaxies over this redshift range. In addition to providing insight into the faint-end slope of the Lyman alpha luminosity function, the spectroscopic redshifts will allow us to better constrain the mass models of the foreground clusters, such as Abell 370, so that we may better understand lensing effects for this and future studies.

Toxoplasmosis Complications and Novel Therapeutic Synergism Combination of Diclazuril plus Atovaquone

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Helieh S Oz

2014-09-01

Full Text Available Toxoplasmosis is a major cause of foodborne disease, congenital complication and morbidity. There is an urgent need for safe and effective therapies to encounter congenital and persisting toxoplasmosis. The hypothesis was: Combination Diclazuril plus Atovaquone to exert a novel therapeutic synergy to prevent toxoplasmosis syndromes. Methods. Pregnant dams were treated with Diclazuril and Atovaquone monotherapy or combination therapy and infected intraperitoneally with Toxoplasma tachyzoites (600. Results. Infected dams developed severe toxoplasmosis associated syndrome with increases in the abdominal adiposity surrounding uteri, gansterointestinal and other internal organs and excessive weight gain. Numerous organisms along with infiltration of inflammatory cells were detected scattered into adipose tissues. Combination therapy (p< 0.01 and to a lesser extent Diclazuril (p< 0.05 protected dams from inflammatory fat and excess weight gains. This was consistent with pancreatitis development in infected dams (versus normal p< 0.05 with infiltration of inflammatory cells, degeneration and necrosis of pancreatic cells followed by the degeneration and loss of islets. Combination and monotherapy protected dams from these inflammatory and pathological aspects of pancreatitis. Infected dams exhibited severe colitis, and colonic tissues significantly shortened in length. Brush border epithelial cells were replaced with infiltration of lymphocytes, granulocytes, and microabscess formations into cryptic microstructures. Combination therapy synergistically preserved colonic structure and normalized pathological damages (p< 0.001 and to a lesser degree Diclazuril monotherapy protected dams from colitis (p< 0.05 and gastrointestinal toxoplasmosis. Other complications included severe splenitis (p<0.001 and hepatitis (p<0.001 which were normalized with combination therapy. Conclusions. Combination Diclazuril plus Atovaquone was safe and with a novel therapeutic

Determination and correlation of spatial distribution of trace elements in normal and neoplastic breast tissues evaluated by μ-XRF

International Nuclear Information System (INIS)

Silva, M.P.; Oliveira, M.A.; Poletti, M.E.

2012-01-01

Full text: Some trace elements, naturally present in breast tissues, participate in a large number of biological processes, which include among others, activation or inhibition of enzymatic reactions and changes on cell membranes permeability, suggesting that these elements may influence carcinogenic processes. Thus, knowledge of the amounts of these elements and their spatial distribution in normal and neoplastic tissues may help in understanding the role of these elements in the carcinogenic process and tumor progression of breast cancers. Concentrations of trace elements like Ca, Fe, Cu and Zn, previously studied at LNLS using TXRF and conventional XRF, were elevated in neoplastic breast tissues compared to normal tissues. In this study we determined the spatial distribution of these elements in normal and neoplastic breast tissues using μ-XRF technique. We analyzed 22 samples of normal and neoplastic breast tissues (malignant and benign) obtained from paraffin blocks available for study at the Department of Pathology HC-FMRP/USP. From the blocks, a small fraction of material was removed and subjected to histological sections of 60 μm thick made with a microtome. The slices where placed in holder samples and covered with ultralen film. Tissue samples were irradiated with a white beam of synchrotron radiation. The samples were positioned at 45 degrees with respect to the incident beam on a table with 3 freedom degrees (x, y and z), allowing independent positioning of the sample in these directions. The white beam was collimated by a 20 μm microcapillary and samples were fully scanned. At each step, a spectrum was detected for 10 s. The fluorescence emitted by elements present in the sample was detected by a Si (Li) detector with 165 eV at 5.9 keV energy resolution, placed at 90 deg with respect to the incident beam. Results reveal that trace elements Ca-Zn and Fe-Cu could to be correlated in malignant breast tissues. Quantitative results, achieved by Spearman

Quantification of late complications after radiation therapy

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Jung, Horst; Beck-Bornholdt, Hans-Peter; Svoboda, Vladimir; Alberti, Winfried; Herrmann, Thomas

2001-01-01

Background: An increasing number of patients survive cancer after having received radiation therapy. Therefore, the occurrence of late normal tissue complications among long-term survivors is of particular concern. Methods: Sixty-three patients treated by radical surgery and irradiation for rectal carcinoma were subjected to an unconventional sandwich therapy. Preoperative irradiation was given in four fractions of 5 Gy each applied within 2 or 3 days; postoperative irradiation consisted mostly of 15x2 Gy (range, 20-40 Gy). A considerable proportion of these patients developed severe late complications (Radiother Oncol 53 (1999) 177). The data allowed a detailed analysis of complication kinetics, leading to a new model which was tested using data from the literature. Results: Data on late complications were obtained for eight different organs with a follow-up of up to 10 years. For the various organs, the percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by exponential regression. From the fit, the parameter p a was obtained, which is the percentage of patients at risk in a given year of developing a complication in a given organ during that year. The rate p a remained about constant with time. Following sandwich therapy, the annual incidence of complications in the bladder, ileum, lymphatic and soft tissue, and ureters was about the same (p a =10-14%/year), whereas complications in bone or dermis occurred at lower rates (4.7 or 7.5%/year, respectively). Discussion: Numerous data sets collected from published reports were analyzed in the same way. Many of the data sets studied were from patients in a series where there was a high incidence of late effects. Three types of kinetics for the occurrence of late effects after radiotherapy were identified: Type 1, purely exponential kinetics; Type 2, exponential kinetics, the slope of which decreased exponentially with time

Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy

International Nuclear Information System (INIS)

Hendry, Jolyon H.

2001-01-01

Purpose: Induced genomic instability generally refers to a type of damage which is transmissible down cell generations, and which results in a persistently enhanced frequency of de novo mutations, chromosomal abnormalities or lethality in a significant fraction of the descendant cell population. The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. Results: The phenomenon of spontaneous genomic instability is well known in some rare genetic diseases (e.g. Gorlin's syndrome), and there is evidence in such cases that it can lead to a greater propensity for carcinogenesis (with shortened latency) which is enhanced after irradiation. It is unclear what role induced genomic instability plays in the response of normal individuals, but persistent chromosomal instability has been detected in vivo in lymphocytes and keratinocytes from irradiated normal individuals. Such induced genomic instability might play some role in tumour response in a subset of tumours with specific defects in damage response genes, but again its contribution to radiocurability in the majority of cancer patients is unclear. In normal tissues, genomic instability induced in wild-type cells leading to delayed cell death might contribute to more severe or prolonged early reactions as a consequence of increased cell loss, a longer time required for recovery, and greater residual injury. In tumours, induced genomic instability reflected in delayed reductions in clonogenic capacity might contribute to the radiosensitivity of primary tumours, and also to a lower incidence, longer latency and slower growth rate of recurrences and metastases. Conclusions: The evidence which is reviewed shows that there is little information at present to support these propositions, but what exists is consistent with their expectations. Also, it is not yet clear to what extent mutations associated with genomic instability

Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.

Science.gov (United States)

Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Gullu Amuran, Gokce; Ozmen, Tolga; Gulluoglu, Bahadır M; Kaya, Handan; Ozer, Ayse

2017-09-01

Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. Telomeres were shorter in tumor tissues compared to controls (Pbreast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association. © 2016 Wiley Periodicals, Inc.

Binding of (/sup 3/H) progesterone to normal and neoplastic tissue samples from tumour bearing breasts

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Pollow, K; Sinnecker, R; Schmidt-Gollwitzer, M; Boquoi, E; Pollow, B [Institut fuer Molekularbiologie und Biochemie, Frauenklinik Charlottenburg der Freien Universitat, Berlin (G.F.R.)

1977-01-01

Macromolecular components of normal human mammary cytosol (obtained from 'non-malignant tissue samples' from cancer bearing breasts) which bind (/sup 3/H)progesterone in vitro were characterized by sucrose gradient centrifugation, gel filtration on Agarose, ion exchange chromatography, isoelectric focusing, competition studies and kinetic parameters. The size of the cytoplasmic binding components vary with the concentration of KCl. In the absence of KCl, the major components are characterized by sedimentation coefficients of about 4 S and 8 S. In solutions containing 0.3M KCl, the cytoplasmic components sediment at 4 S in sucrose gradient. The corticosteroid-binding component of normal human mammary cytosol both sediment at about the same rate in the presence of 0.3M KCl and chromatograph as a single component on Agarose. The isoelectric point of the progesterone-binding component of normal human mammary cytosol was located around pH 5.0. The progesterone-binding component was more thermo-labile than serum CBG. CBG was inactivated at temperatures above 45 deg C but temperature above 20 deg C destroyed specific progesterone receptor binding. Progesterone receptor concentrations in normal mammary cytosol of premenopausal women depended on the menstrual cycle. The binding of progesterone was highest around the time of ovulation. In breast tumor tissue samples the progesterone receptor concentration was lower than in the normal mammary cytosol (obtained in each case from the same tumor-bearing breast). In 5 out of 37 breast tumor samples progesterone binding activity could not be detected.

Unusual Complications of Quinalphos Poisoning

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Stalin Viswanathan

2013-01-01

Full Text Available This 40-year-old man was treated for suicidal quinalphos 25%EC consumption. He developed intermediate syndrome with normal response to repetitive nerve stimulation, pancreatitis with high enzyme elevations, and normal computed tomography and excreted black, brown, and orange urine sequentially over the first nine days of hospitalization. The last complication has not been previously reported with any organophosphate compound. He finally succumbed to complication of ventilator associated pneumonia related septic shock and ventricular tachycardia.

Normal Values of Tissue-Muscle Perfusion Indexes of Lower Limbs Obtained with a Scintigraphic Method.

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Manevska, Nevena; Stojanoski, Sinisa; Pop Gjorceva, Daniela; Todorovska, Lidija; Miladinova, Daniela; Zafirova, Beti

2017-09-01

Introduction Muscle perfusion is a physiologic process that can undergo quantitative assessment and thus define the range of normal values of perfusion indexes and perfusion reserve. The investigation of the microcirculation has a crucial role in determining the muscle perfusion. Materials and method The study included 30 examinees, 24-74 years of age, without a history of confirmed peripheral artery disease and all had normal findings on Doppler ultrasonography and pedo-brachial index of lower extremity (PBI). 99mTc-MIBI tissue muscle perfusion scintigraphy of lower limbs evaluates tissue perfusion in resting condition "rest study" and after workload "stress study", through quantitative parameters: Inter-extremity index (for both studies), left thigh/right thigh (LT/RT) left calf/right calf (LC/RC) and perfusion reserve (PR) for both thighs and calves. Results In our investigated group we assessed the normal values of quantitative parameters of perfusion indexes. Indexes ranged for LT/RT in rest study 0.91-1.05, in stress study 0.92-1.04. LC/RC in rest 0.93-1.07 and in stress study 0.93-1.09. The examinees older than 50 years had insignificantly lower perfusion reserve of these parameters compared with those younger than 50, LC (p=0.98), and RC (p=0.6). Conclusion This non-invasive scintigraphic method allows in individuals without peripheral artery disease to determine the range of normal values of muscle perfusion at rest and stress condition and to clinically implement them in evaluation of patients with peripheral artery disease for differentiating patients with normal from those with impaired lower limbs circulation.

Nonlinear optical microscopy for histology of fresh normal and cancerous pancreatic tissues.

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Wenyan Hu

Full Text Available BACKGROUND: Pancreatic cancer is a lethal disease with a 5-year survival rate of only 1-5%. The acceleration of intraoperative histological examination would be beneficial for better management of pancreatic cancer, suggesting an improved survival. Nonlinear optical methods based on two-photon excited fluorescence (TPEF and second harmonic generation (SHG of intrinsic optical biomarkers show the ability to visualize the morphology of fresh tissues associated with histology, which is promising for real-time intraoperative evaluation of pancreatic cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate whether the nonlinear optical imaging methods have the ability to characterize pancreatic histology at cellular resolution, we studied different types of pancreatic tissues by using label-free TPEF and SHG. Compared with other routine methods for the preparation of specimens, fresh tissues without processing were found to be most suitable for nonlinear optical imaging of pancreatic tissues. The detailed morphology of the normal rat pancreas was observed and related with the standard histological images. Comparatively speaking, the preliminary images of a small number of chemical-induced pancreatic cancer tissues showed visible neoplastic differences in the morphology of cells and extracellular matrix. The subcutaneous pancreatic tumor xenografts were further observed using the nonlinear optical microscopy, showing that most cells are leucocytes at 5 days after implantation, the tumor cells begin to proliferate at 10 days after implantation, and the extracellular collagen fibers become disordered as the xenografts grow. CONCLUSIONS/SIGNIFICANCE: In this study, nonlinear optical imaging was used to characterize the morphological details of fresh pancreatic tissues for the first time. We demonstrate that it is possible to provide real-time histological evaluation of pancreatic cancer by the nonlinear optical methods, which present an

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

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Milliat, F

2007-05-15

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

Arterial complications of vascular Ehlers-Danlos syndrome.

Science.gov (United States)

Eagleton, Matthew J

2016-12-01

Vascular Ehlers-Danlos syndrome (EDS) is a relatively rare genetic syndrome that occurs owing to disorders in the metabolism of fibrillary collagen. These defects affect the soft connective tissues resulting in abnormalities in the skin, joints, hollow organs, and blood vessels. Patients with these defects frequently present at a young age with spontaneous arterial complications involving the medium-sized arteries. Complications involving the hollow organs, such as spontaneous colonic perforation, are observed as well. Given the fragility of the soft tissue, open and endovascular intervention on patients with vascular EDS is fraught with high complication rates. A PubMed search was performed to identify manuscripts published related to vascular EDS. This search included more than 747 articles. These findings were cross-referenced using key terms, including endovascular, embolization, surgery, genetics, pathophysiology, connective tissue disorders, vascular complications, systematic review, type III collagen, and COL3A1. The references in key articles and review articles were evaluated for additional resources not identified in the PubMed search. Care must be taken to balance the risk of intervention vs the risk of continued observation. Life-threatening hemorrhage, however, mandates intervention. With careful, altered approaches to tissue handling, endovascular approaches may provide a safer option for managing the arterial complications observed in patients with vascular EDS. Additional hope may also be found in the use of pharmacologic agents that reduce the incidence and severity of the arterial complications. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The effect of Lyman α self-absorption on population inversions between quantum states 2 and 3 of hydrogen-like ions in recombining plasmas

International Nuclear Information System (INIS)

Tallents, G.J.

1978-01-01

The effect in recombining plasmas of Lyman α self-absorption on quasi-steady-state population inversions between quantum states n = 2 and 3 of hydrogen-like ions is theoretically investigated. It is shown how the electron density range over which population inversion is possible diminishes as Lyman α self-absorption increases. The highest degree of absorption which can be tolerated and still achieve an inversion is shown to occur when the thermal limit corresponds to n approximately equal to 4. The results of the computations are related to the conditions to be found in the expansion plume of laser-produced plasmas. (author)

The composition of engineered cartilage at the time of implantation determines the likelihood of regenerating tissue with a normal collagen architecture.

Science.gov (United States)

Nagel, Thomas; Kelly, Daniel J

2013-04-01

The biomechanical functionality of articular cartilage is derived from both its biochemical composition and the architecture of the collagen network. Failure to replicate this normal Benninghoff architecture in regenerating articular cartilage may in turn predispose the tissue to failure. In this article, the influence of the maturity (or functionality) of a tissue-engineered construct at the time of implantation into a tibial chondral defect on the likelihood of recapitulating a normal Benninghoff architecture was investigated using a computational model featuring a collagen remodeling algorithm. Such a normal tissue architecture was predicted to form in the intact tibial plateau due to the interplay between the depth-dependent extracellular matrix properties, foremost swelling pressures, and external mechanical loading. In the presence of even small empty defects in the articular surface, the collagen architecture in the surrounding cartilage was predicted to deviate significantly from the native state, indicating a possible predisposition for osteoarthritic changes. These negative alterations were alleviated by the implantation of tissue-engineered cartilage, where a mature implant was predicted to result in the formation of a more native-like collagen architecture than immature implants. The results of this study highlight the importance of cartilage graft functionality to maintain and/or re-establish joint function and suggest that engineering a tissue with a native depth-dependent composition may facilitate the establishment of a normal Benninghoff collagen architecture after implantation into load-bearing defects.

Recovering the systemic redshift of galaxies from their Lyman-alpha line profile

Science.gov (United States)

Verhamme, A.; Garel, T.; Ventou, E.; Contini, T.; Bouché, N.; Herenz, E. C.; Richard, J.; Bacon, R.; Schmidt, K. B.; Maseda, M.; Marino, R. A.; Brinchmann, J.; Cantalupo, S.; Caruana, J.; Clément, B.; Diener, C.; Drake, A. B.; Hashimoto, T.; Inami, H.; Kerutt, J.; Kollatschny, W.; Leclercq, F.; Patrício, V.; Schaye, J.; Wisotzki, L.; Zabl, J.

2018-04-01

The Lyman alpha (Lyα) line of Hydrogen is a prominent feature in the spectra of star-forming galaxies, usually redshifted by a few hundreds of km s-1 compared to the systemic redshift. This large offset hampers follow-up surveys, galaxy pair statistics and correlations with quasar absorption lines when only Lyα is available. We propose diagnostics that can be used to recover the systemic redshift directly from the properties of the Lyα line profile. We use spectroscopic observations of Lyman-Alpha Emitters (LAEs) for which a precise measurement of the systemic redshift is available. Our sample contains 13 sources detected between z ≈ 3 and z ≈ 6 as part of various Multi Unit Spectroscopic Explorer (MUSE) Guaranteed Time Observations (GTO). We also include a compilation of spectroscopic Lyα data from the literature spanning a wide redshift range (z ≈ 0 - 8). First, restricting our analysis to double-peaked Lyα spectra, we find a tight correlation between the velocity offset of the red peak with respect to the systemic redshift, V_peak^red, and the separation of the peaks. Secondly, we find a correlation between V_peak^red and the full width at half maximum of the Lyα line. Fitting formulas, to estimate systemic redshifts of galaxies with an accuracy of ≤100 km s-1 when only the Lyα emission line is available, are given for the two methods.

[O III] EMISSION AND GAS KINEMATICS IN A LYMAN-ALPHA BLOB AT z {approx} 3.1

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McLinden, Emily M. [McDonald Observatory, University of Texas at Austin, Austin, TX 78712 (United States); Malhotra, Sangeeta; Rhoads, James E. [School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85287 (United States); Hibon, Pascale [Gemini Observatory, La Serena (Chile); Weijmans, Anne-Marie [Dunlap Institute for Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, ON M5S 3H4 (Canada); Tilvi, Vithal [George P. and Cynthia Woods Mitchell Institute for Fundamental Physics and Astronomy, and Department of Physics and Astronomy, Texas A and M University, College Station, TX 77843 (United States)

2013-04-10

We present spectroscopic measurements of the [O III] emission line from two subregions of strong Ly{alpha} emission in a radio-quiet Lyman-alpha blob (LAB). The blob under study is LAB1 at z {approx} 3.1, and the [O III] detections are from the two Lyman break galaxies (LBGs) embedded in the blob halo. The [O III] measurements were made with LUCIFER on the 8.4 m Large Binocular Telescope and NIRSPEC on 10 m Keck Telescope. Comparing the redshift of the [O III] measurements to Ly{alpha} redshifts from SAURON allows us to take a step toward understanding the kinematics of the gas in the blob. Using both LUCIFER and NIRSPEC we find velocity offsets between the [O III] and Ly{alpha} redshifts that are modestly negative or consistent with 0 km s{sup -1} in both subregions studied (ranging from -72 {+-} 42- + 6 {+-} 33 km s{sup -1}). A negative offset means Ly{alpha} is blueshifted with respect to [O III] a positive offset then implies Ly{alpha} is redshifted with respect to [O III]. These results may imply that outflows are not primarily responsible for Lyman alpha escape in this LAB, since outflows are generally expected to produce a positive velocity offset. In addition, we present an [O III] line flux upper limit on a third region of LAB1, a region that is unassociated with any underlying galaxy. We find that the [O III] upper limit from the galaxy-unassociated region of the blob is at least 1.4-2.5 times fainter than the [O III] flux from one of the LBG-associated regions and has an [O III] to Ly{alpha} ratio measured at least 1.9-3.4 times smaller than the same ratio measured from one of the LBGs.

The Canada-France deep fields survey-II: Lyman-break galaxies and galaxy clustering at z ~ 3

Science.gov (United States)

Foucaud, S.; McCracken, H. J.; Le Fèvre, O.; Arnouts, S.; Brodwin, M.; Lilly, S. J.; Crampton, D.; Mellier, Y.

2003-10-01

We present a large sample of z ~ 3 U-band dropout galaxies extracted from the Canada-France deep fields survey (CFDF). Our catalogue covers an effective area of ~ 1700 arcmin2 divided between three large, contiguous fields separated widely on the sky. To IAB=24.5, the survey contains 1294 Lyman-break candidates, in agreement with previous measurements by other authors, after appropriate incompleteness corrections have been applied to our data. Based on comparisons with spectroscopic observations and simulations, we estimate that our sample of Lyman-break galaxies is contaminated by stars and interlopers (lower-redshift galaxies) at no more than { ~ } 30%. We find that omega (theta ) is well fitted by a power-law of fixed slope, gamma =1.8, even at small (theta University of Hawaii, and at the Cerro Tololo Inter-American Observatory and Mayall 4-meter Telescopes, divisions of the National Optical Astronomy Observatories, which are operated by the Association of Universities for Research in Astronomy, Inc. under cooperative agreement with the National Science Foundation.

DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing.

Science.gov (United States)

Rübe, Claudia E; Grudzenski, Saskia; Kühne, Martin; Dong, Xiaorong; Rief, Nicole; Löbrich, Markus; Rübe, Christian

2008-10-15

Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced radiosensitivity. Using a preclinical mouse model, the highly sensitive gammaH2AX-foci approach was tested to verify even subtle, genetically determined DSB repair deficiencies known to be associated with increased normal tissue radiosensitivity. By enumerating gammaH2AX-foci in blood lymphocytes and normal tissues (brain, lung, heart, and intestine), the induction and repair of DSBs after irradiation with therapeutic doses (0.1-2 Gy) was investigated in repair-proficient and repair-deficient mouse strains in vivo and blood samples irradiated ex vivo. gammaH2AX-foci analysis allowed to verify the different DSB repair deficiencies; even slight impairments caused by single polymorphisms were detected similarly in both blood lymphocytes and solid tissues, indicating that DSB repair measured in lymphocytes is valid for different and complex organs. Moreover, gammaH2AX-foci analysis of blood samples irradiated ex vivo was found to reflect repair kinetics measured in vivo and, thus, give reliable information about the individual DSB repair capacity. gammaH2AX analysis of blood and tissue samples allows to detect even minor genetically defined DSB repair deficiencies, affecting normal tissue radiosensitivity. Future studies will have to evaluate the clinical potential to identify patients more susceptible to radiation toxicities before radiotherapy.

Quantitative assessment of irradiated lung volume and lung mass in breast cancer patients treated with tangential fields in combination with deep inspiration breath hold (DIBH)

International Nuclear Information System (INIS)

Kapp, Karin Sigrid; Zurl, Brigitte; Stranzl, Heidi; Winkler, Peter

2010-01-01

Purpose: Comparison of the amount of irradiated lung tissue volume and mass in patients with breast cancer treated with an optimized tangential-field technique with and without a deep inspiration breath-hold (DIBH) technique and its impact on the normal-tissue complication probability (NTCP). Material and Methods: Computed tomography datasets of 60 patients in normal breathing (NB) and subsequently in DIBH were compared. With a Real-Time Position Management Respiratory Gating System (RPM), anteroposterior movement of the chest wall was monitored and a lower and upper threshold were defined. Ipsilateral lung and a restricted tangential region of the lung were delineated and the mean and maximum doses calculated. Irradiated lung tissue mass was computed based on density values. NTCP for lung was calculated using a modified Lyman-Kutcher-Burman (LKB) model. Results: Mean dose to the ipsilateral lung in DIBH versus NB was significantly reduced by 15%. Mean lung mass calculation in the restricted area receiving ≤ 20 Gy (M 20 ) was reduced by 17% in DIBH but associated with an increase in volume. NTCP showed an improvement in DIBH of 20%. The correlation of individual breathing amplitude with NTCP proved to be independent. Conclusion: The delineation of a restricted area provides the lung mass calculation in patients treated with tangential fields. DIBH reduces ipsilateral lung dose by inflation so that less tissue remains in the irradiated region and its efficiency is supported by a decrease of NTCP. (orig.)

A cosmic web filament revealed in Lyman-α emission around a luminous high-redshift quasar.

Science.gov (United States)

Cantalupo, Sebastiano; Arrigoni-Battaia, Fabrizio; Prochaska, J Xavier; Hennawi, Joseph F; Madau, Piero

2014-02-06

Simulations of structure formation in the Universe predict that galaxies are embedded in a 'cosmic web', where most baryons reside as rarefied and highly ionized gas. This material has been studied for decades in absorption against background sources, but the sparseness of these inherently one-dimensional probes preclude direct constraints on the three-dimensional morphology of the underlying web. Here we report observations of a cosmic web filament in Lyman-α emission, discovered during a survey for cosmic gas fluorescently illuminated by bright quasars at redshift z ≈ 2.3. With a linear projected size of approximately 460 physical kiloparsecs, the Lyman-α emission surrounding the radio-quiet quasar UM 287 extends well beyond the virial radius of any plausible associated dark-matter halo and therefore traces intergalactic gas. The estimated cold gas mass of the filament from the observed emission-about 10(12.0 ± 0.5)/C(1/2) solar masses, where C is the gas clumping factor-is more than ten times larger than what is typically found in cosmological simulations, suggesting that a population of intergalactic gas clumps with subkiloparsec sizes may be missing in current numerical models.

Comparison of normal tissue pharmacokinetics with 111In/9Y monoclonal antibody m170 for breast and prostate cancer

International Nuclear Information System (INIS)

Lehmann, Joerg; DeNardo, Gerald L.; Yuan, Aina; Shen Sui; O'Donnell, Robert T.; Richman, Carol M.; De Nardo, Sally J.

2006-01-01

Purpose: Radioactivity deposition in normal tissues limits the dose deliverable by radiopharmaceuticals (RP) in radioimmunotherapy (RIT). This study investigated the absorbed radiation dose in normal tissues for prostate cancer patients in comparison to breast cancer patients for 2 RPs using the monoclonal antibody (MAb) m170. Methods and Materials: 111 In-DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine amide (GGGF)-m170 and 111 In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) 2-iminothiolane (2IT)-m170, representing the same MAb and chelate with and without a cleavable linkage, were studied in 13 breast cancer and 26 prostate cancer patients. Dosimetry for 9 Y was calculated using 111 In MAb pharmacokinetics from the initial imaging study for each patient, using reference man- and patient-specific masses. Results: The reference man-specific radiation doses (cGy/MBq) were not significantly different for the breast and the prostate cancer patients for both RPs in all but one tissue-RP combination (liver, DOTA-2IT). The patient-specific doses had differences between the groups most of which can be related to weight differences. Conclusions: Similar normal tissue doses were calculated for two groups of patients having different cancers and genders. This similarity combined with continued careful analysis of the imaging data might allow the use of higher starting doses in early phase RIT studies

Dynamic contrast-enhanced magnetic resonance imaging: a non-invasive method to evaluate significant differences between malignant and normal tissue

International Nuclear Information System (INIS)

Rudisch, Ansgar; Kremser, Christian; Judmaier, Werner; Zunterer, Hildegard; DeVries, Alexander F.

2005-01-01

Purpose: An ever recurring challenge in diagnostic radiology is the differentiation between non-malignant and malignant tissue. Based on evidence that microcirculation of normal, non-malignant tissue differs from that of malignant tissue, the goal of this study was to assess the reliability of dynamic contrast-enhanced Magnetic Resonance Imaging (dcMRI) for differentiating these two entities. Materials and methods: DcMRI data of rectum carcinoma and gluteus maximus muscles were acquired in 41 patients. Using an fast T1-mapping sequence on a 1.5-T whole body scanner, T1-maps were dynamically retrieved before, during and after constant rate i.v. infusion of a contrast medium (CM). On the basis of the acquired data sets, PI-values were calculated on a pixel-by-pixel basis. The relevance of spatial heterogeneities of microcirculation was investigated by relative frequency histograms of the PI-values. Results: A statistically significant difference between malignant and normal tissue was found for the mean PI-value (P < 0.001; 8.95 ml/min/100 g ± 2.45 versus 3.56 ml/min/100 g ± 1.20). Additionally relative frequency distributions of PI-values with equal class intervals of 2.5 ml/min/100 g revealed significant differences between the histograms of muscles and rectum carcinoma. Conclusion: We could show that microcirculation differences between malignant and normal, non-malignant tissue can be reliably assessed by non-invasive dcMRI. Therefore, dcMRI holds great promise in the aid of cancer assessment, especially in patients where biopsy is contraindicated

Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia

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Liyuan Chen

2018-03-01

Full Text Available Background: Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.Methods: After 14 weeks of high-fat diet (HFD-fed mice, unilateral hind limb ischemia was performed. Subcutaneous white adipose tissue (WAT and brown adipose tissue (BAT fat pads were harvested from normal EGFP mice, and subcutaneously transplanted over the region of the adductor muscles of HFD mice. Blood flow was measured using Laser Doppler Scanner. Vascular density, macrophages infiltration, and macrophage polarization were examined by RT-qPCR, and immunohistochemistry.Results: We found that the transplantation of WAT derived from normal mice improved functional blood flow in HFD-fed mice compared to mice transplanted with BAT and sham-treated mice. WAT transplantation increased the recruitment of pericytes associated with nascent blood vessels, but did not affect capillary formation. Furthermore, transplantation of WAT ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the release of arteriogenic factors in ischemic muscles. Mice receiving WAT also displayed a marked reduction in several proinflammatory cytokines. In contrast, mice transplanted with BAT were glucose intolerant and demonstrated increased IL-6 levels in ischemic muscles.Conclusion: These results indicate that transplantation of adipose tissue elicits improvements in blood perfusion and beneficial effects on systemic glucose homeostasis and could be a promising therapeutic option for the treatment of diabetic peripheral arterial disease.

Complicated acute appendicitis presenting as a rapidly progressive soft tissue infection of the abdominal wall: a case report.

Science.gov (United States)

Beerle, Corinne; Gelpke, Hans; Breitenstein, Stefan; Staerkle, Ralph F

2016-12-01

We report a case of a rare complication of acute appendicitis with perforation through the abdominal wall. The case points out that an intraabdominal origin should be considered in patients presenting with rapidly spreading soft tissue infections of the trunk. A 58-year-old European woman presented to our hospital with a 1-week history of severe abdominal pain accompanied by rapidly spreading erythema and emphysema of the lower abdomen. On admission, the patient was in septic shock with leukocytosis and elevation of C-reactive protein. Among other diagnoses, necrotizing fasciitis was suspected. Computed tomography showed a large soft tissue infection with air-fluid levels spreading through the lower abdominal wall. During the operation, we found a perforated appendicitis breaking through the fascia and causing a rapidly progressive soft tissue infection of the abdominal wall. Appendicitis was the origin of the soft tissue infection. The abdominal wall was only secondarily involved. Even though perforated appendicitis as an etiology of a rapidly progressive soft tissue infection of the abdominal wall is very rare, it should be considered in the differential diagnosis of abdominal wall cellulitis. The distinction between rapidly spreading subcutaneous infection with abscess formation and early onset of necrotizing fasciitis is often difficult and can be confirmed only by surgical intervention.

Non-invasive characterization of normal and pathological tissues through dynamic infrared imaging in the hamster cheek pouch oral cancer model

Science.gov (United States)

Herrera, María. S.; Monti Hughes, Andrea; Salva, Natalia; Padra, Claudio; Schwint, Amanda; Santa Cruz, Gustavo A.

2017-05-01

Biomedical infrared thermography, a non-invasive and functional imaging method, provides information on the normal and abnormal status and response of tissues in terms of spatial and temporal variations in body infrared radiance. It is especially attractive in cancer research due to the hypervascular and hypermetabolic activity of solid tumors. Moreover, healthy tissues like skin or mucosa exposed to radiation can be examined since inflammation, changes in water content, exudation, desquamation, erosion and necrosis, between others, are factors that modify their thermal properties. In this work we performed Dynamic Infrared Imaging (DIRI) to contribute to the understanding and evaluation of normal tissue, tumor and precancerous tissue response and radiotoxicity in an in vivo model, the hamster cheek pouch, exposed to Boron Neutron Capture Therapy. In this study, we particularly focused on the observation of temperature changes under forced transient conditions associated with mass moisture transfer in the tissue-air interface, in each tissue with or without treatment. We proposed a simple mathematical procedure that considerers the heat transfer from tissue to ambient through convection and evaporation to model the transient (exponential decay o recover) thermal study. The data was fitted to determined the characteristic decay and recovery time constants of the temperature as a function of time. Also this model allowed to explore the mass flux of moisture, as a degree of evaporation occurring on the tissue surface. Tissue thermal responses under provocation tests could be used as a non-invasive method to characterize tissue physiology.

Study of interplanetary hydrogen from Lyman alpha emission and absorption determination

International Nuclear Information System (INIS)

Cazes, Serge.

1979-09-01

The purpose of the work submitted in this paper is to contribute to the study of interplanetary hydrogen from Lyman alpha emission and absorption measurements, carried out on board the D2A, OSO-8 and Copernicus satellites. This study, which was undertaken from the D2A satellite, moved us to study the interplanetary environment as from observations made from the following experiments placed on board the OSO-8 and Copernicus satellites. The experiment set up on board the OSO-8 satellite made it possible to obtain the profile of the solar alpha Lyman emission. An absorption profile was observed for the first time on these profiles and this made it possible to attribute them to interplanetary hydrogen and enabled us to make a direct and local determination of the solar ionization rate. - The spectrometer set up on board Copernicus made it possible to obtain the emission spectrum of the interplanetary environment at the same time as the geocorona. The overall velocity of the interplanetary environment was deduced from the Doppler shift between the two spectra. In the first part, the principle of the REA and POLAR experiments is recalled but only the REA experiment is described in detail, particularly the problems arising from the construction and calibration of the cell. In the second part, a study of the interplanetary environment made from the D2A determinations is presented in synthesized form. On the other hand, the study to which theses initial results led us is presented in detail. Finally, in the third part, the results obtained by means of the OSO-8 and Copernicus satellites are given [fr

Abdominal Adipose Tissue was Associated with Glomerular Hyperfiltration among Non- Diabetic and Normotensive Adults with a Normal Body Mass Index.

Directory of Open Access Journals (Sweden)

Jeonghwan Lee

Full Text Available Glomerular hyperfiltration is recognized as an early marker of progressive kidney dysfunction in the obese population. This study aimed to identify the relationship between glomerular hyperfiltration and body fat distribution measured by computed tomography (CT in healthy Korean adults. The study population included individuals aged 20-64 years who went a routine health check-up including an abdominal CT scan. We selected 4,378 individuals without diabetes and hypertension. Glomerular filtration rate was estimated using the CKD-EPI equation, and glomerular hyperfiltration was defined as the highest quintile of glomerular filtration rate. Abdominal adipose tissue areas were measured at the level of the umbilicus using a 16-detector CT scanner, and the cross-sectional area was calculated using Rapidia 2.8 CT software. The prevalence of glomerular hyperfiltration increased significantly according to the subcutaneous adipose tissue area in men (OR = 1.74 (1.16-2.61, P for trend 0.016, for the comparisons of lowest vs. highest quartile and visceral adipose tissue area in women (OR = 2.34 (1.46-3.75, P for trend < 0.001 in multivariate analysis. After stratification by body mass index (normal < 23 kg/m2, overweight ≥ 23 kg/m2, male subjects with greater subcutaneous adipose tissue, even those in the normal BMI group, had a higher prevalence of glomerular hyperfiltration (OR = 2.11 (1.17-3.80, P for trend = 0.009. Among women, the significance of visceral adipose tissue area on glomerular hyperfiltration resulted from the normal BMI group (OR = 2.14 (1.31-3.49, P for trend = 0.002. After menopause, the odds ratio of the association of glomerular hyperfiltration with subcutaneous abdominal adipose tissue increased (OR = 2.96 (1.21-7.25, P for trend = 0.013. Subcutaneous adipose tissue areas and visceral adipose tissue areas are positively associated with glomerular hyperfiltration in healthy Korean adult men and women, respectively. In post

Generation of continuous coherent radiation at Lyman-alpha and 1S-2P Spectroscopy of atomic hydrogen

NARCIS (Netherlands)

Pahl, A.; Fendel, P.; Henrich, B.R.; Walz, J.; Hansch, T.W.; Eikema, K.S.E.

2005-01-01

Continuous coherent radiation from wavelengths from 121 to 123 nm in the vacuum ultraviolet (VUV) was generated by four-wave sum-frequency mixing in mercury vapor. A yield of 20 nW at Lyman-alpha (121.57 nm) was achieved. We describe the experimental setup in detail and present a calculation of the

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

Energy Technology Data Exchange (ETDEWEB)

Milliat, F

2007-05-15

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

Mammary stem cell and macrophage markers are enriched in normal tissue adjacent to inflammatory breast cancer.