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Sample records for acute normal tissue

  1. Factors determining acute normal tissue reactions during postoperative radiotherapy in endometrial cancer: analysis of 317 consecutive cases

    analysis demonstrated that the independent risk factors for acute bladder events were BRT dose rate (P=0.002) and low parity (P=0.042) and there was a trend for EBRT dose (P=0.076). In multivariate analysis there was no impact of other clinical factors (FIGO stage, diabetes mellitus, hypertension, prior abdominal surgery) on the risk of acute bowel and/or bladder reactions nor was the impact of surgery-to-radiotherapy interval, overall radiotherapy time and overall treatment time. Conclusions: The risk of acute reactions depends both on treatment-related (BRT dose rate, EBRT dose) and patient-related factors (age, parity). Precise treatment prescription, planning and verification are of paramount concern. Further studies are warranted to evaluate the impact of extrinsic and intrinsic factors associated with acute normal tissue injury

  2. Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy

    Wijsman, R.; Dankers, F.; Troost, E.G.; Hoffman, A.L.; Heijden, E. van der; Geus-Oei, L.F. de; Bussink, J.

    2015-01-01

    BACKGROUND AND PURPOSE: The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to d

  3. Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with high-dose-rate brachytherapy for large prostate volumes

    Purpose: to evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and methods: one hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results: median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p-0.04). There was no ≥ Grade 3 acute toxicity. Conclusions: dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. (author)

  4. Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with high-dose-rate brachytherapy for large prostate volumes

    Yang, George; Strom, Tobin J.; Shrinath, Kushagra; Mellon, Eric A.; Fernandez, Daniel C.; Biagioli, Matthew C. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Wilder, Richard B., E-mail: mcbiagioli@yahoo.com [Cancer Treatment Centers of America, Newnan, GA (United States)

    2015-05-15

    Purpose: to evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and methods: one hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results: median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p-0.04). There was no ≥ Grade 3 acute toxicity. Conclusions: dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. (author)

  5. TU-F-12A-09: GLCM Texture Analysis for Normal-Tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast-Cancer Radiotherapy

    Purpose: To evaluate the morphologic and structural integrity of the breast glands using sonographic textural analysis, and identify potential early imaging signatures for radiation toxicity following breast-cancer radiotherapy (RT). Methods: Thirty-eight patients receiving breast RT participated in a prospective ultrasound imaging study. Each participant received 3 ultrasound scans: 1 week before RT (baseline), and at 6-week and 3-month follow-ups. Patients were imaged with a 10-MHz ultrasound on the four quadrant of the breast. A second order statistical method of texture analysis, called gray level co-occurrence matrix (GLCM), was employed to assess RT-induced breast-tissue toxicity. The region of interest (ROI) was 28 mm × 10 mm in size at a 10 mm depth under the skin. Twenty GLCM sonographic features, ratios of the irradiated breast and the contralateral breast, were used to quantify breast-tissue toxicity. Clinical assessment of acute toxicity was conducted using the RTOG toxicity scheme. Results: Ninety-seven ultrasound studies (776 images) were analyzed; and 5 out of 20 sonographic features showed significant differences (p < 0.05) among the baseline scans, the acute toxicity grade 1 and 2 groups. These sonographic features quantified the degree of tissue damage through homogeneity, heterogeneity, randomness, and symmetry. Energy ratio value decreased from 108±0.05 (normal) to 0.99±0.05 (Grade 1) and 0.84±0.04 (Grade 2); Entropy ratio value increased from 1.01±0.01 to 1.02±0.01 and 1.04±0.01; Contrast ratio value increased from 1.03±0.03 to 1.07±0.06 and 1.21±0.09; Variance ratio value increased from 1.06±0.03 to 1.20±0.04 and 1.42±0.10; Cluster Prominence ratio value increased from 0.98±0.02 to 1.01±0.04 and 1.25±0.07. Conclusion: This work has demonstrated that the sonographic features may serve as imaging signatures to assess radiation-induced normal tissue damage. While these findings need to be validated in a larger cohort, they suggest

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

    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 (V45) using the logistic model. Results: Twenty-three patients (46%) had Grade ≥2 GI toxicity. The mean (SD) V45 was 143 mL (99). The mean V45 values for patients with and without Grade ≥2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V45 >150 mL. The proportion of patients with Grade ≥2 GI toxicity with and without V45 >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 V45 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 V45 is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V45 could reduce the risk of Grade ≥2 GI toxicity by approximately 50% per 100 mL of bowel spared.

  7. Genetic indicators of radiotherapy normal tissue response

    Full text: The aims of this study are to identify a genetic signature for adverse normal tissue damage from clinical radiotherapy (RT) in breast cancer patients, and to characterize the differentially-regulated genes involved. We have chosen to use skin expression profiling for four main reasons; (1) skin is the tissue that expresses the damage and so is directly relevant to the investigation, (2) skin biopsies can be snap frozen to preserve and maintain the in vivo expression profile of the patient, (3) skin punch biopsies are minimally invasive which equates to a high participation rate from RT patients (4) radiosensitivity testing and similar assays of cultured cells have only a low correlation with clinical adverse reaction. We expect our molecular profiling approach will give insight into the inherent genetic status of the patient that has not been demonstrated in cellular assays. We have begun collecting and processing skin punch biopsies from unirradiated sites from informed, consenting patients with adverse (severe acute or late) reaction to the skin or subcutaneous tissue following a standard course of RT, and normal controls. We have profiled biopsies from 7 adverse normal tissue reaction patients and 4 controls. Analyses of this data has identified 202 differentially expressed genes (p<0.01) and a class prediction algorithm correctly identified as adverse reaction or normal reaction 6/7 (86%) of our test samples that it could predict. We plan to focus on the function of some of these genes to determine their biological and clinical relevance. This will include detailed analysis of several of the gene products in an effort to address why these genes are associated with clinical reaction and what signaling pathways are involved. We plan to expand our sample number to 50 severe normal tissue late reaction (RTOG Grade 3 or 4), 50 severe acute normal tissue reaction and 50 no late or acute reaction to RT (RTOG 0) patients. An expected outcome is to fabricate

  8. Radiobiological models of normal tissue reactions

    Purpose: The present review summarizes radiobiological models of normal tissue responses to radiation and their consequences for potential therapeutic interventions. Material and Methods: Common radiobiological principles and pathogenetic models can be established for classes of tissues. These models may support the development of general modalities, both therapeutic and supportive, for the modulation of these responses. Results: The stem cell concept, based on studies in standard tissue culture, describes the clonogenic survival after radiation treatment. The factors affecting cell survival are summarized as the 4 Rs of radiotherapy. Based on the stem cell concept, the reactions of normal tissue to ionising radiation were considered a consequence exclusively of the proliferative sterilisation of cells of a given target cell population. Once stem cells are inactivated, responses develop in a passive manner. However, recent studies into the pathogenesis of radiation tissue injury have clearly shown that numerous postirradiation events occur during the symptom-free latent time in irradiated cells and tissues, which modulate the manifestation of damage. These are summarized by models of tissue radiation pathology. Conclusions: Cellular radiobiology and the tissue models based on the stem cell concept assume that exclusively the sterilisation of target cells is the radiation effect which results in both acute and late tissue responses. As a consequence, the radiation sensitivity can only be modulated by modification of radiobiological parameters at the time of irradiation, while at later time points only symptomatic treatment can be applied. Tissue radiation pathology, in contrast, allows for post-irradiation modification of the manifestation of radiation sequelae in tissues. (orig.)

  9. The {sup 57}Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    Oshtrakh, M. I., E-mail: oshtrakh@gmail.com; Alenkina, I. V. [Ural Federal University, Department of Physical Techniques and Devices for Quality Control, Institute of Physics and Technology (Russian Federation); Vinogradov, A. V.; Konstantinova, T. S. [Ural State Medical University (Russian Federation); Semionkin, V. A. [Ural Federal University, Department of Physical Techniques and Devices for Quality Control, Institute of Physics and Technology (Russian Federation)

    2015-04-15

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the {sup 57}Fe hyperfine parameters for normal and patient’s tissues were detected and related to small variations in the {sup 57}Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients’ spleen and liver tissues.

  10. The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57Fe hyperfine parameters for normal and patient’s tissues were detected and related to small variations in the 57Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients’ spleen and liver tissues

  11. Endothelial perturbations and therapeutic strategies in normal tissue radiation damage

    Most cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Radiotherapy side-effects diminish patients’ quality of life, yet effective biological interventions for normal tissue damage are lacking. Protecting microvascular endothelial cells from the effects of irradiation is emerging as a targeted damage-reduction strategy. We illustrate the concept of the microvasculature as a mediator of overall normal tissue radiation toxicity through cell death, vascular inflammation (hemodynamic and molecular changes) and a change in functional capacity. Endothelial cell targeted therapies that protect against such endothelial cell perturbations and the development of acute normal tissue damage are mostly under preclinical development. Since acute radiation toxicity is a common clinical problem in cutaneous, gastrointestinal and mucosal tissues, we also focus on damage in these tissues

  12. Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

    Bazan, Jose G.; Luxton, Gary; Kozak, Margaret M.; Anderson, Eric M.; Hancock, Steven L.; Kapp, Daniel S.; Kidd, Elizabeth A.; Koong, Albert C.; Chang, Daniel T., E-mail: dtchang@stanford.edu

    2013-12-01

    Purpose: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. Methods and Materials: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. Results: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0normal tissue complication probability curve compared with treatment with Cis. Dose tolerance of PBM and the LSS subsite may be lower for

  13. Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

    Purpose: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. Methods and Materials: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. Results: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (050 = 31 Gy for LSS in the MMC group and n=1, m = 0.27, TD50 = 35 Gy for LSS in the Cis group. Conclusions: The incidence of HT3+ depends on type of chemotherapy received. Patients receiving P-IMRT ± 5FU have better bone marrow tolerance than those receiving irradiation concurrent with either Cis or MMC. Treatment with MMC has a lower TD50 and more steeply rising normal tissue complication probability curve compared with treatment with Cis. Dose tolerance of PBM and the LSS subsite may be lower for patients treated with MMC compared with Cis

  14. Radioprotection of normal tissue cells

    Maier, Patrick; Wenz, Frederik; Herskind, Carsten [Heidelberg University, Department of Radiation Oncology Universitaetsmedizin Mannheim, Medical Faculty Mannheim, Mannheim (Germany)

    2014-08-15

    Improvements of radiotherapy in combination with surgery and systemic therapy have resulted in increased survival rates of tumor patients. However, radiation-induced normal tissue toxicity is still dose limiting. Several strategies have been pursued with the goal to develop substances which may prevent or reduce damage to normal tissue. Drugs applied before radiotherapy are called radioprotectors; those given after radiotherapy to reduce long-term effects are radiomitigators. Despite more than 50 years of research, until now only two substances, amifostine and palifermin, have overcome all obstacles of clinical approval and are applied during radiotherapy of head and neck cancer or total body irradiation, respectively. However, better understanding of the cellular pathways involved in radiation response has allowed the development of several highly promising drugs functioning as scavengers of reactive oxygen species or targeting specific molecules involved in regulation of cell death pathways or cell cycle arrest. The present review describes the major targets for radioprotectors or radiomitigators currently tested in clinical trials. (orig.) [German] Verbesserungen in der Radiotherapie in Kombination mit Chirurgie und Chemotherapie fuehrten zu erhoehten Ueberlebensraten von Tumorpatienten. Trotzdem sind Strahlenfolgen am Normalgewebe weiterhin dosislimitierend. Verschiedene Ansaetze wurden verfolgt, um Substanzen zu entwickeln, die Normalgewebstoxizitaeten verhindern oder verringern. Medikamente, die vor der Radiotherapie verabreicht werden, heissen Radioprotektoren, solche die danach gegeben werden, um langfristige Effekte zu reduzieren, Radiomitigatoren. Trotz mehr als 50 Jahre Forschung ueberwanden nur zwei Substanzen, Amifostin und Palifermin, alle Huerden der klinischen Pruefung und sind fuer die Anwendung waehrend der Radiotherapie von Kopf-Hals-Tumoren bzw. bei Ganzkoerperbestrahlung zugelassen. Jedoch erlaubte das bessere Verstaendnis der Signalwege

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

    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 (AICc), 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 (Dc = 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

  16. Radiogenomics: predicting clinical normal tissue radiosensitivity

    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...

  17. Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

    Dong, Lihua [Department of Radiation Oncology, The First Hospital of Jilin University, Changchun (China); Cui, Jingkun [Department of Internal Medicine, Nanling School District Hospital of Jilin University, Changchun (China); Tang, Fengjiao; Cong, Xiaofeng [Cancer Center, The First Hospital of Jilin University, Changchun (China); Han, Fujun, E-mail: fujun_han@aliyun.com [Cancer Center, The First Hospital of Jilin University, Changchun (China)

    2015-04-01

    Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATM polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was

  18. Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

    Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATM polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was

  19. Prevalence and peak incidence of acute and late normal tissue morbidity in the DAHANCA 6&7 randomised trial with accelerated radiotherapy for head and neck cancer

    Mortensen, Hanna R.; Overgaard, Jens; Specht, Lena;

    2012-01-01

    BACKGROUND AND PURPOSE: The aim of this report was to describe the incidence and prevalence of acute and late morbidity in the DAHANCA 6&7 multicentre randomised trial with accelerated radiotherapy for squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: The DAHANCA 6&7 study...

  20. Radiation-induced normal tissue damage: implications for radiotherapy

    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)

  1. Apoptosis in normal oral tissues and odontogenesis

    Ruchita Bali

    2013-01-01

    Full Text Available Programmed cell death or apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development, and chemical-induced cell death. Inappropriate apoptosis (either too little or too much is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders, and many types of cancers. The process of apoptosis is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. An understanding of its role in the pathophysiology of oral tissues is pertinent to the development of novel therapeutic approaches. The developing tooth passes through the various morphologic stages and apoptosis is observed selectively in certain locations. This review focuses on the current knowledge of apoptosis emphasizing its role in normal oral tissues and odontogenesis.

  2. Acute Pancreatitis with Normal Serum Lipase: A Case Series

    Anish M Shah

    2010-07-01

    Full Text Available Context Acute pancreatitis is diagnosed on the basis of clinical features, biochemical tests and imaging studies. Normal serum amylase level has been reported in the setting of acute pancreatitis but normal serum lipase level in acute pancreatitis is extremely rare. Case report Herein, we present a case series of acute pancreatitis with normal serum lipase levels along with a review of the topic. Conclusion In appropriate clinical setting, the diagnosis of acute pancreatitis should be entertained even with normal serum amylase and lipase levels.

  3. Normal tissue protection for improving radiotherapy: Where are the Gaps?

    Prasanna, Pataje G S; Stone, Helen B; Wong, Rosemary S; Capala, Jacek; Bernhard, Eric J; Vikram, Bhadrasain; Coleman, C N

    2012-06-01

    Any tumor could be controlled by radiation therapy if sufficient dose were delivered to all tumor cells. Although technological advances in physical treatment delivery have been developed to allow more radiation dose conformity, normal tissues are invariably included in any radiation field within the tumor volume and also as part of the exit and entrance doses relevant for particle therapy. Mechanisms of normal tissue injury and related biomarkers are now being investigated, facilitating the discovery and development of a next generation of radiation protectors and mitigators. Bringing recent research advances stimulated by development of radiation countermeasures for mass casualties, to clinical cancer care requires understanding the impact of protectors and mitigators on tumor response. 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 to improve outcome of radiation therapy. Such advances in knowledge of tissue and organ biology, mechanisms of injury, development of predictive biomarkers and mechanisms of radioprotection have re-energized the field of normal tissue protection and mitigation. Since various factors, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response vary among tissues, successful development of radioprotectors/mitigators/treatments may require multiple approaches to address cancer site specific needs. In this review, we discuss examples of important adverse effects of radiotherapy (acute and intermediate to late occurring, when it is delivered either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors and/or mitigators for improving radiation therapy. Also, we are providing general concepts for drug development for

  4. Factors of late radiosensitivity of normal tissues

    The impact of curative radiotherapy depends mainly on the total dose delivered homogeneously in the targeted volume. Nevertheless, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. Two different side effects (acute and late) can occur during and after radiotherapy. Of particular interest are the radiation-induced sequelae due to their irreversibility and the potential impact on daily quality of life. In a same population treated in one centre with the same technique, it appears that individual radiosensitivity clearly exists. In the hypothesis that genetic is involved in this area of research, lymphocytes seem to be the tissue of choice due to easy accessibility. Recently, low percentage of CD4 and CD8 lymphocyte apoptosis were shown to be correlated with high grade of sequelae. In addition, recent data suggest that patients with severe radiation-induced late side effects possess four or more single nucleotide polymorphisms (SNP) in candidate genes (ATM, SOD2, TGFB1, XRCC1, and XRCC3) and low radiation-induced CD8 lymphocyte apoptosis in vitro. On-going studies are being analyzing the entire genome using a Genome-wide association study (GWAS) analysis. (authors)

  5. Normal tissue tolerance to external beam radiation therapy: The vagina

    The vagina is a virtual cavity involved in sexual reproduction field. Due to its anatomical location, it may be exposed in whole or in part to ionizing radiation in external radiotherapy and/or brachytherapy of the pelvic region. This review aims to describe the vaginal acute and late side effects due to radiation, probably inadequately reported in the literature. Medline and PubMed literature searches were performed using the keywords -vaginal - radiotherapy - toxicity. The acute and late functional changes after external beam radiation consist mainly of drought. Their incidences are poorly described in the literature and the delivered doses even less. Recommendations are non-existent as the normal tissue complication probability (NTCP). Brachytherapy delivers high and heterogeneous doses, making it difficult to estimate the dose. The concomitant administration of chemotherapy appears to be a factor increasing the risk of toxicity. Modern techniques of conformal radiotherapy with modulated intensity appear to have little impact on this body. Only a maximum dose on each third of the vagina appears to be currently proposed to avoid the risk of side effects. (authors)

  6. Apoptosis in normal oral tissues and odontogenesis

    Ruchita Bali; Akhilesh Chandra; Renuka Verma

    2013-01-01

    Programmed cell death or apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development, and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders, and many types of cancers. The process of apoptosis is generally ch...

  7. Fluorescence Lifetimes of Normal and Carcinomatous Human Nasopharyngeal Tissues

    Chen, M.; Li, H.; Li, B.; Chen, R.; Zheng, G.; Song, C.

    2016-03-01

    Time-resolved fluorescence spectra of normal and carcinomatous in vitro human nasopharyngeal tissues are compared. By fitting the time-resolved emission with exponential decays, mean lifetimes were obtained. There were marked differences between the lifetimes of the carcinomatous and the normal tissues. Thus, early diagnosis of nasopharyngeal carcinoma is possible. In general, comprehensive information from human tissue autofluorescence can be acquired via both time-resolved and steady-state fluorescence spectra.

  8. Pathologic evaluation of normal and perfused term placental tissue

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

    2014-01-01

    "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...... with addition of antibiotics to the medium. In the "normal" tissue, certain lesions were very frequent and showed only fair or poor interobserver agreement. Revised minimum criteria for these lesions were defined and found reproducible. This study has emphasized the value of pathologic examination as a...

  9. A radiation damage repair model for normal tissues

    Partridge, Mike [Institute of Cancer Research, Downs Road, Sutton, SM2 5PT (United Kingdom)

    2008-07-07

    A cellular Monte Carlo model describing radiation damage and repair in normal epithelial tissues is presented. The deliberately simplified model includes cell cycling, cell motility and radiation damage response (cell cycle arrest and cell death) only. Results demonstrate that the model produces a stable equilibrium system for mean cell cycle times in the range 24-96 h. Simulated irradiation of these stable equilibrium systems produced a range of responses that are shown to be consistent with experimental and clinical observation, including (i) re-epithelialization of radiation-induced lesions by a mixture of cell migration into the wound and repopulation at the periphery; (ii) observed radiosensitivity that is quantitatively consistent with both rate of induction of irreparable DNA lesions and, independently, with the observed acute oral and pharyngeal mucosal reactions to radiotherapy; (iii) an observed time between irradiation and maximum toxicity that is consistent with experimental data for skin; (iv) quantitatively accurate predictions of low-dose hyper-radiosensitivity; (v) Gomperzian repopulation for very small lesions ({approx}2000 cells) and (vi) a linear rate of re-epithelialization of 5-10 {mu}m h{sup -1} for large lesions (>15 000 cells)

  10. A radiation damage repair model for normal tissues

    Partridge, Mike

    2008-07-01

    A cellular Monte Carlo model describing radiation damage and repair in normal epithelial tissues is presented. The deliberately simplified model includes cell cycling, cell motility and radiation damage response (cell cycle arrest and cell death) only. Results demonstrate that the model produces a stable equilibrium system for mean cell cycle times in the range 24-96 h. Simulated irradiation of these stable equilibrium systems produced a range of responses that are shown to be consistent with experimental and clinical observation, including (i) re-epithelialization of radiation-induced lesions by a mixture of cell migration into the wound and repopulation at the periphery; (ii) observed radiosensitivity that is quantitatively consistent with both rate of induction of irreparable DNA lesions and, independently, with the observed acute oral and pharyngeal mucosal reactions to radiotherapy; (iii) an observed time between irradiation and maximum toxicity that is consistent with experimental data for skin; (iv) quantitatively accurate predictions of low-dose hyper-radiosensitivity; (v) Gomperzian repopulation for very small lesions (~2000 cells) and (vi) a linear rate of re-epithelialization of 5-10 µm h-1 for large lesions (>15 000 cells).

  11. Epithelial cell cultures from normal and cancerous human tissues.

    Owens, R B; Smith, H S; Nelson-Rees, W A; Springer, E L

    1976-04-01

    Thirty epithelial cell strains were isolated from human carcinomas and normal epithelial tissues by collagenase digestion and selective removal of fibroblasts with trypsin-Versene. Most strains were obtained from metastatic carcinomas or epithelia of the urinary and intestinal tracts. The success rate for growth of both neoplastic and normal tissues (excluding skin) was 38%. Six of these strains showed gross morphologic and chromosome changes typical of malignant cells. Nine resembled normal epithelium. The other 15 exhibited some degree of morphologic change from normal. PMID:176412

  12. New Fusion Transcripts Identified in Normal Karyotype Acute Myeloid Leukemia

    Hongxiu Wen; Yongjin Li; Malek, Sami N.; Kim, Yeong C.; Jia Xu; Peixian Chen; Fengxia Xiao; Xin Huang; Xianzheng Zhou; Zhenyu Xuan; Shiva Mankala; Guihua Hou; Rowley, Janet D.; Zhang, Michael Q; San Ming Wang

    2012-01-01

    Genetic aberrations contribute to acute myeloid leukemia (AML). However, half of AML cases do not contain the well-known aberrations detectable mostly by cytogenetic analysis, and these cases are classified as normal karyotype AML. Different outcomes of normal karyotype AML suggest that this subgroup of AML could be genetically heterogeneous. But lack of genetic markers makes it difficult to further study this subgroup of AML. Using paired-end RNAseq method, we performed a transcriptome analy...

  13. Computer modeling the boron compound factor in normal brain tissue

    The macroscopic distribution of borocaptate sodium (Na2B12H11SH 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

  14. Immunolocalization of transforming growth factor alpha in normal human tissues

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    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...... 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...

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

    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.)

  16. Analytical formulae in fractionated irradiation of normal tissue

    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

  17. Early and late effects of radiation on normal tissues

    The key to successful radiation therapy is obviously not the dose that is required to sterilize the last clonogenic cell in a given tumor, but the dose that can be tolerate by the immediately surrounding and unavoidably irradiated normal tissues that are vital to the patient's survival and normal functioning. Throughout the development of radiation oncology as a treatment discipline, a major goal has been the improvement of dose distribution and dose localization so that less and less normal tissue is irradiated to high doses, and therefore tumor doses can be and have been significantly increased. Thus, it is extremely important to understand the nature of radiation injury in normal tissue, the effects of tissue type and volume of tissue irradiated on the tolerance, and indeed the definition and establishment of tolerance doses themselves. This paper outlines the general principles of radiation injury in various organs, the pathophysiology of injury, and the effect of volume irradiated on the level of injury and on tolerance doses

  18. Alpha-amylase gene transcription in tissues of normal dog.

    Mocharla, H; Mocharla, R; Hodes, M E

    1990-01-01

    We studied the distribution of alpha-amylase mRNA in normal dog tissues by northern blotting (NB) and reverse transcription-polymerase chain reaction (RT-PCR) with human pancreatic (AMY2) and salivary (AMY1) alpha-amylase cDNA-specific primers. Analysis of poly(A+) RNA from various normal tissues by NB indicated the presence of detectable levels of alpha-amylase mRNA transcripts only in pancreas. Dot-blot analysis of DNA amplified with primers common to both (human) isoamylase mRNAs showed pr...

  19. Lung tissue remodeling in the acute respiratory distress syndrome

    Souza Alba Barros de

    2003-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibropro­liferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patient?s prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

  20. Role of endothelium in radiation-induced normal tissue damages

    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)

  1. Terahertz spectroscopic investigation of human gastric normal and tumor tissues

    Human dehydrated normal and cancerous gastric tissues were measured using transmission time-domain terahertz spectroscopy. Based on the obtained terahertz absorption spectra, the contrasts between the two kinds of tissue were investigated and techniques for automatic identification of cancerous tissue were studied. Distinctive differences were demonstrated in both the shape and amplitude of the absorption spectra between normal and tumor tissue. Additionally, some spectral features in the range of 0.2∼0.5 THz and 1∼1.5 THz were revealed for all cancerous gastric tissues. To systematically achieve the identification of gastric cancer, principal component analysis combined with t-test was used to extract valuable information indicating the best distinction between the two types. Two clustering approaches, K-means and support vector machine (SVM), were then performed to classify the processed terahertz data into normal and cancerous groups. SVM presented a satisfactory result with less false classification cases. The results of this study implicate the potential of the terahertz technique to detect gastric cancer. The applied data analysis methodology provides a suggestion for automatic discrimination of terahertz spectra in other applications. (paper)

  2. Optimal fractionation in radiotherapy with multiple normal tissues.

    Saberian, Fatemeh; Ghate, Archis; Kim, Minsun

    2016-06-01

    The goal in radiotherapy is to maximize the biological effect (BE) of radiation on the tumour while limiting its toxic effects on healthy anatomies. Treatment is administered over several sessions to give the normal tissue time to recover as it has better damage-repair capabilities than tumour cells. This is termed fractionation. A key problem in radiotherapy involves finding an optimal number of treatment sessions (fractions) and the corresponding dosing schedule. A major limitation of existing mathematically rigorous work on this problem is that it includes only a single normal tissue. Since essentially no anatomical region of interest includes only one normal tissue, these models may incorrectly identify the optimal number of fractions and the corresponding dosing schedule. We present a formulation of the optimal fractionation problem that includes multiple normal tissues. Our model can tackle any combination of maximum dose, mean dose and dose-volume type constraints for serial and parallel normal tissues as this is characteristic of most treatment protocols. We also allow for a spatially heterogeneous dose distribution within each normal tissue. Furthermore, we do not a priori assume that the doses are invariant across fractions. Finally, our model uses a spatially optimized treatment plan as input and hence can be seamlessly combined with any treatment planning system. Our formulation is a mixed-integer, non-convex, quadratically constrained quadratic programming problem. In order to simplify this computationally challenging problem without loss of optimality, we establish sufficient conditions under which equal-dosage or single-dosage fractionation is optimal. Based on the prevalent estimates of tumour and normal tissue model parameters, these conditions are expected to hold in many types of commonly studied tumours, such as those similar to head-and-neck and prostate cancers. This motivates a simple reformulation of our problem that leads to a closed

  3. Radiosensitization effects of nicotinamide on malignant and normal mouse tissue

    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

  4. DNA Double-Strand Break Rejoining in Complex Normal Tissues

    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

  5. Compensatory proliferation in normal tissues and tumours after irradiation

    Prolonged fractionation in radiotherapy has become standard because it has been shown to work empirically. It can now be shown that one of the rationales for this is wrong: normal tissues do not always show faster compensatory proliferation during treatment than tumours. The time of onset of compensatory proliferation depends upon the time at which cell depletion is recognised. Cell loss occurs early in rapid turnover tissues e.g. small intestine, but somewhat later in skin, and much later in slow turnover tissues such as bladder. This paper demonstrates that compensatory, rapid cell proliferation follows cell depletion and is therefore delayed for many months in some tissues. Conversely changes in the proliferation rate of experimental tumours after irradiation have been observed, resulting either from shortened cell cycle times or increased growth fractions. (Auth.)

  6. Influence of dose rate on normal tissue tolerance

    Dose rate is one of the most important factors that determine the biological effects of a given dose of radiation. In general, the effects of radiation decrease with a decrease in dose rate. Dose rates that have been used in radiation therapy range from a few cGy/day for permanently implanted interstitial sources for a few Gy/min for external beam radiation therapy and high-dose-rate intracavitary brachytherapy. Processes such as repair of sublethal and potential lethal damage, cell cycle progression and redistribution, repopulation, and reoxygenation that are important for biological effects of fractionated external beam radiation therapy are also important for low-dose-rate intracavitary brachytherapy and brachytherapy and temporarily implanted interstitial sources. Repair of sublethal damage during continuous low-dose-rate irradiation (CLDRI) is probably the most important factor underlying the dose-rate effects observed in animal and human cell lines in vitro and tumor and normal tissues in vivo (1,2). The extent to which these processes determine the effect of dose rate varies with the intrinsic radiosensitivity, repair capacity, and proliferative kinetics of the stromal cells comprising the tissue. In this paper the influence of clinically relevant dose rate on normal tissue tolerance is discussed. To quantify the dose-rate effect, the dose-rate factor (DRF), which is a ratio of the isoeffect dose for a given dose rate and the isoeffect dose of the reference dose rate, has been estimated for each normal tissue whenever possible

  7. Electrical impedance characterization of normal and cancerous human hepatic tissue

    The four-electrode method was used to measure the ex vivo complex electrical impedance of tissues from 14 hepatic tumors and the surrounding normal liver from six patients. Measurements were done in the frequency range 1–400 kHz. It was found that the conductivity of the tumor tissue was much higher than that of the normal liver tissue in this frequency range (from 0.14 ± 0.06 S m−1 versus 0.03 ± 0.01 S m−1 at 1 kHz to 0.25 ± 0.06 S m−1 versus 0.15 ± 0.03 S m−1 at 400 kHz). The Cole–Cole models were estimated from the experimental data and the four parameters (ρ0, ρ∞, α, fc) were obtained using a least-squares fit algorithm. The Cole–Cole parameters for the cancerous and normal liver are 9 ± 4 Ω m−1, 2.2 ± 0.7 Ω m−1, 0.5 ± 0.2, 140 ± 103 kHz and 50 ± 28 Ω m−1, 3.2 ± 0.6 Ω m−1, 0.64 ± 0.04, 10 ± 7 kHz, respectively. These data can contribute to developing bioelectric applications for tissue diagnostics and in tissue treatment planning with electrical fields such as radiofrequency tissue ablation, electrochemotherapy and gene therapy with reversible electroporation, nanoscale pulsing and irreversible electroporation

  8. Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

    A critical appraisal is given of the possible benefit from a reliable pre-treatment knowledge of individual normal-tissue sensitivity to radiotherapy. The considerations are in part, but not exclusively, based on the recent experience with in vitro colony-forming assays of the surviving fraction at 2 Gy, the SF2. Three strategies are reviewed: (1) to screen for rare cases with extreme radiosensitivity, so-called over-reactors, and treat these with reduced total dose, (2) to identify the sensitive tail of the distribution of 'normal' radiosensitivities, refer these patients to other treatment, and to escalate the dose to the remaining patients, or (3) to individualize dose prescriptions based on individual radiosensitivity, i.e. treating to isoeffect rather than to a specific dose-fractionation schedule. It is shown that these strategies will have a small, if any, impact on routine radiotherapy. Screening for over-reactors is hampered by the low prevalence of these among otherwise un-selected patients that leads to a low positive predictive value of in vitro radiosensitivity assays. It is argued, that this problem may persist even if the noise on current assays could be reduced to (the unrealistic value of) zero, simply because of the large biological variation in SF2. Removing the sensitive tail of the patient population, will only have a minor effect on the dose that could be delivered to the remaining patients, because of the sigmoid shape of empirical dose-response relationships. Finally, individualizing dose prescriptions based exclusively on information from a normal-tissue radiosensitivity assay, leads to a nearly symmetrical distribution of dose-changes that would produce a very small gain, or even a loss, of tumor control probability if implemented in the clinic. From a theoretical point of view, other strategies could be devised and some of these are considered in this review. Right now the most promising clinical use of in vitro radiosensitivity assays

  9. Boron distribution in normal and impaired vascular tissue

    The microdistribution of boron compounds and the response to Boron Neutron Capture Therapy (BNCT) in normal or impaired vascular structures have not been fully investigated. In this study, we measured the boron concentrations in rat normal vascular tissue for a potential application of BNCT to prevent restenosis following carotid stenting. Male inbred Wistar rats, 6 weeks of age, were used. After intravenous administration of boron compounds (BSH, BPA, or boron porphyrins), rats were killed at either 1, 2, or 3 hours, and the aortic arch, vena cava, blood, liver, kidney, muscle, skin, and brain were collected for measuring boron concentrations in the sample. Boron concentrations in vascular structures, although dependent on the time after administration, are higher than those in blood and surrounding tissue such as muscle or skin. Given that boron compounds such as boron porphyrins are incorporated into arterial tissues, and more into impaired than in normal intima, BNCT might be effective in inhibiting restenosis following carotid artery stenting or coronary artery stenting. (author)

  10. Randomized clinical trial on continuous 7-days-a-week postoperative radiotherapy for high-risk squamous cell head-and-neck cancer: A report on acute normal tissue reactions

    Background and purpose: To analyse acute mucosal reactions in patients treated with continuous accelerated postoperative irradiation (p-CAIR) compared to conventionally fractionated postoperative radiotherapy (p-CF). Patients and methods: The patients were randomly assigned to receive 63 Gy in 1.8 Gy fractions 7-days-a-week given over a period of 5 weeks (n=88), or 63 Gy in 1.8 Gy fractions given 5-days-a-week over 7 weeks (n=87). It represents 65% of an overall trial size. Acute mucosal reactions were scored using modified Dische system. Polychotomous logistic regression was used to estimate the influence of the selected variables on maximum grade of mucositis, and percent of the body weight loss during radiotherapy. Results: The average maximum Dische score and percent of the patients with confluent mucositis were higher in patients treated with p-CAIR, compared to p-CF (13.3 vs. 10.8 and 54 vs. 27%). Polychotomous logistic regression analysis revealed that fractionation scheme and tumour site have significantly influenced maximum Dische score. Tumour site (laryngeal vs. other) had even stronger influence on maximum Dische score than fractionation scheme. The average residual Dische score 8 weeks after radiotherapy was higher in p-CAIR compared to p-CF (2.1 vs. 1.4), and was, most frequently, related to persistent mucosal erythema (70 vs. 57% of pts.). No severe consequential toxicity of radiotherapy was observed, so far, in the trial. Conclusions: While the incidence, intensity and duration of mucosal reactions was higher in p-CAIR than in p-CF the accelerated treatment can be considered tolerable with respect to acute toxicity. In both arms of the trial slight or moderate mucosal erythema was the most frequent acute side effect, which did not completely subside within 8 weeks after irradiation

  11. Reliability of Quantitative Ultrasonic Assessment of Normal-Tissue Toxicity in Breast Cancer Radiotherapy

    Purpose: We have recently reported that ultrasound imaging, together with ultrasound tissue characterization (UTC), can provide quantitative assessment of radiation-induced normal-tissue toxicity. This study’s purpose is to evaluate the reliability of our quantitative ultrasound technology in assessing acute and late normal-tissue toxicity in breast cancer radiotherapy. Method and Materials: Our ultrasound technique analyzes radiofrequency echo signals and provides quantitative measures of dermal, hypodermal, and glandular tissue toxicities. To facilitate easy clinical implementation, we further refined this technique by developing a semiautomatic ultrasound-based toxicity assessment tool (UBTAT). Seventy-two ultrasound studies of 26 patients (720 images) were analyzed. Images of 8 patients were evaluated for acute toxicity (<6 months postradiotherapy) and those of 18 patients were evaluated for late toxicity (≥6 months postradiotherapy). All patients were treated according to a standard radiotherapy protocol. To assess intraobserver reliability, one observer analyzed 720 images in UBTAT and then repeated the analysis 3 months later. To assess interobserver reliability, three observers (two radiation oncologists and one ultrasound expert) each analyzed 720 images in UBTAT. An intraclass correlation coefficient (ICC) was used to evaluate intra- and interobserver reliability. Ultrasound assessment and clinical evaluation were also compared. Results: Intraobserver ICC was 0.89 for dermal toxicity, 0.74 for hypodermal toxicity, and 0.96 for glandular tissue toxicity. Interobserver ICC was 0.78 for dermal toxicity, 0.74 for hypodermal toxicity, and 0.94 for glandular tissue toxicity. Statistical analysis found significant changes in dermal (p < 0.0001), hypodermal (p = 0.0027), and glandular tissue (p < 0.0001) assessments in the acute toxicity group. Ultrasound measurements correlated with clinical Radiation Therapy Oncology Group (RTOG) toxicity scores of patients

  12. Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.

    Kosti, Idit; Jain, Nishant; Aran, Dvir; Butte, Atul J; Sirota, Marina

    2016-01-01

    The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples. A comprehensive tissue- and gene-specific analysis revealed that across the 14 tissues, correlation between mRNA and protein expression was positive and ranged from 0.36 to 0.5. We also identified 1,012 genes whose RNA and protein expression was correlated across all the tissues and examined genes and proteins that were concordantly and discordantly expressed for each tissue of interest. We extended our analysis to look for genes and proteins that were differentially correlated in cancer compared to normal tissues, showing higher levels of correlation in normal tissues. Finally, we explored the implications of these findings in the context of biomarker and drug target discovery. PMID:27142790

  13. Dietary carotenoids in normal and pathological tissues of corpus uteri.

    Sławomir Wołczyński

    2008-12-01

    Full Text Available Carotenoids and retinyl esters are the source of vitamin A in the human body and its natural derivatives takes part in the regulation of cell replication and differentiation in the human endometrium, may induce the leiomyoma growth and has a role in differentiation of endometrial adenocarcinoma. The aim of the study was to demonstrate the presence of carotenoids in tissues from the normal uterus and from various tumors of the uterine corpus, as well as to compare the total content, major carotenoids and % of carotenoids belonging to the provitamin A group between the tissues examined. Using three independent methods of chromatography (CC, TLC, HPLC we analysed 140 human samples. We identified 13 carotenoids belonging to the eg. provitamin A group and epoxy carotenoids. In all the samples beta-carotene, beta-cryptoxanthin, lutein, neoxanthin, violaxanthin and mutatoxanthin were isolated. In normal tissues, the mean carotenoid content was the highest in the follicular phase endometrium (9.9 microg/g, while the highest percentage of carotenoids belonging to provitamin A group was found in the luteal phase (18.2%. In the pathological group, the highest mean values were demonstrated for epithelial lesions (8.0 microg/g, and within this group - in endometrioid adenocarcinoma (10.8 microg/g. In both groups, violaxanthin, beta-cryptoxanthin, lutein epoxide and mutatoxanthin were the predominant carotenoids. We have demonstrated that all uterine tissues show a concentration of beta-carotene and beta-cryptoxanthin, being the source of vitamin A. The highest total values of carotenoids obtained in the group of endometrioid adenocarcinoma seem to confirm certain enzymatic defects in carotenoid metabolism in the course of the neoplastic process or some metabolic modifications. The finding of astaxanthin - the major antioxidant among carotenoids - in 63% of tissues examined is also significant.

  14. Dopamine regulates angiogenesis in normal dermal wound tissues.

    Shome, Saurav; Rana, Tapasi; Ganguly, Subhalakshmi; Basu, Biswarup; Chaki Choudhury, Sandipan; Sarkar, Chandrani; Chakroborty, Debanjan; Dasgupta, Partha Sarathi; Basu, Sujit

    2011-01-01

    Cutaneous wound healing is a normal physiological process and comprises different phases. Among these phases, angiogenesis or new blood vessel formation in wound tissue plays an important role. Skin is richly supplied by sympathetic nerves and evidences indicate the significant role of the sympathetic nervous system in cutaneous wound healing. Dopamine (DA) is an important catecholamine neurotransmitter released by the sympathetic nerve endings and recent studies have demonstrated the potent anti-angiogenic action of DA, which is mediated through its D(2) DA receptors. We therefore postulate that this endogenous catecholamine neurotransmitter may have a role in the neovascularization of dermal wound tissues and subsequently in the process of wound healing. In the present study, the therapeutic efficacy of D(2) DA receptor antagonist has been investigated for faster wound healing in a murine model of full thickness dermal wound. Our results indicate that treatment with specific D(2) DA receptor antagonist significantly expedites the process of full thickness normal dermal wound healing in mice by inducing angiogenesis in wound tissues. The underlined mechanisms have been attributed to the up-regulation of homeobox transcription factor HoxD3 and its target α5β1 integrin, which play a pivotal role in wound angiogenesis. Since D(2) DA receptor antagonists are already in clinical use for other disorders, these results have significant translational value from the bench to the bedside for efficient wound management along with other conventional treatment modalities. PMID:21949884

  15. Gene expression profiles in liver cancer and normal liver tissues

    Lian Xin Liu; Hong Chi Jiang; An Long Zhu; Jin Zhou; Xiu Qin Wang; Min Wu

    2000-01-01

    AIM To describe a liver cancer = specific gene expression profile and to identify genes that showed alteredexpression between liver cancer tissues and their adjacent nearly normal tissues.METHODS The cDNA probes which were labeled with a-32P dATP were synthesized from total RNA ofliver cancer and adjacent normal tissues and hybridized separately to two identical Atlas human cancer eDNAexpression array membranes containing 588 known genes.RESULTS Autoradiographic results were analyzed by specific Atlas ImageTM (version 1. 0) software.Among the 588 genes analyzed, 18 genes were found up-regulated in cancer, including TFDP2, Aktl, E2F-3etc, and 25 genes were down-regulated in cancer, including TDGF1, BAK, LAR, etc. Expression levels ofgenes that associated with the regulation of cell proliferation, apoptosis, differentiation, cell-cellinteraction, invasion regulators and eytokines altered mostly.CONCLUSION The result obtained from Atlas microarray provides a comprehensive liver cancer-specificexpression profile. The results can lead to the identification of liver cancer-specific biomarkers and may behelpful in early diagnosis and dentifiction of target genes for designing rational therapeutic strategies.

  16. Chronic histological effects of ultrasonic hyperthermia on normal feline brain tissue.

    Lyons, B E; Obana, W G; Borcich, J K; Kleinman, R; Singh, D; Britt, R H

    1986-05-01

    The histopathological changes associated with ultrasonic heating of normal cat brain have been correlated with thermal distributions. Ultrasound energy was applied for 50 min at different intensities to generate tissue temperatures from 42 to 48 degrees C. Animals were sacrificed at various intervals from 1 to 56 days. The organization and resolution of thermal damage was characterized by three stages of histopathological changes within the nervous tissue. The acute stage (Days 1-3) was defined by (1) extensive coagulation necrosis, (2) pyknosis of neuronal elements in the gray matter, (3) edema and vacuolation in the white matter, and (4) polymorphonuclear leukocytes. The subacute stage (Days 3-21) was characterized by (1) the appearance of lipid-laden macrophages, (2) liquefaction of the necrotic regions, (3) fibroblastic proliferation, and (4) vascular proliferation with some perivascular inflammatory infiltration (lymphocytes). Lastly, the chronic stage (Days 21-56) was defined by (1) fibrosis (reticulin and collagen formation) and (2) gliosis (reactive astrocytic proliferation) occurring around the fluid-filled necrotic center. Analysis of these data has also included a study of the lesion size versus the dose (temperature for 50 min) of heating. The results demonstrate a significant linear dose-response correlation. The results of this study indicate that the histological appearance and time course of repair of thermal injury in the normal brain tissue are analogous to acute brain necrosis resulting from cerebral infarction, except the thermal damage does not result in significant hemorrhage. PMID:3704114

  17. Mathematical model of normal tissue injury in telegammatherapy

    Belov, S.A.; Lyass, F.M.; Mamin, R.G.; Minakova, E.I.; Raevskaya, S.A. (Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Nejrokhirurgii)

    1983-03-01

    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 injuries 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 courses. Correlation with an irradiation field has been obtained for the skin. A conclusion has been made that the concept of isoefficacy of irradiation courses is conditional. Spatial-time fractionation is a promising direction in the development of radiation therapy.

  18. Targets for radiation in normal and tumor tissues

    Stem/clonogenic cell damage is generally considered an autonomous response to radiation, and the magnitude of normal and tumor tissue injury a reflection of the intrinsic radiosensitivity of these cells. However, recent studies indicated that radiation-induced microvascular dysfunction may play a critical role in stem/clonogenic cell response to radiation in several normal and tumor tissue models. Radiation-induced jejunal crypt damage, organ failure and death from the gastrointestinal syndrome were prevented at the range of 8-15 Gy when endothelial apoptosis was inhibited pharmacologically by intravenous administration of basic fibroblast growth factor (bFGF), or genetically by deletion of the acid sphingomyelinase gene. Whereas endothelium but not crypt cells expressed FGF receptor transcripts, and bFGF inhibited initial crypt damage but did not affect regeneration of surviving crypts, these data indicated that the endothelial lesion occurs prior to and may regulate crypt stem cell damage in the evolution of the GI syndrome. MCA/129 fibrosarcoma and B16F1 melanoma grown in apoptosis-resistant acid sphingomyelinase (asmase)- or Bax-deficient mice displayed markedly reduced baseline microvascular endothelial apoptosis and grew 200-400% faster than tumors on wild-type microvasculature. These data provided genetic evidence that endothelial apoptosis is a homeostatic factor regulating angiogenesis-dependent tumor growth. Furthermore, these tumors exhibited reduced endothelial apoptosis upon irradiation, and unlike wild type mice were resistant to single-dose radiation up to 20 Gy. These studies indicate that microcirculatory function may regulate normal and tumor tissue stem/clonogen cell response to radiation at the clinically relevant dose range

  19. Discrimination of premalignant lesions and cancer tissues from normal gastric tissues using Raman spectroscopy

    Luo, Shuwen; Chen, Changshui; Mao, Hua; Jin, Shaoqin

    2013-06-01

    The feasibility of early detection of gastric cancer using near-infrared (NIR) Raman spectroscopy (RS) by distinguishing premalignant lesions (adenomatous polyp, n=27) and cancer tissues (adenocarcinoma, n=33) from normal gastric tissues (n=45) is evaluated. Significant differences in Raman spectra are observed among the normal, adenomatous polyp, and adenocarcinoma gastric tissues at 936, 1003, 1032, 1174, 1208, 1323, 1335, 1450, and 1655 cm-1. Diverse statistical methods are employed to develop effective diagnostic algorithms for classifying the Raman spectra of different types of ex vivo gastric tissues, including principal component analysis (PCA), linear discriminant analysis (LDA), and naive Bayesian classifier (NBC) techniques. Compared with PCA-LDA algorithms, PCA-NBC techniques together with leave-one-out, cross-validation method provide better discriminative results of normal, adenomatous polyp, and adenocarcinoma gastric tissues, resulting in superior sensitivities of 96.3%, 96.9%, and 96.9%, and specificities of 93%, 100%, and 95.2%, respectively. Therefore, NIR RS associated with multivariate statistical algorithms has the potential for early diagnosis of gastric premalignant lesions and cancer tissues in molecular level.

  20. Reg IV Protein is Expressed in Normal Rat Tissue

    Starčević-Klasan, Gordana; Ažman, Josip; Picard, Anne; Jurišić-Eržen, Dubravka; Nikolić, Marina; Jerković, Romana

    2008-01-01

    The Reg IV gene has been documented in the colon, small intestine, stomach and pancreas of the human. Expression of the Reg IV in different cell types has been associated with regeneration, cell growth and cell survival, cell adhesion and resistance to apoptosis. It is unknown whether the Reg IV protein is present in the normal rat tissue. The aim of this study was to reveal the expression of the Reg IV protein in the rat spleen and colon. Western blot analysis using antibody spec...

  1. Toward Signaling-Driven Biomarkers Immune to Normal Tissue Contamination.

    Stansfield, John C; Rusay, Matthew; Shan, Roger; Kelton, Conor; Gaykalova, Daria A; Fertig, Elana J; Califano, Joseph A; Ochs, Michael F

    2016-01-01

    The goal of this study was to discover a minimally invasive pathway-specific biomarker that is immune to normal cell mRNA contamination for diagnosing head and neck squamous cell carcinoma (HNSCC). Using Elsevier's MedScan natural language processing component of the Pathway Studio software and the TRANSFAC database, we produced a curated set of genes regulated by the signaling networks driving the development of HNSCC. The network and its gene targets provided prior probabilities for gene expression, which guided our CoGAPS matrix factorization algorithm to isolate patterns related to HNSCC signaling activity from a microarray-based study. Using patterns that distinguished normal from tumor samples, we identified a reduced set of genes to analyze with Top Scoring Pair in order to produce a potential biomarker for HNSCC. Our proposed biomarker comprises targets of the transcription factor (TF) HIF1A and the FOXO family of TFs coupled with genes that show remarkable stability across all normal tissues. Based on validation with novel data from The Cancer Genome Atlas (TCGA), measured by RNAseq, and bootstrap sampling, the biomarker for normal vs. tumor has an accuracy of 0.77, a Matthews correlation coefficient of 0.54, and an area under the curve (AUC) of 0.82. PMID:26884679

  2. Acute effects of food, 2-deoxy-D-glucose and noradrenaline on metabolic rate and brown adipose tissue in normal and atropinised lean and obese (fa/fa) Zucker rats.

    Rothwell, N J; Saville, M E; Stock, M J

    1981-12-01

    1. Intragastric feeding (40 kJ) produced a 17% rise in metabolic rate in lean Zucker rats but only an 8% increase in obese (fa/fa) rats, and both of these responses were significantly reduced by beta-adrenergic blockade with propranolol (10 mg/kg, s.c.). 2. Parasympathetic blockade with atropine (0.5 mg/kg, s.c.) caused a doubling of the response to food in lean rats and a threefold increase in the obese mutants, such that all atropinised animals showed the same increase in metabolic rate after food. 3. Feeding also caused a significant rise in interscapular brown adipose tissue temperature, which was greatest in the lean animals and was enhanced by atropine in both groups. 4. Injection of noradrenaline (250 micrograms/kg, s.c.) caused a similar (40%) rise in metabolic rate in lean and obese animals but this response was unaffected by atropine. 5. 2-Deoxy-D-glucose injection (360 mg/kg, s.c.) depressed oxygen consumption by 25 and 8% in lean and obese rats respectively and this effect was totally abolished by atropine. 6. These results suggest that the rise in metabolic rate after a meal is partly due to sympathetic activation of brown adipose tissue. The reduced thermic response in obese Zucker rats is not due to insensitivity to noradrenaline, but may be partly due to parasympathetic inhibition of thermogenesis and partly to insensitivity to glucose availability. PMID:7322844

  3. Microbial transformation from normal oral microbiota to acute endodontic infections

    Hsiao William WL

    2012-07-01

    Full Text Available Abstract Background Endodontic infections are a leading cause of oro-facial pain and tooth loss in western countries, and may lead to severe life-threatening infections. These infections are polymicrobial with high bacterial diversity. Understanding the spatial transition of microbiota from normal oral cavities through the infected root canal to the acute periapical abscess can improve our knowledge of the pathogenesis of endodontic infections and lead to more effective treatment. We obtained samples from the oral cavity, infected root canal and periapical abscess of 8 patients (5 with localized and 3 with systemic infections. Microbial populations in these samples were analyzed using next-generation sequencing of 16S rRNA amplicons. Bioinformatics tools and statistical tests with rigorous criteria were used to elucidate the spatial transition of the microbiota from normal to diseased sites. Results On average, 10,000 partial 16S rRNA gene sequences were obtained from each sample. All sequences fell into 11 different bacterial phyla. The microbial diversity in root canal and abscess samples was significantly lower than in the oral samples. Streptococcus was the most abundant genus in oral cavities while Prevotella and Fusobacterium were most abundant in diseased samples. The microbiota community structures of root canal and abscess samples were, however, more similar to each other than to the oral cavity microbiota. Using rigorous criteria and novel bioinformatics tools, we found that Granulicatella adiacens, Eubacterium yurii, Prevotella melaninogenica, Prevotella salivae, Streptococcus mitis, and Atopobium rimae were over-represented in diseased samples. Conclusions We used a novel approach and high-throughput methodologies to characterize the microbiota associated normal and diseased oral sites in the same individuals.

  4. Genetic variation in normal tissue toxicity induced by ionizing radiation

    Radiotherapy is an important weapon in the treatment of cancer, but adverse reactions developing in the co-irradiated normal tissue can be a threat for patients. Early reactions might disturb the usual application schedule and limit the radiation dose. Late appearing and degenerative reactions might reduce or destroy normal tissue function. Genetic markers conferring the ability to identify hyper-sensitive patients in advance would considerably improve therapy. Association studies on genetic variation and occurrence of side effects should help to identify such markers. This survey includes published studies and novel data from our own laboratory. It illustrates the presence of candidate polymorphisms in genes involved in the cellular response to irradiation which could be used as predictive markers for radiosensitivity in breast or prostate cancer patients. For other tumor types such as head and neck cancers or brain tumors, the available data are much more limited. In any case, further validation of these markers is needed in large patient cohorts with systematically recorded data on side effects and patient characteristics. Genetic variation contributing to radiosensitivity should be screened on a broader basis using newly developed, more comprehensive approaches such as genome-wide association studies.

  5. Con A affinity glycoproteomics of normal human liver tissue

    2007-01-01

    In order to establish the novel high throughput, high efficiency and low cost technological platform for the research of N-glycoproteomics, to resolve the significance of characteristic expression profile of glycoprotein and to find the proteins with biological functional importance, the glycoproteins with high-mannose core and the two antennary types were purified and enriched by the Con A affinity chromatography. Con A affinity protein expression profiles of normal human liver tissue were gener- ated by using SDS-PAGE, two-dimensional electrophoresis (2-DE) followed by fast fluorescence stain- ing based on multiplexed proteomics (MP) technology. 301 visible protein spots on the gel were de- tected and 85 of glycoproteins were further successfully identified via peptide mass fingerprinting (PMF) by a matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF- MS/MS) and annotated to IPI databases. Identified glycoproteins definitely take part in the regulation of cell cycle and metabolic processes. The glycosylation sites were predicted with NetNGlyc 1.0 and NetOGlyc 3.1 software, meanwhile they were classified according to the geneontology methods. The construction of Con A affinity glycoprotein database of normal human liver tissue would contribute to the subsequent research.

  6. Options and pitfalls of normal tissues complication probability models

    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 6th '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

  7. Mineral density volume gradients in normal and diseased human tissues.

    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.

  8. Mineral density volume gradients in normal and diseased human tissues.

    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: 2820-3095 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. PMID:25856386

  9. Studies in tissue glycogen in acute stress.

    De, A K; Dey, C; Debnath, P K

    1978-01-01

    The glycogen was estimated in liver, cardiac and skeletal muscles during the recovery period after electro-shock. The supercompensation in the level of glycogen was observed in cardiac and skeletal muscles at 1 1/2 and 5 hrs respectively during the recovery period, after electro-shock. The liver glycogen level was lower than the control value after electro-shock at least upto 5 hrs of recovery period. Further, the glycogen level was observed to be minimum when the ventricular glycogen showed its supercompensation at 1 1/2 hr of recovery period. The glycogen level of those three tissues returned to control level after 24 hrs of electro-shock. PMID:567192

  10. Histopathologic reactions of normal tissues after percutaneous injection of hot saline : an experimental study in pigs

    To determine the histopathologic changes occurring in normal pig organs after percutaneous injection of hot saline. Under sonographic guidance, the livers, the gallbladders, kidneys, stomachs, and lungs of ten pigs weighing 15-20kg were punctured with a fine needle, Physiologic saline mixed with contrast medium and lipiodol was heated to 100 deg C and injected under fluoroscopic guidance. One to four weeks after injection, the animals were sacrificed and histophathologic examination was performed to investigate acute and chronic tissue responses. In all organs, coagulation necroses developed during the acute phase. Histopathologic changes observed four weeks after injection were as follows: in the liver, most damage was restored, though central necrosis persisted; in the kidney, parenchymal and uroepithelial damage fully recovered, and in the gallbladder and stomach, superficially located damage also fully recovered. In the lung, however, extensive pneumonic infiltration developed during the chronic phase. Fluoroscopic examination revealed that saline in the liver or kidneys tended to leak easily into blood vessels, the bile duct, or ureter, and corresponding regions showed mild to moderate damage during the acute phase which fully recovered in the chronic phase. In normal pigs, significant chronic damage after the injection of hot saline mixture occurred only in the lungs. (author)

  11. Normal Tissue Protectors Against Radiation Injury (Review Paper

    P. Uma Devi

    2011-02-01

    Full Text Available Radiation damages normal tissues that can adversely affect the success of cancer radiotherapy, safety of nuclear installation workers and military personnel, and public exposed to nuclear accidents. Certain chemicals are able to protect against the harmful effects of radiation. But more than 50 years of research has produced only one approved radioprotective drug, WR-2721 or amifostine. The general utility of WR-2721 is limited by its inherent toxicity and high cost. Efforts to find non-toxic radioprotectors have revealed the promising properties of some medicinal plants. This is an attempt to review the recent publications on radioprotectors and to identify the research needs relevant to developing countries.Defence Science Journal, 2011, 61(2, pp.105-112, DOI:http://dx.doi.org/10.14429/dsj.61.829

  12. Normal tissue toxicity after small field hypofractionated stereotactic body radiation

    Constine Louis S

    2008-10-01

    Full Text Available Abstract Stereotactic body radiation (SBRT is an emerging tool in radiation oncology in which the targeting accuracy is improved via the detection and processing of a three-dimensional coordinate system that is aligned to the target. With improved targeting accuracy, SBRT allows for the minimization of normal tissue volume exposed to high radiation dose as well as the escalation of fractional dose delivery. The goal of SBRT is to minimize toxicity while maximizing tumor control. This review will discuss the basic principles of SBRT, the radiobiology of hypofractionated radiation and the outcome from published clinical trials of SBRT, with a focus on late toxicity after SBRT. While clinical data has shown SBRT to be safe in most circumstances, more data is needed to refine the ideal dose-volume metrics.

  13. Statistical Validation of Normal Tissue Complication Probability Models

    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; Veld, Aart A. van' t; Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schilstra, Cornelis [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Radiotherapy Institute Friesland, Leeuwarden (Netherlands)

    2012-09-01

    Purpose: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. Methods and Materials: A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Results: Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Conclusion: Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use.

  14. The claudin gene family: expression in normal and neoplastic tissues

    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

  15. The claudin gene family: expression in normal and neoplastic tissues

    Agarwal Rachana

    2006-07-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  16. Normal breast tissue stiffness measured by a new ultrasound technique: Virtual touch tissue imaging quantification (VTIQ)

    Golatta, Michael, E-mail: Michael.Golatta@med.uni-heidelberg.de [Breast Unit, University of Heidelberg, Im Neuenheimer Feld 440, D-69120 Heidelberg (Germany); Schweitzer-Martin, Mirjam; Harcos, Aba; Schott, Sarah; Junkermann, Hans [Breast Unit, University of Heidelberg, Im Neuenheimer Feld 440, D-69120 Heidelberg (Germany); Rauch, Geraldine [Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg (Germany); Sohn, Christof; Heil, Jörg [Breast Unit, University of Heidelberg, Im Neuenheimer Feld 440, D-69120 Heidelberg (Germany)

    2013-11-01

    Objective: To evaluate normal breast tissue stiffness with virtual touch tissue imaging quantification (VTIQ) using prospectively collected data. Materials and Methods: B-mode ultrasound and VTIQ were performed in 132 breasts in 97 women. Mean values of VTIQ for parenchyma and fatty tissue were compared between those measured in healthy breasts and in the surrounding of histologically proven benign and malignant breast lesions. Moreover we reviewed VTIQ values according to breast density measured by the American College of Radiology (ACR) categories. In addition we analyzed re-test reliability of VTIQ. Results: In 132 breasts the mean VTIQ values in parenchyma were significantly higher than in fatty tissue (3.23 m/s ± 0.74 versus 2.5 m/s ± 0.61; p < 0.0001). In healthy breasts as well as in the surrounding of a benign or malignant lesions the VTIQ values of parenchyma were similar (p = 0.12). In fatty tissue, small differences between mean VTIQ values of 2.25 m/s ± 0.51, 2.52 m/s ± 0.48 and 2.65 m/s ± 0.71 (p = 0.01) in the respective groups were observed. The comparison of mean VTIQ values of parenchyma and fatty tissue in more and less dense breasts (ACR 1 + 2 versus ACR 3 + 4 breasts) also yielded no statistically significant difference. The re-test reliability of VTIQ assessed with three independent measurements was moderate (interclass-correlation of 0.52 (p < 0.0001)). Conclusion: VTIQ is a reliable method for measuring the stiffness of breast tissue. We propose standard values for healthy parenchyma and fatty tissues independent of the surrounding tissue or the ACR category.

  17. Normal breast tissue stiffness measured by a new ultrasound technique: Virtual touch tissue imaging quantification (VTIQ)

    Objective: To evaluate normal breast tissue stiffness with virtual touch tissue imaging quantification (VTIQ) using prospectively collected data. Materials and Methods: B-mode ultrasound and VTIQ were performed in 132 breasts in 97 women. Mean values of VTIQ for parenchyma and fatty tissue were compared between those measured in healthy breasts and in the surrounding of histologically proven benign and malignant breast lesions. Moreover we reviewed VTIQ values according to breast density measured by the American College of Radiology (ACR) categories. In addition we analyzed re-test reliability of VTIQ. Results: In 132 breasts the mean VTIQ values in parenchyma were significantly higher than in fatty tissue (3.23 m/s ± 0.74 versus 2.5 m/s ± 0.61; p < 0.0001). In healthy breasts as well as in the surrounding of a benign or malignant lesions the VTIQ values of parenchyma were similar (p = 0.12). In fatty tissue, small differences between mean VTIQ values of 2.25 m/s ± 0.51, 2.52 m/s ± 0.48 and 2.65 m/s ± 0.71 (p = 0.01) in the respective groups were observed. The comparison of mean VTIQ values of parenchyma and fatty tissue in more and less dense breasts (ACR 1 + 2 versus ACR 3 + 4 breasts) also yielded no statistically significant difference. The re-test reliability of VTIQ assessed with three independent measurements was moderate (interclass-correlation of 0.52 (p < 0.0001)). Conclusion: VTIQ is a reliable method for measuring the stiffness of breast tissue. We propose standard values for healthy parenchyma and fatty tissues independent of the surrounding tissue or the ACR category

  18. Tissue harmonic imaging in the evaluation of acute pancreatitis

    To evaluate the role of tissue harmonic imaging (THI) in acute pancreatitis, and to compare its findings with conventional grey-scale sonography and contrast-enhanced computed tomography (CECT) scan, we evaluated 25 patients diagnosed with acute pancreatitis on clinical examination and laboratory findings. Conventional grey-scale ultrasound followed by tissue harmonic sonography was done on the same machine followed by a CECT within 12 h of the ultrasound examination. The present study showed that sonograms obtained with THI were of much better quality than those obtained conventionally, especially for the pancreatic tail. The benefits of harmonic imaging were more apparent in obese patients and in others whose body habitus was unfavourable for sonography. In the assessment of pancreatic image quality, grey-scale imaging had an accuracy of 60, 80 and 28% in relation to the head, body and tail, respectively. In comparison, THI had a far higher accuracy of 80, 92 and 60% in relation to the head, body and tail, respectively, with the superiority being most obvious in the pancreatic tail region. There were no cases in which tissue harmonic sonography provided less information than conventional sonography. However, CECT scan remained the best modality in all patients for the evaluation of acute pancreatitis. It showed superior demonstration of all the morphological changes, ranging from minimal pancreatic oedema to extensive fluid collections, necrosis and the haemorrhage that developed in fulminant severe pancreatitis. Our experience thus suggests that THI cannot replace CT scan as the gold standard in the assessment of acute pancreatitis, as it is poor in evaluating the pancreatic tail, cannot clearly distinguish phlegmon from necrosis, and is inferior to CT in the assessment of the complications of acute pancreatitis Copyright (2004) Blackwell Publishing Asia Pty Ltd

  19. Tissue-specific splicing mutation in acute intermittent porphyria

    An inherited deficiency of porphobilinogen deaminase in humans is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease. It was previously demonstrated that porphobilinogen deaminase is encoded by two distinct mRNA species expressed in a tissue-specific manner. Analysis of the genomic sequences indicated that these two mRNAs are transcribed from two promoters and only differ in their first exon. The first mutation identified in the human porphobilinogen deaminase gene is a single-base substitution (G → A) in the canonical 5' splice donor site of intron 1. This mutation leads to a particular subtype of acute intermittent porphyria characterized by the restriction of the enzymatic defect to nonerythropoietic tissues. Hybridization analysis using olignonucleotide probes after in vitro amplification of genomic DNA offers another possibility of detecting asymptomatic carriers of the mutation in affected families

  20. Tissue-specific splicing mutation in acute intermittent porphyria

    Grandchamp, B.; Picat, C. (Laboratoire de Genetique Moleculaire, Paris (France)); Mignotte, V.; Romeo, P.H.; Goossens, M. (Institut National de la Sante et de la Recherche Medicale, Creteil (France)); Wilson, J.H.P.; Sandkuyl, L. (Erasmus Univ., Rotterdam (Netherlands)); Te Velde, K. (Saint Geertruiden Hospital, Deventer (Netherlands)); Nordmann, Y. (Hopital Louis Mourier, Colombes (France))

    1989-01-01

    An inherited deficiency of porphobilinogen deaminase in humans is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease. It was previously demonstrated that porphobilinogen deaminase is encoded by two distinct mRNA species expressed in a tissue-specific manner. Analysis of the genomic sequences indicated that these two mRNAs are transcribed from two promoters and only differ in their first exon. The first mutation identified in the human porphobilinogen deaminase gene is a single-base substitution (G {yields} A) in the canonical 5{prime} splice donor site of intron 1. This mutation leads to a particular subtype of acute intermittent porphyria characterized by the restriction of the enzymatic defect to nonerythropoietic tissues. Hybridization analysis using olignonucleotide probes after in vitro amplification of genomic DNA offers another possibility of detecting asymptomatic carriers of the mutation in affected families.

  1. On radiation damage to normal tissues and its treatment. Pt. 2; Anti-inflammatory drugs

    Michalowski, A.S. (MRC Cyclotron Unit, Hammersmith Hospital, London (United Kingdom))

    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[sub 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.).

  2. Prolonged bone marrow T1-relaxation in acute leukaemia. In vivo tissue characterization by magnetic resonance imaging

    Thomsen, C; Sørensen, P G; Karle, H;

    1987-01-01

    osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla. In the...

  3. Radiobiological studies on the behavior of normal and tumor plant tissues cultivated in vitro

    Vegetable tumoral tissue are more radiosensitive than the homologous normal tissue. Tumoral tissue are more stimulated by yeast extract and yeast s-ARN than normal tissue. Yeast extracts and s-RNA extracts from yeast also restore more the growth of tumorous tissue than normal tissue, which were subjected to gamma radiation from 60Co. A mixture of mononucleotides obtained from fractionated s-RNA has the same stimulatory effect. It is suggested that the active principle from yeast and s-RNA is a cytokinin like substance, which have been detected in yeast extract and in soluble ribonucleic acid from yeast

  4. Angiotensin-converting enzyme inhibitors - a new paradigm for protecting normal tissue from radiation injury

    Full text: Normal tissue complications after radiation therapy for cancer treatment are rare, but when they occur they can be life threatening or have devastating effects on a patient's quality of life. We present compelling evidence that angiotensin-converting enzyme inhibitors, ACEi, reduce normal tissue injury after radiation exposure. ACEi inhibits the conversion of Ang I to Ang II, a potent vasoactive hormone whose overproduction stimulates a number of cytokines, including TGF-β. Radiation protection is illustrated with results from two tissue models, mouse skin, an early responding tissue and rat optic nerve, a late responding tissue. Mouse hind legs were irradiated to 60Gy in 10 equal fractions over 2 wks. Mice were given 2.5mg/kg/day of ramipril in their drinking water. ACEi treated mice demonstrated significantly less damage than the mice in the non-drug treated, radiation alone group assessed using acute (hair loss), subacute (desquamation), and late endpoints (leg contraction). In a separate study, rat brains were irradiated stereotactically with a single focused beam of 30Gy. Six months after irradiation and 1.5mg/kg/day of ramipril, rats were assessed for optic nerve damage functionally using evoked potential to a light stimulus, structurally using Mn++ contrast-enhanced MRI, and histologically using H and E and Luxol-Fast-Blue stain for myelin. Of note is that all rat groups, including ACEi treated rats demonstrated damaged optic nerve by MRI and histology. Preliminary results indicate that ramipril conferred significant functional radiation protection since rats receiving radiation alone had a two to three times delay in the duration of the visual evoked potential, whereas 75% of rats receiving ramipril and radiation had evoked potentials that resembled that of normal untreated control rats. Our studies are unique and important for at least three reasons. This is the first report of the radiation protective effects of carboxyl-containing ACEi

  5. Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype

    Akagi, Tadayuki; Ogawa, Seishi; Dugas, Martin; KAWAMATA, NORIHIKO; Yamamoto, Go; Nannya, Yasuhito; Sanada, Masashi; Miller, Carl W.; Yung, Amanda; Schnittger, Susanne; Haferlach, Torsten; Haferlach, Claudia; Koeffler, H. Phillip

    2009-01-01

    In this study, single-nucleotide polymorphism microarray analysis was employed to identify hidden genomic abnormalities in patients with acute myeloid leukemia. The findings suggest that at least one half of cases with normal karyotype have readily identifiable genomic abnormalities.

  6. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

    Duann, Pu; Lianos, Elias A.; Ma, Jianjie; Lin, Pei-Hui

    2016-01-01

    Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed. PMID:27153058

  7. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

    Pu Duann

    2016-05-01

    Full Text Available Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed.

  8. Fluorescence lifetime of normal, benign, and malignant thyroid tissues

    Brandao, Mariana; Iwakura, Ricardo; Basilio, Fagne; Haleplian, Kaique; Ito, Amando; de Freitas, Luiz Carlos Conti; Bachmann, Luciano

    2015-06-01

    Fine-needle aspiration cytology is the standard technique to diagnose thyroid pathologies. However, this method results in a high percentage of inconclusive and false negatives. The use of time-resolved fluorescence techniques to detect biochemical composition and tissue structure alterations could help to develop a portable, minimally invasive, and nondestructive method to assist during surgical procedures. This study aimed to use fluorescence lifetimes to differentiate healthy and benign tissues from malignant thyroid tissue. The thyroid tissue was excited at 298-300 nm and the fluorescence decay registered at 340 and 450 nm. We observed fluorescence lifetimes at 340 nm emission of 0.80±0.26 and 3.94±0.47 ns for healthy tissue; 0.90±0.24 and 4.05±0.46 ns for benign lesions; and 1.21±0.14 and 4.63±0.25 ns for malignant lesions. For 450 nm emissions, we obtain lifetimes of 0.25±0.18 and 3.99±0.39 ns for healthy tissue, 0.24±0.17 and 4.20±0.48 ns for benign lesions, 0.33±0.32 and 4.55±0.55 ns for malignant lesions. Employing analysis of variance, we differentiate malignant lesions from benign and healthy tissues. In addition, we use quadratic discriminant analysis to distinguish malignant from benign and healthy tissues with an accuracy of 76.1%, sensitivity of 74.7%, and specificity of 83.3%. These results indicate that time-resolved fluorescence can assist medical evaluation of thyroid pathologies during surgeries.

  9. Normal tissue tolerance to external beam radiation therapy: Skin

    Acute skin toxicity is frequent during radiation therapy and can lead to temporary arrest of the treatment. Chronic toxicity can occur and conduct to cosmetic problems. Alopecia is the most frequent toxicity concerning hair and is most of the time reversible. Several factors linked to patients influence skin toxicity, such as under-nutrition, old age, obesity, smoking, skin diseases, autoimmune diseases, failure of DNA reparation. Skin, hair and nail toxicities depend also on radiation schedule. Acute toxicity is greater when dose per fraction increases. Chronic and acute toxicities are more often when total dose increases. Under 45 Gy, the risk of severe skin toxicity is low, and begins above 50 Gy. Skin toxicity depends also on the duration of radiotherapy and split course schedules are associated with less toxicities. Irradiation surface seems to influence skin toxicity but interaction is more complex. Reirradiation is often feasible in case of cancer recurrence but with a risk of grade 3-4 toxicity above all in head and neck cancer. The benefit/risk ratio has to be always precisely evaluated. Permanent alopecia is correlated with the follicle dose. Modern techniques of radiation therapy allow to spare skin. (authors)

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

    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.

  11. Normal tissue tolerance to external beam radiation therapy: Small bowel

    The small bowel is a hollow organ involved in the transit and absorption of food. In relation to its anatomical location, a significant amount of this organ is exposed in whole or in part to ionizing radiation in external radiotherapy during abdominal or pelvic irradiation either for primary cancers or metastasis. The acute functional changes during external beam radiation are mainly leading to diarrhea, abdominal pain and bloating. The main late side effects of irradiation of the small intestine are chronic diarrhea, malabsorption with steatorrhoea, abdominal spasms, intestinal obstruction, bleeding and fistulas. The architecture of the small intestine may be considered as parallel with a significant correlation between the irradiated volume of small bowel and the likelihood of acute toxicity, whatever the dose. The literature analysis recommends to consider the volume of small bowel receiving 15 Gy (threshold of 100 to 200 cm3) but also 30 and 50 Gy (thresholds of 35 to 300 cm3, depending on the level of dose considered). Modern techniques of conformal radiotherapy with modulated intensity will probably have beneficial impact on small bowel toxicity. (authors)

  12. Reference genes for normalization: A study of rat brain tissue

    Bonefeld, Birgit; Elfving, Betina; Wegener, Gregers

    2008-01-01

    Quantitative real-time polymerase chain reaction (qPCR) has become a widely used tool in the search for disease genes. When examining gene expression with qPCR in psychiatric diseases, endogenous reference gene(s) must be used for normalization. Traditionally, genes such as beta-actin (ActB), Gapd...

  13. Relationship between in vitro radiosensitivity of normal human skin fibroblasts and the occurrence of late normal tissue reactions after radiotherapy

    Late complications in normal tissues are limiting for the doses that can be administered during clinical radiotherapy. Awareness of these complications, and comprehension of the underlying biological mechanisms, is extremely important to improve cancer treatment. Fibrosis is one of the most critical injuries to radiotherapy. It varies significantly among patients despite of identical treatments. The large patient-to-patient variability of normal tissue sections to clinical radiation can possibly be accounted for by the considerable individual variation in cellular radiosensitivity of normal human fibroblasts, as shown in vitro. The purpose of the present investigation has been to analyze individual cellular radiosensitivity of normal human skin fibroblasts, as measured in a colony-forming assay, and the relationship to the occurrence of subcutaneous fibrosis after radiotherapy for breast cancer. (au) 97 refs

  14. Validation of Reference Genes for Normalization Gene Expression in Reverse Transcription Quantitative PCR in Human Normal Thyroid and Goiter Tissue

    Raquel Weber

    2014-01-01

    Full Text Available Reverse transcription quantitative polymerase chain reaction (RT-qPCR has been recognized as the most accurate method for quantifying mRNA transcripts, but normalization of samples is a prerequisite for correct data interpretation. So, this study aimed to evaluate the most stable reference gene for RT-qPCR in human normal thyroid and goiter tissues. Beta-actin (ACTB; glyceraldehyde-3-phosphate dehydrogenase (GAPDH; succinate dehydrogenase, subunit A, flavoprotein (Fp (SDHA; hypoxanthine phosphoribosyltransferase I (HPRTI; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ; and beta-2-microglobulin (B2M were evaluated in 14 thyroid tissue samples (7 normal and 7 goiter tissues by RT-qPCR. The mean Cq and the maximum fold change (MFC and NormFinder software were used to assess the stability of the genes. As a result, ACTB gene was more stable than GAPDH, SDHA, HPRTI, YWHAZ, and B2M. In conclusion, ACTB could be used to normalize RT-qPCR data in normal thyroid and goiter tissues.

  15. Human colon tissue in organ culture: preservation of normal and neoplastic characteristics

    Dame, Michael K.; Bhagavathula, Narasimharao; Mankey, Cohra; DaSilva, Marissa; Paruchuri, Tejaswi; Aslam, Muhammad Nadeem; Varani, James

    2010-01-01

    Normal and neoplastic human colon tissue obtained at surgery was used to establish conditions for organ culture. Optimal conditions included an atmosphere of 5% CO2 and 95% O2; tissue partially submerged with mucosa at the gas interface; and serum-free medium with 1.5 mM Ca2+ and a number of growth supplements. Histological, histochemical, and immunohistochemical features that distinguish normal and neoplastic tissue were preserved over a 2-d period. With normal tissue, this included the pres...

  16. Epicardial Fat Tissue Thickness in Preeclamptic and Normal Pregnancies

    Can, Mehmet Mustafa; Can, Esra; Ozveren, Olcay; Okuyan, Ertugrul; Ayca, Burak; Dinckal, Mustafa Hakan

    2012-01-01

    Background. Epicardial fat tissue, another form of visceral adiposity, has been proposed as a new cardiometabolic risk factor, and the possible association of epicardial fat with hypertension has been shown in some recent studies. Although epicardial fat thickness (EFT) is associated with hypertension, the relationship between preeclampsia and EFT is still unknown. The purpose of this paper is to investigate the association between the echocardiographic EFT and the severity of preeclampsia in...

  17. Expression of BCRP Gene in the Normal Lung Tissue and Lung Cancer

    2001-01-01

    Objective: To investigate the expression of novel multidrugresistance transporter (BCRP gene) from human MCF-7/AdrVp breast cancer cells in normal lung tissue and non-small lung cancer tissue. Methods: RNA was extracted immediately from fresh normal lung tissue and viable tumor tissue harvested from surgically resected specimens of non-small cell lung cancer patients. cDNA of BCRP gene was prepared by RT-PCR and was then amplified by PCR. cDNA products from those specimens were transferred to blotting membrane through electrophoresis and transferring technique and southern blot hybridization was eventually performed to detect the expression of BCRP gene. Results: RNA were extracted from 8 tumor tissue alone and 12 pairs of tumor tissue and normal lung tissue harvested from the same lung. Four patients' RNA samples with poor quality due to degrading were discarded. cDNA products of BCRP gene were obtained by RT-PCR and were then amplified by PCR in the remain 16 patients' RNA samples. Through southern blot hybridization, BCRP gene was found to be slightly expressed in various amounts in all normal lung tissue (10/10) and only in a half of tumor tissue samples (8/16). Conclusion: BCRP gene is slightly expressed in different amount in all normal lung tissue and only in a half of tumor tissue of non-small cell lung cancer patients. It is possible to induce it's overexpression and to develop multidrug resistance during chemotherapy if using anthracycline anticancer drugs.

  18. Discrimination between normal breast tissue and tumor tissue using CdTe series detector developed for photon-counting mammography

    Okamoto, Chizuru; Ihori, Akiko; Yamakawa, Tsutomu; Yamamoto, Shuichiro; Okada, Masahiro; Kato, Misa; Nakajima, Ai; Kodera, Yoshie

    2016-03-01

    We propose a new mammography system using a cadmium telluride (CdTe) series photon-counting detector, having high absorption efficiency over a wide energy range. In a previous study, we showed that the use of high X-ray energy in digital mammography is useful from the viewpoint of exposure dose and image quality. In addition, the CdTe series detector can acquire X-ray spectrum information following transmission through a subject. This study focused on the tissue composition identified using spectral information obtained by a new photon-counting detector. Normal breast tissue consists entirely of adipose and glandular tissues. However, it is very difficult to find tumor tissue in the region of glandular tissue via a conventional mammogram, especially in dense breast because the attenuation coefficients of glandular tissue and tumor tissue are very close. As a fundamental examination, we considered a simulation phantom and showed the difference between normal breast tissue and tumor tissue of various thicknesses in a three-dimensional (3D) scatter plot. We were able to discriminate between both types of tissues. In addition, there was a tendency for the distribution to depend on the thickness of the tumor tissue. Thinner tumor tissues were shown to be closer in appearance to normal breast tissue. This study also demonstrated that the difference between these tissues could be made obvious by using a CdTe series detector. We believe that this differentiation is important, and therefore, expect this technology to be applied to new tumor detection systems in the future.

  19. Quantitative methylation profiling in tumor and matched morphologically normal tissues from breast cancer patients

    In the present study, we determined the gene hypermethylation profiles of normal tissues adjacent to invasive breast carcinomas and investigated whether these are associated with the gene hypermethylation profiles of the corresponding primary breast tumors. A quantitative methylation-specific PCR assay was used to analyze the DNA methylation status of 6 genes (DAPK, TWIST, HIN-1, RASSF1A, RARβ2 and APC) in 9 normal breast tissue samples from unaffected women and in 56 paired cancerous and normal tissue samples from breast cancer patients. Normal tissue adjacent to breast cancer displayed statistically significant differences to unrelated normal breast tissues regarding the aberrant methylation of the RASSF1A (P = 0.03), RARβ2 (P = 0.04) and APC (P = 0.04) genes. Although methylation ratios for all genes in normal tissues from cancer patients were significantly lower than in the cancerous tissue from the same patient (P ≤ 0.01), in general, a clear correlation was observed between methylation ratios measured in both tissue types for all genes tested (P < 0.01). When analyzed as a categorical variable, there was a significant concordance between methylation changes in normal tissues and in the corresponding tumor for all genes tested but RASSF1A. Notably, in 73% of patients, at least one gene with an identical methylation change in cancerous and normal breast tissues was observed. Histologically normal breast tissues adjacent to breast tumors frequently exhibit methylation changes in multiple genes. These methylation changes may play a role in the earliest stages of the development of breast neoplasia

  20. Toward Signaling-Driven Biomarkers Immune to Normal Tissue Contamination

    Stansfield, John C.; Matthew Rusay; Roger Shan; Conor Kelton; Daria A. Gaykalova; Elana J Fertig; Califano, Joseph A.; Ochs, Michael F.

    2016-01-01

    The goal of this study was to discover a minimally invasive pathway-specific biomarker that is immune to normal cell mRNA contamination for diagnosing head and neck squamous cell carcinoma (HNSCC). Using Elsevier’s MedScan natural language processing component of the Pathway Studio software and the TRANSFAC database, we produced a curated set of genes regulated by the signaling networks driving the development of HNSCC. The network and its gene targets provided prior probabilities for gene ex...

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

    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 b

  2. Radioprotection by macerated extract of Nigella sativa in normal tissues of fibrosarcoma bearing mice

    Reelma Velho-Pereira; Kumar, A.; Pandey, B. N.; Mishra, K. P.; Aarti G Jagtap

    2012-01-01

    The current study was undertaken to study the effect of a macerated extract of Nigella sativa seeds in normal as well as in tumour bearing mice against gamma radiation-induced cellular damage to normal tissues. This was done to mimic the clinical setting where in, normal tissues of cancer patients undergoing radiotherapy are exposed to the deleterious effects of radiation. The protection of cellular DNA was analysed in peripheral blood leucocytes of whole body irradiated mice following pretre...

  3. Radiation-induced hypoxia may perpetuate late normal tissue injury

    Purpose: The purpose of this study was to determine whether or not hypoxia develops in rat lung tissue after radiation. Methods and Materials: Fisher-344 rats were irradiated to the right hemithorax using a single dose of 28 Gy. Pulmonary function was assessed by measuring the changes in respiratory rate every 2 weeks, for 6 months after irradiation. The hypoxia marker was administered 3 h before euthanasia. The tissues were harvested at 6 weeks and 6 months after irradiation and processed for immunohistochemistry. Results: A moderate hypoxia was detected in the rat lungs at 6 weeks after irradiation, before the onset of functional or histopathologic changes. The more severe hypoxia, that developed at the later time points (6 months) after irradiation, was associated with a significant increase in macrophage activity, collagen deposition, lung fibrosis, and elevation in the respiratory rate. Immunohistochemistry studies revealed an increase in TGF-β, VEGF, and CD-31 endothelial cell marker, suggesting a hypoxia-mediated activation of the profibrinogenic and proangiogenic pathways. Conclusion: A new paradigm of radiation-induced lung injury should consider postradiation hypoxia to be an important contributing factor mediating a continuous production of a number of inflammatory and fibrogenic cytokines

  4. Gene expression arrays as a tool to unravel mechanisms of normal tissue radiation injury and prediction of response

    Jacqueline JCM Kruse; Fiona A Stewart

    2007-01-01

    Over the past 5 years there has been a rapid increase in the use of microarray technology in the field of cancer research. The majority of studies use microarray analysis of tumor biopsies for profiling of molecular characteristics in an attempt to produce robust classifiers for prognosis. There are now several published gene sets that have been shown to predict for aggressive forms of breast cancer, where patients are most likely to benefit from adjuvant chemotherapy and tumors most likely to develop distant metastases, or be resistant to treatment. The number of publications relating to the use of microarrays for analysis of normal tissue damage, after cancer treatment or genotoxic exposure, is much more limited. A PubMed literature search was conducted using the following keywords and combination of terms: radiation, normal tissue, microarray, gene expression profiling, prediction. With respect to normal tissue radiation injury, microarrays have been used in three ways: (1) to generate gene signatures to identify sensitive and resistant populations (prognosis); (2) to identify sets of biomarker genes for estimating radiation exposure, either accidental or as a result of terrorist attack (diagnosis); (3) to identify genes and pathways involved in tissue response to injury (mechanistic). In this article we will review all (relevant) papers that covered our literature search criteria on microarray technology as it has been applied to normal tissue radiation biology and discuss how successful this has been in defining predisposition markers for radiation sensitivity or how it has helped us to unravel molecular mechanisms leading to acute and late tissue toxicity. We also discuss some of the problems and limitations in application and interpretation of such data.

  5. Perfusion changes in the RIF-1 tumour and normal tissues after carbogen and nicotinamide, individually and combined.

    Honess, D. J.; Bleehen, N.M.

    1995-01-01

    The strategy of combining carbogen breathing and nicotinamide to overcome chronic and acute hypoxia respectively is being evaluated clinically. The effects of both agents individually and in combination on relative perfusion of 400-700 mm3 RIF-1 tumours and normal tissues were measured by 86Rb extraction. Carbogen breathing alone for 6 min increased relative tumour perfusion by 50-70% compared with control at flow rates of 50 to 200 ml min-1, but the effect was lost at 300 ml min-1. All flow ...

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

    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

  7. ACUTE RENAL FAILURE WITH NORMAL PLASMA UREA LEVEL SECONDARY TO ACUTE PYELONEPHITIS IN A SINGLE KIDNEY PATIENT

    Algranati L

    2007-04-01

    Full Text Available SUMMARY: Acute renal failure is a syndrome that usually runs with an increase in creatinine and urea plasma levels. However, there are clinical situations in which this syndrome may run with an increase in plasma creatinine keeping normal the urea one. In this report we present a case of acute renal failure with normal plasma urea level secondary to an acute pyelonephritis in a single kidney patient. The patient had an increased fractional excretion of urea which could explain the normal plasma urea levels found despite of his reduced glomerular filtration. This increased urea excretion state was interpreted as a consequence of the nephrogenic diabetes insipidus and alteration of the intra-renal urea reciclying process that the acute pyelonephritis induced. In conclusion: Acute pyelonephritis in a single kidney patient can appear as a pattern of acute renal failure with normal plasma urea levels.RESUMEN: La insuficiencia renal aguda es un sindrome que característicamente cursa con niveles plasmáticos elevados de urea y creatinina. Sin embargo, hay situaciones clínicas en las cuales este sindrome puede cursar con un incremento de la creatininemia sin presentar elevación de la uremia. En este reporte presentamos un caso clínico de una insuficiencia renal aguda con uremia normal secundaria a una pielonefritis aguda en un paciente con riñón único. El paciente presentaba una elevada excreción fraccional de urea lo cual podía explicar su uremia normal pese a estar cursando una caída del filtrado gomerular. Dicha excreción de urea elevada fue interpretada como secundaria a una diabetes insipida nefrogénica y una alteración en el recirculado intra-renal de la urea ambos producto de la pielonefritis aguda. Concluimos que la pielonefritis aguda en un paciente mono-reno puede presentarse con un patrón de insuficiencia renal aguda con uremia normal.

  8. Detection of Hyperechoic Inflammatory Fatty Tissue during Transabdominal Ultrasonography: Diagnostic Role in Acute Abdomen

    Park, Seong Jin; Lee, Hae Kyung; Yi, Bum Ha [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Kim, Hyun Cheol [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of)

    2005-12-15

    To assess the incidence and diagnostic role of hyperechoic inflammatory fatty tissue (HIFT) in transabdominal ultrasonography (TAUS) for acute abdomen. With TAUS, we examined 98 consecutive patients (68 women, 30 men: mean age, 32 years: age range, 4-84 years) having acute abdominal pain. We examined the abdomen and pelvis by TAUS to determine the cause of acute abdomen, to check for the presence of HIFT, and to investigate whether it was easier and earlier to find the main cause and HIFT presence. We also prospectively evaluated the shape, distribution, and diagnostic role of HIFT. Final diagnoses consisted of 47 cases of acute appendicitis, 14 of enterocolitis, 13 of PID, 7 of gynecological hemoperitoneum, 5 of colonic diverticulitis, 3 of ovarian torsion, 2 of colon perforation, 2 of only presence of non-specific HIFT, 1 of mesenteric lymphadenitis, and 4 of normal. HIFT were seen in 67 patients (68.4%), including 44/47(93.6%) of acute appendicitis, 2/14(14.3%) of enterocolitis, 11/13(84.6%) of PID, 0/7 of hemoperitoneum, 5/5 of colonic diverticulitis, 0/3 of ovarian torsion, 2/2 of colon perforation, and 1/1 mesenteric lymphadenitis. HIFT were detected earlier than the main cause in 17/44 of acute appendicitis, 6/11 of PID, and 4/5 of colonic diverticulitis. In acute appendicitis, the shape of HIFT appeared as fat thickening along the mesoappendix in 12/44, fat thickening along the mesoappendix and the opposite side in 13/44, fat encircled appendix in 6/44, fatty mass wrapping abscess in 10/44, and diffuse intraperitoneal fat thickening in 3/44. In PID, HIFT appeared as a single fatty mass in the pelvis and lower abdomen in 6/11, wrapping pelvic abscess in 2/11, and multiple fatty masses scattered in abdomen and pelvis in 3/11. In colonic diverticulitis, all 5 cases appeared as hyperechoic hemispheric mass covering the inflamed diverticulum. HIFT are a usual US finding in patients with acute abdomen, particularly on abdominal and pelvic inflammatory conditions

  9. Normal tissue radioprotection by amifostine via Warburg-type effects.

    Koukourakis, Michael I; Giatromanolaki, Alexandra; Zois, Christos E; Kalamida, Dimitra; Pouliliou, Stamatia; Karagounis, Ilias V; Yeh, Tzu-Lan; Abboud, Martine I; Claridge, Timothy D W; Schofield, Christopher J; Sivridis, Efthimios; Simopoulos, Costantinos; Tokmakidis, Savvas P; Harris, Adrian L

    2016-01-01

    The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly understood. The effects of amifostine on human basal metabolism, mouse liver metabolism and on normal and tumor hepatic cells were studied. Indirect calorimetric canopy tests showed significant reductions in oxygen consumption and of carbon dioxide emission in cancer patients receiving amifostine. Glucose levels significantly decreased and lactate levels increased in patient venous blood. Although amifostine in vitro did not inhibit the activity of the prolyl-hydroxylase PHD2, experiments with mouse liver showed that on a short timescale WR-1065 induced expression of the Hypoxia Inducible Factor HIF1α, lactate dehydrogenase LDH5, glucose transporter GLUT2, phosphorylated pyruvate dehydrogenase pPDH and PDH-kinase. This effect was confirmed on normal mouse NCTC hepatocytes, but not on hepatoma cells. A sharp reduction of acetyl-CoA and ATP levels in NCTC cells indicated reduced mitochondrial usage of pyruvate. Transient changes of mitochondrial membrane potential and reactive oxygen species ROS production were evident. Amifostine selectively protects NCTC cells against radiation, whilst HepG2 neoplastic cells are sensitized. The radiation protection was correlates with HIF levels. These findings shed new light on the mechanism of amifostine cytoprotection and encourage clinical research with this agent for the treatment of primary and metastatic liver cancer. PMID:27507219

  10. Preparing normal tissue cells for space flight experiments.

    Koch, Claudia; Kohn, Florian P M; Bauer, Johann

    2016-01-01

    Deterioration of health is a problem in modern space flight business. In order to develop countermeasures, research has been done on human bodies and also on single cells. Relevant experiments on human cells in vitro are feasible when microgravity is simulated by devices such as the Random Positioning Machine or generated for a short time during parabolic flights. However, they become difficult in regard to performance and interpretation when long-term experiments are designed that need a prolonged stay on the International Space Station (ISS). One huge problem is the transport of living cells from a laboratory on Earth to the ISS. For this reason, mainly rapidly growing, rather robust human cells such as cancer cells, embryonic cells, or progenitor cells have been investigated on the ISS up to now. Moreover, better knowledge on the behavior of normal mature cells, which mimic the in vivo situation, is strongly desirable. One solution to the problem could be the use of redifferentiable cells, which grow rapidly and behave like cancer cells in plain medium, but are reprogrammed to normal cells when substances like retinoic acid are added. A list of cells capable of redifferentiation is provided, together with names of suitable drugs, in this review. PMID:25806650

  11. Normal tissue radioprotection by amifostine via Warburg-type effects

    Koukourakis, Michael I.; Giatromanolaki, Alexandra; Zois, Christos E.; Kalamida, Dimitra; Pouliliou, Stamatia; Karagounis, Ilias V.; Yeh, Tzu-Lan; Abboud, Martine I.; Claridge, Timothy D. W.; Schofield, Christopher J.; Sivridis, Efthimios; Simopoulos, Costantinos; Tokmakidis, Savvas P.; Harris, Adrian L.

    2016-01-01

    The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly understood. The effects of amifostine on human basal metabolism, mouse liver metabolism and on normal and tumor hepatic cells were studied. Indirect calorimetric canopy tests showed significant reductions in oxygen consumption and of carbon dioxide emission in cancer patients receiving amifostine. Glucose levels significantly decreased and lactate levels increased in patient venous blood. Although amifostine in vitro did not inhibit the activity of the prolyl-hydroxylase PHD2, experiments with mouse liver showed that on a short timescale WR-1065 induced expression of the Hypoxia Inducible Factor HIF1α, lactate dehydrogenase LDH5, glucose transporter GLUT2, phosphorylated pyruvate dehydrogenase pPDH and PDH-kinase. This effect was confirmed on normal mouse NCTC hepatocytes, but not on hepatoma cells. A sharp reduction of acetyl-CoA and ATP levels in NCTC cells indicated reduced mitochondrial usage of pyruvate. Transient changes of mitochondrial membrane potential and reactive oxygen species ROS production were evident. Amifostine selectively protects NCTC cells against radiation, whilst HepG2 neoplastic cells are sensitized. The radiation protection was correlates with HIF levels. These findings shed new light on the mechanism of amifostine cytoprotection and encourage clinical research with this agent for the treatment of primary and metastatic liver cancer. PMID:27507219

  12. Acute intermittent porphyria in two patients on anticonvulsant therapy and with normal erythrocyte porphobilinogen deaminase activity.

    Herrick, A. L.; McColl, K E; Moore, M R; Brodie, M J; Adamson, A R; Goldberg, A

    1989-01-01

    1. Acute intermittent porphyria (AIP) is sometimes termed a 'pharmacogenetic' disease. patients with genetic deficiency of the enzyme porphobilinogen deaminase are liable to develop acute attacks of porphyria if exposed to a variety of drugs. 2. Two patients are reported who had no evidence of deficiency of erythrocyte porphobilinogen deaminase yet developed typical attacks of AIP while on anticonvulsant therapy. 3. Normal activity of erythrocyte porphobilinogen deaminase does not completely ...

  13. Normal tissue tolerance to external beam radiation therapy: Peripheral nerves

    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)

  14. Normal tissue effects of the radiotherapy of head and neck cancer

    The radiation responses of several normal tissues in the treatment of tumors of the head and neck have been discussed. The severity of damage to normal tissues can vary considerably according to the quantity and quality of the radiation, amounts of tissue irradiated, temporal aspects of treatment as well as numerous biological factors. The radiation effects of several normal tissues including bone, larynx, spinal cord, ear and eye, have not been addressed in this report, but nevertheless are important in the treatment of a variety of head and neck tumors. Attention to potential normal tissue complications in the radiotherapy of head and neck cancer must be considered an integral part of the therapy. Proper management of complications may improve response to therapy and improve the quality of life

  15. Doppler sonography in renal transplants; differential diagnosis of normal from acute rejection

    We undertook a combined retrospective and prospective analysis of duplex Doppler examinations performed over a perion of 10 months in order to assess the value of Doppler study(DS)in evaluating renal allograft dysfunction. A total of 110 DS on 82 transplant patients were performed including 79 normal transplants, 29 acute rejections and 2 acute tubular necrosis(ATN). Resistive Index(RI) in 79 normal transplants ranged from 0.44 to 0.7 (Mean;0.59+0.07) in the arcuate artery, and from 0.45 to 0.75(mean;0.61+0.08) in the interlobar artery. RI in 29 cases of acute rejection ranged from 0.61 to 1.0(mean ;0.77+0.10)in the interlobar artery. In ATNRI ranged from 0.59 to 0.63(mean 0.62) in the arcuate artery, and from 0.59 to 0.62(mean 0.61) in the interlobar artery. The RI in acute rejection is significantly higher than that of the normal transplants (p<0.001). With a resistive index greater than 0.8, 100% positive predictive value was obtained for the diagnosis of acute rejection. The value less than 0.7 was unlikely to suggest acute rejection(negative predictive value 92%)

  16. Sheep bronchoalveolar carcinoma: tissue associated protein complex (TAPC) in normal lung tissue and in the tumor differed quantitatively.

    Livneh, O; Hod, I; Yegana, Y; Mashiah, A; Ben-Menahem, N; Ron, A; Sternfeld, M

    1988-01-01

    Sheep lungs experimentally and naturally affected by bronchoalveolar carcinoma were washed out exhaustively of soluble components by phosphate-buffered saline, pH 7.4 (PBS), followed by glycine buffer, pH 2.8 (GB), and then again by 1M KCl followed by PBS. The tissue matrix (TM) of the tumor-free region and the tumor-affected tissue were analysed separately by sodium dodecyl sulfate (SDS) polyacrylamide electrophoresis. Normal lung tissues obtained from normal sheep served as controls. Several protein fractions and fragments, identified in both the normal and the tumorous lung, have the molecular weight (MW) of 130,000-228,000, as compared with the major soluble tissue associated protein having MW of 70,000. Coomassie blue staining used in the SDS polyacrylamide system and alkaline phosphatase immunoreaction used in the Enzyme Linked Immunosorbant Assay (ELISA) showed tenfold increased concentration of the TAPC in the TM of the tumor tissue and in the blood of tumor-affected animals, respectively. Total concentration of the TAPC in the serum of tumor-affected animals was higher than in the normal. Immunofluorescent antibody test (IAT) detected the TAPC in the cytoplasm of tumor as well as in normal lung cells, and the study suggested that the TAPC reaches the peripheral blood during tissue destruction occurring at the tumor site, as observed by light and electron microscopy (LM and EM). The concentration of each of the TAPC fractions was higher in the tumor-affected sheep lung as compared with normal sheep lung. Antibodies prepared against the TAPC fractions were toxic to sheep lung cells in tissue culture. Tumor cells were more susceptible. PMID:2839292

  17. ACUTE RENAL FAILURE WITH NORMAL PLASMA UREA LEVEL SECONDARY TO ACUTE PYELONEPHITIS IN A SINGLE KIDNEY PATIENT

    Imperiali N

    2006-03-01

    Full Text Available SUMMARYAcute renal failure is a syndrome that usually runs with an increase in creatinine and urea plasma levels. However, there are clinical situations in which this syndrome may run with an increase in plasma creatinine keeping normal the urea one.In this report we present a case of acute renal failure with normal plasma urea level secondary to an acute pyelonephritis in a single kidney patient. The patient had an increased fractional excretion of urea which could explain the normal plasma urea levels found despite of his reduced glomerular filtration. This increased urea excretion state was interpreted as a consequence of the nephrogenic diabetes insipidus and alteration of the intra-renal urea reciclying process that the acute pyelonephritis induced. In conclusion: Acute pyelonephritis in a single kidney patient can appear as a pattern of acute renal failure with normal plasma urea levels. RESUMEN:La insuficiencia renal aguda es un sindrome que característicamente cursa con niveles plasmáticos elevados de urea y creatinina. Sin embargo, hay situaciones clínicas en las cuales este sindrome puede cursar con un incremento de la creatininemia sin presentar elevación de la uremia.En este reporte presentamos un caso clínico de una insuficiencia renal aguda con uremia normal secundaria a una pielonefritis aguda en un paciente con riñón único. El paciente presentaba una elevada excreción fraccional de urea lo cual podía explicar su uremia normal pese a estar cursando una caída del filtrado gomerular. Dicha excreción de urea elevada fue interpretada como secundaria a una diabetes insipida nefrogénica y una alteración en el recirculado intra-renal de la urea ambos producto de la pielonefritis aguda. Concluimos que la pielonefritis aguda en un paciente mono-reno puede presentarse con un patrón de insuficiencia renal aguda con uremia normal.

  18. Functional evaluation of transplanted kidneys in normal function and acute rejection using BOLD MR imaging

    In this study, we evaluated a large number of subjects using BOLD MRI to provide more information about oxygen metabolism in the normal function of transplanted kidneys and to distinguish acute graft rejection from normal function kidneys. This study included 122 subjects (20 volunteers, 72 patients with normal functioning transplants, and 21 patients with acute rejection), and 9 patients had normal function grafts received examination while grafts dysfunction occurred within 6 months during the follow-up. The R2* (1/s) values in the cortex and medulla as well as the R2* ratio of the medulla to cortex (R2* ratio of M/C) were recorded. The R2* values of the medulla were higher than those of the cortex in the normal function group and the volunteers which have a steep R2* ratio of M/C. All the R2* values in the acute rejection group were lower than those in the normal function grafts group (P 1.1) is an important reason for keeping clinical normal function.

  19. Acute tissue death (white syndrome) affects the microenvironment of tabular Acropora corals

    Andersen, Sandra Breum; Vestergaard, Maj; Ainsworth, Tracy D.;

    2010-01-01

    White syndrome (WS) is a collective term for coral diseases that cause acute tissue loss, resulting in apparently healthy tissue bordering on exposed skeleton. In this study, the microenvironmental condition and tissue structure of WS-affected tabular acroporid corals were assessed by O2 microele......White syndrome (WS) is a collective term for coral diseases that cause acute tissue loss, resulting in apparently healthy tissue bordering on exposed skeleton. In this study, the microenvironmental condition and tissue structure of WS-affected tabular acroporid corals were assessed by O2...

  20. Adipose tissue infiltration in normal-weight subjects and its impact on metabolic function.

    Moreno-Indias, Isabel; Oliva-Olivera, Wilfredo; Omiste, Antonio; Castellano-Castillo, Daniel; Lhamyani, Said; Camargo, Antonio; Tinahones, Francisco J

    2016-06-01

    Discordant phenotypes, metabolically healthy obese and unhealthy normal-weight individuals, are always interesting to provide important insights into the mechanistic link between adipose tissue dysfunction and associated metabolic alterations. Macrophages can release factors that impair the proper activity of the adipose tissue. Thus, studying subcutaneous and visceral adipose tissues, we investigated for the first time the differences in monocyte/macrophage infiltration, inflammation, and adipogenesis of normal-weight subjects who differed in their degree of metabolic syndrome. The study included 92 normal-weight subjects who differed in their degree of metabolic syndrome. Their anthropometric and biochemical parameters were measured. RNA from subcutaneous and visceral adipose tissues was isolated, and mRNA expression of monocyte/macrophage infiltration (CD68, CD33, ITGAM, CD163, EMR-1, CD206, MerTK, CD64, ITGAX), inflammation (IL-6, tumor necrosis factor alpha [TNFα], IL-10, IL-1b, CCL2, CCL3), and adipogenic and lipogenic capacity markers (PPARgamma, FABP4) were measured. Taken together, our data provide evidence of a different degree of macrophage infiltration between the adipose tissues, with a higher monocyte/macrophage infiltration in subcutaneous adipose tissue in metabolically unhealthy normal-weight subjects, whereas visceral adipose tissue remained almost unaffected. An increased macrophage infiltration of adipose tissue and its consequences, such as a decrease in adipogenesis function, may explain why both the obese and normal-weight subjects can develop metabolic diseases or remain healthy. PMID:26829067

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

    The effective atomic number (Zeff) and electron density (Ne) 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 Zeff and Ne of normal kidney and cancerous kidney in the various energy ranges and for total and partial photon interactions are tabulated. The variation of effective Ne 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 Zeff in the dual-energy dividing radiography is also discussed. The values of Zeff and Ne 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 Zeff 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)

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

    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°, 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: ► X-ray scatter spectra from normal and neoplastic breast tissues were measured. ► Shape (FWHM) of Compton peak was related with elemental composition and characteristics of each tissue type. ► A statistical hypothesis test showed clear differences between normal and neoplastic breast tissues. ► There is a strong correlation between experimental values of FWHM and effective atomic number. ► Shape (FWHM) of Compton peak can be used to provide information about elemental composition of the tissues.

  3. Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

    Benderitter, Marc; Caviggioli, Fabio; Chapel, Alain; Coppes, Robert P.; Guha, Chandan; Klinger, Marco; Malard, Olivier; Stewart, Fiona; Tamarat, Radia; Van Luijk, Peter; Limoli, Charles L.

    2014-01-01

    Significance: Targeted irradiation is an effective cancer therapy but damage inflicted to normal tissues surrounding the tumor may cause severe complications. While certain pharmacologic strategies can temper the adverse effects of irradiation, stem cell therapies provide unique opportunities for re

  4. Acetazolamide during acute hypoxia improves tissue oxygenation in the human brain.

    Wang, Kang; Smith, Zachary M; Buxton, Richard B; Swenson, Erik R; Dubowitz, David J

    2015-12-15

    Low doses of the carbonic anhydrase inhibitor acetazolamide provides accelerated acclimatization to high-altitude hypoxia and prevention of cerebral and other symptoms of acute mountain sickness. We previously observed increases in cerebral O2 metabolism (CMRO2 ) during hypoxia. In this study, we investigate whether low-dose oral acetazolamide (250 mg) reduces this elevated CMRO2 and in turn might improve cerebral tissue oxygenation (PtiO2 ) during acute hypoxia. Six normal human subjects were exposed to 6 h of normobaric hypoxia with and without acetazolamide prophylaxis. We determined CMRO2 and cerebral PtiO2 from MRI measurements of cerebral blood flow (CBF) and cerebral venous O2 saturation. During normoxia, low-dose acetazolamide resulted in no significant change in CBF, CMRO2 , or PtiO2 . During hypoxia, we observed increases in CBF [48.5 (SD 12.4) (normoxia) to 65.5 (20.4) ml·100 ml(-1)·min(-1) (hypoxia), P < 0.05] and CMRO2 [1.54 (0.19) to 1.79 (0.25) μmol·ml(-1)·min(-1), P < 0.05] and a dramatic decline in PtiO2 [25.0 to 11.4 (2.7) mmHg, P < 0.05]. Acetazolamide prophylaxis mitigated these rises in CBF [53.7 (20.7) ml·100 ml(-1)·min(-1) (hypoxia + acetazolamide)] and CMRO2 [1.41 (0.09) μmol·ml(-1)·min(-1) (hypoxia + acetazolamide)] associated with acute hypoxia but also reduced O2 delivery [6.92 (1.45) (hypoxia) to 5.60 (1.14) mmol/min (hypoxia + acetazolamide), P < 0.05]. The net effect was improved cerebral tissue PtiO2 during acute hypoxia [11.4 (2.7) (hypoxia) to 16.5 (3.0) mmHg (hypoxia + acetazolamide), P < 0.05]. In addition to its renal effect, low-dose acetazolamide is effective at the capillary endothelium, and we hypothesize that local interruption in cerebral CO2 excretion accounts for the improvements in CMRO2 and ultimately in cerebral tissue oxygenation during hypoxia. This study suggests a potentially pivotal role of cerebral CO2 and pH in modulating CMRO2 and PtiO2 during acute hypoxia. PMID:26472861

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

    Ai, H [IU School of Medicine, Indianapolis, IN (United States); Zhang, H [Northwestern Memorial Hospital, Chicago, IL (United States)

    2014-06-01

    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.

  6. Expression of Resistin Protein in Normal Human Subcutaneous Adipose Tissue and Pregnant Women Subcutaneous Adipose Tissue and Placenta

    ZHOU Yongming; GUO Tiecheng; ZHANG Muxun; GUO Wei; YU Meixia; XUE Keying; HUANG Shiang; CHEN Yanhong; ZHU Huanli; XU Lijun

    2006-01-01

    The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta and the relationship between obesity, type 2 diabetes mellitus (T2DM), pregnant physiological insulin resistance (IR) and gestational diabetes mellitus (GDM) was investigated. The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta was detected by using Western blotting method.Fasting serum glucose concentration was measured by glucose oxidase assay. Serum cholesterol (CHOL), serum triglycerides (TG), serum HDL cholesterol (HDL-C) and serum LDL cholesterol (LDL-C) were determined by full automatic biochemical instrument. Fasting insulin was measured by enzyme immunoassay to calculate insulin resistance index (IRI). Height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured to calculate body mass index (BMI) and body fat percentage (BF %). Resistin protein expression in pregnant women placental tissue (67 905±8441) (arbitrary A values) was much higher than that in subcutaneous adipose tissue in pregnant women abdomen (40 718 ± 3818, P < 0.01), non-pregnant women abdomen (38 288±2084, P<0.01), normal human abdomen (39 421±6087, P<0.01)and thigh (14 942 ±6706, P<0. 001) respectively. The resistin expression in abdominal subcutaneous adipose tissue showed no significant difference among pregnant, non-pregnant women and normal human, but much higher than that in thigh subcutaneous adipose tissue (P<0. 001). Pearson analysis revealed that resistin protein was correlated with BMI (r=0.42), fasting insulin concentration (r=0.38),IRI (r=0. 34), BF % (r=0.43) and fasting glucose (r=0. 39), but not with blood pressure,CHOL, TG, HDL-C and LDL-C. It was suggested that resistin protein expression in human abdominal subcutaneous adipose tissue was much higher

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

    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 cm3 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% (1σ) for a mean dose response gradient γ in the range 2 - 3. For more steeply responding tumors and normal tissues even stricter requirements may be desirable. (author). 15 refs, 6 figs

  8. Localization of the ABCG2 mitoxantrone resistance-associated protein in normal tissues

    Fetsch, Patricia A; Abati, Andrea; Litman, Thomas;

    2006-01-01

    determine the expression and localization of the 72kDa ABC half-transporter ABCG2 in normal tissues. Formalin-fixed, paraffin embedded archival tissue from 31 distinct normal tissues with an average of eight separate tissue samples of each were immunostained with rabbit-anti-ABCG2 antibody 405 using a...... modified avidin-biotin procedure. As a negative control, each sample was also stained with antibody pre-adsorbed with peptide to assess background staining. As a means of verification, selected tissues were also stained with the commercially available monoclonal antibody 5D3. ABCG2 positivity was...... ABCG2 have a significant secretory function. These data suggest a dual function for ABCG2 in some tissues: the excretion of toxins and xenobiotics including anti-cancer agents and a potential, as-yet undefined role in the secretion of endogenous substrates....

  9. Spectral Absorption and Scattering Properties of Normal and Bruised Apple Tissue

    Knowledge of the spectral absorption and scattering properties of apple tissue, especially bruised tissue, can help us develop an effective method for detecting bruises during postharvest sorting and grading. This research was intended to determine the optical properties of normal and bruised apple ...

  10. Diffusion optical spectroscopy of cancerous and normal prostate tissues in time-resolved and frequency domain

    Zhou, Kenneth J.; Pu, Yang; Chen, Jun

    2014-03-01

    It is well-known that light transport can be well described using Maxwell's electromagnetic theory. In biological tissue, the scattering particles cause the interaction of scattered waves from neighboring particles. Since such interaction cannot be ignored, multiple scattering occurs. The theoretical solution of multiple scattering is complicated. A suitable description is that the wavelike behavior of light is ignored and the transport of an individual photon is considered to be absorbed or scattered. This is known as the Radiative Transfer Equation (RTE) theory. Analytical solutions to the RTE that explicitly describes photon migration can be obtained by introducing some proper approximations. One of the most popular models used in the field of tissue optics is the Diffusion Approximation (DA). In this study, we report on the results of our initial study of optical properties of ex vivo normal and cancerous prostate tissues and how tissue parameters affect the near infrared light transporting in the two types of tissues. The time-resolved transport of light is simulated as an impulse isotropic point source of energy within a homogeneous unbounded medium with different absorption and scattering properties of cancerous and normal prostate tissues. Light source is also modulated sinusoidally to yield a varied fluence rate in frequency domain at a distant observation point within the cancerous and normal prostate tissues. Due to difference of the absorption and scattering coefficients between cancerous and normal tissues, the expansion of light pulse, intensity, phase are found to be different.

  11. Distribution of phospholipase C isozymes in normal human lung tissue and their immunohistochemical localization.

    Hwang, S. C.; Park, K. H.; Ha, M. J.; Noh, I. S.; Park, T. B.; Lee, Y. H.

    1996-01-01

    Phospholipase C(PLC) plays a central role in signal transduction and it is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC identified and cloned. However, there are no report of PLC distribution in human lung tissue or their significances in pulmonary diseases. Presence of various PLC isozymes in normal human lung tissue was studied from surgical specimens. PLC isozymes in tissue extracts of the lung were partially puri...

  12. Distribution of somatostatin receptors in normal and neoplastic human tissues: recent advances and potential relevance.

    Reubi, J. C.; Schaer, J C; Markwalder, R.; Waser, B; Horisberger, U.; Laissue, J

    1997-01-01

    This short review describes the localization of somatostatin receptors with in vitro receptor autoradiography techniques in several non-classical, normal human somatostatin target tissues as well as in selected human tumors. In addition to brain, gut and neuroendocrine localizations, somatostatin receptors are expressed in most lymphatic tissues, including gut-associated lymphatic tissue, spleen and thymus; in the cortical and medullary area of the kidney; in the stroma of the prostate and in...

  13. Using the laser-induced fluorescence spectroscopy in the differentiation between normal and neoplastichuman breast tissue.

    Hage, R; Galhanone, P R; Zângaro, R A; Rodrigues, K C; Pacheco, M T T; Martin, A A; Netto, M M; Soares, F A; da Cunha, I W

    2003-01-01

    This article reports results of the in vitro study for potential evaluation of the laser-induced fluorescence spectroscopy in the differentiation between normal and neoplastic human breast tissue. A coumarine dye laser pumped by nitrogen laser generated an excitation light centered at 458 nm. In order to collect the fluorescence signal was used an optical fiber catheter coupled to a spectrometer and CCD detector. Fluorescence spectra were recorded from normal and neoplastic (benign and malignant) human breast tissue, adding up 94 different areas. The discrimination between normal and neoplasm groups reach a sensitivity and specificity of 100%. PMID:14505202

  14. Ultrasonic tissue characterization with integrated backscatter. Acute myocardial ischemia, reperfusion, and stunned myocardium in patients

    We have previously shown in studies of experimental animals that myocardium exhibits a cardiac cycle-dependent variation of integrated backscatter that reflects regional myocardial contractile performance and that is blunted promptly after arterial occlusion and recovers after reperfusion. To define the clinical utility of ultrasonic tissue characterization with integrated backscatter for detection of acute myocardial infarction and reperfusion, 21 patients (14 men and seven women) were studied in the cardiac care unit within the first 24 hours (mean time, 11.3 hours; range, 3.5-23.8 hours) after the onset of symptoms indicative of acute myocardial infarction with conventional two-dimensional and M-mode echocardiography and with analysis of integrated backscatter. The magnitude of cyclic variation of integrated backscatter was measured from several sites within acute infarct regions and normal regions remote from the infarct zone for each patient. The average magnitude of cyclic variation among all patients (n = 21) was 4.8 +/- 0.5 dB in normal regions compared with 0.8 +/- 0.3 dB in infarct regions (p less than 0.05) within the first 24 hours after the onset of symptoms. Among the patients who had two studies, 15 (mean, 7.1 days; range, 2-31 days for second study) underwent coronary arteriography to define vessel patency. In patients with vessels with documented patency (n = 10), the magnitude of cyclic variation in infarct regions increased over time from 1.3 +/- 0.6 to 2.5 +/- 0.5 dB from the initial to final study (p less than 0.05). Patients with occluded infarct-related arteries (n = 5) exhibited no significant recovery of cyclic variation (0.3 +/- 0.3-0.6 +/- 0.3 dB). A blinded analysis of standard two-dimensional echocardiographic images revealed no significant recovery of wall thickening in either group over the same time intervals

  15. Human colon tissue in organ culture: preservation of normal and neoplastic characteristics

    Bhagavathula, Narasimharao; Mankey, Cohra; DaSilva, Marissa; Paruchuri, Tejaswi; Aslam, Muhammad Nadeem; Varani, James

    2009-01-01

    Normal and neoplastic human colon tissue obtained at surgery was used to establish conditions for organ culture. Optimal conditions included an atmosphere of 5% CO2 and 95% O2; tissue partially submerged with mucosa at the gas interface; and serum-free medium with 1.5 mM Ca2+ and a number of growth supplements. Histological, histochemical, and immunohistochemical features that distinguish normal and neoplastic tissue were preserved over a 2-d period. With normal tissue, this included the presence of elongated crypts with small, densely packed cells at the crypt base and mucin-containing goblet cells in the upper portion. Ki67 staining, for proliferating cells, was confined to the lower third of the crypt, while expression of extracellular calcium-sensing receptor was seen in the upper third and surface epithelium. E-cadherin and β-catenin were expressed throughout the epithelium and confined to the cell surface. In tumor tissue, the same disorganized, abnormal glandular structures seen at time zero were present after 2 d. The majority of cells in these structures were mucin-poor, but occasional goblet cells were seen and mucin staining was present. Ki67 staining was seen throughout the abnormal epithelium and calcium-sensing receptor expression was weak and variable. E-cadherin was seen at the cell surface (similar to normal tissue), but in some places, there was diffuse cytoplasmic staining. Finally, intense cytoplasmic and nuclear β-catenin staining was observed in cultured neoplastic tissue. PMID:19915935

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

    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

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

    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

  18. Control of sulfatase activity by nomegestrol acetate in normal and cancerous human breast tissues.

    Chetrite, Gérard Samuel; Thomas, Jean-Louis; Shields-Botella, Jaqueline; Cortes-Prieto, Joaquin; Philippe, Jean-Claude; Pasqualini, Jorge Raul

    2005-01-01

    Nomegestrol acetate (NOMAC), a 17alpha-hydroxy-nor-progesterone derivative (17alpha-acetoxy-6-methyl-19-nor-4,6-pregnadiene-3,20-dione, the active substance in Lutenyl), is a potent and useful clinical synthetic progestin for the treatment of menopausal complaints and is under current development for oral contraception. Previous studies in this laboratory demonstrated that NOMAC can block sulfatase and 17beta-hydroxysteroid dehydrogenase, the enzymes involved in the biosynthesis and transformation of estradiol (E2) in hormone-dependent MCF-7 and T-47D breast cancer cells. In the present study, the effect of NOMAC on sulfatase activity using total breast cancer tissue, compared to the effect in normal breast tissue, was explored. Slices of tumoral or normal breast tissues (45-65 mg) were incubated in buffer (20 mM Tris-HCl, pH 7.2) with physiological concentrations of [3H]-estrone sulfate (5x10(-9) M), alone or in the presence of nomegestrol acetate (5x10(-5) - 5x10(-7) - 5x10(-9) M), for 4 h at 37 degrees C. Estrone sulfate (E1S), estrone (E1) and E2 were characterized by thin layer chromatography and quantified using the corresponding standard. It was observed that [3H]- E1S was only converted to [3H]- E1 and not to [3H]- E2, in normal or cancerous breast tissues, which suggests a low or no 17beta-HSD activity under these experimental conditions. The sulfatase activity was more intense with breast cancer tissue than normal tissue, since the concentrations of E1 were 42.5 +/- 3.4 and 27.2 +/- 2.5 pg/mg tissue, respectively. NOMAC, at the concentration of 5x10(-5) M, inhibited this conversion by 49.2% and 40.8% in cancerous and normal breast tissues, respectively. The sulfatase inhibition at low concentration (5x10(-7) M) was 32.5% and 22.8%, respectively. It is concluded that sulfatase activity is almost twice as potent in cancerous breast tissues than in normal tissues. Nomegestrol acetate is a strong anti-sulfatase agent, in particular with cancerous breast

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

    Ben-Zhou Feng

    2016-01-01

    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.

  20. Normal tissue tolerance to external beam radiation therapy: The vagina; Dose de tolerance a l'irradiation des tissus sains: le vagin Normal

    Magne, N. [Unite de curietherapie, departement de radiotherapie, institut de cancerologie de la Loire, 42 - Saint-Priest-en-Jarez (France); Chargari, C. [Service d' oncologie radiotherapie, hopital d' instruction des armees du Val-de-Grace, 75 - Paris (France); Pointreau, Y. [Clinique d' oncologie radiotherapie, centre Henry-S.-Kaplan, hopital de Bretonneau, CHU de Tours, 37 - Tours (France); Haie-Meder, C. [Service de curietherapie, departement de radiotherapie, institut Gustave-Roussy, 94 - Villejuif (France)

    2010-07-15

    The vagina is a virtual cavity involved in sexual reproduction field. Due to its anatomical location, it may be exposed in whole or in part to ionizing radiation in external radiotherapy and/or brachytherapy of the pelvic region. This review aims to describe the vaginal acute and late side effects due to radiation, probably inadequately reported in the literature. Medline and PubMed literature searches were performed using the keywords -vaginal - radiotherapy - toxicity. The acute and late functional changes after external beam radiation consist mainly of drought. Their incidences are poorly described in the literature and the delivered doses even less. Recommendations are non-existent as the normal tissue complication probability (NTCP). Brachytherapy delivers high and heterogeneous doses, making it difficult to estimate the dose. The concomitant administration of chemotherapy appears to be a factor increasing the risk of toxicity. Modern techniques of conformal radiotherapy with modulated intensity appear to have little impact on this body. Only a maximum dose on each third of the vagina appears to be currently proposed to avoid the risk of side effects. (authors)

  1. β class II tubulin predominates in normal and tumor breast tissues

    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

  2. Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors

    Typical high throughput microarrays experiments compare gene expression across two specimen classes – an experimental class and baseline (or comparison) class. The choice of specimen classes is a major factor in the differential gene expression patterns revealed by these experiments. In most studies of prostate cancer, histologically malignant tissue is chosen as the experimental class while normal appearing prostate tissue adjacent to the tumor (adjacent normal) is chosen as the baseline against which comparison is made. However, normal appearing prostate tissue from tumor free organ donors represents an alterative source of baseline tissue for differential expression studies. To examine the effect of using donor normal tissue as opposed to adjacent normal tissue as a baseline for prostate cancer expression studies, we compared, using oligonucleotide microarrays, the expression profiles of primary prostate cancer (tumor), adjacent normal tissue and normal tissue from tumor free donors. Statistical analysis using Significance Analysis of Microarrays (SAM) demonstrates the presence of unique gene expression profiles for each of these specimen classes. The tumor v donor expression profile was more extensive that the tumor v adjacent normal profile. The differentially expressed gene lists from tumor v donor, tumor v adjacent normal and adjacent normal v donor comparisons were examined to identify regulated genes. When donors were used as the baseline, similar genes are highly regulated in both tumor and adjacent normal tissue. Significantly, both tumor and adjacent normal tissue exhibit significant up regulation of proliferation related genes including transcription factors, signal transducers and growth regulators compared to donor tissue. These genes were not picked up in a direct comparison of tumor and adjacent normal tissues. The up-regulation of these gene types in both tissue types is an unexpected finding and suggests that normal appearing prostate tissue

  3. Acute hyperglycemia alters von Willebrand factor but not the fibrinolytic system in elderly subjects with normal or impaired glucose tolerance.

    Coppola, Ludovico; Coppola, Antonino; Grassia, Antonio; Mastrolorenzo, Luigia; Lettieri, Biagio; De Lucia, Domenico; De Nanzio, Annarita; Gombos, Giorgio

    2004-10-01

    To assess whether acute hyperglycemia affects fibrinolytic balance in elderly subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT), 40 non-obese elderly subjects (20 NGT, age 68 +/- 8 years; and 20 IGT, age 69 +/- 11 years) were studied. On two experimental days, randomly allocated and spaced 1 week apart, plasma concentrations of glucose, insulin, fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor type 1 and von Willebrand factor (vWF) were measured in each subject at baseline (0) and 30, 60, 90, 120 min after the ingestion of 75 g glucose or a similarly sweet dose of aspartame (250 mg) (control test). In both NGT and IGT elderly subjects, tissue plasminogen activator, plasminogen activator inhibitor type 1 and fibrinogen plasma levels did not significantly change after both oral aspartame and glucose load. In IGT subjects, vWF plasmatic levels decreased after glucose (not aspartame) oral load, reaching the minimum level at 90 min after load (82.7 +/- 7.8 versus 93.7 +/- 10.2, P <0.01). These results demonstrate that acute hyperglycemia does not modify plasma fibrinolysis in elderly subjects. The decrease of plasma concentration of vWF in IGT elderly subjects requires cautious interpretation and further extensive investigations. PMID:15613917

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

    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.

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

    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.

  6. Tissue factor pathway inhibitor relates to fibrin degradation in patients with acute deep venous thrombosis

    Sidelmann, Johannes J; Bladbjerg, Else-Marie; Gram, Jørgen;

    2008-01-01

    studied the association between inflammation, endothelial cell perturbation, fibrin degradation and the concentration of tissue factor pathway inhibitor in patients suspected for acute deep venous thrombosis. We determined the tissue factor pathway inhibitor -33T/C polymorphism, free and total tissue....... The significant relationship is not associated with the -33T/C polymorphism, inflammation or endothelial cell perturbation, but is most likely related to release of tissue factor pathway inhibitor from fibrin deposits....

  7. Prevention of radiation induced normal tissue damage by cytokines and hyperbaric oxygen

    Purpose/Objective: Radiation therapy (XRT) is an effective cancer treatment. A goal of therapy is minimization of side effects. Bone growth after XRT of children is one limiting normal tissue tolerance. The goal of the current experiment is to identify the possible protective effect of hyperbaric oxygen (HBO) and basic fibroblast growth factor (FGF) on bone growth after lower extremity radiation. Material and Methods: 170 five weeks old female C3H mice were divided into 17 study groups. Groups 1-4 are controls which received XRT at 0, 10, 20, and 30 Gy single fraction without subsequent HBO. Groups 5-7 had XRT at 10 Gy with HBO at weeks 1-4, weeks 5-8, and weeks 9-12 after XRT. Groups 8-10 had XRT at 20 Gy with HBO at weeks 1-4, weeks 5-8, and weeks 9-12 after XRT. Groups 11-13 had XRT at 30 Gy with HBO at weeks 1-4, weeks 5-8, and weeks 9-12 after XRT. Groups 14-17 had XRT at 30 Gy and iv FGF with or without HBO at weeks 1-4 (groups 14, 15), and at weeks 5-8 (groups 16, 17) after XRT. Using fluoroscopy, the animals were positioned so that the beam was directed to irradiate the entire right hindlimb, including the majority of the femur. Dosimetry was confirmed by TLD in mouse phantoms. HBO treatments were given 5 days per week for 4 weeks to each study group using 2 ATA (max. 15 PSI) of 100% oxygen for 3 hours/day. FGF was given intravenously at 6 μg twice a week for 4 weeks. X-ray films were taken to measure the leg (tibia and femur) length of animals before and 18 weeks after radiation. The acute and chronic side effects of skin in the irradiated area were checked daily according to standard criteria. The leg bones and soft tissue were collected at the end of experiment for histologic study. Result: HBO significantly reduces the retardation of bone growth induced by XRT for 10 and 20 Gy groups. For example, at the 18th week, leg length discrepancy is 0.0±1.6% for control, 4.2±1.3% for 10 Gy, and 8.2±1.8% for 20 Gy. HBO in 10 Gy groups decreased these

  8. A miRNA expression signature that separates between normal and malignant prostate tissues

    Lubovac Zelmina

    2011-05-01

    Full Text Available Abstract Background MicroRNAs (miRNAs constitute a class of small non-coding RNAs that post-transcriptionally regulate genes involved in several key biological processes and thus are involved in various diseases, including cancer. In this study we aimed to identify a miRNA expression signature that could be used to separate between normal and malignant prostate tissues. Results Nine miRNAs were found to be differentially expressed (p Conclusions We found an expression signature based on nine differentially expressed miRNAs that with high accuracy (85% could classify the normal and malignant prostate tissues in patients from the Swedish Watchful Waiting cohort. The results show that there are significant differences in miRNA expression between normal and malignant prostate tissue, indicating that these small RNA molecules might be important in the biogenesis of prostate cancer and potentially useful for clinical diagnosis of the disease.

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

    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 60Co 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

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

    Yang Ximing J

    2006-03-01

    Full Text Available Abstract Background 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. Methods 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. Results 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

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

    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

  12. FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics

    Wang, Lei; Xu, Wei-lai; Meng, Hai-tao; Qian, Wen-bin; Mai, Wen-yuan; Tong, Hong-yan; Mao, Li-Ping; Tong, Yin; Qian, Jie-jing; Lou, Yin-jun; Chen, Zhi-mei; Wang, Yun-Gui; Jin, Jie

    2010-01-01

    Mutations of fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) exon 12 genes are the most common abnormalities in adult acute myeloid leukemia (AML) with normal cytogenetics. To assess the prognostic impact of the two gene mutations in Chinese AML patients, we used multiplex polymerase chain reaction (PCR) and capillary electrophoresis to screen 76 AML patients with normal cytogenetics for mutations in FLT3 internal tandem duplication (FLT3/ITD) and exon 12 of the NPM1 gene. FLT3/ITD...

  13. Static jaw collimation settings to minimize radiation dose to normal brain tissue during stereotactic radiosurgery

    Han, Eun Young, E-mail: eyhan@uams.edu [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States); Zhang Xin; Yan Yulong; Sharma, Sunil; Penagaricano, Jose [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States); Moros, Eduardo [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL (United States); Corry, Peter [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States)

    2012-01-01

    At University of Arkansas for Medical Sciences (UAMS) intracranial stereotactic radiosurgery (SRS) is performed by using a linear accelerator with an add-on micromultileaf collimator (mMLC). In our clinical setting, static jaws are automatically adapted to the furthest edge of the mMLC-defined segments with 2-mm (X jaw) and 5-mm (Y jaw) margin and the same jaw values are applied for all beam angles in the treatment planning system. This additional field gap between the static jaws and the mMLC allows additional radiation dose to normal brain tissue. Because a radiosurgery procedure consists of a single high dose to the planning target volume (PTV), reduction of unnecessary dose to normal brain tissue near the PTV is important, particularly for pediatric patients whose brains are still developing or when a critical organ, such as the optic chiasm, is near the PTV. The purpose of this study was to minimize dose to normal brain tissue by allowing minimal static jaw margin around the mMLC-defined fields and different static jaw values for each beam angle or arc. Dose output factors were measured with various static jaw margins and the results were compared with calculated doses in the treatment planning system. Ten patient plans were randomly selected and recalculated with zero static jaw margins without changing other parameters. Changes of PTV coverage, mean dose to predefined normal brain tissue volume adjacent to PTV, and monitor units were compared. It was found that the dose output percentage difference varied from 4.9-1.3% for the maximum static jaw opening vs. static jaw with zero margins. The mean dose to normal brain tissue at risk adjacent to the PTV was reduced by an average of 1.9%, with negligible PTV coverage loss. This dose reduction strategy may be meaningful in terms of late effects of radiation, particularly in pediatric patients. This study generated clinical knowledge and tools to consistently minimize dose to normal brain tissue.

  14. Magnetic resonance spectroscopy features of normal-appearing white matter in patients with acute brucellosis

    We aimed to evaluate whether the subtle metabolic cerebral changes are present in normal-appearing white matter on conventional MRI, in patients with acute brucellosis, by using MR spectroscopy (MRS). Sixteen patients with acute brucellosis and 13 healthy control subjects were investigated with conventional MRI and single-voxel MRS. Voxels were placed in normal-appearing parietal white matter (NAPWM). N-Acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were calculated. There was no significant difference between the study subjects and the control group in NAA/Cr ratios obtained from NAPWM. However, the Cho/Cr ratios were significantly higher in patients with acute brucellosis compared to controls (p = 0.01). MRS revealed metabolic changes in normal-appearing white matter of patients with brucellosis. Brucellosis may cause subtle cerebral alterations, which may only be discernible with MRS. Increased Cho/Cr ratio possibly represents an initial phase of inflammation and/or demyelination process of brucellosis

  15. Magnetic resonance spectroscopy features of normal-appearing white matter in patients with acute brucellosis

    Kayabas, Uner [Department of Infectious Disease and Clinical Microbiology, Inonu University, Medical Faculty, TR-44280 Malatya (Turkey)], E-mail: ukayabas@inonu.edu.tr; Alkan, Alpay; Firat, Ahmet Kemal; Karakas, Hakki Muammer [Department of Radiology, Inonu University, Medical Faculty, TR-44280 Malatya (Turkey); Bayindir, Yasar; Yetkin, Funda [Department of Infectious Disease and Clinical Microbiology, Inonu University, Medical Faculty, TR-44280 Malatya (Turkey)

    2008-03-15

    We aimed to evaluate whether the subtle metabolic cerebral changes are present in normal-appearing white matter on conventional MRI, in patients with acute brucellosis, by using MR spectroscopy (MRS). Sixteen patients with acute brucellosis and 13 healthy control subjects were investigated with conventional MRI and single-voxel MRS. Voxels were placed in normal-appearing parietal white matter (NAPWM). N-Acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were calculated. There was no significant difference between the study subjects and the control group in NAA/Cr ratios obtained from NAPWM. However, the Cho/Cr ratios were significantly higher in patients with acute brucellosis compared to controls (p = 0.01). MRS revealed metabolic changes in normal-appearing white matter of patients with brucellosis. Brucellosis may cause subtle cerebral alterations, which may only be discernible with MRS. Increased Cho/Cr ratio possibly represents an initial phase of inflammation and/or demyelination process of brucellosis.

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

    Raju, G.J. Naga [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Sarita, P. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Kumar, M. Ravi [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Murty, G.A.V. Ramana [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Reddy, B. Seetharami [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Lakshminarayana, S. [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India); Vijayan, V. [Institute of Physics, Bhubaneswar 751 001 (India); Lakshmi, P.V.B. Rama [Pathology Department, Andhra Medical College, Visakhapatnam 530 002 (India); Gavarasana, Satyanarayana [Lions Cancer Hospital, Visakhapatnam 530 013 (India); Reddy, S. Bhuloka [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam 530 003 (India)]. E-mail: sbr_r@yahoo.com

    2006-06-15

    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.

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

    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.)

  18. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

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

    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

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

    Nardulli Ann M

    2010-01-01

    Full Text Available Abstract Background 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. Methods 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. Results We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Conclusions 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.

  1. Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues

    Purpose: High-dose synchrotron microbeam radiation therapy (MRT) can be effective at destroying tumors in animal models while causing very little damage to normal tissues. The aim of this study was to investigate the cellular processes behind this observation of potential clinical importance. Methods and Materials: MRT was performed using a lattice of 25 μm-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-μm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of γ-H2AX allowed precise localization of irradiated cells, which were also assessed for proliferation and apoptosis. Results: MRT significantly reduced tumor cell proliferation by 24 h post-irradiation (p = 0.002). An unexpected finding was that within 24 h of MRT, peak and valley irradiated zones were indistinguishable in tumors because of extensive cell migration between the zones. This was not seen in MRT-treated normal skin, which appeared to undergo a coordinated repair response. MRT elicited an increase in median survival times of EMT-6.5 and 67NR tumor-inoculated mice similar to that achieved with conventional radiotherapy, while causing markedly less normal tissue damage. Conclusions: This study provides evidence of a differential response at a cellular level between normal and tumor tissues after synchrotron MRT.

  2. Measurements of magnetic relaxation times of normal tissue and renal cell carcinoma

    Spin-lattice (T1) and spin-spin (T2) magnetic relaxation times of 25 human renal cell carcinomas and their assorted normal tissues were measured with a Bruker NMR spectrometer operating at 20 MHz. The tissue samples were examined within four hours after surgery. The results (mean±SD) were as follows: renal cell carcinoma, T1=638±168 msec and T2=109±41 msec; normal renal tissue, T1=594±165 msec and T2=100±24 msec. These results indicate that there was no significant difference in T1 and T2 between normal renal tissue and carcinoma. Our results suggest that it is difficult to separate relaxation times of renal cancer from those of normal parenchyma and that the difference between T1 and T2 alone dose not permit recognition of renal cell cancer. Paramagnetic contrast agents may be useful in MR imaging to differentiate renal cancer from normal parenchyma. (author)

  3. 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

    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

  4. Role of gelatinases MMP-2 and MMP-9 in tissue remodeling following acute lung injury

    M. Corbel

    2000-07-01

    Full Text Available Acute lung injury is characterized by a severe disruption of alveolo-capillary structures and includes a variety of changes in lung cell populations. Evidence suggests the occurrence of rupture of the basement membranes and interstitial matrix remodeling during acute lung injury. The dynamic equilibrium of the extracellular matrix (ECM under physiological conditions is a consequence of the balance between the regulation of synthesis and degradation of ECM components. Matrix metalloproteinases (MMPs represent a group of enzymes involved in the degradation of most of the components of the ECM and therefore participate in tissue remodeling associated with pathological situations such as acute lung injury. MMP activity is regulated by proteolytic activation of the latent secreted proenzyme and by interaction with specific tissue inhibitors of metalloproteinases. This review details our knowledge of the involvement of MMPs, namely MMP-2 and MMP-9, in acute lung injury and acute respiratory distress syndrome.

  5. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

    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.

  6. Photon linear attenuation coefficients and water content of normal and pathological breast tissues

    Normal and pathological breast tissue samples were scanned using a Photon Transmission Tomography (PTT) technique in order to determine their averaged photon linear attenuation coefficients (μ). Subsequent to being freeze-dried the samples were examined, using a high purity germanium detector (HPGe) and the γ-rays of energy 59.5 keV from an americium source, and the results were corrected for the water reduction by the use of the Mixture Rule. The ratio of our experimental findings to the published data for μ for various breast tissues were 88, 96 and 88% for adipose, glandular and tumour tissues, respectively. The mean accuracy in our study, investigated relative to standard chemical compounds, was about 3%. The water content of each tissue type was determined as the weight loss during the freeze drying process. This work was initiated in order to evaluate the suitability of new tissue substitute materials for mammography applications. (Author)

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

    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.

  8. Individualized Radical Radiotherapy of Non-Small-Cell Lung Cancer Based on Normal Tissue Dose Constraints: A Feasibility Study

    Purpose: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Methods and Materials: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An 18F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Results: Mean delivered dose was 63.0 ± 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Conclusions: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising

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

    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.

  10. Interleukin 1 increases thymidine labeling index of normal tissues of mic but not the tumor

    This study was conducted to investigate the action of human recombinant interleukin 1 as a radioprotector for different mouse normal cells other than bone marrow cells. Semi-continuous injections of tritiated thymidine were administered every 6 h, over 24 h to determine thymidine labeling index. Mice were injected with recombinant human interleukin 1 24 h prior to tritiated thymidine and were compared to control animals that did not receive interleukin 1. Mice were killed 1 h after the last thymidine injection. The 24 h thymidine labeling index for normal tissues and RIF-1 tumor was determined. Labeling indices were also determined 1-14 days after a series of fractionated irradiations with or without pretreatment with a single dose of interleukin 1 administered 24 h prior to the first radiation. The thymidine labeling index of normal tissues was higher following the injection of recombinant human interleukin 1 24 h before radiolabeling. This was found in all normal tissues tested. The thymidine labeling index of RIF-1 fibrosarcoma was not affected by interleukin 1 injection. A single interleukin 1 injection 24 h before the first radiation fraction also increased the thymidine labeling indices of normal tissues after localized fractionated irradiation. The thymidine labeling index of RIF-1 tumor was not increased by interleukin 1 administration except after relatively high radiation doses (20 Gy in five fractions). The ability of interleukin 1 to enhance the thymidine labeling index declined after the first day following the completion of fractionated irradiation. Recombinant human interleukin 1 increased the 24 h thymidine labeling index in normal tissues in mice, but not in RIF-1 tumor. Fractionated irradiation could maintain the effect of a single dose of interleukin 1, administered 24 h prior to the first fraction, up to 24 h after the end of radiation. 25 refs., 3 figs., 1 tab

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

    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, AdnexaR, AdnexaL, Prostate, SeminalVesc, PenileBulb, FemurR, and FemurL. 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.

  12. A large volume of visceral adipose tissue leads to severe acute pancreatitis

    Obesity plays an important role in acute pancreatitis. Assuming that the volume of visceral adipose tissue (VAT) directly influences the severity of acute pancreatitis, we investigated the relationship between VAT and acute pancreatitis. Data were collected consecutively from 124 patients who were diagnosed with acute pancreatitis. Body mass index (BMI) was calculated from the database. Computed tomography was performed in all patients, and VAT, subcutaneous adipose tissue (SAT), and waist circumference (WC) were measured at the level of the intervertebral disk between L2 and L3. Atlanta criteria were adopted to define severe acute pancreatitis. Clinical courses were investigated, and the Ranson and acute physiology and chronic health evaluation II (APACHE II) scores were calculated for all patients. Forty-eight patients had severe acute pancreatitis (38.7%), and 76 were mild cases. BMI, VAT, SAT, and WC were correlated with the severity of acute pancreatitis in a univariate analysis, but only VAT had a strong correlation with severe acute pancreatitis in the multivariate analysis. In a trend analysis, not only severity but also the presence of pseudocysts (local complication) and prognostic factors (Ranson and APACHE II scores) were significantly related to VAT volume. In particular, the presence of a pancreatic pseudocyst was strongly related to VAT volume (p<0.001). In acute pancreatitis, peripancreatic VAT has a stronger correlation with severe acute pancreatitis than BMI or WC. VAT volume is strongly correlated with the formation of a pseudocyst and with systemic inflammatory response syndrome in patients with acute pancreatitis and high VAT volume may lead to severe acute pancreatitis. (author)

  13. Clearance of aerosolized Tc-99m DTPA from normal vs. acutely smoke-injured dog lungs

    Acute cigarette smoke exposure is known to reversibly increase the clearance rate of aerosolized DTPA from human lungs. The authors studied DTPA clearance after acute severe plywood smoke exposure, on the order of that experienced by burn victims, since current diagnostic methods (Xe-133 and radiographs) for major inhalation injury are insensitive and/or non-specific. Smoke generated from burning plywood sawdust and kerosene was delivered via endotracheal tube at 370C. Skin burns were not inflicted (so the pulmonary consequences of thermal injury were not factors). Chest radiographs and Xe-133 studies were obtained before and after smoke injury but before DTPA aerosol delivery. Six normal and 7 smoke-exposed anesthetized mongrel dogs were studied with 3 mCi of Tc-99m DTPA delivered by aerosol for 5 minutes. Pulmonary Tc-99m DTPA activity was quantitated by computer. Data were acquired over the lungs at 1 frame per 10 secs. for 16 minutes, and the t/sub 1/2/ of DTPA washout from the lungs was calculated. The mean t/sub 1/2/ of 6 normal dogs was 36.52 min. (S.D. 17.73), while the t/sub 1/2/ of 7 smoke-injured dogs was 6.08 min. (S.D. 1.99). The longest t/sub 1/2/ of an injured lung (9.68 min.) was slightly more than half of the shortest t/sub 1/2/ of a normal lung (15.36 min). Thus, acutely smoke-injured dog lungs clear Tc-99m DTPA much faster than normal lungs, consistent with an increase in lung epithelial permeability. This technique may be promising clinically, since early diagnosis of inhalation injury is important for optimal therapy

  14. Elemental composition of hypertrophic scar and normal skin tissue using proton induced X-ray emission

    Hypertrophic scars are a particular type of scar that can form after any type of dermal trauma. They are unsightly, red and elevated above normal skin level. At present no-one knows why these scars form and what form the treatment should take. Full thickness hypertrophic skin tissue as well as full thickness normal skin samples, obtained form the Restoration of Appearance and Function Trust (RAFT), Institute of Plastic Surgery, Mount Vernon Hospital, were analysed, using simultaneously both PIXE and RBS, with a 2 MeV proton beam. The epidermis was compared to the dermis on both normal and scarred tissue, and each was compared to the other, to see if there were any variations in elemental composition. In all the samples C, N and O detected by RBS and P, S, Cl, K, Ca, Fe detected by PIXE were found. In the majority of samples Zn and Cd were found, and in a few samples Sn was determined. Significant differences in concentrations, for the elements P, S, K and Cd, between the epidermis and dermis in both hypertrophic scarred and normal skin tissue were found. A difference was also detected between elemental concentrations in normal and scarred skin for the elements Ca, P, S, Fe and Cd. (author)

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

    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, γ, 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 α and β. 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

  16. High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

    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.

  17. Biobanking of Fresh-Frozen Human Adenocarcinomatous and Normal Colon Tissues: Which Parameters Influence RNA Quality?

    Galissier, Thibaut; Schneider, Christophe; Nasri, Saviz; Kanagaratnam, Lukshe; Fichel, Caroline; Coquelet, Christelle; Diebold, Marie-Danièle; Kianmanesh, Reza; Bellon, Georges; Dedieu, Stéphane; Marchal Bressenot, Aude

    2016-01-01

    Medical research projects become increasingly dependent on biobanked tissue of high quality because the reliability of gene expression is affected by the quality of extracted RNA. Hence, the present study aimed to determine if clinical, surgical, histological, and molecular parameters influence RNA quality of normal and tumoral frozen colonic tissues. RNA Quality Index (RQI) was evaluated on 241 adenocarcinomas and 115 matched normal frozen colon tissues collected between October 2006 and December 2012. RQI results were compared to patients’ age and sex, tumor site, kind of surgery, anastomosis failure, adenocarcinoma type and grade, tumor cell percentage, necrosis extent, HIF-1α and cleaved caspase-3 immunohistochemistry, and BRAF, KRAS and microsatellites status. The RQI was significantly higher in colon cancer tissue than in matched normal tissue. RQI from left-sided colonic cancers was significantly higher than RQI from right-sided cancers. The RNA quality was not affected by ischemia and storage duration. According to histological control, 7.9% of the samples were unsatisfactory because of inadequate sampling. Biobanked tumoral tissues with RQI ≥5 had lower malignant cells to stromal cells ratio than samples with RQI <5 (p <0.05). Cellularity, necrosis extent and mucinous component did not influence RQI results. Cleaved caspase-3 and HIF-1α immunolabelling were not correlated to RQI. BRAF, KRAS and microsatellites molecular status did not influence RNA quality. Multivariate analysis revealed that the tumor location, the surgical approach (laparoscopy versus open colectomy) and the occurrence of anastomotic leakage were the only parameters influencing significantly RQI results of tumor samples. We failed to identify parameter influencing RQI of normal colon samples. These data suggest that RNA quality of colonic adenocarcinoma biospecimens is determined by clinical and surgical parameters. More attention should be paid during the biobanking procedure of

  18. Methylation profiling defines an extensive field defect in histologically normal prostate tissues associated with prostate cancer.

    Yang, Bing; Bhusari, Sachin; Kueck, Jessica; Weeratunga, Pushpa; Wagner, Jennifer; Leverson, Glen; Huang, Wei; Jarrard, David F

    2013-04-01

    Prostate cancer (PCa) is typically found as a multifocal disease suggesting the potential for molecular defects within the morphologically normal tissue. The frequency and spatial extent of DNA methylation changes encompassing a potential field defect are unknown. A comparison of non-tumor-associated (NTA) prostate to histologically indistinguishable tumor-associated (TA) prostate tissues detected a distinct profile of DNA methylation alterations (0.2%) using genome-wide DNA arrays based on the Encyclopedia of DNA Elements 18 sequence that tile both gene-rich and poor regions. Hypomethylation (87%) occurred more frequently than hypermethylation (13%). Several of the most significantly altered loci (CAV1, EVX1, MCF2L, and FGF1) were then used as probes to map the extent of these DNA methylation changes in normal tissues from prostates containing cancer. In TA tissues, the extent of methylation was similar both adjacent (2 mm) and at a distance (>1 cm) from tumor foci. These loci were also able to distinguish NTA from TA tissues in a validation set of patient samples. These mapping studies indicate that a spatially widespread epigenetic defect occurs in the peripheral prostate tissues of men who have PCa that may be useful in the detection of this disease. PMID:23555185

  19. Methylation Profiling Defines an Extensive Field Defect in Histologically Normal Prostate Tissues Associated with Prostate Cancer

    Bing Yang

    2013-04-01

    Full Text Available Prostate cancer (PCa is typically found as a multifocal disease suggesting the potential for molecular defects within the morphologically normal tissue. The frequency and spatial extent of DNA methylation changes encompassing a potential field defect are unknown. A comparison of non-tumor-associated (NTA prostate to histologically indistinguishable tumor-associated (TA prostate tissues detected a distinct profile of DNA methylation alterations (0.2% using genome-wide DNA arrays based on the Encyclopedia of DNA Elements 18 sequence that tile both gene-rich and poor regions. Hypomethylation (87% occurred more frequently than hypermethylation (13%. Several of the most significantly altered loci (CAV1, EVX1, MCF2L, and FGF1 were then used as probes to map the extent of these DNA methylation changes in normal tissues from prostates containing cancer. In TA tissues, the extent of methylation was similar both adjacent (2 mm and at a distance (>1 cm from tumor foci. These loci were also able to distinguish NTA from TA tissues in a validation set of patient samples. These mapping studies indicate that a spatially widespread epigenetic defect occurs in the peripheral prostate tissues of men who have PCa that may be useful in the detection of this disease.

  20. Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumors.

    Izquierdo, M A; Scheffer, G L; Flens, M J; Giaccone, G; Broxterman, H J; Meijer, C J; van der Valk, P; Scheper, R J

    1996-03-01

    Multidrug resistance (MDR) to anticancer drugs is a major cause of treatment failure in cancer. The lung resistance protein LRP is a newly described protein related to MDR in several in vitro models. LRP has been shown to be a strong predictor of poor response to chemotherapy and prognosis in acute myeloid leukemia and in ovarian carcinoma patients. Recently, based on a 57% and 88% amino acid identity with major vault proteins from Dictyostelium discoideum and Rattus norvegicus, respectively, we identified LRP as the human major vault protein, the main component of highly conserved cellular organelles named vaults. We have studied the immunohistochemical expression of LRP in freshly frozen normal human tissues and 174 cancer specimens of 28 tumor types. LRP was broadly distributed in normal and malignant cells, but distinct patterns of expression were noticed. High LRP expression was seen in bronchus, digestive tract, renal proximal tubules, keratinocytes, macrophages, and adrenal cortex whereas varying ing levels were observed in other organs. LRP was detected in all tumor types examined, but its frequency varied, fairly reflecting the chemosensitivity of different cancers. For example, low rates of LRP positivity were seen in testicular cancer, neuroblastoma, and acute myeloid leukemia; intermediate in ovarian cancer; and high in colon, renal, and pancreatic carcinomas. The wide occurrence of LRP in normal and transformed cells in humans, its similar distribution to that of vaults in other species, as well as the high level of conservation among eukaryotic cells of both the amino acid sequence of the major vault protein and the composition and structure of vaults, suggest that vault function is important to eukaryotic cells. PMID:8774142

  1. Expression and significance of SOCS3 in liver tissue of rats with severe acute pancreatitis complicated by liver injury

    Wang, Bin; Zhang, Xiao-Hua; Miao-fan YANG; Xiao-wei WU; Xu, Xiao-Bing; Mei-xia GUO; Min-li LI

    2012-01-01

    Objective  To investigate the expression and mechanism of action of suppressor of cytokine signaling 3 (SOCS3) in liver tissue of rats with experimental severe acute pancreatitis (SAP) concurring with liver injury. Methods  The rat model of SAP was reproduced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct. Thirty-two male SD rats were randomly assigned into 4 groups (8 each): normal control group (NC), SAP 6h, 12h, and 18h groups. The levels of serum amylase (...

  2. Evaluation of algorithm methods for fluorescence spectra of cancerous and normal human tissues

    Pu, Yang; Wang, Wubao; Alfano, Robert R.

    2016-03-01

    The paper focus on the various algorithms on to unravel the fluorescence spectra by unmixing methods to identify cancerous and normal human tissues from the measured fluorescence spectroscopy. The biochemical or morphologic changes that cause fluorescence spectra variations would appear earlier than the histological approach; therefore, fluorescence spectroscopy holds a great promise as clinical tool for diagnosing early stage of carcinomas and other deceases for in vivo use. The method can further identify tissue biomarkers by decomposing the spectral contributions of different fluorescent molecules of interest. In this work, we investigate the performance of blind source un-mixing methods (backward model) and spectral fitting approaches (forward model) in decomposing the contributions of key fluorescent molecules from the tissue mixture background when certain selected excitation wavelength is applied. Pairs of adenocarcinoma as well as normal tissues confirmed by pathologist were excited by selective wavelength of 340 nm. The emission spectra of resected fresh tissue were used to evaluate the relative changes of collagen, reduced nicotinamide adenine dinucleotide (NADH), and Flavin by various spectral un-mixing methods. Two categories of algorithms: forward methods and Blind Source Separation [such as Principal Component Analysis (PCA) and Independent Component Analysis (ICA), and Nonnegative Matrix Factorization (NMF)] will be introduced and evaluated. The purpose of the spectral analysis is to discard the redundant information which conceals the difference between these two types of tissues, but keep their diagnostically significance. The facts predicted by different methods were compared to the gold standard of histopathology. The results indicate that these key fluorophores within tissue, e.g. tryptophan, collagen, and NADH, and flavin, show differences of relative contents of fluorophores among different types of human cancer and normal tissues. The

  3. Comparison of SUVs normalized by lean body mass determined by CT with those normalized by lean body mass estimated by predictive equations in normal tissues

    Standardized uptake values (SUVs)normalized by lean body mass (LBM)determined by CT were compared with those normalized by LBM estimated using predictive equations (PEs)in normal liver, spleen, and aorta using 18F FDG PET/CT. Fluorine 18 fluorodeoxyglucose (F FDG)positron emission tomography/computed tomography (PET/CT)was conducted on 453 patients. LBM determined by CT was defined in 3 ways (LBMCT1-3). Five PEs were used for comparison (LBMPE1-5). Tissue SUV normalized by LBM (SUL) was calculated using LBM from each method (SULCT1-3, SULPE1-5). Agreement between methods was assessed by Bland Altman analysis. Percentage difference and percentage error were also calculated. For all liver SULCTS vs. liver SULPES except liver SULPE3, the range of biases, SDs of percentage difference and percentage errors were -0.17-0.24 SUL, 6.15-10.17%, and 25.07-38.91%, respectively. For liver SULCTs vs. liver SULPE3, the corresponding figures were 0.47-0.69 SUL, 10.90-11.25%, and 50.85-51.55%, respectively, showing the largest percentage errors and positive biases. Irrespective of magnitudes of the biases, large percentage errors of 25.07-51.55% were observed between liver SULCT1-3 and liver SULPE1-5. The results of spleen and aorta SULCTs and SULPEs comparison were almost identical to those for liver. The present study demonstrated substantial errors in individual SULPEs compared with SULCTs as a reference value. Normalization of SUV by LBM determined by CT rather than PEs may be a useful approach to reduce errors in individual SULPEs

  4. Acute ethanol administration induces oxidative changes in rat pancreatic tissue.

    Altomare, E; Grattagliano, I; Vendemiale, G.; V. Palmieri; Palasciano, G

    1996-01-01

    BACKGROUND--There is mounting clinical evidence that ethanol toxicity to the pancreas is linked with glutathione depletion from oxidative stress but there is not experimental proof that this occurs. AIMS AND METHODS--The effect of acute ethanol ingestion (4 g/kg) on the pancreatic content of reduced (GSH) and oxidised (GSSG) glutathione, malondialdehyde (MDA), and carbonyl proteins were therefore studied in the rat. RESULTS--Ethanol caused a significant reduction in GSH (p < 0.02) and an incr...

  5. Distribution of common acute lymphoblastic leukemia antigen in nonhematopoietic tissues

    1981-01-01

    The common acute lymphoblastic leukemia antigen (CALLA), as defined by J-5 murine monoclonal antibodies, was detected on renal tubular and glomerular cells from fetal and adult donors by an indirect immunoperoxidase technique. CALLA could also be detected on epithelial cells of the fetal small intestine and on myoepithelial cells of adult breast but not on myoepithelial cells of the salivary gland. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immunoprecipitated 125I-l...

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

    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)

  7. FT-IR Spectroscopic Analysis of Normal and Malignant Human Oral Tissues

    Krishnakumar, N.; Madhavan, R. Nirmal; Sumesh, P.; Palaniappan, Pl. Rm.; Venkatachalam, P.; Ramachandran, C. R.

    2008-11-01

    FT-IR spectroscopy has been used to explore the changes in the vibrational bands of normal and oral squamous cell carcinoma (OSCC) tissues in the region 4000-400 cm-1. Significant changes in the spectral features were observed. The spectral changes were the results of characteristics structural alterations at the molecular level in the malignant tissues. These alterations include structural changes of proteins and possible increase of its content, an increase in the nucleic-to-cytoplasm ratio, an increase in the relative amount of DNA, an increase in the rate of phosphorylation process induced by carcinogenesis, a loss of hydrogen bonding of the C-OH groups in the amino acid residues of proteins, a decrease in the relative amount of lipids compared to normal epithelial oral tissues. The results of the present study demonstrate that the FT-IR technique has the feasibility of discriminating malignant from normal tissues and other pathological states in a short period of time and may detect malignant transformation earlier than the standard histological examination stage.

  8. Poly (ADP-ribose polymerase 1 protein expression in normal and neoplastic prostatic tissue

    M. Salemi

    2013-04-01

    Full Text Available A genetic background has been implicated in the development of prostate cancer. Protein microarrays have enabled the identification of proteins, some of which associated with apoptosis, that may play a role in the development of such a tumor. Inhibition of apoptosis is a co-factor that contributes to the onset and progression of prostate cancer, though the molecular mechanisms are not entirely understood. Poly (ADP-ribose polymerase 1 (PARP-1 gene is required for translocation of the apoptosis-inducing factor (AIF from the mitochondria to the nucleus. Hence, it is involved in programmed cell death. Different PARP-1 gene expression has been observed in various tumors such as glioblastoma, lung, ovarian, endometrial, and skin cancers. We evaluated the expression of PARP-1 protein in prostatic cancer and normal prostate tissues by immunohistochemistry in 40 men with prostate cancer and in 37 normal men. Positive nuclear PARP-1 staining was found in all samples (normal prostate and prostate cancer tissues. No cytoplasmic staining was observed in any sample. PARP-1-positive cells resulted significantly higher in patients with prostate carcinoma compared with controls (P<0.001. PARP-1 over-expression in prostate cancer tissue compared with normal prostate suggests a greater activity of PARP-1 in these tumors. These findings suggest that PARP-1 expression in prostate cancer is an attempt to trigger apoptosis in this type of tumor similarly to what reported in other cancers.

  9. Wilms Tumor 1 Gene Mutations in Patients with Cytogenetically Normal Acute Myeloid Leukemia

    Salah Aref; Solafa El Sharawy; Mohamed Sabry; Emad Azmy; Dalia Abdel Raouf; Nadia El Menshawy

    2014-01-01

    Objective: This study aimed to assess the prognostic impact of Wilms tumor 1 (WT1) mutations in cytogenetically normal acute myeloid leukemia (CN-AML) among Egyptian patients. Materials and Methods: Exons 1, 2, 3, 7, 8, and 9 of WT1 were screened for mutations in samples from 82 CN-AML patients out of 203 newly diagnosed AML patients, of age ranging from 21 to 74 years, using high-resolution capillary electrophoresis. Results: Eleven patients out of 82 (13.41%) harbored WT1 mutations. Mutatio...

  10. Radioprotection by seed extract of Syzygium cumini in normal tissues of fibrosarcoma bearing mice

    Syzygium cumini Linn. (family Myrtaceae), commonly known as Jamun, is a medicinal plant and utilizable species which is widely used for its antioxidant activities to treat different ailments in many parts of the world. The current study was undertaken to study the effect of seed extract of Syzygium cumini in normal as well as in tumor bearing mice against gamma radiation-induced cellular damage in biological tissues. This was done to mimic the clinical setting wherein, normal tissues of cancer patients undergoing, radiotherapy are exposed to the deleterious effects of radiation. The protection of cellular DNA was analyzed in peripheral blood leucocytes of whole-body irradiated mice following pretreatment with hydo-alcoholic seed extract of Syzygium cumini (100 mg/kg b. wt./day), using alkaline comet assay and by estimating biochemical parameters such as antioxidant enzymes i.e. (superoxide dismutase and catalase), GSH, LPO and total proteins in organs like spleen, liver and intestine. For this purpose, Swiss albino mice were administered Syzygium cumini extract (SCE) orally once daily for 5 consecutive days, then exposed to a single dose of 3, 6 and 9 Gy of gamma radiation. The results showed that the seed extract of Syzygium cumini protected the liver, spleen and intestine both in normal as well as tumor bearing mice. This study concludes that seed extract of Syzygium cumini has protective effects against radiation-induced cellular damage and biochemical alterations which could be attributed to the ability to scavenge free radicals and its antioxidant properties. Hence, seed extract of Syzygium cumini may be used in combination with radiation to protect against oxidative stress in normal tissues and improving the quality of life of cancer patients by mitigating side effects of radiation to normal tissues during radiotherapy. (author)

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

    Saiki, Mitiko; Genezini, Frederico A., E-mail: mitiko@ipen.br, E-mail: fredzini@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro do Reator de Pesquisas; Leite, Renata E.P.; Grinberg, Lea T.; Ferretti, Renata E.L.; Suemoto, Claudia; Pasqualucci, Carlos A.; Jacob-Filho, Wilson, E-mail: renataleite@usp.br, E-mail: lea@grinberg.com.br, E-mail: reloah@usp.br, E-mail: farfel@usp.br, E-mail: csuemoto@gmail.com, E-mail: cpasqua@usp.br, E-mail: wijac@usp.br [Universidade de Sao Paulo (FM/USP), Sao Paulo, SP (Brazil). Fac. de Medicina

    2013-07-01

    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)

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

    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)

  13. Metabolic imaging in microregions of tumors and normal tissues with bioluminescence and photon counting

    A method has been developed for metabolic imaging on a microscopic level in tumors, tumor spheroids, and normal tissues. The technique makes it possible to determine the spatial distribution of glucose, lactate, and ATP in absolute terms at similar locations within tissues or cell aggregates. The substrate distributions are registered in serial cryostat sections from tissue cryobiopsies or from frozen spheroids with the use of bioluminescence reactions. The light emission is measured directly by a special imaging photon counting system enabling on-line image analysis. The technique has been applied to human breast cancer xenografts, to spheroids originating from a human colon adenocarcinoma, and to skeletal rat muscle. Preliminary data obtained indicate that heterogeneities in the substrate distributions measured are much more pronounced in tumors than in normal tissue. There was no obvious correlation among the three quantities measured at similar locations within the tissues. The distribution of ATP corresponded well with the histological structure of larger spheroids; values were low in the necrotic center and high in the viable rim of these cell aggregates

  14. Static jaw collimation settings to minimize radiation dose to normal brain tissue during stereotactic radiosurgery

    At University of Arkansas for Medical Sciences (UAMS) intracranial stereotactic radiosurgery (SRS) is performed by using a linear accelerator with an add-on micromultileaf collimator (mMLC). In our clinical setting, static jaws are automatically adapted to the furthest edge of the mMLC-defined segments with 2-mm (X jaw) and 5-mm (Y jaw) margin and the same jaw values are applied for all beam angles in the treatment planning system. This additional field gap between the static jaws and the mMLC allows additional radiation dose to normal brain tissue. Because a radiosurgery procedure consists of a single high dose to the planning target volume (PTV), reduction of unnecessary dose to normal brain tissue near the PTV is important, particularly for pediatric patients whose brains are still developing or when a critical organ, such as the optic chiasm, is near the PTV. The purpose of this study was to minimize dose to normal brain tissue by allowing minimal static jaw margin around the mMLC-defined fields and different static jaw values for each beam angle or arc. Dose output factors were measured with various static jaw margins and the results were compared with calculated doses in the treatment planning system. Ten patient plans were randomly selected and recalculated with zero static jaw margins without changing other parameters. Changes of PTV coverage, mean dose to predefined normal brain tissue volume adjacent to PTV, and monitor units were compared. It was found that the dose output percentage difference varied from 4.9–1.3% for the maximum static jaw opening vs. static jaw with zero margins. The mean dose to normal brain tissue at risk adjacent to the PTV was reduced by an average of 1.9%, with negligible PTV coverage loss. This dose reduction strategy may be meaningful in terms of late effects of radiation, particularly in pediatric patients. This study generated clinical knowledge and tools to consistently minimize dose to normal brain tissue.

  15. Myocardial infarction following recombinant tissue plasminogen activator treatment for acute ischemic stroke: a dangerous complication

    ZHOU Zhi-gang; WANG Rui-lan; YU Kang-long

    2012-01-01

    Thrombolysis with intravenous tissue plasminogen activator (t-PA) is currently an approved therapy for patients with acute ischemic stroke.Acute myocardial infarction (AMI) immediately following t-PA treatment for stroke is a rare but serious complication.A case of acute myocardial infarction (MI) following IV t-PA infusion for acute stroke was observed.This is a 52-year-old male with a known history of hypertension and chest pain,who subsequently developed MI four hours after IV t-PA was administered for acute ischemic stroke.The disruption of intra-cardiac thrombus and subsequent embolization to the coronary arteries may be an important mechanism.In addition.spontaneous recanalization of infarct-related arteries may be associated with 9reater myocardial salvage and better prognosis.

  16. Calculation of RBE for normal tissue complications based on charged particle track structure

    A new approach for the calculation of RBE for normal tissue complications after charged particle and neutron irradiation is discussed. It is based on the extension of a model originally developed for the application to cell survival. It can be shown, that according to the model RBE values are determined largely by the α/β-ratio of the photon dose response curve, but are expected to be nearly independent of the absolute values of α and β. Thus, the model can be applied to normal tissue complications as well, where α/β-ratios can be determined by means of fractionation experiments. Agreement of model predictions and experimental results obtained in animal experiments confirm the appliability of the model even in the case of complex biological endpoints. (orig.)

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

    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. PMID:20171511

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

    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.)

  19. The myofibroblast, multiple origins for major roles in normal and pathological tissue repair

    Micallef Ludovic

    2012-06-01

    Full Text Available Abstract Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by (myofibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete (scar formation but the functionality of the tissue is only rarely perfectly restored. At the end of the normal repair process, myofibroblasts disappear by apoptosis but in pathological situations, myofibroblasts likely remain leading to excessive scarring. Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts. However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair. These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases.

  20. Uptake of 153Sm-EDTMP in normal, benign and malignant tumor tissue

    Riegel, A

    2001-01-01

    The present study was designed to investigate and compare the uptake of 153Sm-EDTMP (153Samarium-ethylenediaminetetramethylene phosphonate)and 99mTc-DPD (99mTechnetium-dicarboxypropane diphosphonate) into different soft tissue sarcoma cell lines and various tissue specimen in vitro. After 10-120 minutes of incubation at 22 sup o C and 37 sup o C with 153Sm-EDTMP, the uptake kinetics of this tracer in human soft tissue sarcoma cells SW 684 (fibrosarcoma) and SW 1353 (chondrosarcoma) were assessed. The uptake was temperature-dependent and higher into fibrosarcoma than in chondrosarconma. Normal bone tissue samples of rat and human were incubated with 153Sm-EDTMP and 99mTc-DPD. The uptake of 99mTc-DPD was higher than that of 153Sm-EDTMP. Various benign and malignant bone and soft tissue tumors and metastases of different primaries were treated in the same way. The uptake was generally very low, in the metastatic tissue specimen in part possibly due to their osteolytic character.

  1. Expression pattern of epithelial cell adhesion molecule on normal and malignant colon tissues

    Xin Xie; Chun-Yan Wang; Yun-Xin Cao; Wei Wang; Ran Zhuang; Li-Hua Chen; Na-Na Dang; Liang Fang; Bo-Quan Jin

    2005-01-01

    AIM: To investigate the expression pattern of epithelial cell adhesion molecule (Ep-CAM) on normal and malignant colon tissues to evaluate its diagnostic and therapeutic significance.METHODS: cDNA encoding Ep-CAv extracellular domain was cloned by reverse transcription-polymerase chain reaction (RT-PCR) from excised malignant colon tissues and inserted into a glutathione S-transferase (GST)-tagged vector. EpCAM-GST fusion protein was induced by isopropyl-β-D-thiogalactopyranoside (IPTG) and purified with glutathionesepharose. The Ep-CAM-GST fusion protein was mixed with Freund's adjuvant and Balb/c mice were immunized with it. Sp2/0 myeloma cells were fused with the spleen cells of the immunized mice. After having selected by indirect ELISA, the anti-Ep-CAM monoclonal antibodies (NAbs) were generated and the corresponding ascites were obtained.Finally, the human colon carcinoma tissue array prepared from seventy individual patients was stained with the antiEp-CAM NAbs.RESULTS: The isolated Ep-CAM cDNA sequence was identical to the data in GenBank. The expressed fusion protein was almost soluble and had a molecular weight (NW) of 53 ku.Four NAbs against Ep-CAM were obtained and designated as FMU-Ep1, FMU-Ep2, FMU-Ep3 and FMU-Ep4 respectively.Among them, FMU-Ep4 could recognize the natural EpCAM on Colo205 and SW480 cells, and all of them could be used for immunohistochemical staining of tissue sections.It was found that Ep-CAM was distributed differently in normal and various malignant colon tissues, including squamous cell carcinoma, signet-ring cell carcinoma and adenocarcinoma.In normal colon gland epithelia, Ep-CAM antigen was mainly distributed on the basolateral membrane and in the region between the basolateral membrane and the cytoplastic part near the nuclei, whereas the expression pattern of colon malignancies was mainly on the whole surface of epithelia and the expression was much higher than the normal colon tissues. The staining pattern of tissue array

  2. Nicotinamide as a radiosensitizer in tumours and normal tissues: the importance of drug dose and timing

    Background and purpose: Nicotinamide is a radiation sensitizer currently undergoing clinical testing. This was an experimental study to determine the importance of drug dose and time interval between drug administration and irradiation for radiosensitization. Materials and methods: Nicotinamide (50-500 mg/kg) was injected intraperitoneally into CDF1 or C3H mice and drug plasma pharmacokinetics were determined by HPLC. Radiosensitization was measured in tumours and normal tissues after local irradiation. The tumours were a C3H mammary carcinoma, the KHT sarcoma and the SCCVII carcinoma. Tumour response was assessed using either growth delay (C3H) or clonogenic survival (KHT/SCCVII). Normal tissue toxicities evaluated included early responding skin (development of moist desquamation of the foot) and late responding bladder (reservoir function estimated by cystometry) and lung (ventilation rate measured by plethysmography). Results: All nicotinamide peak plasma concentrations were seen within 30 min after injection. Irradiating tumours at peak times resulted in enhancement ratios (ERs) of 1.27 (C3H), 1.75 (KHT) and 1.45 (SCCVII) with high nicotinamide doses and 1.27 (C3H), 1.28 (KHT) and 1.36 (SCCVII) after giving clinically relevant doses (100-200 mg/kg). Lower ERs were observed when the time interval between drug injection and irradiation was increased beyond the peak time. Irradiating normal tissues at peak times after injecting 100-200 mg/kg nicotinamide gave ERs of 1.20 (skin), 0.90 (bladder) and 1.02 (lung). Conclusions: Clinically achievable doses of nicotinamide will enhance tumour radiation damage while having minimal effects in normal tissues, but for the best tumour effect radiation should be given at the time of peak plasma drug concentrations

  3. Reirradiation of normal tissues: Preclinical radiobiological data; Reirradiation des tissus sains: donnees radiobiologiques precliniques

    Bourgier, C.; Vozenin, M.C.; Deutsch, E. [Departement de radiotherapie et laboratoire Upres EA2710, institut Gustave-Roussy, 94 - Villejuif (France)

    2010-10-15

    Reirradiation represent an unfrequent particular clinical situation. The risk/benefit ratio assessment must be taken into account, considering both clinical and dosimetric aspects. There is a relatively limited amount of preclinical data available to date and clinicians should cautiously perform re-irradiations in selected indications. This review summarizes the experimental data available on reirradiation of normal tissues, the consequences on early and late toxicities as well as the intrinsic limitations of these models. (authors)

  4. Regulation of ongoing DNA synthesis in normal and neoplastic brain tissue

    Yakisich, Juan Sebastián

    2005-01-01

    The treatment of human brain tumour is challenging in part due to the blood brain barrier and in part due to the specific biology of brain tumours that confer resistance to chemotherapy. For instance, the 5 years survival rate for patients carrying intracranial glioblastoma multiforme has remained at 4-5 % for the last 30 years. The knowledge of the brain tumour biology as well as the biology of the normal brain tissue would help to design new therapeutic strategies and to d...

  5. Novel antioxidants are not toxic to normal tissues but effectively kill cancer cells

    Kovalchuk, Anna; Aladedunye, Felix; Rodriguez-Juarez, Rocio; Li, Dongping; Thomas, James; Kovalchuk, Olga; Przybylski, Roman

    2013-01-01

    Free radicals are formed as a result of cellular processes and play a key role in predisposition to and development of numerous diseases and of premature aging. Recently, we reported the syntheses of a number of novel phenolic antioxidants for possible application in food industry. In the present study, analyses of the cellular processes and molecular gene expression effects of some of the novel antioxidants in normal human tissues and in cancer cells were undertaken. Results indicated that w...

  6. Impact of different IMRT techniques to improve conformity and normal tissue sparing in upper esophageal cancer

    Amin E Amin; Mohamed Kelaney; Samah K Elshamndy; Osiris W. Guirguis

    2015-01-01

    Purpose: Intensity modulated radiotherapy (IMRT) for cervical esophageal cancer is challenging. Although IMRT techniques using inverse planning algorithms are facilitating the treatment planning process, the irradiation dose to the normal tissues can be a critical issue. This study was performed to investigate the effect of beam numbers and their directions and local optimization on: (1) dose conformity and homogeneity to the planning target volume (PTV) and (2) dose to the organ at risks (OA...

  7. Evolving Clinical Cancer Radiotherapy: Concerns Regarding Normal Tissue Protection and Quality Assurance

    Choi, Won Hoon; Cho, Jaeho

    2016-01-01

    Radiotherapy, which is one of three major cancer treatment methods in modern medicine, has continued to develop for a long period, more than a century. The development of radiotherapy means allowing the administration of higher doses to tumors to improve tumor control rates while minimizing the radiation doses absorbed by surrounding normal tissues through which radiation passes for administration to tumors, thereby reducing or removing the incidence of side effects. Such development of radio...

  8. Phospholipase A2 changes and its significance on brain tissue of rat in severe acute pancreatitis

    Yao Xuan; Chen Xi; Ji Zongzheng

    2007-01-01

    Objective To survey changes and the significance of phospholipase A2(PLA2) on brain tissue of SD rat in acute pancreatitis. Methods With retrograde injection of 3% taurocholate sodium into pancreatic and biliary duct, rat model of severe acute pancreatitis (SAP) was made,and it included four groups: the control group, the sham-operation group, the SAP group and the PLA2 inhibitor-treated group of SAP. Serum amylases, PLA2 and PLA2 in brain tissue were measured and the brain tissue changes were observed. Results There were no significant difference in serum amylases, PLA2 and PLA2 in brain tissue between the sham-operation and the control groups; the levels of serum amylases, PLA2 and PLA2 in brain tissue in the SAP group were higher than those in the control. In the SAP group expansion and hemorrhage of meninges, intracephalic arteriolar hyperemia, in meninges and cephalic-parenchyma infiltration of inflammatory cells and interval broaden were observed, significant differences were found between two groups.Compared with the SAP group, the level of serum amylase, PLA2 and PLA2 in brain tissue were reduced significantly in the treatment group of SAP. Pathological damages in the treatment group were significantly reduced when compared with the SAP group. Conclusion PLA2 might play an important role in brain tissue damages in severe acute pancreatitis.

  9. Tissue Pharmacology of Da-Cheng-Qi Decoction in Experimental Acute Pancreatitis in Rats

    Xianlin Zhao

    2015-01-01

    Full Text Available Objectives. The Chinese herbal medicine Da-Cheng-Qi Decoction (DCQD can ameliorate the severity of acute pancreatitis (AP. However, the potential pharmacological mechanism remains unclear. This study explored the potential effective components and the pharmacokinetic characteristics of DCQD in target tissue in experimental acute pancreatitis in rats. Methods. Acute pancreatitis-like symptoms were first induced in rats and then they were given different doses of DCQD (6 g/kg, 12 g/kg, and 24 g/kg body weight orally. Tissue drug concentration, tissue pathological score, and inflammatory mediators in pancreas, intestine, and lung tissues of rats were examined after 24 hours, respectively. Results. Major components of DCQD could be found in target tissues and their concentrations increased in conjunction with the intake dose of DCQD. The high-dose compounds showed maximal effect on altering levels of anti-inflammatory (interleukin-4 and interleukin-10 and proinflammatory markers (tumor necrosis factor α and interleukin-6 and ameliorating the pathological damage in target tissues P<0.05. Conclusions. DCQD could alleviate pancreatic, intestinal, and lung injury by altering levels of inflammatory cytokines in AP rats with tissue distribution of its components.

  10. Acute Rhabdomyolysis Associated with Coadministration of Levofloxacin and Simvastatin in a Patient with Normal Renal Function

    Maria Paparoupa

    2014-01-01

    Full Text Available We report a rare case of severe acute rhabdomyolysis in association with coadministration of levofloxacin and simvastatin in a patient with normal renal function. A 70-year-old Caucasian male was treated due to community acquired pneumonia with levofloxacin in a dosage of 500 mg once and then twice a day. On the 8th day of hospitalization the patient presented with acute severe rhabdomyolysis requiring an intensive care support. After discontinuation of levofloxacin and concomitant medication with simvastatin 80 mg/day, clinical and laboratory effects were totally reversible. Up to now, levofloxacin has been reported to induce rhabdomyolysis mainly in patients with impaired renal function, as the medication has a predominant renal elimination. In our case renal function remained normal during the severe clinical course. According to a recent case report rhabdomyolysis was observed due to interaction of simvastatin and ciprofloxacin. To our best knowledge this is the first case of interaction between simvastatin and levofloxacin to be reported. This case emphasizes the need of close monitoring of creatine kinase in patients under more than one potentially myotoxic medication especially when patients develop muscle weakness.

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

    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

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

    '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)

  13. The feasibility of using poroelastographic techniques for distinguishing between normal and lymphedematous tissues in vivo

    Righetti, Raffaella; Garra, Brian S.; Mobbs, Louise M.; Kraemer-Chant, Christina M.; Ophir, Jonathan; Krouskop, Thomas A.

    2007-11-01

    Lymphedema is a common condition involving an abnormal accumulation of lymphatic fluid in the interstitial space that causes swelling, most often in the arm(s) and leg(s). Lymphedema is a significant lifelong concern that can be congenital or develop following cancer treatment or cancer metastasis. Common methods of evaluation of lymphedema are mostly qualitative making it difficult to reliably assess the severity of the disease, a key factor in choosing the appropriate treatment. In this paper, we investigate the feasibility of using novel elastographic techniques to differentiate between lymphedematous and normal tissues. This study represents the first step of a larger study aimed at investigating the combined use of elastographic and sonographic techniques for the detection and staging of lymphedema. In this preliminary study, poroelastographic images were generated from the leg (8) and arm (4) subcutis of five normal volunteers and seven volunteers having lymphedema, and the results were compared using statistical analyses. The preliminary results reported in this paper suggest that it may be feasible to perform poroelastography in different lymphedematous tissues in vivo and that poroelastography techniques may be of help in differentiating between normal and lymphedematous tissues.

  14. The feasibility of using poroelastographic techniques for distinguishing between normal and lymphedematous tissues in vivo

    Righetti, Raffaella [Department of Diagnostic and Interventional Imaging, Ultrasonics Laboratory, University of Texas Medical School, Houston, TX (United States); Garra, Brian S [Department of Radiology, University of Vermont College of Medicine, Burlington, VT (United States); Mobbs, Louise M [Department of Radiology, Fletcher Allen Health Care, Burlington, VT (United States); Kraemer-Chant, Christina M [Department of Radiology, University of Vermont College of Medicine, Burlington, VT (United States); Ophir, Jonathan [Department of Diagnostic and Interventional Imaging, Ultrasonics Laboratory, University of Texas Medical School, Houston, TX (United States); Krouskop, Thomas A [Department of Diagnostic and Interventional Imaging, Ultrasonics Laboratory, University of Texas Medical School, Houston, TX (United States)

    2007-11-07

    Lymphedema is a common condition involving an abnormal accumulation of lymphatic fluid in the interstitial space that causes swelling, most often in the arm(s) and leg(s). Lymphedema is a significant lifelong concern that can be congenital or develop following cancer treatment or cancer metastasis. Common methods of evaluation of lymphedema are mostly qualitative making it difficult to reliably assess the severity of the disease, a key factor in choosing the appropriate treatment. In this paper, we investigate the feasibility of using novel elastographic techniques to differentiate between lymphedematous and normal tissues. This study represents the first step of a larger study aimed at investigating the combined use of elastographic and sonographic techniques for the detection and staging of lymphedema. In this preliminary study, poroelastographic images were generated from the leg (8) and arm (4) subcutis of five normal volunteers and seven volunteers having lymphedema, and the results were compared using statistical analyses. The preliminary results reported in this paper suggest that it may be feasible to perform poroelastography in different lymphedematous tissues in vivo and that poroelastography techniques may be of help in differentiating between normal and lymphedematous tissues.

  15. ALERT. Adverse late effects of cancer treatment. Vol. 2. Normal tissue specific sites and systems

    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.

  16. Analysis of differentially expressed proteins in cancerous and normal colonic tissues

    Lay-Harn Gam; Chiuan-Herng Leow; Che Nin Man; Boon-Hui Gooi; Manjit Singh

    2006-01-01

    AIM: To identify and analyze the differentially expressed proteins in normal and cancerous tissues of four patients suffering from colon cancer.METHODS: Colon tissues (normal and cancerous)were homogenized and the proteins were extracted using three protein extraction buffers. The extraction buffers were used in an orderly sequence of increasing extraction strength for proteins with hydrophobic properties. The protein extracts were separated using the SDS-PAGE method and the images were captured and analyzed using Quantity One software. The target protein bands were subjected to in-gel digestion with trypsin and finally analyzed using an ESI-ion trap mass spectrometer.RESULTS: A total of 50 differentially expressed proteins in colonic cancerous and normal tissues were identified.CONCLUSION: Many of the identified proteins have been reported to be involved in the progression of similar or other types of cancers. However, some of the identified proteins have not been reported before. In addition, a number of hypothetical proteins were also identified.

  17. ALERT. Adverse late effects of cancer treatment. Vol. 2. Normal tissue specific sites and systems

    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.

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

    Satoshi Matsuzaki

    2004-12-19

    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 {sigma}{sub {lambda}}, as well as the standard hole burning parameters (namely, {gamma} 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 (f{Delta}{mu}) for MF680 in tissue samples when burn laser polarization is parallel to the Stark field. Differences are detected between f{Delta}{mu}s 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

  19. Modulation of radiotherapy- and chemotherapy-induced normal tissue response as prophylaxis of their side effects

    Background. Ionising radiation and cytostatic agents used in cancer therapy induce an immune response in normal tissues mediated by cytokines and adhesion molecules. Strategies modulating this response may downregulate cancer therapy side effects. The data published on the given topic have been reviewed. Conclusions. The strategies influencing the tissue immune response with the aim to reduce the side effects of chemotherapy and radiotherapy are conflicting. Some of them inhibit this response supposing that an exaggerated reaction may have a damaging effect (e.g. corticosteroids, nonsteroidal anti-inflammatory drugs (NSAID), lisofylline, anti-cytokine antibodies, anti-sense oligonucleotides, sialyl Lewis X analogues), others promote this reaction by inducing endogenous production of cytokines (AS101) or use recombinant forms of appropriate cytokines involved in this response in order to intensify the physiologic tissue response. In clinical practice, corticosteroids and NSAID are widely used to modulate this response, while other agents are still experimental. (author)

  20. Histotopography of the chromaffin tissue of the mouse heart on critical stages of the normal cardioembryogenesis

    Dyagovets K.I.

    2015-12-01

    Full Text Available Background. Pheochromocytoma is tumor of chromaffin tissue, which is very hard to diagnose. Chromaffin tissue present not only in the adrenal gland, but also some cells determined in all organs of the head, neck and body. Heart population of chromaffin tissue has signs of the high developmental level during the embryonic period. It’s known, that chromaffin cells develop from neuroectoderm, like neural crest cells. There is an opinion that neural crest cells differentiate into the chromaffin tissue. Objective. Determine histotopography of the chromaffin tissue of the mouse heart on critical stages of the normal cardioembryogenesis. Methods. Embryonic mice hearts line С56BL/6 were fixed by 10%-formalin and then were subjected to the standard histological procedures. The sections 5 µm thickness were stained by the Vizel. Results and conclusion. It was established that among neural crest cells or condense mesenchyma determined cells with specific granules. These granules had specific semilunar shape and bilberry color. Cells which have same granules named like chromaffin cells. They differentiate from neural crest cells according to the opinions of some scientists. These cells have much less proliferation activity than neuroblasts. Chromaffin cells still had a few of phenotypic differences during the migration from the aortic arches. They might to be determined since the beginning of this migration. We observed that in our results. Summing up, there were defined two populations of chromaffin cells in embryo heart during the critical rotation and septation stages. They were located on subendocardial regions of the embryo heart mostly and had focal signs. Citation: Dyagovets KI. [Histotopography of the chromaffin tissue of the mouse heart on critical stages of the normal cardioembryogenesis]. Morphologia. 2015;9(4:26-30. Ukrainian.

  1. STUDY OF ECK GENE EXON-3 FROM HUMAN NORMAL TISSUE AND BREAST CANCER CELL LINE

    李瑶琛; 孔令洪; 王一理; 司履生

    2003-01-01

    Objective To establish a method cloning the exon 3 of eck gene from normal tissue and ZR-75-1 cell line (a human breast cancer cell line)and study whether these genes exist mutant. Methods Designed a pair of specific primers and amplified the exon 3 of eck gene fragment from the extracted genomic DNA derived from normal epithelial cells from skin tissue and ZR-75-1 cell line respectively by PCR technique. Transformed the E.coil. JM109 with recombinant plamids constructed by inserting the amplified fragments into medium vector pUCm-T and sequenced these amplified fragments after primary screening of endonuclease restriction digestion and PCR amplification. Results ① Obtained the genomic DNA of human normal epithelial cells and ZR-75-1 cell line respectively. ② Obtained the amplified fragments of human exon 3 of eck gene through PCR technique. ③ Obtained the cloning vectors of exon 3 of eck gene of human normal epithelial cells and ZR-75-1 cell line respectively. ④ ZR-75-1 cell line exists mutation of nucleotides. Conclusion Successfully established the method of cloning the human exon 3 of eck gene and found some mutations in the detected samples. This study lays a foundation for further studying the function of eck gene in tumorgenesis.

  2. Life-threatening acute pneumonitis in mixed connective tissue disease: a case report and literature review.

    Rath, Eva; Zandieh, Shahin; Löckinger, Alexander; Hirschl, Mirko; Klaushofer, Klaus; Zwerina, Jochen

    2015-10-01

    Mixed connective tissue disease (MCTD) is a rare connective tissue disease frequently involving the lungs. The main characteristic is a systemic sclerosis-like picture of slowly progressing interstitial lung disease consistent with lung fibrosis, while pulmonary arterial hypertension is rare. Herein, we present a case of a newly diagnosed MCTD patient developing life-threatening acute pneumonitis similar to lupus pneumonitis. Previous literature on this exceptionally rare complication of MCTD is reviewed and differential diagnosis and management discussed. PMID:26142172

  3. Optical properties of human normal small intestine tissue determined by Kubelka-Munk method in vitro

    Hua-Jiang Wei; Da Xing; Guo-Yong Wu; Ying Jin; Huai-Min Gu

    2003-01-01

    AIM: To study the optical properties of human normal small intestine tissue at 476.5 nm, 488 nm, 496.5 nm, 514.5 nm,532 nm, 808 nm wavelengths of laser irradiation.METHODS: A double-integrating-sphere system, the basic principle of measuring technology of light radiation, and an optical model of biological tissues were used in the study.RESULTS: The results of measurement showed that there were no significant differences in the absorption coefficients of human normal small intestine tissue at 476.5 nm, 488 nm,496.5 nm laser in the Kubelka-Munk two-flux model (P>0.05).The absorption coefficients of the tissue at 514.5 nm, 532 nm,808 nm laser irradiation were obviously increased with the decrease of these wavelengths. The scattering coefficients of the tissue at 476.5 nm, 488 nm, 496.5 nm laser irradiation were increased with the decrease of these wavelengths.The scattering coefficients at 496.5 nm, 514.5 nm, 532 nm laser irradiation were obviously increased with the increase of these wavelengths. The scattering coefficient of the tissue at 532 nm laser irradiation was bigger than that at 808 nm.There were no significant differences in the total attenuation coefficient of the tissue at 476.5 nm and 488 nm laser irradiation (P>0.05). The total attenuation coefficient of the tissue at 488 nm, 496.5 nm, 514.5 nm, 532 nm, 808 nm laser irradiation was obviously increased with the decrease of these wavelengths, and their effective attenuation coefficient revealed the same trend. There were no significant differences among the forward scattered photon fluxe,backward scattered photon fiuxe, and total scattered photon fiuxe of the tissue at 476.5 nm, 488 nm, 496.5 nm laser irradiation. They were all obviously increased with attenuation of tissue thickness. The attenuations of forward and backward scattered photon fluxes, and the total scattered photon fiuxe of the tissue at 514.5 nm laser irradiation were slower than those at 476.5 nm, 488 nm, 496.5 nm laser irradiation

  4. Tissue and subcellular distribution of zinc-65 in normal and zinc sulphate administered rats

    Uptake of 65Zn by various organs of normal and ZnSO4 administered rats has been studied. Except duodenum and blood all the organs show low 65Zn incorporation in treated rats. The lower 65Zn incorporation in the tissues of ZnSO4 treated rats is due to the active turnover of zinc in these tissues. The maximum activity of 65Zn is exhibited by skin, followed in decreasing order by liver, intestine, spleen, rectum, kidney, prostate, urinary bladder, stomach, pancreas, adrenals, trachea, lungs, heart, thymus, seminal vesicles, testis, cauda epididymis, caput epididymis, brain, and muscle. Since ZnSO4 administration enhanced the levels of inert zinc in liver and intestine it is likely that accumulated inert zinc in the tissues may inhibit the further incorporation of 65Zn in these tissues. At subcellular level, the cytosol fraction (11000 g supernatant fraction) exhibits the higher 65Zn activity, followed in decreasing order by 300 g fraction (cell membranes and cell debris), 900 g fraction (nuclei), 6000 g fraction (heavy mitochondria) and 1000 g fraction (light mitochondria). The 65Zn activity/mgprotein in 11000 g fraction (light mitochondria) is more than the 900 g fraction (nuclei) and 6000 g fraction (heavy mitochondria). Subcellular distribution pattern of 65Zn in liver, intestine, kidney and testis is similar. ZnSO4 administration does not change the tissue and subcellular distribution pattern of 65Zn. (author). 18 refs., 3 tables

  5. Time-resolved spectroscopy of mitochondria, cells and tissues under normal and pathological conditions.

    Beauvoit, B; Chance, B

    1998-07-01

    In this study, the detailed dependence of light scattering on tissue architecture and intracellular composition has been investigated. Firstly, we simulated the reduced scattering coefficient (mu(s)') of the rat liver using the Mie theory, the Rayleigh-Debye-Gans approximation and electron microscopy data. Then, the reduced scattering coefficient of isolated rat liver mitochondria, isolated hepatocytes and various rat tissues (i.e. perfused liver, brain, muscle, tumors) was measured at 780 nm by using time-resolved spectroscopy and a sample-substitution protocol. The comparison of the isolated mitochondria data with the isolated hepatocyte and whole liver measurements suggests that the mitochondrial compartment is the primary factor for light propagation in hepatic tissue, thus strengthening the relevance of the preliminary theoretical study. Nevertheless, the possibility that other intracellular components, such as peroxisomes and lysosomes, interfere with light propagation in rat liver is discussed. Finally, we demonstrate that light scattering in normal rat tissues and tumors is roughly proportional to the mitochondrial content, according to estimates of the mitochondrial protein content of the tissues. PMID:9746339

  6. Which parameters of the dose distribution are best related to the radiation response of tumours and normal tissues?

    Based on simple radiobiological models the effect of the distribution of absorbed dose in therapy beams on the radiation response of tumour 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 cm3 size volumes) will generally be better related to tumor control and the highest dose to significant portions of normal tissue correlates best to complications. (author). 14 refs, 10 figs

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

    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

  8. Impact of High-Normal Blood Pressure Measured in Emergency Room on Adverse Cardiac Events in Acute Myocardial Infarction

    Yoon, Nam Sik; Jeong, Myung Ho; Ahn, Youngkeun; Kim, Jong Hyun; Chae, Shung Chull; Kim, Young Jo; Hur, Seung Ho; Seong, In Whan; Hong, Taek Jong; Choi, Donghoon; Cho, Myeong Chan; Kim, Chong Jin; Seung, Ki Bae; Chung, Wook Sung; Jang, Yang Soo

    2012-01-01

    Background and Objectives Prehypertension according to JNC7 is common and is associated with increased vascular mortality. The importance of management in high-normal blood pressure (BP) is underemphasized. Subjects and Methods We analyzed major adverse cardiac events (MACEs) in the Korea Acute Myocardial Infarction Registry in normal BP (group I) and high-normal BP (group II) patients. Results Among 14871 patients, 159 (61±12.3 years, 122 males) satisfied the study indication. Six-month and ...

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

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

    2015-02-01

    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.

  10. Reactions of tumors and normal tissues in therapy with fast neutrons at the U-120 cyclotron

    Results of clinical studies are presented to show the effectiveness of therapy with 6.3 MeV fast neutrons in 45 patients with superficial tumors in the head and neck area. The reactions of tumors and normal tissues were studied in dependence on different physical and biological factors. Two variants of neutron therapy planning were estimated by means of mathematical models of a factor of time-dose-fractionation for neutron (TDFN) from clinical point of view. Results of changes in oxygen tension within the tumor are presented in 20 patients with metastases in cervical lymph nodes during neutron therapy. The data obtained show a correlation of regression and reoxigenizing rate of the tumor to its initial volume. The reaction of the tumor with fast neutrons was studied in dependence on its morphological structure. Complete regression of epidermoid and nonepidermoid cancer types was seen in 42 or 89% of the cases. With corrections for adipose tissue and the extent of dose fraction of fast neutrons the clinical test of the mathematical model of the TDFN factor made discernible that the reaction of normal tissue can be prognosticated quite exactly by means of this model in neutron therapy. (author)

  11. Comparison of steroid receptor expression in normal, dysplastic, and neoplastic canine and feline mammary tissues.

    Millanta, F; Calandrella, M; Bari, G; Niccolini, M; Vannozzi, I; Poli, A

    2005-12-01

    Steroid receptor expression was assessed by immunohistochemistry in neoplastic, hyperplastic/dysplastic, and normal mammary tissue samples removed from 68 queens and 47 bitches, using monoclonal antibodies against human oestrogen-alpha (ER) and progesterone receptors (PR). Mammary lesions were classified according to World Health Organization (WHO) criteria, and all animals with invasive carcinomas were clinically followed for 2 years. Stromal and/or lymphatic invasion and histological grading were also recorded. In both species, ER expression was significantly higher in healthy tissues, hyperplastic/dysplastic lesions, and benign tumours than in carcinomas. The loss of ER expression was more marked in feline than in canine carcinomas. In queens, PR expression increased in dysplastic lesions and "in situ" carcinomas and decreased in invasive carcinomas, even if parts of these tumours were still PR-positive. In bitches no significant variation in PR expression was observed between normal tissue, dysplasias, and benign neoplasms, but was significantly lower in carcinomas. In both species ER and PR expression in invasive carcinomas did not correlate either with histological parameters or overall survival time. This study demonstrates several differences in steroid hormone dependency between the two species. The percentage of PR-positive feline carcinomas suggests a possible role of progesterone in promoting early tumour cell growth in queens. The low percentage of ER-positive invasive carcinomas further demonstrated the aggressive phenotype and behaviour of feline mammary tumours. PMID:16054892

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

    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

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

    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

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

    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

  15. Pathogenesis of Radiation effects in normal tissues and options for intervention

    Full text: Early (acute) side-effects of radio(chemo)therapy are observed during or shortly after a course of radiotherapy. In contrast, late (chronic) side-effects become clinically manifest after latent times of months to many years. Early effects are usually found in tissues with a high proliferative activity that balances a permanent cell loss (turnover tissues), such as bone marrow, or mucosae of the intestinal tract. The symptoms are based on radiation-induced impairment of cell production, resulting in progressive cell depletion. Late radiation side-effects are basically found in all organs. In contrast to the development of early side-effects, the pathogenetic pathways of chronic side-effects are more complex. The dominating processes occur in the parenchyma of the organs (i.e. in the tissue-specific compartments) and in the connective and vascular tissue compartments. Regularly, the immune system (macrophages, mast cells) contributes to the tissue reaction. Late radiation sequelae, with few exceptions, are irreversible and progressive, with severity increasing with longer follow-up times. Therefore, the longer the survival times of the patients (i.e. the better radiation therapy) the higher is the number of patients at risk for late reactions. Early and late radiation effects are independent with regard to their pathogenesis and, in general, conclusions from the severity of early reactions on the risk of late effects cannot be drawn. However, interactions between early and chronic reactions can result in consequential late effects (CLE), when the early-responding tissue compartments (e.g. epithelia) have a protective function against mechanical and/or chemical exposure. Hence, cell depletion allows for secondary traumata to the target structures of the late sequelae, in addition to the direct effects of radiation. Consequential late effects have e.g. been demonstrated for intestine, urinary tract, oral mucosa and lung. Interventions in the 'tissular

  16. [Acute myocardial infarction with angiographically normal coronary arteries: what are we missing?].

    Niccoli, Giampaolo; Scalone, Giancarla; Crea, Filippo

    2013-12-01

    Myocardial infarction with normal coronary arteries (MINCA) can be observed in a relevant subset of patients with MI. It can be considered a syndrome, since it includes several clinical entities with specific pathogenetic mechanisms. Its prevalence is extremely variable, accounting for 5-25% of all acute myocardial infarctions. MINCA may arise from epicardial, microvascular, or myocardial localizations. Clinical history, echocardiography, coronary angiography and left ventriculography represent the first diagnostic step; however, additional tests are often required to confirm the diagnosis. The prognosis is extremely variable, depending on the causes of MINCA. Therefore, the identification of the correct etiology of MINCA is crucial to stratify patients appropriately and, hence, select the best treatment approach. In this review article, the pathogenesis, diagnosis, prognosis and therapy of MINCA are discussed, highlighting that coronary angiography alone is not sufficient for the complete understanding of the pathogenic mechanisms. PMID:24336597

  17. Emergency management of an acute tension pneumocephalus following ventriculoperitoneal shunt surgery for normal pressure hydrocephalus.

    Aydoseli, Aydın; Akcakaya, Mehmet Osman; Aras, Yavuz; Boyali, Osman; Unal, Omer Faruk

    2013-01-01

    Tension pneumocephalus is a rare and life threatening complication of intracranial surgical procedures, and requires immediate recognition and surgical intervention. Tension pneumocephalus following ventriculoperitoneal shunt surgery is extremely rare and commonly seen as a delayed complication. To our knowledge, early postoperative tension pneumocephalus after shunt surgery was reported only in one other publication. We present a case of acute tension pneumocephalus following ventriculoperitoneal shunt surgery for normal pressure hydrocephalus, which was managed well with close neurological follow-up and rapid surgical intervention. The use of the portable CT scanner in this case saved significant time, without the transport of the patient to the radiology unit, made early surgical intervention possible, and prevented morbidity and mortality. PMID:24101285

  18. Nonlinear optical microscopy for histology of fresh normal and cancerous pancreatic tissues.

    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

  19. High-risk human papilloma virus in archival tissues of oral pathosis and normal oral mucosa

    Raghu Dhanapal

    2015-01-01

    Full Text Available Objectives: Oral cancer ranks third among all cancers in the Indian population. Human papilloma virus (HPV plays a significant role in oral carcinogenesis. Population-based subtype variations are present in the HPV prevalence. This study gives an emphasis on the parameters to be considered in formalin fixed paraffin embedded tissues for polymerase chain reaction (PCR-based research work. Materials and Methods: Cross-sectional study on archival paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC, epithelial dysplasia, and normal oral mucosa surrounding impacted tooth was amplified by PCR for the E6 gene of HPV type 16 and E1 gene of HPV type 18. Results: HPV 18 was positive in three OSCC cases. There was no statistically significant association of the positivity of HPV with the age, gender or habit. The HPV positive patients had a tobacco habit and were of a younger age group. Conclusion: The presence of HPV in carcinomatous tissue highlights the possible role of HPV in carcinogenesis and archival paraffin embedded tissue specimen can be used for this analysis. Recent studies on genomic analyses have highlighted that the HPV positive tumors are a separate subgroup based on genomic sequencing. The results of a larger retrospective study will help further in our understanding of the role of HPV in carcinogenesis, this study could form the baseline for such follow-up studies.

  20. Fully unsupervised inter-individual IR spectral histology of paraffinized tissue sections of normal colon.

    Nguyen, Thi Nguyet Que; Jeannesson, Pierre; Groh, Audrey; Piot, Olivier; Guenot, Dominique; Gobinet, Cyril

    2016-05-01

    In label-free Fourier-transform infrared histology, spectral images are individually recorded from tissue sections, pre-processed and clustered. Each single resulting color-coded image is annotated by a pathologist to obtain the best possible match with tissue structures revealed after Hematoxylin-Eosin staining. However, the main limitations of this approach are the empirical choice of the number of clusters in unsupervised classification, and the marked color heterogeneity between the clustered spectral images. Here, using normal murine and human colon tissues, we developed an automatic multi-image spectral histology to simultaneously analyze a set of spectral images (8 images mice samples and 72 images human ones). This procedure consisted of a joint Extended Multiplicative Signal Correction (EMSC) to numerically deparaffinize the tissue sections, followed by an automated joint K-Means (KM) clustering using the hierarchical double application of Pakhira-Bandyopadhyay-Maulik (PBM) validity index. Using this procedure, the main murine and human colon histological structures were correctly identified at both the intra- and the inter-individual levels, especially the crypts, secreted mucus, lamina propria and submucosa. Here, we show that batched multi-image spectral histology procedure is insensitive to the reference spectrum but highly sensitive to the paraffin model of joint EMSC. In conclusion, combining joint EMSC and joint KM clustering by double PBM application allows to achieve objective and automated batched multi-image spectral histology. PMID:26872124

  1. Estimation of the effects of normal tissue sparing using equivalent uniform dose-based optimization

    K Senthilkumar

    2016-01-01

    Full Text Available In this study, we intend to estimate the effects of normal tissue sparing between intensity modulated radiotherapy (IMRT treatment plans generated with and without a dose volume (DV-based physical cost function using equivalent uniform dose (EUD. Twenty prostate cancer patients were retrospectively selected for this study. For each patient, two IMRT plans were generated (i EUD-based optimization with a DV-based physical cost function to control inhomogeneity (EUDWith DV and (ii EUD-based optimization without a DV-based physical cost function to allow inhomogeneity (EUDWithout DV. The generated plans were prescribed a dose of 72 Gy in 36 fractions to planning target volume (PTV. Mean dose, D30%, and D5%were evaluated for all organ at risk (OAR. Normal tissue complication probability was also calculated for all OARs using BioSuite software. The average volume of PTV for all patients was 103.02 ± 27 cm3. The PTV mean dose for EUDWith DVplans was 73.67 ± 1.7 Gy, whereas for EUDWithout DVplans was 80.42 ± 2.7 Gy. It was found that PTV volume receiving dose more than 115% of prescription dose was negligible in EUDWith DV plans, whereas it was 28% in EUDWithout DV plans. In almost all dosimetric parameters evaluated, dose to OARs in EUDWith DVplans was higher than in EUDWithout DVplans. Allowing inhomogeneous dose (EUDWithout DV inside the target would achieve better normal tissue sparing compared to homogenous dose distribution (EUDWith DV. Hence, this inhomogeneous dose could be intentionally dumped on the high-risk volume to achieve high local control. Therefore, it was concluded that EUD optimized plans offer added advantage of less OAR dose as well as selectively boosting dose to gross tumor volume.

  2. Estimation of the effects of normal tissue sparing using equivalent uniform dose-based optimization.

    Senthilkumar, K; Maria Das, K J; Balasubramanian, K; Deka, A C; Patil, B R

    2016-01-01

    In this study, we intend to estimate the effects of normal tissue sparing between intensity modulated radiotherapy (IMRT) treatment plans generated with and without a dose volume (DV)-based physical cost function using equivalent uniform dose (EUD). Twenty prostate cancer patients were retrospectively selected for this study. For each patient, two IMRT plans were generated (i) EUD-based optimization with a DV-based physical cost function to control inhomogeneity (EUDWith DV) and (ii) EUD-based optimization without a DV-based physical cost function to allow inhomogeneity (EUDWithout DV). The generated plans were prescribed a dose of 72 Gy in 36 fractions to planning target volume (PTV). Mean dose, D30%, and D5% were evaluated for all organ at risk (OAR). Normal tissue complication probability was also calculated for all OARs using BioSuite software. The average volume of PTV for all patients was 103.02 ± 27 cm(3). The PTV mean dose for EUDWith DV plans was 73.67 ± 1.7 Gy, whereas for EUDWithout DV plans was 80.42 ± 2.7 Gy. It was found that PTV volume receiving dose more than 115% of prescription dose was negligible in EUDWith DV plans, whereas it was 28% in EUDWithout DV plans. In almost all dosimetric parameters evaluated, dose to OARs in EUDWith DV plans was higher than in EUDWithout DV plans. Allowing inhomogeneous dose (EUDWithout DV) inside the target would achieve better normal tissue sparing compared to homogenous dose distribution (EUDWith DV). Hence, this inhomogeneous dose could be intentionally dumped on the high-risk volume to achieve high local control. Therefore, it was concluded that EUD optimized plans offer added advantage of less OAR dose as well as selectively boosting dose to gross tumor volume. PMID:27217624

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

    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

  4. Fourier transform infrared microspectroscopy as a diagnostic tool for distinguishing between normal and malignant human gastric tissue

    Abasalt Hosseinzadeh Colagar; Mohammad Javad Chaichi; Tahereh Khadjvand

    2011-09-01

    Fourier transform infrared (FTIR) microspectroscopy can be considered to be a fast and non-invasive tool for distinguishing between normal and cancerous cells and tissues without the need for laborious and invasive sampling procedures. Gastric samples from four patients (age, 65±2 years) were analysed. Samples were obtained from the organs removed during gastrectomy and then classified as normal or cancerous. Classification was based on histopathological examinations at our institution. Formalin-fixed sections of gastric tissue were analysed by FTIR-microspectroscopy. To characterize differences between sections of normal and cancerous tissue, specific regions of the spectra were analysed to study variations in the levels of metabolites. To distinguish between two conditions (normal and cancerous), changes in the relative intensity of bands in the range 600–4000 cm−1 were analysed. A FTIR spectral map of the bands in the region 2800–3100 cm–1 and 900–1800 cm–1 were created to analyse pathological changes in tissues. The limited data available showed that normal gastric tissue had stronger absorption than cancerous tissue over a wide region in the four patients. There was a significant decrease in total biomolecular components for cancerous tissue compared with normal tissue.

  5. Treatment of mild to moderate pain of acute soft tissue injury: diflunisal vs acetaminophen with codeine.

    Muncie, H L; King, D E; DeForge, B

    1986-08-01

    Acute soft tissue injuries create pain and limitation of function. Treatment requires analgesia and time for full recovery. Acetaminophen with codeine (650 mg plus 60 mg, respectively, every 4 to 6 hours) is used frequently as the analgesic of choice. Diflunisal (1,000 mg initially then 500 mg twice a day) vs acetaminophen with codeine was prospectively studied in the treatment of acute mild to moderate pain from soft tissue injuries. Thirty-five patients with acute strains, sprains, or low back pain were randomized to treatment (17 acetaminophen with codeine vs 18 diflunisal). Both groups were similar in the amount of pain and type of injury at initiation of therapy. Patient pain rating went from 3.3 +/- 0.6 to 1.6 +/- 1.5 for acetaminophen with codeine and from 3.3 +/- 0.6 to 1.3 +/- 1.1 for diflunisal. However, 65 percent of acetaminophen with codeine patients experienced side effects, with 35 percent of these patients stopping the medication because of intolerable side effects. In the diflunisal group, 28 percent of the patients experienced side effects and 5 percent had to stop the medication early. Diflunisal was found to be an effective analgesic in mild to moderate pain of acute soft tissue injuries, and caused fewer and more tolerable side effects than did acetaminophen with codeine. PMID:2942630

  6. Factors of late radiosensitivity of normal tissues; Facteurs de radiosensibilite tardive des tissus sains

    Azria, A. [CRLC Val d' Aurelle-Paul-Lamarque, departement de radiotherapie, 34 - Montpellier (France); Pointreau, Y. [CHRU Bretonneau, 37 - Tours (France); Toledano, A. [Clinique Hartman, 92 - Neuilly-sur-Seine (France); Ozsahin, M. [CHU Vaudois, Lausanne (Switzerland)

    2010-07-15

    The impact of curative radiotherapy depends mainly on the total dose delivered homogeneously in the targeted volume. Nevertheless, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. Two different side effects (acute and late) can occur during and after radiotherapy. Of particular interest are the radiation-induced sequelae due to their irreversibility and the potential impact on daily quality of life. In a same population treated in one centre with the same technique, it appears that individual radiosensitivity clearly exists. In the hypothesis that genetic is involved in this area of research, lymphocytes seem to be the tissue of choice due to easy accessibility. Recently, low percentage of CD4 and CD8 lymphocyte apoptosis were shown to be correlated with high grade of sequelae. In addition, recent data suggest that patients with severe radiation-induced late side effects possess four or more single nucleotide polymorphisms (SNP) in candidate genes (ATM, SOD2, TGFB1, XRCC1, and XRCC3) and low radiation-induced CD8 lymphocyte apoptosis in vitro. On-going studies are being analyzing the entire genome using a Genome-wide association study (GWAS) analysis. (authors)

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

    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)

  8. Biomarkers and Surrogate Endpoints for Normal-Tissue Effects of Radiation Therapy: The Importance of Dose-Volume Effects

    Biomarkers are of interest for predicting or monitoring normal tissue toxicity of radiation therapy. Advances in molecular radiobiology provide novel leads in the search for normal tissue biomarkers with sufficient sensitivity and specificity to become clinically useful. This article reviews examples of studies of biomarkers as predictive markers, as response markers, or as surrogate endpoints for radiation side effects. Single nucleotide polymorphisms are briefly discussed in the context of candidate gene and genomewide association studies. The importance of adjusting for radiation dose distribution in normal tissue biomarker studies is underlined. Finally, research priorities in this field are identified and discussed.

  9. MRI in the assessment of the supportive soft tissues of the cervical spine in acute trauma in children

    We carried out a retrospective analysis of imaging and clinical findings in 52 children with a history of cervical spinal trauma. No patient had evidence of a fracture on plain films or CT. All had MRI at 1.5 T because of persistent or delayed symptoms, unexplained findings of injury or instability, or as further assessment of the extent of soft-tissue injury. Clinical follow-up ranged from 6 months to 3.5 years. MRI was evaluated for its influence on therapy and outcome. MRI was positive in 16 (31 %) of 52 patients. Posterior soft-tissue or ligamentous injury was the most common finding in the 10 patients with mild to moderate trauma, while acute disc bulges and longitudinal ligament disruption, each seen in one case, were uncommon. MRI was superior to CT for assessment of the extent of soft-tissue injury and for identification of spinal cord injuries and intracanalicular hemorrhage in the six patients with more severe trauma. MRI specifically influenced the management of all four patients requiring surgery by extending the level of posterior stabilization. No patients with normal MRI or any of the 10 with radiographically stable soft-tissue injury on MRI, developed delayed clinical or radiographic evidence of instability or deformity. (orig.)

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

    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

  11. Elemental composition of 'normal' and Alzheimer brain tissue by INA and PIXE analyses

    Instrumental methods based on the nuclear and atomic properties of the elements have been used for many years to determine elemental concentrations in a variety of materials for biomedical, industrial and environmental applications. These methods offer high sensitivity for accurate trace element measurements, suffer few interfering or competing effects. Present no blank problems and are convenient for both research and routine analyses. The present article describes the use of two trace element techniques. Firstly the use of activation of stable nuclei irradiated by neutrons in the core of a low power research reactor as a means of detection of elements through the resulting gamma-rays emitted. Secondly, the observations of the interactions of energetic ion beams with the material in order to identify elemental species. Over recent years there has been some interest in determining the elemental composition of 'normal' and Alzheimer affected brain tissue, however literature findings are inconsistent. Possible reasons for discrepancies need to be identified for further progress to be made. Here, post-mortem tissue samples, provided by the Alzheimer's Disease Brain Bank, Institute of Psychiatry, London, were taken from the frontal, occipital, parietal and temporal lobes of both hemispheres of brains from 13 'normal' and 19 Alzheimer subjects. The elemental composition of the samples was determined using the analytical techniques of INAA (instrumental neutron activation analysis), RBS (Rutherford back-scattering) and PIXE (particle induced x-ray emission). The principal findings are summarised here. (author)

  12. Association of serum reactive oxygen metabolite levels with normal tissue damages by carbon-ion radiotherapy

    Oxygen is required for respiration and the energetic processes that enable aerobic life. Free radical and reactive oxygen metabolite (ROM) formations create oxidative stress and contribute to various processes including aging, degenerative diseases and cancer. Additionally, they may have a role in the radiotherapy for various types of cancer. In this study, we aimed to investigate the degree of oxidative stress for carbon-ion radiotherapy in locally recurrent rectal cancer and pancreas cancer, and to find out whether the degree of oxidative stress shows any difference among different grade of normal tissue damages. It can be used as an index for their differential diagnosis. Sixteen patients with locally recurrent rectal cancer and 6 pancreas cancers were included in the study. The BAP levels were lower before carbon-ion treatment than after treatment. The ROM levels were significantly lower before treatment than after treatment. It might be possible to conclude that the serum BAP and ROM levels may be an index parameter for normal tissue damages. (author)

  13. Clinical evaluation of normal tissue toxicity induced by ionizing radiation in cases of laryngeal carcinoma

    Laryngeal cancer is the second most frequent head and neck cancer in the Brazilian male population. For treatment, radiotherapy combined with chemotherapy is now used in substitution for total laryngectomy, becoming the standard treatment for advanced larynx cancer cases, with the aim of organ preservation. However, this method needs assessment of the side effects caused to normal tissue and organ functionality after treatment and the relation of these clinical factors to the individual characteristics of patients. Thus, the clinical characteristics of 229 patients with laryngeal cancer treated with radiotherapy were evaluated by medical records analysis in relation to normal tissue radiosensibility. Significant relations between smoking (p = 0.018) and combined chemoradiotherapy assistance (p = 0.03) were identified with high frequency of treatment suspension cases. The application of combined chemoradiotherapy also resulted in a higher incidence of oral mucositis (p = 0.04), xerostomia (p = 0.001) and treatment side effects to GIT (p = 0.04). Advanced clinical staging was associated with worse prognosis (p = 0.002) and a higher occurrence of treatment failure (p < 0.001). Radiotherapy was also less effective depending on the primary tumor location (p = 0.001). (author)

  14. Clinical evaluation of normal tissue toxicity induced by ionizing radiation in cases of laryngeal carcinoma

    Ramos, Adriano de Paula; Marques, Gustavo Inacio de Gomes; Soares, Renata da Bastos Ascenco; Dourado, Juliana Castro Dourado [Pontificia Universidade Catolica de Goias (PUCGO), Goiania, GO (Brazil). Dept. of Medicine; Mendonca, Yuri de Abreu, E-mail: renata.soares@pucgoias.edu.br [Goias Association Against Cancer, Goiania, GO (Brazil). Lab. of Radiobiology and Oncogenetics

    2012-07-01

    Laryngeal cancer is the second most frequent head and neck cancer in the Brazilian male population. For treatment, radiotherapy combined with chemotherapy is now used in substitution for total laryngectomy, becoming the standard treatment for advanced larynx cancer cases, with the aim of organ preservation. However, this method needs assessment of the side effects caused to normal tissue and organ functionality after treatment and the relation of these clinical factors to the individual characteristics of patients. Thus, the clinical characteristics of 229 patients with laryngeal cancer treated with radiotherapy were evaluated by medical records analysis in relation to normal tissue radiosensibility. Significant relations between smoking (p = 0.018) and combined chemoradiotherapy assistance (p = 0.03) were identified with high frequency of treatment suspension cases. The application of combined chemoradiotherapy also resulted in a higher incidence of oral mucositis (p = 0.04), xerostomia (p = 0.001) and treatment side effects to GIT (p = 0.04). Advanced clinical staging was associated with worse prognosis (p = 0.002) and a higher occurrence of treatment failure (p < 0.001). Radiotherapy was also less effective depending on the primary tumor location (p = 0.001). (author)

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

    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

  16. Tissue damage in the canine normal esophagus by photoactivation with talaporfin sodium (laserphyrin: a preclinical study.

    Takahiro Horimatsu

    Full Text Available BACKGROUND: Treatment failure at the primary site after chemoradiotherapy is a major problem in achieving a complete response. Photodynamic therapy (PDT with porfimer sodium (Photofrin® has some problems such as the requirement for shielding from light for several weeks and a high incidence of skin phototoxicity. PDT with talaporfin sodium (Laserphyrin is less toxic and is expected to have a better effect compared with Photofrin PDT. However, Laserphyrin PDT is not approved for use in the esophagus. In this preclinical study, we investigated tissue damage of the canine normal esophagus caused by photoactivation with Laserphyrin. METHODOLOGY/PRINCIPAL FINDINGS: Diode laser irradiation was performed at 60 min after administration. An area 5 cm oral to the esophagogastric junction was irradiated at 25 J/cm(2, 50 J/cm(2, and 100 J/cm(2 using a three-step escalation. The irradiated areas were evaluated endoscopically on postirradiation days 1 and 7, and were subjected to histological examination after autopsy. The areas injured by photoactivation were 52 mm(2, 498 mm(2, and 831 mm(2 after irradiation at 25 J/cm(2, 50 J/cm(2, and 100 J/cm(2, respectively. Tissue injury was observed in the muscle layer or even deeper at any irradiation level and became more severe as the irradiation dose increased. At 100 J/cm(2 both inflammatory changes and necrosis were seen histologically in extra-adventitial tissue. CONCLUSIONS/SIGNIFICANCE: To minimize injury of the normal esophagus by photoactivation with Laserphyrin, diode laser irradiation at 25 J/cm(2 appears to be safe. For human application, it would be desirable to investigate the optimal laser dose starting from this level.

  17. An application of GA to normal and malignant tissues cluster analysis

    Li, Xiang; Zhang, Guangjun; Yuan, Yan; Li, Qingbo; Wu, Jinguang

    2008-10-01

    In this paper, an application of genetic algorithm (GA) which makes the spectra of malignant tissue and that of normal tissue cluster respectively is investigated. Cluster analysis is a typical optimization problem of permutation and combination. The results of traditional algorithms closely depend on whether the parameters are rightly set. Besides, the physical understanding of sample spectra which has not been clearly known is usually needed to obtain a better result. The high dimension of the spectral data also adds difficulty in the analysis. Thus, it is almost impossible to set every parameter properly. Furthermore, since the variables and object functions are always discrete, there are a mass of local extremums. Conventional methods have no good strategy to deal with these inferior solutions. Therefore, the final cluster result is greatly influenced by the initial cluster centers and the order how the samples are input. Genetic algorithm is established based on the theory of nature selection and evolution. For GA, the understanding of the physical meaning is not necessary. Meanwhile, GA performs in a considerable high efficiency way. In the experiment, the sum of the inter-cluster distances is regarded as the object function. After smoothing, standard normal variate (SNV) processing, and outlier detection on sample spectra, Principal component analysis (PCA) is processed. Then selection, mutation and crossover are carried out on chromosomes whose ith bit value indicates which class sample i belongs to. Once the GA clustering is finished, tissue samples could be easily discriminated based on the characteristic absorbance peaks of protein, fat, nucleic acid and water. In this paper, three kinds of clustering algorithms are processed, and it shows that comparing to the conventional method, GA obtains a better result.

  18. Distribution of porfiromycin in EMT6 solid tumors and normal tissues of BALB/c mice.

    Keyes, S R; Rockwell, S; Kennedy, K A; Sartorelli, A C

    1991-05-01

    The distribution of porfiromycin was studied in BALB/c mice bearing EMT6 mammary tumors. The levels of 3H in blood and most tissues peaked approximately 15 minutes after intraperitoneal injection of [3H]porfiromycin. The levels of radioactivity present in most of the tissues and in the tumors were similar at 4 hours and 24 hours after administration. Most of the normal tissues showed uniform, low grain densities when analyzed by autoradiography; the liver and the small intestine had the highest labeling densities. Only kidney, bladder, and tumor showed differential distributions of grains from [3H]porfiromycin. In the kidney, higher grain counts were found in cortex than in medullary regions; grains were uniformly distributed within each region. In the bladder, the highest labeling densities were found in regions near the lumen. Tumor regions that had some necrotic features or regions of necrosis that included some viable cells showed higher labeling intensities than healthy-looking tumor regions, probably because the abnormal microenvironments in these regions led to increased rates of activation of porfiromycin to electrophilic species. These findings show that porfiromycin can reach and be activated in tumor regions containing cells resistant to many chemotherapeutic agents and to x rays. The results also support the concept that agents such as porfiromycin can target cells in specific microenvironmental subpopulations of solid tumors. PMID:2023281

  19. Utility of Normal Tissue-to-Tumor α/β Ratio When Evaluating Isodoses of Isoeffective Radiation Therapy Treatment Plans

    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 α/β ratio divided by the tumor α/β 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.

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

    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.

  1. The treatment of acute soft tissue trauma in Danish emergency rooms

    Johannsen, F; Langberg, Henning

    1997-01-01

    Rest, ice, compression, elevation (RICE) is the most recommended treatment for acute traumatic soft tissue injuries. A questionnaire was given to all Danish emergency rooms (n = 5) regarding their routines for acute treatment of ankle sprains and muscle contusions. Complete answers were received...... from 37 emergency rooms (73%), covering the treatment of 111 ankle sprains and 101 muscle contusions. Treatment with RICE was given in a minority of injuries, ice (21%), compression (32%) and elevation (58%) similarly between injury types. A complete RICE treatment was rarely applied (3%). Verbal...... information on RICE and rehabilitation was given in less than half of the cases. We conclude that the acute treatment of ankle sprains and muscle contusions in the Danish emergency rooms is not applied in accordance with consensus from international literature, and that the instruction in rehabilitation...

  2. Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics

    Virtaneva, Kimmo; Wright, Fred A; Tanner, Stephan M.; Yuan, Bo; William J. Lemon; Caligiuri, Michael A.; Bloomfield, Clara D.; de la Chapelle, Albert; Krahe, Ralf

    2001-01-01

    Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Normal cytogenetics (CN) constitutes the single largest group, while trisomy 8 (+8) as a sole abnormality is the most frequent trisomy. How trisomy contributes to tumorigenesis is unknown. We used oligonucleotide-based DNA microarrays to study global gene expression in AML+8 patients with +8 as the sole chromosomal abnormality and AML-CN patients. CD34+ cells purified from normal bone marrow (BM) we...

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

    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, (α/β)effNT, 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 (α/β)effNT 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 (α/β)effNT exhibits a weak dependence on the number of fractions. As n is increased, (α/β)effNT 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 (α/β)effNT 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. (paper)

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

    Hoffmann, Aswin L.; Nahum, Alan E.

    2013-10-01

    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, (\\alpha /\\beta )_{eff}^{NT}, 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 (\\alpha /\\beta )_{eff}^{NT} 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 (\\alpha /\\beta )_{eff}^{NT} exhibits a weak dependence on the number of fractions. As n is increased, (\\alpha /\\beta )_{eff}^{NT} 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 (\\alpha /\\beta )_{eff}^{NT} 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.

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

    Hoffmann, Aswin L; Nahum, Alan E

    2013-10-01

    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. PMID:24029492

  6. IMRT sparing of normal tissues in locoregional treatment of breast cancer

    This clinical study was designed to prospectively evaluate the acute and moderately-late cardiac and lung toxicities of intensity modulated radiation therapy delivered by helical tomotherapy (IMRT-HT) for locoregional breast radiation treatment including the internal mammary nodes (IMN). 30 patients with stage III breast cancers have been accrued in this study. All patients received adjuvant chemotherapy. Target volumes were defined as follows: the PTV included breast/chest wall, axillary level II, III, infra/supraclavicular, IM nodes CTVs plus 3 mm margins. The heart with subunits and the lungs were defined as critical organs. Dose to PTV was 50 Gy in 25 fractions. Acute toxicities were assessed every week and 2 weeks post treatment using the CTCAE v3.0.scale. The moderately-late toxicities were assessed clinically plus by cardiac myoview perfusion tests scheduled at baseline, 3 and 12-month follow-up, as well a CT chest at the 6 month follow-up. The data analysis is descriptive. All participants completed the 5-week course of radiation without interruption. Skin erythema was modest and mainly grade 1–2 between the 3rd and the 5th week of radiation treatment. Only 4/30 patients experienced grade 3 skin reactions, mostly seen 2 weeks post radiation. Only 5 patients demonstrated grade 1 or 2 dyspnea, but 3 of them already had symptoms pre-radiation treatment. With a median follow-up of 58 (24–76) months, there have been infrequent moderately-late side effects. Most were grade 1 and were sometimes present at the baseline assessment. Cardiac myoview tests done at baseline and 1-year follow-up for 15 out of 18 left sided breast cancers did not show any abnormalities related to radiation. The 6-month follow-up chest CT-scans done for 25 out of 30 patients showed minimal anterior lung fibrosis for 7 patients and were completely normal for the other 18. No locoregional recurrence has been recorded and the 5-year survival is 78% (95% CI: 70-97%). IMRT-HT for

  7. Prediction of radiation-induced normal tissue complications in radiotherapy using functional image data

    Nioutsikou, Elena; Partridge, Mike; Bedford, James L.; Webb, Steve

    2005-03-01

    The aim of this study has been to explicitly include the functional heterogeneity of an organ as a factor that contributes to the probability of complication of normal tissues following radiotherapy. Situations for which the inclusion of this information can be advantageous to the design of treatment plans are then investigated. A Java program has been implemented for this purpose. This makes use of a voxelated model of a patient, which is based on registered anatomical and functional data in order to enable functional voxel weighting. Using this model, the functional dose-volume histogram (fDVH) and the functional normal tissue complication probability (fNTCP) are then introduced as extensions to the conventional dose-volume histogram (DVH) and normal tissue complication probability (NTCP). In the presence of functional heterogeneity, these tools are physically more meaningful for plan evaluation than the traditional indices, as they incorporate additional information and are anticipated to show a better correlation with outcome. New parameters mf, nf and TD50f are required to replace the m, n and TD50 parameters. A range of plausible values was investigated, awaiting fitting of these new parameters to patient outcomes where functional data have been measured. As an example, the model is applied to two lung datasets utilizing accurately registered computed tomography (CT) and single photon emission computed tomography (SPECT) perfusion scans. Assuming a linear perfusion-function relationship, the biological index mean perfusion weighted lung dose (MPWLD) has been extracted from integration over outlined regions of interest. In agreement with the MPWLD ranking, the fNTCP predictions reveal that incorporation of functional imaging in radiotherapy treatment planning is most beneficial for organs with a large volume effect and large focal areas of dysfunction. There is, however, no additional advantage in cases presenting with homogeneous function. Although presented

  8. Myeloid tissue factor does not modulate lung inflammation or permeability during experimental acute lung injury

    Shaver, Ciara M.; Grove, Brandon S.; Clune, Jennifer K.; Nigel Mackman; Lorraine B. Ware; Bastarache, Julie A

    2016-01-01

    Tissue factor (TF) is a critical mediator of direct acute lung injury (ALI) with global TF deficiency resulting in increased airspace inflammation, alveolar-capillary permeability, and alveolar hemorrhage after intra-tracheal lipopolysaccharide (LPS). In the lung, TF is expressed diffusely on the lung epithelium and intensely on cells of the myeloid lineage. We recently reported that TF on the lung epithelium, but not on myeloid cells, was the major source of TF during intra-tracheal LPS-indu...

  9. Association of Geographical Factors With Administration of Tissue Plasminogen Activator for Acute Ischemic Stroke

    Kunisawa, Susumu; Morishima, Toshitaka; Ukawa, Naoto; Ikai, Hiroshi; Otsubo, Tetsuya; Ishikawa, Koichi B.; Yokota, Chiaki; Minematsu, Kazuo; Fushimi, Kiyohide; Imanaka, Yuichi

    2013-01-01

    Background Intravenous tissue plasminogen activator (tPA) is an effective treatment for acute ischemic stroke if administered within a few hours of stroke onset. Because of this time restriction, tPA administration remains infrequent. Ambulance use is an effective strategy for increasing tPA administration but may be influenced by geographical factors. The objectives of this study are to investigate the relationship between tPA administration and ambulance use and to examine how patient trave...

  10. Brown sequard syndrome secondary of soft tissue infection in a patient with acute lymphocyte leukemia

    A 42-year-old Latin American female with acute lymphocytic leukemia in second relapse developed a small ecthymic lesion around the entrance site of a left subclavian line. This was followed by development of left-sided hemiparesis with contralateral loss of pain and temperature sensation. CT of the neck revealed a diffuse inflammatory process with soft tissue involvement and several bubbles of air in the anterior paraspinal muscles and within the spinal canal in the epidural location. (orig.)

  11. Photoacoustic spectroscopy of ovarian normal, benign, and malignant tissues: a pilot study

    Kamath, Sudha D.; Ray, Satadru; Mahato, Krishna K.

    2011-06-01

    Photoacoustic spectra of normal, benign, and malignant ovarian tissues are recorded using 325-nm pulsed laser excitation in vitro. A total of 102 (34 normal, 38 benign, and 30 malignant) spectra are obtained from 22 samples belonging to normal, benign, and malignant subjects. Applying multi-algorithm approach, comprised of methods such as, principal component analysis (PCA) based k-nearest neighbor (k-NN) analysis, artificial neural network (ANN) analysis, and support vector machine (SVM) analysis, classification of the data has been carried out. For PCA, first the calibration set is formed by pooling 45 spectra, 15 belonging to each of pathologically certified normal, benign, and malignant samples. PCA is then performed on the data matrix, comprised of the six spectral features extracted from each of 45 calibration samples, and three principal components (PCs) containing maximum diagnostic information are selected. The scores of the selected PCs are used to train the k-NN, ANN, and SVM classifiers. The ANN used is a classical multilayer feed forward network with back propagation algorithm for its training. For k-NN, the Euclidean distance based algorithm is used and for SVM, one-versus-rest multiclass kernel-radial basis function is used. The performance evaluation of the classification results are obtained by calculating statistical parameters like specificity and sensitivity. ANN and k-NN techniques showed identical performance with specificity and sensitivity values of 100 and 86.76%, whereas SVM had these values at 100 and 80.18%, respectively. In order to determine the relative diagnostic performance of the techniques, receiver operating characteristics analysis is also performed.

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

    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)

  13. Validity of bioeffect dose response models for normal tissue early and late complications of the skin

    Background: The bioeffect of a physical dose depends on the nature of the tissue, fractionation scheme, dose rate and treatment time. Certainly, experienced radiotherapists are convinced of the existence of patient-to-patient variability in normal tissue response to radiotherapy for malignant tumours. The absorbed dose needs to be translated into a bioeffect dose, which takes into account treatment variables and the radiobiological characteristics of the relevant tissue. Various bioeffect models such as NSD, CRE, TDF and BED have been proposed to predict the biological effect of radiotherapy treatments. Aim: This study was aimed at deriving tolerance bioeffect dose values for normal tissue complication rate. Materials/Methods: Compiled clinical data of time dose fractionation schedules and incidence of erythema, desquamation and telangiectasia were used for the present analysis. Results: For erythema and desquamation the radiation dose varied from 23.9 to 55.1 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 40 days. For telangiectasia (score .1 at 3 years) the radiation dose varied from 25.8 to 55.1 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 40 days. For telangiectasia (score .2 at 5 years) the radiation dose varied from 25.8 to 63.0 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 68 days. For telangiectasia (score .1, .2, .3, .4 at 10 years) the radiation dose varied from 25.8 to 63.0 Gy in 04 to 35 fractions (dose per fraction 1.7 to 7.3 Gy) in 22 to 68 days. TDF and LQF values for erythema, desquamation and telangiectasia were evaluated with a/b values of 7.5 Gy, 11.2 Gy and 2.8 Gy respectively. TDF and LQF had a statistically significant correlation with probability of erythema, desquamation and telangiectasia (p<0.001). Conclusions: TDF and LQF values should be limited to 60 and 86 Gy in order to limit the probability of telangiectasia. (authors)

  14. Isolation of Streptococci from Milk Samples of Normal, Acute and Subclinical Mastitis Cows and Determination of Their Antibiotic Susceptibility Patterns

    Azizollah Ebrahimi

    2008-01-01

    Full Text Available Streptococci are frequently isolated from bovine mastitis in dairy cows with only limited information available on the antimicrobial susceptibility of these organisms. A total of 42 Streptococci isolated from 148 milk samples of normal, sub acute and acute bovine mastitis cases. Overall, 35% of the strains tested were Streptococcus dysgalactiae, Streptococcus agalactiae 26%, Streptococcus uberis 18 and 4% were Enterococcus sp. Differences between the number of isolations in acute and sub acute groups were statistically significant, (p<0.5. The antimicrobial susceptibility for these organisms was determined for the following antimicrobial agents: cephalexine, penicillin, clindamycin, cloxaciline, gentamicin, streptomycin, amoxicillin, tetracycline, kanamycin, oxytetracycline, ampicillin, chloramphenicol and erythromycin. S. agalactiae, S. dysgalactiae, S. uberis and Enterococci demonstrated high level of resistance against streptomycin, penicillin and cloxaciline. Low level of sensitivity to other tested antimicrobials was demonstrated.

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

    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%.

  16. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    Nie, Yuting; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Chen, Jianxin

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  17. Steepness of the dose response curve both for tumor cure and normal tissue injury

    At the Christie Hospital in Manchester, 4 MeV radiation was introduced in 1955. In consequence of a lack of knowledge of absolute dose definition and R.B.E. factor, patients were treated over a range of dosage. Three hundred fourteen patients with laryngeal cancer, treated over a time interval of three weeks, received doses over a range of 5000 rads to 5800 rads. Recurrence, morbidity and necrosis rates are plotted against dose. In T1 tumors there is very little variation in recurrence rate, and such tumors may be safely treated at the lower doses thus avoiding morbidity and necrosis. T3 tumors, however, show a considerable variation in recurrence rate being 68 percent at the lower end of the range, dropping to 30 percent at the high end. Necrosis nil at the lower end rises to some 8 percent at the high end. The balance of advantage of tumor sterilization versus the disadvantage of normal tissue damage is discussed

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

    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.

  19. Experimental determination of linear attenuation coefficient of normal, benign and malignant breast tissues

    The linear attenuation coefficients for normal (adipose and glandular) and neoplastic (benign and malignant) breast tissues were measured using monoenergetic X-ray beams at the energy range of 8-30 keV, combining narrow beam geometry and high energy resolution obtained using a diffracted X-ray beam. The measured values are compared with predicted ones calculated according to the mixture rule and with previous experimental data showing a good agreement within the experimental uncertainties. Our results show that there is some degree of overlap among glandular, benign and malignant values. Nevertheless, significant differences (p < 0.05) exist in the linear attenuation coefficient between glandular and malignant at energies below 28 keV. Finally, a fitting procedure was applied to values for each group (mean and extremes values) in order to summarize all data.

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

    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.

  1. A new marker for normal tissue and tumor responses to irradiation in vivo

    Impairment of normal tissue is one of the major concerns associated with radiotherapy of tumors. Side effects such as enterobrosia and cognitive problems are reported after exposure to radiation during and after cancer therapy. This study evaluated the ability of 14C-Thymidine for detecting the early effects of irradiation on tumor, gut and skin proliferation-rate. To measured 14C-Thymidine uptake, mice were intravenously injected with tracers. The linear energy transfer (LET) and dose-related decrease in 14C-Thymidine in NFSa tumor were observed 12 hours after carbon-beam irradiation. Furthermore, the reduction in 14C-Thymidine uptake at 12 hours was correlated with tumor-volume at 14 days after irradiation. These findings demonstrated that the thymidine uptake could be an appropriate marker for investigating tumor proliferation-rate after radiotherapy of malignant diseases. Thymidine uptake could predict for or allow for rapid monitoring of response to radiotherapy. (author)

  2. Wilms Tumor 1 Gene Mutations in Patients with Cytogenetically Normal Acute Myeloid Leukemia

    Salah Aref

    2014-03-01

    Full Text Available OBJECTIVE: This study aimed to assess the prognostic impact of Wilms tumor 1 (WT1 mutations in cytogenetically normal acute myeloid leukemia (CN-AML among Egyptian patients. METHODS: Exons 1, 2, 3, 7, 8, and 9 of WT1 were screened for mutations in samples from 82 CNAML patients out of 203 newly diagnosed AML patients, of age ranging from 21 to 74 years, using high-resolution capillary electrophoresis. RESULTS: Eleven patients out of 82 (13.41% harbored WT1 mutations. Mutations were detected in exon 7 (n=7, exon 9 (n=2, exon 8 (n=1, and exon 3 (n=1, but not in exons 1 or 2. There was no statistically significant difference between the WT1 mutants and wild types as regards age, sex, French-American-British subtypes, and the prevalence of success of induction remission therapy (p=0.966; 28.6% vs. 29.3%. Patients with WT1 mutations had overall survival lower than patients with the wild type (HR=1.38; 95% CI 4.79-6.86; p=0.004. CONCLUSION: CN-AML patients with WT1 mutations have poor clinical outcome. We recommend molecular testing for WT1 mutations in patients with CN-AML at diagnosis in order to improve risk stratification of those patients.

  3. Long-term effects of an intracavitary treatment with californium-252 on normal tissue

    About one hundred fifty swine were exposed to either radium-226 or californium-252 sources in the uterine cervix to determine an RBE for both acute and long-term effects. That value for early changes in the tissues at risk in the treatment of cervical cancer was between 6.2 and 6.8. The incidence of complications increased with time after exposure, especially among animals treated with 252Cf. Analysis of rectal injury showed that ulceration occurred frequently within a year postexposure at doses between 1600 and 2400 rad calculated at 2 cm lateral to the source midline. Fat necrosis and smooth muscle atrophy, resulting in a local rectal stricture, were delayed changes observed in some animals. The lower ureter was the site for a greater frequency of complications than the GI tract. Ureteral stricture often occurred at doses of 1200 rad from 252Cf and 7000 rad from 226Ra. Observation of delayed effects in the uterine-cervix in animals held up to 4 years postexposure indicate that the RBE for 252Cf may be increased to a value as high as 18, while repair may have even decreased it to about 5.6 in the rectum. Fifty swine are still being observed for long-term effects after doses above 800 rad from 252Cf and 5000 rad from 226Ra

  4. Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

    Wendler, J. J., E-mail: johann.wendler@med.ovgu.de; Porsch, M.; Huehne, S.; Baumunk, D. [University of Magdeburg, Department of Urology (Germany); Buhtz, P. [Institute of Pathology, University of Magdeburg (Germany); Fischbach, F.; Pech, M. [University of Magdeburg, Department of Radiology (Germany); Mahnkopf, D. [Institute of Medical Technology and Research (Germany); Kropf, S. [Institute of Biometry, University of Magdeburg (Germany); Roessner, A. [Institute of Pathology, University of Magdeburg (Germany); Ricke, J. [University of Magdeburg, Department of Radiology (Germany); Schostak, M.; Liehr, U.-B. [University of Magdeburg, Department of Urology (Germany)

    2013-04-15

    Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.

  5. Methylation profiling of 48 candidate genes in tumor and matched normal tissues from breast cancer patients.

    Li, Zibo; Guo, Xinwu; Wu, Yepeng; Li, Shengyun; Yan, Jinhua; Peng, Limin; Xiao, Zhi; Wang, Shouman; Deng, Zhongping; Dai, Lizhong; Yi, Wenjun; Xia, Kun; Tang, Lili; Wang, Jun

    2015-02-01

    Gene-specific methylation alterations in breast cancer have been suggested to occur early in tumorigenesis and have the potential to be used for early detection and prevention. The continuous increase in worldwide breast cancer incidences emphasizes the urgent need for identification of methylation biomarkers for early cancer detection and patient stratification. Using microfluidic PCR-based target enrichment and next-generation bisulfite sequencing technology, we analyzed methylation status of 48 candidate genes in paired tumor and normal tissues from 180 Chinese breast cancer patients. Analysis of the sequencing results showed 37 genes differentially methylated between tumor and matched normal tissues. Breast cancer samples with different clinicopathologic characteristics demonstrated distinct profiles of gene methylation. The methylation levels were significantly different between breast cancer subtypes, with basal-like and luminal B tumors having the lowest and the highest methylation levels, respectively. Six genes (ACADL, ADAMTSL1, CAV1, NPY, PTGS2, and RUNX3) showed significant differential methylation among the 4 breast cancer subtypes and also between the ER +/ER- tumors. Using unsupervised hierarchical clustering analysis, we identified a panel of 13 hypermethylated genes as candidate biomarkers that performed a high level of efficiency for cancer prediction. These 13 genes included CST6, DBC1, EGFR, GREM1, GSTP1, IGFBP3, PDGFRB, PPM1E, SFRP1, SFRP2, SOX17, TNFRSF10D, and WRN. Our results provide evidence that well-defined DNA methylation profiles enable breast cancer prediction and patient stratification. The novel gene panel might be a valuable biomarker for early detection of breast cancer. PMID:25636590

  6. Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

    Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.

  7. Inflammatory cytokine gene expression in mesenteric adipose tissue during acute experimental colitis.

    W Conan Mustain

    Full Text Available BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT has been implicated in the pathogenesis of inflammatory bowel disease (IBD. Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT. METHODS: Experimental colitis was induced in 6-month-old C57BL/6 mice by administration of dextran sulfate sodium (2% in drinking water for up to 5 days. The induction of cytokine mRNA within various adipose tissues, including mesenteric, epididymal, and subcutaneous, was analyzed by qRT-PCR. These adipose tissues were also examined for histological evidence of inflammation. The level of cytokine mRNA during acute colitis was compared between mature mesenteric adipocytes, mesenteric stromal vascular fraction (SVF, and mesenteric lymph nodes. RESULTS: During acute colitis, MAT exhibited an increased presence of infiltrating mononuclear cells and fibrotic structures, as well as decreased adipocyte size. The mRNA levels of TNF-α, IL-1β, and IL-6 were significantly increased in MAT but not other adipose tissue depots. Within the MAT, induction of these cytokines was observed mainly in the SVF. CONCLUSIONS: Acute experimental colitis causes a strong site-specific inflammatory response within MAT, which is mediated by cells of the SVF, rather than mature adipocytes or mesenteric lymph nodes.

  8. Classification between normal and tumor tissues based on the pair-wise gene expression ratio

    Precise classification of cancer types is critically important for early cancer diagnosis and treatment. Numerous efforts have been made to use gene expression profiles to improve precision of tumor classification. However, reliable cancer-related signals are generally lacking. Using recent datasets on colon and prostate cancer, a data transformation procedure from single gene expression to pair-wise gene expression ratio is proposed. Making use of the internal consistency of each expression profiling dataset this transformation improves the signal to noise ratio of the dataset and uncovers new relevant cancer-related signals (features). The efficiency in using the transformed dataset to perform normal/tumor classification was investigated using feature partitioning with informative features (gene annotation) as discriminating axes (single gene expression or pair-wise gene expression ratio). Classification results were compared to the original datasets for up to 10-feature model classifiers. 82 and 262 genes that have high correlation to tissue phenotype were selected from the colon and prostate datasets respectively. Remarkably, data transformation of the highly noisy expression data successfully led to lower the coefficient of variation (CV) for the within-class samples as well as improved the correlation with tissue phenotypes. The transformed dataset exhibited lower CV when compared to that of single gene expression. In the colon cancer set, the minimum CV decreased from 45.3% to 16.5%. In prostate cancer, comparable CV was achieved with and without transformation. This improvement in CV, coupled with the improved correlation between the pair-wise gene expression ratio and tissue phenotypes, yielded higher classification efficiency, especially with the colon dataset – from 87.1% to 93.5%. Over 90% of the top ten discriminating axes in both datasets showed significant improvement after data transformation. The high classification efficiency achieved suggested

  9. Cysteine proteinase inhibitor level in tumor and normal tissues in control and cured mice.

    Poteryaeva, O N; Falameyeva, O V; Korolenko, T A; Kaledin, V I; Djanayeva, S J; Nowicky, J W; Sandula, J

    2000-01-01

    Ukrain or carboxymethylated beta-1, 3-glucan (CMG) increased this index in both groups. Spleen cystatin C concentrations decreased about 5-fold in LS lymphosarcoma compared with controls and combined treatment with cyclophosphane plus Ukrain restored the index to the normal value. We can conclude that both murine tumors studied were characterized by low cystatin C concentrations in tumor tissues and decreased cystatin C concentrations (to a lesser degree) were also observed in liver and spleen as a result of the "toxic" effect of tumor bearing. Effective treatment in all cases (especially with Ukrain or a combination of cyclophosphane plus Ukrain) induced a significant increase in cystatin C. Obviously, the decrease in cystatin C concentration predominantly in tumor tissue was connected with tumor development and restoration of cystatin C level may be used as a marker of efficacy of antitumor therapy. PMID:11345042

  10. Radiosensitisation in normal tissues with oxygen, carbogen or nicotinamide: therapeutic gain comparisons for fractionated x-ray schedules

    Methods: Radiosensitisation with oxygen, carbogen or nicotinamide alone and oxygen or carbogen combined with nicotinamide was compared in early and late responding normal tissues in rodents. X-ray treatments were delivered as single doses or fractionated schedules of 2 fractions in 1 day, 2, 12 and 36 fractions in an overall time of 12 days and 10 fractions in 5 or 12 days. Acute skin reactions, survival of intestinal crypts, breathing rate, reduction in the packed red-cell volume and clearance of 51Cr-EDTA were used as assays of epidermal, gut, lung and renal damage. Results: Relative to air-breathing mice, carbogen or oxygen produced a small, and not always significant, increase in sensitivity (enhancement ratios ≤ 1.15) in gut, lung and kidneys; however, in skin a dose enhancement of 1.2-1.3 was observed. The effect of nicotinamide in air, carbogen or oxygen was studied only in lung and gut. The drug produced variable but generally significant increases in radiosensitisation (≤ 1.26) in all three gases. Relative to treatments in air, enhancement ratios for nicotinamide alone were usually slightly higher than those observed when either carbogen or oxygen were administered without the drug. With all three modifiers (i.e. oxygen, carbogen, nicotinamide alone or for the drug-gas combinations) there was no significant change in the enhancement ratios observed as the number of radiation dose fractions was varied. Conclusions: Comparisons with fractionated X-ray studies done previously in rodent tumours indicate that a therapeutic benefit, relative to lung, gut and renal damage, would be observed with oxygen or carbogen alone but not with nicotinamide alone. The greatest gain would be achieved with the combination of carbogen and nicotinamide, with which a benefit was observed even relative to epidermal damage. These results indicate that some decrease in normal tissue tolerance could be observed when using these modifiers in clinical radiotherapy and, although

  11. Acute pergolide exposure stiffens engineered valve interstitial cell tissues and reduces contractility in vitro.

    Capulli, Andrew K; MacQueen, Luke A; O'Connor, Blakely B; Dauth, Stephanie; Parker, Kevin Kit

    2016-01-01

    Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the US market in 1997 and pergolide, a Parkinson's disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market and continued use of similar drugs reaffirm the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 h) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness, but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD. PMID:27174867

  12. Automatic segmentation of histological structures in normal and neoplastic mammary gland tissue sections

    Fernandez-Gonzalez, Rodrigo; Deschamps, Thomas; Idica, Adam K.; Malladi, Ravi; Ortiz de Solorzano, Carlos

    2003-01-18

    In this paper we present a scheme for real time segmentation of histological structures in microscopic images of normal and neoplastic mammary gland sections. Paraffin embedded or frozen tissue blocks are sliced, and sections are stained with hematoxylin and eosin (H&E). The sections are then imaged using conventional bright field microscopy. The background of the images is corrected by arithmetic manipulation using a ''phantom.'' Then we use the fast marching method with a speed function that depends on the brightness gradient of the image to obtain a preliminary approximation to the boundaries of the structures of interest within a region of interest (ROI) of the entire section manually selected by the user. We use the result of the fast marching method as the initial condition for the level set motion equation. We run this last method for a few steps and obtain the final result of the segmentation. These results can be connected from section to section to build a three-dimensional reconstruction of the entire tissue block that we are studying.

  13. Atypical locations of retropharyngeal abscess: beware of the normal lateral soft tissue neck X-ray.

    Uzomefuna, Vincent

    2012-02-01

    Retropharyngeal abscesses (RPA) are uncommon but potentially lethal deep neck space infections, over 95% of which occur in children under six years of age. Without a high index of suspicion, early recognition and prompt intervention, catastrophic consequences can ensue, and mortality can be as high as 60% if jugular vein thrombosis or mediastinitis occurs. While older children may have specific complaints referable to the pharynx, infants and young children may present with vague symptoms. To date, a lot of emphasis continues to be placed on the importance of lateral soft tissue neck X-ray in the diagnosis and management of patients with suspected retropharyngeal abscesses; and lateral neck X-ray has been cited as the most useful radiological view of the laryngopharynx. While we recognise the role of lateral neck X-rays in retropharyngeal and other upper airway pathologies, we present three case series in which lateral neck X-rays were normal and diagnosis was made only after CT scanning. These three cases were unusual as the abscesses were located high in the naso-pharynx making them impossible to detect on the lateral soft tissue neck X-rays and this underscores the need for high index of suspicion and prompt CT or MRI scanning, in any child with symptoms or signs suggestive of a possible retropharyngeal abscess.

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

    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.)

  15. The Function of Steroid Receptor Coactivator-1 in Normal Tissues and Cancer

    Claire A. Walsh, Li Qin, Jean Ching-Yi Tien, Leonie S. Young, Jianming Xu

    2012-01-01

    Full Text Available In 1995, the steroid receptor coactivator-1 (SRC-1 was identified as the first authentic steroid receptor coactivator. Since then, the SRC proteins have remained at the epicenter of coregulator biology, molecular endocrinology and endocrine-related cancer. Cumulative works on SRC-1 have shown that it is primarily a nuclear receptor coregulator and functions to construct highly specific enzymatic protein complexes which can execute efficient and successful transcriptional activation of designated target genes. The versatile nature of SRC-1 enables it to respond to steroid dependent and steroid independent stimulation, allowing it to bind across many families of transcription factors to orchestrate and regulate complex physiological reactions. This review highlights the multiple functions of SRC-1 in the development and maintenance of normal tissue functions as well as its major role in mediating hormone receptor responsiveness. Insights from genetically manipulated mouse models and clinical data suggest SRC-1 is significantly overexpressed in many cancers, in particular, cancers of the reproductive tissues. SRC-1 has been associated with cellular proliferation and tumor growth but its major tumorigenic contributions are promotion and execution of breast cancer metastasis and mediation of resistance to endocrine therapies. The ability of SRC-1 to coordinate multiple signaling pathways makes it an important player in tumor cells' escape of targeted therapy.

  16. Analysis of heavy-ion irradiation induced adverse effect on normal tissue in murine model

    The purpose of this study was to clarify the molecular mechanism of C-ion radiation induced late injury of lung and urinary bladder in normal tissue, using murine model. Exposures were conducted using horizontal carbon-12 beams with 290 MeV/u at a dose rate of approximately 3 Gy/min within the 6-cm spread-out Bragg peak (SOBP). To evaluate the effects of C-ion irradiation on lungs, pathological changes after thoracic irradiation were analyzed. To evaluate the adverse effects on the bladder, pathological evaluation were performed. The gene expression analysis were performed using total RNA derived from irradiated tissues on 6 hour after irradiation to elucidate the molecular response to irradiation. Survival assay revealed the subacute phase death by hemorrhagic pneumonitis in C3H/He and the late phase death by pulmonary fibrosis in C57BL/6J after C-ion irradiation. Microarray analysis presented the genes with strain variance after C-ion irradiation. Immunohistochemical staining of LAMP family proteins, which relates bladder contraction, in the irradiated urinary bladder were different between strains. (author)

  17. Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue.

    Lilge, L; Portnoy, M; Wilson, B C

    2000-10-01

    The apoptotic response of normal brain and intracranial VX2 tumour following photodynamic therapy (PDT) mediated by 5 different photosensitizers (Photofrin, 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX), chloroaluminium phthalocyanine (AlCIPc), Tin Ethyl Etiopurpurin (SnET(2)), and meta -tetra(hydroxyphenyl)chlorin (m THPC)) was evaluated following a previous analysis which investigated the necrotic tissue response to PDT at 24 h post treatment. Free DNA ends, produced by internucleosomal DNA cleavage in apoptotic cells, were stained using a TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling) assay. Confocal laser scanning microscopy (CLSM) was used to quantify the local incidence of apoptosis and determine its spatial distribution throughout the brain. The incidence of apoptosis was confirmed by histopathology, which demonstrated cell shrinkage, pyknosis and karyorrhexis. At 24 h post PDT, AlClPc did not cause any detectable apoptosis, while the other photosensitizers produced varying numbers of apoptotic cells near the region of coagulative necrosis. The apoptotic response did not appear to be related to photosensitizer dose. These results suggest that at this time point, a minimal and fairly localized apoptotic effect is produced in brain tissues, the extent of which depends largely on the particular photosensitizer. PMID:10993661

  18. FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics.

    Wang, Lei; Xu, Wei-lai; Meng, Hai-tao; Qian, Wen-bin; Mai, Wen-yuan; Tong, Hong-yan; Mao, Li-ping; Tong, Yin; Qian, Jie-jing; Lou, Yin-jun; Chen, Zhi-mei; Wang, Yun-gui; Jin, Jie

    2010-10-01

    Mutations of fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) exon 12 genes are the most common abnormalities in adult acute myeloid leukemia (AML) with normal cytogenetics. To assess the prognostic impact of the two gene mutations in Chinese AML patients, we used multiplex polymerase chain reaction (PCR) and capillary electrophoresis to screen 76 AML patients with normal cytogenetics for mutations in FLT3 internal tandem duplication (FLT3/ITD) and exon 12 of the NPM1 gene. FLT3/ITD mutation was detected in 15 (19.7%) of 76 subjects, and NPM1 mutation in 20 (26.3%) subjects. Seven (9.2%) cases were positive for both FLT3/ITD and NPM1 mutations. Significantly more FLT3/ITD aberration was detected in subjects with French-American-British (FAB) M1 (42.8%). NPM1 mutation was frequently detected in subjects with M5 (47.1%) and infrequently in subjects with M2 (11.1%). FLT3 and NPM1 mutations were significantly associated with a higher white blood cell count in peripheral blood and a lower CD34 antigen expression, but not age, sex, or platelet count. Statistical analysis revealed that the FLT3/ITD-positive group had a lower complete remission (CR) rate (53.3% vs. 83.6%). Survival analysis showed that the FLT3/ITD-positive/NPM1 mutation-negative group had worse overall survival (OS) and relapse-free survival (RFS). The FLT3/ITD-positive/NPM1 mutation-positive group showed a trend towards favorable survival compared with the FLT3/ITD-positive/NPM1 mutation-negative group (P=0.069). Our results indicate that the FLT3/ITD mutation might be a prognostic factor for an unfavorable outcome in Chinese AML subjects with normal cytogenetics, while NPM1 mutation may be a favorable prognostic factor for OS and RFS in the presence of FLT3/ITD. PMID:20872983

  19. Estimate of normal tissue damage in treatment planning for stereotactic radiotherapy

    A personal computer (PC) system was developed to perform treatment planning for radiosurgery and stereotactic radiotherapy. These techniques of irradiation of the brain may be accomplished with a linear accelerator by performing several non-coplanar arcs of a highly collimated beam focused at a fixed point. The PC system allows the acquisition, reconstruction and the visualization of the target volume from CT or MR images, and then it permits to calculate a three-dimensional (3-D) dose distribution due to small photon beams and to visualize it. The software calculates not only total dose distribution, administered fractionated or in single fraction, but also in NTD2 (normalized total dose) predicted to have a biological effect equivalent to the single irradiation. The choice of the best technique is supported by the dose volume histograms (DVH) calculation and by an estimate of complication probability to the brain normal tissue (NTCP). The algorithm for NTCP calculation is based on two models: The linear quadratic and the logistic. A comparison of three different dose calculations for a typical cerebral target volume is presented to demonstrate the system performances. (orig.)

  20. Correlation of cutaneous tension distribution and tissue oxygenation with acute external tissue expansion

    Marquardt C

    2009-11-01

    Full Text Available Abstract Today, the biomechanical fundamentals of skin expansion are based on viscoelastic models of the skin. Although many studies have been conducted in vitro, analyses performed in vivo are rare. Here, we present in vivo measurements of the expansion at the skin surface as well as measurement of the corresponding intracutaneous oxygen partial pressure. In our study the average skin stretching was 24%, with a standard deviation of 11%, excluding age or gender dependency. The measurement of intracutaneous oxygen partial pressure produced strong inter-individual fluctuations, including initial values at the beginning of the measurement, as well as varying individual patient reactions to expansion of the skin. Taken together, we propose that even large defect wounds can be closed successfully using the mass displacement caused by expansion especially in areas where soft, voluminous tissue layers are present.

  1. Positron imaging feasibility studies: Short term uptake of thymidine in normal and neoplastic tissues

    The uptake of labeled thymidine (TdR) as measured by labelling index has provided useful experimental and clinical data regarding tumor cell cycle. This approach is limited by the requirement for repeated tissue sampling, but could potentially be extended to in vivo measurements using C-11 TdR and positron emission tomography (PET). Since TdR is rapidly cleared from the circulation, there is concern that the distribution in vivo might reflect blood flow and not cellular metabolism. Therefore, uptake of H-3 TdR was studied in AKR mice, both normal and with spontaneous lymphoma, and in organs and tumors of dogs with spontaneous tumors. Uptake was compared to relative blood flow as measured by the distribution of C-14 iodantipyrine. Metabolic H-3 water was removed by air drying the samples before oxidizing them for counting. The initial distribution of thymidine in normal mice, measured 20 seconds after injection, correlated with relative perfusion measurements. However, between one and sixty minutes after injection there was no correlation of TdR uptake with perfusion in any of the systems studied. This indicates that the distribution more than one minute after injection is primarily dependent on subsequent redistribution and/or metabolism of TdR, rather than the initial distribution by blood flow. The time activity curve of TdR content in normal mouse organs demonstrated that organs with high rates of proliferation retail all the labeled TdR initially taken up. Organs with low rates of proliferation lost their label in a nearly exponential wash out. These studies provide further evidence of the feasibility of using C-11 TdR for PET and provide the experimental basis for developing kinetic models of TdR metabolism to interpret PET studies

  2. Comparative Study on Antioxidative System in Normal and Vitrified Shoots of Populus suaveolens in Tissue Culture

    Lin Shanzhi; Zhang Zhiyi; Lin Yuanzhen; Liu Wenfeng; Guo Huan; Zhang Wei; Zhang Chong

    2004-01-01

    To explore the physiological and biochemical mechanism of the occurrence of vitrified shoots of Populus suaveolens in tissue culture, the changes in water, chlorphyll, lignin, H2O2, phenylalanine ammonialyase (PAL), malonaldehyde (MDA), protective enzymatic systems, and some key enzymes involved in the ascorbate- glutathione cycle were comparatively studied in both normal and vitrified shoots of P. Suaveolens. The results show that the lower activities of peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), glutathione reductase (GR) and PAL, and the less contents of chlorphyll, lignin, ascorbate (ASA) and reduced glutathione (GSH) as well as the lower ratios of ASA / DHA and GSH / GSSG are observed in vitrified shoots than in normal ones during the whole culture period. While in comparison with normal shoots, the higher activity of superoxide dismutase (SOD) and the more concentrations of water, H2O2, MDA, dehydroascorbate (DHA) and oxidized glutathione (GSSG) are found in vitrified shoots. Statistical analysis indicates that the enhanced activity of SOD and the decreased activities of CAT and POD as well as some enzymes involved in the ascorbate-glutathione cycle might be closely correlated to the accumulation of H2O2. The less regeneration of ASA and GSH and the lower capacity of the ascorbate-glutathione cycle observed in vitrified shoots might be due to a significant decrease in APX, MDAR, DHAR and GR activities and a decline in redox status of ASA and GSH. The decreases in chlorphyll content might result in a decline in photosynthesis. The lower activities of POD and PAL could result in the decrease of lignin synthesis and cell wall ligination, which might be the key factor leading to the increase in water content. It is concluded that the deficiency of detoxification capacity caused by the lower capacity of the ascorbate-glutathione pathway and the decreased activity of protective enzymatic system might lead to the

  3. A simple method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation

    Since volumetric dose distributions are available with 3-dimensional radiotherapy treatment planning they can be used in statistical evaluation of response to radiation. This report presents a method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation. The mathematical expression for the calculation of normal tissue complication probability has been derived combining the Lyman model with the histogram reduction method of Kutcher et al. and using the normalized total dose (NTD) instead of the total dose. The fitting of published tolerance data, in case of homogeneous or partial brain irradiation, has been considered. For the same total or partial volume homogeneous irradiation of the brain, curves of normal tissue complication probability have been calculated with fraction size of 1.5 Gy and of 3 Gy instead of 2 Gy, to show the influence of fraction size. The influence of dose distribution inhomogeneity and α/β value has also been simulated: Considering α/β=1.6 Gy or α/β=4.1 Gy for kidney clinical nephritis, the calculated curves of normal tissue complication probability are shown. Combining NTD calculations and histogram reduction techniques, normal tissue complication probability can be estimated taking into account the most relevant contributing factors, including the volume effect. (orig.)

  4. Acute myocardial infarction in a young adult with myocardial bridging and normal coronary arteries

    Moris Chansky; Adriana Regina Perez; Nilo Lima

    2004-01-01

    The authors present a case of a young adult with acute myocardialinfarction, attended at the Emergency Department of HospitalIsraelita Albert Einstein. Acute myocardial infarction caused bymyocardial bridge (intramyocardial tunneled coronary artery) is arare clinical entity. The finding of this condition in patients withnormal arteries (non-obstructed vessels) is uncommon; it isusually associated with extracardiac triggering factors. The casereported presented an acute myocardial infarction c...

  5. Acute pseudo-obstruction of the large bowel with caecal perforation following normal vaginal delivery: a case report

    Seenath Marlon

    2010-04-01

    Full Text Available Abstract Introduction Acute pseudo-obstruction of the large bowel following normal vaginal delivery is an extremely rare complication of normal vaginal delivery. It can be fatal if not recognized early. Only one previous report has been found in the English literature. Case presentation A 36-year old Caucasian, normally fit woman presented with abdominal distension and vomiting five days post-normal vaginal delivery at term. Localised peritonitis in the right iliac fossa developed in the next few days, and caecal perforation was found at laparotomy, without evidence of appendicitis or colitis. Conclusion Although very rare, Ogilvie's syndrome should be considered by obstetricians, general surgeons and general practitioners as a potential cause of vomiting and abdominal pain following normal vaginal delivery. Early recognition and management are essential to minimize the possibility of developing serious complications.

  6. Molecular Ultrasound Imaging of Tissue Inflammation Using an Animal Model of Acute Kidney Injury

    Hoyt, Kenneth; Warram, Jason M.; Wang, Dezhi; Ratnayaka, Sithira; Traylor, Amie; Agarwal, Anupam

    2016-01-01

    Purpose The objective of this study was to evaluate the use of molecular ultrasound (US) imaging for monitoring the early inflammatory effects following acute kidney injury. Procedures A population of rats underwent 30 min of renal ischemia (acute kidney injury, N=6) or sham injury (N=4) using established surgical methods. Animals were divided and molecular US imaging was performed during the bolus injection of a targeted microbubble (MB) contrast agent to either P-selectin or vascular cell adhesion molecule 1 (VCAM-1). Imaging was performed before surgery and 4 and 24 h thereafter. After manual segmentation of renal tissue space, the molecular US signal was calculated as the difference between time-intensity curve data before MB injection and after reaching steady-state US image enhancement. All animals were terminated after the 24 h imaging time point and kidneys excised for immunohistochemical (IHC) analysis. Results Renal inflammation was analyzed using molecular US imaging. While results using the P-selectin and VCAM-1 targeted MBs were comparable, it appears that the former was more sensitive to biomarker expression. All molecular US imaging measures had a positive correlation with IHC findings. Conclusions Acute kidney injury is a serious disease in need of improved noninvasive methods to help diagnose the extent of injury and monitor the tissue throughout disease progression. Molecular US imaging appears well suited to address this challenge and more research is warranted. PMID:25905474

  7. Developing Multivariable Normal Tissue Complication Probability Model to Predict the Incidence of Symptomatic Radiation Pneumonitis among Breast Cancer Patients.

    Tsair-Fwu Lee

    Full Text Available Symptomatic radiation pneumonitis (SRP, which decreases quality of life (QoL, is the most common pulmonary complication in patients receiving breast irradiation. If it occurs, acute SRP usually develops 4-12 weeks after completion of radiotherapy and presents as a dry cough, dyspnea and low-grade fever. If the incidence of SRP is reduced, not only the QoL but also the compliance of breast cancer patients may be improved. Therefore, we investigated the incidence SRP in breast cancer patients after hybrid intensity modulated radiotherapy (IMRT to find the risk factors, which may have important effects on the risk of radiation-induced complications.In total, 93 patients with breast cancer were evaluated. The final endpoint for acute SRP was defined as those who had density changes together with symptoms, as measured using computed tomography. The risk factors for a multivariate normal tissue complication probability model of SRP were determined using the least absolute shrinkage and selection operator (LASSO technique.Five risk factors were selected using LASSO: the percentage of the ipsilateral lung volume that received more than 20-Gy (IV20, energy, age, body mass index (BMI and T stage. Positive associations were demonstrated among the incidence of SRP, IV20, and patient age. Energy, BMI and T stage showed a negative association with the incidence of SRP. Our analyses indicate that the risk of SPR following hybrid IMRT in elderly or low-BMI breast cancer patients is increased once the percentage of the ipsilateral lung volume receiving more than 20-Gy is controlled below a limitation.We suggest to define a dose-volume percentage constraint of IV20< 37% (or AIV20< 310cc for the irradiated ipsilateral lung in radiation therapy treatment planning to maintain the incidence of SPR below 20%, and pay attention to the sequelae especially in elderly or low-BMI breast cancer patients. (AIV20: the absolute ipsilateral lung volume that received more than

  8. Using neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy for nasopharyngeal carcinoma with intracranial invasion to protect critical normal tissue

    To investigate the feasibility of neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy (IMRT) for intracranial invasion nasopharyngeal carcinoma (NPC). From June 2007 to January 2012, 32 patients with intracranial invasion NPC treated with TPF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, 5-FU 2500 mg/m2 every 3 weeks for 3 cycles) neoadjuvant chemotherapy, and replanning IMRT with concurrent chemotherapy were retrospectively studied. The first IMRT plan for each patient was generated based on the original planning CT scan acquired before the start of treatment. Because of tumor shrinkage during radiotherapy, modified gross tumor volume of primary tumor (GTV-P) and high risk clinical target volume (CTV-H), and a new plan was generated and used to complete the course of IMRT. The DVHs of IMRT plan with or without replanning were compared. There weren’t statistically significant differences in the V95, D-mean, D-95, and D-99 to the modified PTVGTV-P and PTVCTV-H with and without replanning IMRT. Replanning reduced the doses to the brain stem, optic nerve, optic chiasm and temporal lobe. Objective responses were 100.0% 3 months after completion of radiotherapy. Acute toxicities were well tolerated, except for the relatively high incidence of neutropenia. The 2-year local control rates and distant-metastasis free survival were 88.2% (95% CI, 72.9% to 100.0%) and 89.6% (95% CI, 75.9% to 100.0%). Neoadjuvant chemotherapy and replanning IMRT according to tumor shrinkage during the treatment is essential to ensure safe doses to normal tissues, and produces encouraging outcome for intracranial invasion NPC

  9. ICRP PUBLICATION 118: ICRP Statement on Tissue Reactions and Early and Late Effects of Radiation in Normal Tissues and Organs – Threshold Doses for Tissue Reactions in a Radiation Protection Context

    This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of ‘practical’ threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40–50 years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1–1.2, and in a few cases 1.5–2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating

  10. The effects of pentoxifylline on brachytherapy induced late normal tissue reactions

    Irradiation is known to stimulate the release of platelet derived growth factor (PDGF) from irradiated platelets. PDGF causes the migration and proliferation of vascular smooth muscle and endothelial elements, and is thought to be a cause of late radiation vasculopathy. Irradiation also causes a significant release of tromboxane that is a potent vasoconstrictor and a strong stimulator of platelet aggregation. On the other hand, petoxifylline increases red blood cell deformability and prostocycline release from platelets, and inhibits neutrophil activity. If damage to microvasculature is responsible for late radiation injury, pentoxifylline (PENTO), by improving blood supply and by increasing the level of prostocycline on irradiated tissue may prevent late radiation reactions. The effects of PENTO on the brachytherapy (BT) induced late normal tissue injury were tested using Ir192 wire (2.378 mCi/cm activity) application via the plastic tube method and the Dosimetric System of Paris in the hind legs of BALB/c mice. 75 Gy were given in 6.98 days, and were divided into saline (0.01 ml/g/day, SC) and PENTO injection (50 mg/kg/day, SC) groups. At the end of three months animals were killed by cervical dislocation, and 40 slices in only BT, 48 slices in BT+PENTO groups were evaluated with light microscopy by the same pathologists. Vascularization, vascular hyalinization endothelial proliferation, inflammatory infiltration, fibrosis, muscle degeneration and mast cell infiltration were graded from 0 to 3+. In the BT+PENTO group were found statistically significant decreases in vascularization, fibrosis and muscle degeneration. Preliminary results of this study are promising and in favor of using PENTO after brachytherapy to reduce late fibrosis and muscle degeneration

  11. Monitoring of permeability of different analytes in human normal and cancerous bladder tissues in vitro using optical coherence tomography

    Bingsong Lei; Xiaoyuan Deng; Huajiang Wei; Zhouyi Guo [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, Guangdong Province (China); Guoyong Wu [Department of Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province (China); Hongqin Yang; Shusen Xie [Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education of China, Fujian Normal University, Fuzhou 350007, Fujian (China); Yonghong He [Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, Guangdong (China)

    2014-12-31

    We report our preliminary results on quantification of glucose and dimethyl sulfoxide (DMSO) diffusion in normal and cancerous human bladder tissues in vitro by using a spectral domain optical coherence tomography (SD-OCT). The permeability coefficients (PCs) of a 30% aqueous solution of glucose are found to be (7.92 ± 0.81) × 10{sup -6} cm s{sup -1} and (1.19 ± 0.13) × 10{sup -5} cm s{sup -1} in normal and cancerous bladder tissues, respectively. The PCs of 50% DMSO are calculated to be (8.99 ± 0.93) × 10{sup -6} cm s{sup -1} and (1.43 ± 0.17) × 10{sup -5} cm s{sup -1} in normal and cancerous bladder tissues, respectively. The obtained results show a statistically significant difference in permeability of normal and cancerous tissue and indicate that the PC of 50% DMSO is about 1.13-and 1.21-fold higher than that of 30% glucose in normal bladder and cancerous bladder tissues, respectively. Thus, the quantitative measurements with the help of PCs from OCT images can be a potentially powerful method for bladder cancer detection. (optical coherence tomography)

  12. Monitoring of permeability of different analytes in human normal and cancerous bladder tissues in vitro using optical coherence tomography

    We report our preliminary results on quantification of glucose and dimethyl sulfoxide (DMSO) diffusion in normal and cancerous human bladder tissues in vitro by using a spectral domain optical coherence tomography (SD-OCT). The permeability coefficients (PCs) of a 30% aqueous solution of glucose are found to be (7.92 ± 0.81) × 10-6 cm s-1 and (1.19 ± 0.13) × 10-5 cm s-1 in normal and cancerous bladder tissues, respectively. The PCs of 50% DMSO are calculated to be (8.99 ± 0.93) × 10-6 cm s-1 and (1.43 ± 0.17) × 10-5 cm s-1 in normal and cancerous bladder tissues, respectively. The obtained results show a statistically significant difference in permeability of normal and cancerous tissue and indicate that the PC of 50% DMSO is about 1.13-and 1.21-fold higher than that of 30% glucose in normal bladder and cancerous bladder tissues, respectively. Thus, the quantitative measurements with the help of PCs from OCT images can be a potentially powerful method for bladder cancer detection. (optical coherence tomography)

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

    The interactions of radiation and seven cancer chemotherapeutic drugs have been investigated in four normal tissues and in a solid C3H 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.)

  14. Large animal normal tissue tolerance using an epithermal neutron beam and borocaptate sodium

    Irradiation of the canine head following intravenous Na2B12H11SH (BSH) administration has provided useful information concerning the tolerance of skin and brain to the resultant complex form of irradiation. The effect of the boron capture reaction in skin and brain has provided estimates of the influence of the microscopic dosimetry involved. Dogs irradiated with the epithermal bam alone provided valuable insight into the relative biological effectiveness (RBE) of the fast neutron component (>10 keV) of the epithermal beam. When comapred with literature values for X-rays for the occurrence of skin necrosis in dogs, an RBE of 4.5 was derived. Previous pharmacokinetic data concerning the distribution of Na2B12H11SH (BSH) to blood and bran has been used to obtain input parameters for computer models of the microvasculature of the brain. Monte Carlo computer models were used to simulate the microscopic distribution of BSH in the normal brain. The term compo- und factor describes the product of the microscopic boron fission fragment dose hitting the nucleus and the relative biologic effectiveness divided by the macroscopic equilibrium dose of the boron reaction in the tissue of interest. The computed compound factor for Na2B12H11SH (BSH) in normal brain was 0.37. This factor agreed very well with the value of 0.32 obtained for the brain necrosis with the dog irradiations. The compound factor for the dog's skin was experimentally derived from the dog experiments and was equal to 0.5. (orig.)

  15. Pulsed Doppler Tissue Imaging for Assessment of Left Ventricular Systolic and Diastolic Synchronicity in Normal Subjects

    Yang Li; Wu Wei; Wang Jingfeng; Zhang Xiaoling

    2006-01-01

    Objectives To quantitatively analyze the longitudinal myocardial systolic and diastolic velocities and time intervals of the left ventricle in normal subjects, and to explore the value of pulsed Doppler tissue imaging (DTI) for the assessment of left ventricular systolic and diastolic synchronicity.Methods Twenty and six healthy subjects were studied by pulsed DTI. The septal and lateral, anterior and inferior walls of the left ventricle were displayed respectively, and basal and middle segments of each wall were selected for myocardial motion spectrum sampling. DTI parameters were: peak systolic myocardial velocity (s), regional pre-ejection period (PEP), time to the peak of s wave (Ts), regional ejection time (ET); peak early diastolic velocity (e),peak late diastolic velocity (a), e/a ratio, time to the beginning of e wave (QE), time to the peak of e wave (Te) and regional isovolumic relaxation time (IVRT).Results The e and e/a were significantly different among basal segments, and s and e/a were significantly different among middle segments, with the highest value in lateral segments and the lowest value in septal segments. The s, e and a were all significantly higher in basal segments than middle segments. None of the systolic time intervals (PEP, Ts and ET) and diastolic time intervals (QE, Te and IVRT) were significantly different among basal segments and middle segments,neither were they when basal segment was compared with middle segment. Conclusions In normal subjects, the longitudinal myocardial systolic and diastolic velocities of the left ventricle are not homogeneous, but the contraction and relaxation are highly synchronized. Pulsed DTI can be used to quantitatively analyze the systolic and diastolic synchronicity of the heart.

  16. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

  17. Determination of trace element distribution in cancerous and normal human tissues by total reflection X-ray fluorescence analysis

    von Czarnowski, D.; Denkhaus, E.; Lemke, K.

    1997-07-01

    The intention of this study was to establish a method for cancer diagnosis. For this purpose, different trace element distributions in carcinomas of the digestive tract and in normal tissues of human stomach, colon and rectum in correlation to the type of cancer were determined by total reflection X-ray fluorescence analysis (TXRF). The tissue samples were frozen and cut by a microtome into 10 μm sections, and a modified sample excision technique was introduced according to the aim of this research. After drying and spiking of the tissue sections, more than 20 elements, especially biologically relevant ones, were determined. The repeatabilities of measurements of element concentrations in malignant and normal tissues were calculated to be 10-30% (RSD) depending on the specific element. The concentration of Ca was found to be virtually constant (0.250±0.025 μg per 0.1 mm 3) in normal tissue and in carcinoma of the digestive organs. A significant diminution of Cr, Fe and Ni in carcinoma of the stomach, of Cr and Co in carcinoma of the colon and a significant accumulation of K in cancerous tissue of the colon and of Fe and K in neoplastic tissue of the rectum were discovered for a very limited population of patients.

  18. Repair of acutely injured spinal cord through constructing tissue-engineered neural complex in adult rats

    PU Yu; GUO Qing-shan; WANG Ai-min; WU Si-yu; XING Shu-xing; ZHANG Zhong-rong

    2007-01-01

    Objective: To construct tissue-engineered neural complex in vitro and study its effect in repairing acutely injured spinal cord in adult rats. Methods: Neural stem cells were harvested from the spinal cord of embryo rats and propagated in vitro. Then the neural stem cells were seeded into polyglycolic acid scaffolds and co-cultured with extract of embryonic spinal cord in vitro. Immunofluorescence histochemistry and scanning electron microscope were used to observe the microstructure of this complex. Animal model of spine semi-transection was made and tissue-engineered neural complex was implanted by surgical intervention. Six weeks after transplantation, functional evaluation and histochemistry were applied to evaluate the functional recovery and anatomic reconstruction. Results: The tissue-engineered neural complex had a distinct structure, which contained neonatal neurons, oligodendrocytes and astrocytes. After tissue-engineered neural complex was implanted into the injured spinal cord, the cell components such as neurons, astrocytes and oligodendrocytes, could survive and keep on developing. The adult rats suffering from spinal cord injury got an obvious neurological recovery in motor skills. Conclusions: The tissue-engineered neural complex appears to have therapeutic effects on the functional recovery and anatomic reconstruction of the adult rats with spinal cord injury.

  19. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): An Introduction to the Scientific Issues

    Advances in dose-volume/outcome (or normal tissue complication probability, NTCP) modeling since the seminal Emami paper from 1991 are reviewed. There has been some progress with an increasing number of studies on large patient samples with three-dimensional dosimetry. Nevertheless, NTCP models are not ideal. Issues related to the grading of side effects, selection of appropriate statistical methods, testing of internal and external model validity, and quantification of predictive power and statistical uncertainty, all limit the usefulness of much of the published literature. Synthesis (meta-analysis) of data from multiple studies is often impossible because of suboptimal primary analysis, insufficient reporting and variations in the models and predictors analyzed. Clinical limitations to the current knowledge base include the need for more data on the effect of patient-related cofactors, interactions between dose distribution and cytotoxic or molecular targeted agents, and the effect of dose fractions and overall treatment time in relation to nonuniform dose distributions. Research priorities for the next 5-10 years are proposed.

  20. 3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

    Goodwin, Thomas J.

    2013-01-01

    Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

  1. Spectral characterization and unmixing of intrinsic contrast in intact normal and diseased gastric tissues using hyperspectral two-photon microscopy.

    Lauren E Grosberg

    Full Text Available BACKGROUND: Living tissues contain a range of intrinsic fluorophores and sources of second harmonic generation which provide contrast that can be exploited for fresh tissue imaging. Microscopic imaging of fresh tissue samples can circumvent the cost and time associated with conventional histology. Further, intrinsic contrast can provide rich information about a tissue's composition, structure and function, and opens the potential for in-vivo imaging without the need for contrast agents. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used hyperspectral two-photon microscopy to explore the characteristics of both normal and diseased gastrointestinal (GI tissues, relying only on their endogenous fluorescence and second harmonic generation to provide contrast. We obtained hyperspectral data at subcellular resolution by acquiring images over a range of two-photon excitation wavelengths, and found excitation spectral signatures of specific tissue types based on our ability to clearly visualize morphology. We present the two-photon excitation spectral properties of four major tissue types that are present throughout the GI tract: epithelium, lamina propria, collagen, and lymphatic tissue. Using these four excitation signatures as basis spectra, linear unmixing strategies were applied to hyperspectral data sets of both normal and neoplastic tissue acquired in the colon and small intestine. Our results show that hyperspectral unmixing with excitation spectra allows segmentation, showing promise for blind identification of tissue types within a field of view, analogous to specific staining in conventional histology. The intrinsic spectral signatures of these tissue types provide information relating to their biochemical composition. CONCLUSIONS/SIGNIFICANCE: These results suggest hyperspectral two-photon microscopy could provide an alternative to conventional histology either for in-situ imaging, or intraoperative 'instant histology' of fresh tissue

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

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

    2009-01-01

    paired frozen and paraffin-embedded samples. Moreover, we studied the impact of amplicon sizes on the efficiency of Q-RT-PCR in paraffin-embedded tissues. Six putative reference genes were tested for stability of expression in 21 pairs of snap-frozen and formalin-fixed, paraffin-embedded lymph nodes and......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 (P<0.01) after normalization 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....

  3. Multivariate statistical analysis of Raman spectra to distinguish normal, tumor, lymph nodes and mastitis in mouse mammary tissues

    Dai, H.; Thakur, J. S.; Serhatkulu, G. K.; Pandya, A. K.; Auner, G. W.; Naik, R.; Freeman, D. C.; Naik, V. M.; Cao, A.; Klein, M. D.; Rabah, R.

    2006-03-01

    Raman spectra ( > 680) of normal mammary gland, malignant mammary gland tumors, and lymph node tissues from mice injected with 4T1 tumor cells have been recorded using 785 nm excitation laser. The state of the tissues was confirmed by standard pathological tests. The multivariate statistical analysis methods (principle component analysis and discriminant functional analysis) have been used to categorize the Raman spectra. The statistical algorithms based on the Raman spectral peak heights, clearly separated tissues into six distinct classes, including mastitis, which is clearly separated from normal and tumor. This study suggests that the Raman spectroscopy can possibly perform a real-time analysis of the human mammary tissues for the detection of cancer.

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

    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

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

    Zhang, Q; Lei, Y; Zheng, D; Zhu, X; Wahl, A; Lin, C; Zhou, S; Zhen, W [University of Nebraska Medical Center, Omaha, NE (United States)

    2015-06-15

    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.

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

    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.

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

    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

  8. Acute exercise increases adipose tissue interstitial adiponectin concentration in healthy overweight and lean subjects

    Højbjerre, Lise; Rosenzweig, Mary; Dela, Flemming;

    2007-01-01

    OBJECTIVE: We studied how an acute bout of exercise influences expression and concentration of adiponectin and regulators of adiponectin in adipose tissue and plasma. DESIGN AND METHODS: Eight overweight and eight lean males were examined by large-pore microdialysis in s.c. abdominal adipose tissue...... increased the SCAAT interstitial adiponectin concentration in both overweight and lean subjects and concentrations did not differ between groups. Plasma adiponectin did not increase during exercise and was similar in overweight and lean subjects. Adiponectin mRNA in SCAAT decreased during exercise and was...... similar in overweight and lean subjects. Surprisingly, the interstitial adiponectin concentration in SCAAT was only 20% of the plasma concentration. SCAAT interleukin-6 (IL-6) microdialyzate and plasma concentrations and SCAAT IL-6 mRNA increased during exercise in both groups. Tumor necrosis factor- (TNF...

  9. The role of HOX genes in normal hematopoiesis and acute leukemia

    Alharbi, RA; Pettengell, R; Pandha, HS; Morgan, R

    2013-01-01

    The HOX genes are a highly conserved family of homeodomain-containing transcription factors that specify cell identity in early development and, subsequently, in a number of adult processes including hematopoiesis. The dysregulation of HOX genes is associated with a number of malignancies including acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), where they have been shown to support the immortalization of leukemic cells both as chimeric partners in fusion genes and when overex...

  10. Cingulin, a specific protein component of tight junctions, is expressed in normal and neoplastic human epithelial tissues.

    Citi, S.; Amorosi, A; Franconi, F.; Giotti, A.; Zampi, G.

    1991-01-01

    Cingulin is a 140-kd protein localized on the cytoplasmic face of avian tight junctions. The expression of cingulin in human normal and neoplastic colonic tissue has been investigated with an antiserum against chicken cingulin. Human cingulin shares its apparent molecular mass and localization with avian cingulin. In normal colonic epithelium, villous adenomas, and differentiated adenocarcinomas, cingulin staining is observed in the junctional region of the polarized cells lining the surface,...

  11. Ultrasound Evaluation of Normal and Abnormal Fetuses: Comparison of Conventional, Tissue Harmonic, and Pulse-Inversion Harmonic Imaging Techniques

    Ryu, Jeong-Ah; Kim, Bohyun; Kim, Sooah; Yang, Soon Ha; Choi, Moon Hae; Ahn, Hyeong sik

    2003-01-01

    Objective To determine the usefulness of tissue harmonic imaging (THI) and pulse-inversion harmonic imaging (PIHI) in the evaluation of normal and abnormal fetuses. Materials and Methods Forty-one pregnant women who bore a total of 31 normal and ten abnormal fetuses underwent conventional ultrasonography (CUS), and then THI and PIHI. US images of six organ systems, namely the brain, spine, heart, abdomen, extremities and face were compared between the three techniques in terms of overall cons...

  12. Automated prediction of tissue outcome after acute ischemic stroke in computed tomography perfusion images

    Vos, Pieter C.; Bennink, Edwin; de Jong, Hugo; Velthuis, Birgitta K.; Viergever, Max A.; Dankbaar, Jan Willem

    2015-03-01

    Assessment of the extent of cerebral damage on admission in patients with acute ischemic stroke could play an important role in treatment decision making. Computed tomography perfusion (CTP) imaging can be used to determine the extent of damage. However, clinical application is hindered by differences among vendors and used methodology. As a result, threshold based methods and visual assessment of CTP images has not yet shown to be useful in treatment decision making and predicting clinical outcome. Preliminary results in MR studies have shown the benefit of using supervised classifiers for predicting tissue outcome, but this has not been demonstrated for CTP. We present a novel method for the automatic prediction of tissue outcome by combining multi-parametric CTP images into a tissue outcome probability map. A supervised classification scheme was developed to extract absolute and relative perfusion values from processed CTP images that are summarized by a trained classifier into a likelihood of infarction. Training was performed using follow-up CT scans of 20 acute stroke patients with complete recanalization of the vessel that was occluded on admission. Infarcted regions were annotated by expert neuroradiologists. Multiple classifiers were evaluated in a leave-one-patient-out strategy for their discriminating performance using receiver operating characteristic (ROC) statistics. Results showed that a RandomForest classifier performed optimally with an area under the ROC of 0.90 for discriminating infarct tissue. The obtained results are an improvement over existing thresholding methods and are in line with results found in literature where MR perfusion was used.

  13. Impact of different IMRT techniques to improve conformity and normal tissue sparing in upper esophageal cancer

    Amin E Amin

    2015-03-01

    Full Text Available Purpose: Intensity modulated radiotherapy (IMRT for cervical esophageal cancer is challenging. Although IMRT techniques using inverse planning algorithms are facilitating the treatment planning process, the irradiation dose to the normal tissues can be a critical issue. This study was performed to investigate the effect of beam numbers and their directions and local optimization on: (1 dose conformity and homogeneity to the planning target volume (PTV and (2 dose to the organ at risks (OARs.Methods: Four upper esophageal cancer cases were randomly selected for this treatment planning study. Eight IMRT plans were generated for each case with the same dose-volume constraints but with different beam numbers and arrangements. Local optimization using regular structures drawn automatically around the PTV with margins from 0.5-1.5 cm was performed. IMRT plans were evaluated with respect to isodose distributions, dose-volume histograms (DVHs parameters, homogeneity index (HI, and conformity index (CI. The statistical comparison between the types of plans was done using the One Way ANOVA test.Results: The results showed that IMRT using three or five beams was not sufficient to obtain good dose optimization. The seven field plans showed the best coverage for the PTV with tolerable doses for the OARs, and the beam orientation was very critical. Increasing beams (Bs number from 7 to 13 did not show significant differences in the PTV coverage, while the mean lung dose was increased. The PTV coverage were 95.1, 95.1, 98.1, 97.3, 97.3, 97.3, 97.0, and 97.0% for 3Bs, 5Bs, 7Bs, 9Bs, 13Bs, 7Bs(30, 7Bs(60 (beam angles were changed from 0o to 30o and 60o, and 7Bs(R (seven IMRT plans with ring, respectively. The mean heart dose did not exceed 0.36 Gy with p < 0.05. For lung doses, the best plan was the one with 9Bs which reduced lung volume doses V20Gy (% and V30Gy (%, and reduced mean lung dose from 5.4 to 4.5 Gy with p < 0.05 for 7Bs(R plans. IMRT improved the

  14. The role of somatostatin receptors in normal tissues in pharmacokinetics of radiolabelled octreotates

    Full text: Radiolabelled somatostatin analogues have great potential for the visualization and treatment of somatostatin receptor-positive tumours and their metastases. But receptors for somatostatin can also be expressed with different density in normal organs and tissues. In this report we studied the effect of somatostatin receptor blockade on distribution profiles and elimination characteristics of DOTA-Tyr3-octreotate (DOTATATE) labelled with 90Y, 111In, and 153Sm in rats. Animal studies were carried out using male Wistar rats. Radiolabelled DOTATATEs we administered to animals intravenously in the dose of 1 μg/kg. To determine the effect of somatostatin receptor blockade to distribution and elimination of the agents, some groups of rats were pretreated by intravenous injection of 0.1 mg/kg unlabelled octreotide (Sandostatin) 15 min before the radiolabelled DOTATATE administration. Somatostatin receptor blockade substantially descreased radioactivity uptake in the adrenals and pancreas of animals. This finding is in agreement with the fact that specific binding sites for somatostatin are present in both the exocrine and endocrine pancreas and also in the adrenals of rats. A partial reduction of radioactivity accumulation in the thyroid, skin and bone of somatostatin receptor-blocked animals was also found. Moreover, a significant decrease of radioactivity in gastrointestinal tract (both stomach and bowels) in pretreated groups was also determined. Radioactivity uptake in the gastrointestinal tract may be partly due to hepatobiliary excretion of the peptides and/or their metabolites and partly due to excretory mechanisms involving specific binding of the agents to somatostatin receptors localized in the gastric wall and a consequent secretion of the radiolabel to the gastric content. According to our results, bile excretion of radiolabelled DOTATATEs determined in the perfused rat liver was very low and negligible. The results suggest that receptor

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

    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. PMID:22779232

  16. In vitro radiosensitivity of skin fibroblasts can identify a group of radiotherapy patients having developed complications in a variety of normal tissues

    A retrospective study of the in vitro radiosensitivity of skin fibroblasts derived from two groups of patients treated by definitive radiotherapy for a variety of tumors who either displayed or did not display severe complications. Seven radiotherapy patients were selected: three treated for head and neck, prostate and non-Hodgkin lymphoma tumors, and did not develop any significant complications (control group); four patients were treated for bladder, thyroid, head and neck and anal canal tumors and developed serious acute and especially late reactions (hypersensitive group), Primary cell cultures of skin fibroblasts were established and their radiosensitivity studied by the clonogenic assay after exposing to single radiation doses ranging between 1 and 8 Gy. The survival fraction at 2 Gy (SF2) ranged from 0.27 to 0.38, with a mean of 0.33 for the control group, and from 0.10 to 0.20 with a mean of 0.17 for the hypersensitive group. The Mann-Whitney non-parametric test hypersensitive group. The Mann-Whitney non-parametric test showed that the difference between the two means was statistically significant (p = 0.03). The data are in favor of a correlation between the radiosensitivity of patients' fibroblasts and the reactions of different normal tissues to radiotherapy. This association supports the use of the clonogenic survival, or a surrogate test, as a predictive assay. The multiplicity of normal tissues and organs implicated in this association suggests the existence of genetic factors that determine, at least in part, the radiosensitivity of target cells involved in the expression of normal tissues complications following radiotherapy. (authors)

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

    Cella, Laura, E-mail: laura.cella@cnr.it [Institute of Biostructures and Bioimaging, National Council of Research, Naples (Italy); Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy); Liuzzi, Raffaele; Conson, Manuel [Institute of Biostructures and Bioimaging, National Council of Research, Naples (Italy); Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy); D’Avino, Vittoria [Institute of Biostructures and Bioimaging, National Council of Research, Naples (Italy); Salvatore, Marco [Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy); Pacelli, Roberto [Institute of Biostructures and Bioimaging, National Council of Research, Naples (Italy); Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy)

    2013-10-01

    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.

  18. Volume effects of late term normal tissue toxicity in prostate cancer radiotherapy

    Bonta, Dacian Viorel

    Modeling of volume effects for treatment toxicity is paramount for optimization of radiation therapy. This thesis proposes a new model for calculating volume effects in gastro-intestinal and genito-urinary normal tissue complication probability (NTCP) following radiation therapy for prostate carcinoma. The radiobiological and the pathological basis for this model and its relationship to other models are detailed. A review of the radiobiological experiments and published clinical data identified salient features and specific properties a biologically adequate model has to conform to. The new model was fit to a set of actual clinical data. In order to verify the goodness of fit, two established NTCP models and a non-NTCP measure for complication risk were fitted to the same clinical data. The method of fit for the model parameters was maximum likelihood estimation. Within the framework of the maximum likelihood approach I estimated the parameter uncertainties for each complication prediction model. The quality-of-fit was determined using the Aikaike Information Criterion. Based on the model that provided the best fit, I identified the volume effects for both types of toxicities. Computer-based bootstrap resampling of the original dataset was used to estimate the bias and variance for the fitted parameter values. Computer simulation was also used to estimate the population size that generates a specific uncertainty level (3%) in the value of predicted complication probability. The same method was used to estimate the size of the patient population needed for accurate choice of the model underlying the NTCP. The results indicate that, depending on the number of parameters of a specific NTCP model, 100 (for two parameter models) and 500 patients (for three parameter models) are needed for accurate parameter fit. Correlation of complication occurrence in patients was also investigated. The results suggest that complication outcomes are correlated in a patient, although

  19. Validation of Normal Tissue Complication Probability Predictions in Individual Patient: Late Rectal Toxicity

    Purpose: To perform validation of risk predictions for late rectal toxicity (LRT) in prostate cancer obtained using a new approach to synthesize published normal tissue complication data. Methods and Materials: A published study survey was performed to identify the dose-response relationships for LRT derived from nonoverlapping patient populations. To avoid mixing models based on different symptoms, the emphasis was placed on rectal bleeding. The selected models were used to compute the risk estimates of grade 2+ and grade 3+ LRT for an independent validation cohort composed of 269 prostate cancer patients with known toxicity outcomes. Risk estimates from single studies were combined to produce consolidated risk estimates. An agreement between the actuarial toxicity incidence 3 years after radiation therapy completion and single-study or consolidated risk estimates was evaluated using the concordance correlation coefficient. Goodness of fit for the consolidated risk estimates was assessed using the Hosmer-Lemeshow test. Results: A total of 16 studies of grade 2+ and 5 studies of grade 3+ LRT met the inclusion criteria. The consolidated risk estimates of grade 2+ and 3+ LRT were constructed using 3 studies each. For grade 2+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.537 compared with 0.431 for the best-fit single study. For grade 3+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.477 compared with 0.448 for the best-fit single study. No evidence was found for a lack of fit for the consolidated risk estimates using the Hosmer-Lemeshow test (P=.531 and P=.397 for grade 2+ and 3+ LRT, respectively). Conclusions: In a large cohort of prostate cancer patients, selected sets of consolidated risk estimates were found to be more accurate predictors of LRT than risk estimates derived from any single study

  20. The relative biological effectiveness of fast neutrons (42MeV/sub d→Be/) for early and late normal tissue injury in the pig

    Early and late radiation damage has been investigated in a number of normal tissues in the pig after irradiation with single doses of neutrons produced by 42MeV deuterons on beryllium. The results have been compared with data obtained after irradiation with single doses of 250kV X rays. In the skin a low RBE value of approximately 1.2 was obtained for the early (3-9 week) epithelial reaction. For the subsequent dermal vascular response, higher RBE values in the range of 1.35-1.6 were obtained; the RBE decreasing with an increase in the neutron dose. For late skin damage, assessed by the relative reduction in the linear dimensions of an irradiated field, a RBE value of approximately 1.5 was obtained. In the kidney the RBE value, for a neutron dose level (550 cGy) at which renal function was just preserved, was 2.0. A lower value of 1.7 was found for doses resulting in a loss of renal function. The results of 133Xenon clearance studies showed two waves of impaired ventilation function in the irradiated lung. In the acute reaction (3-9 months), at a dose level consistent with just preserving normal ventilation function, the RBE value was <1.2. For late lung damage (15-24 months) the RBE value was higher, 1.4. For the rectum, methods are presently only available for assessing acute damage. A RBE of 2.0 was found for neutron doses in the range 350-575 cGy. The RBE values for early endpoints in the skin, lung and gut of the pig are comparable with those published previously for other species, including man. The values for late effects in pig skin and lung were higher than for early damage in those tissues

  1. Comparison of salbutamol with normal saline and salbutamol with magnesium sulphate in the treatment of severe acute asthma.

    Ahmed, S; Sutradhar, S R; Miah, A H; Bari, M A; Hasan, M J; Alam, M K; Tariquzzaman, M; Sarker, C N

    2013-01-01

    This study compared the efficacy and safety of nebulized magnesium sulphate with salbutamol to normal saline with salbutamol as the initial treatment of severe acute asthma patients. The present study was designed as a randomized open controlled clinical trial. The study was conducted Mymensingh Medical College Hospital over a period of 11 months from December 2009 to October 2010. Patients admitted with severe acute asthma having inclusion criteria were the study population. Among 120 study population 60 were in salbutamol with magnesium sulphate group and 60 were in salbutamol with normal saline group. The study finding showed that peak flow at baseline was similar in two groups. At 10 minutes after nebulization, the mean±SD percentage increase in peak flow was greater in magnesium sulphate group (20±4%) than in the normal saline salbutamol group (13±3%). At 20 minutes the percentage increase in peak flow was greater in magnesium sulphate group (35±7%) than in the normal saline salbutamol group (24±6%) p value sulphate plus salbutamol group reached PEF near to 60% which is not in saline salbutamol group. There was no significant changed in respiratory rate, pulse rate, systolic, diastolic blood pressure and clinical evidence of unwanted adverse effect. PMID:23416800

  2. Differences in supratentorial white matter diffusion after radiotherapy - New biomarker of normal brain tissue damage?

    Ravn, Soeren; Jens Broendum Froekaer, Jens [Dept. of Radiology, Aalborg Univ. Hospital, Aalborg (Denmark)], e-mail: sorl@rn.dk; Holmberg, Mats [Dept. of Oncology, Aalborg Univ. Hospital, Aalborg (Denmark); Soerensen, Preben [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark); Carl, Jesper [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark)

    2013-10-15

    Introduction: Therapy-induced injury to normal brain tissue is a concern in the treatment of all types of brain tumours. The purpose of this study was to investigate if magnetic resonance diffusion tensor imaging (DTI) could serve as a potential biomarker for the assessment of radiation-induced long-term white matter injury. Material and methods: DTI- and T1-weighted images of the brain were obtained in 19 former radiotherapy patients [nine men and 10 women diagnosed with astrocytoma (4), pituitary adenoma (6), meningioma (8) and craniopharyngioma (1), average age 57.8 (range 35-71) years]. Average time from radiotherapy to DTI scan was 4.6 (range 2.0-7.1) years. NordicICE software (NIC) was used to calculate apparent diffusion coefficient maps (ADC-maps). The co-registration between T1 images and ADC-maps were done using the auto function in NIC. The co-registration between the T1 images and the patient dose plans were done using the auto function in the treatment planning system Eclipse from Varian. Regions of interest were drawn on the T1-weighted images in NIC based on iso curves from Eclipse. Data was analysed by t-test. Estimates are given with 95 % CI. Results: A mean ADC difference of 4.6(0.3;8.9) X 10{sup -5} mm{sup 2}/s, p = 0.03 was found between paired white matter structures with a mean dose difference of 31.4 Gy. Comparing the ADC-values of the areas with highest dose from the paired data (dose > 33 Gy) with normal white matter (dose < 5 Gy) resulted in a mean dose difference of 44.1 Gy and a mean ADC difference of 7.87(3.15;12.60) X 10{sup -5} mm{sup 2}/s, p = 0.003. Following results were obtained when looking at differences between white matter mean ADC in average dose levels from 5 to 55 Gy in steps of 10 Gy with normal white matter mean ADC: 5 Gy; 1.91(-1.76;5.58) X 10{sup -5} mm{sup 2}/s, p = 0.29; 15 Gy; 5.81(1.53;10.11) X 10{sup -5} mm{sup 2}/s, p = 0.01; 25 Gy; 5.80(2.43;9.18) X 10{sup -5} mm{sup 2}/s, p = 0.002; 35 Gy; 5.93(2.89;8.97) X 10

  3. The early response of p53-dependent proteins during radiotherapy in human rectal carcinoma and in adjacent normal tissue

    Stift, A; Prager, G; Selzer, E; Widder, J; Kandioler, D; Friedl, J; Teleky, B; Herbst, F; Wrba, F; Bergmann, M

    2003-01-01

    The aim of this study was to investigate the activation of the p53 pathway and the induction of apoptosis during preoperative radiotherapy in normal human rectal tissue and in rectal carcinoma. Twelve patients with rectal cancer of the lower third were enrolled in this study. Tumor specimens and adj

  4. Approach for reduction of late effects caused by radiation therapy on normal tissue for patients of prostate cancer

    By means of 6 prostate cancer patients the dose distribution of the tumor and the normal tissue is discussed in a treatment planning comparison study of protons and photons. Output factors like minimum dose to the tumor, maximum dose to the normal tissue or organ at risk, isodose - lines, integral dose and dose volume histograms (DVH) point up the advantages of particle radiotherapy. As an example for the benefit of particle the therapy dose to the planning target volume (PTV) is compared for the mentioned techniques by DVHs. With respect to the different treatment techniques the wall of the rectum will get a significant higher dose, while using a photon 4-fields technique than a 2-field or 4-field proton technique. Treatment planning comparisons can help to decrease side- and late- effects by the calculation of the tumor control probability and the normal tissue complication probability. In any case, predicting the outcome of cancer treatment implies the knowledge of many specific parameters, like the tolerance dose (TD5/5, TD50/5) to the normal tissue or organ at risk. Nevertheless proton therapy is limited to the appropriateness of available particle therapy facilities, but can support advanced prostate cancer therapy by better tumor coverage and less side- and late- effects. (authors)

  5. The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues.

    Croop, J M; Raymond, M; Haber, D; Devault, A; Arceci, R. J.; Gros, P.; Housman, D.E.

    1989-01-01

    The gene responsible for multidrug resistance (mdr), which encodes the P-glycoprotein, is a member of a multigene family. We have identified distinct mdr gene transcripts encoded by three separate mdr genes in the mouse. Expression levels of each mdr gene are dramatically different in various mouse tissues. Specific mdr RNA transcripts of approximately 4.5, 5, and 6 kilobases have been detected. Each of the mdr genes has a specific RNA transcript pattern. These results should be considered in...

  6. Malondialdehyde-derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue.

    Williams, Joshua D; Bermudez, Yira; Park, Sophia L; Stratton, Steven P; Uchida, Koji; Hurst, Craig A; Wondrak, Georg T

    2014-03-01

    Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than threefold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored. PMID:24584085

  7. Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

    Na Zhang; Gen-Yang Cheng; Xian-Zhi Liu; Feng-Jiang Zhang

    2014-01-01

    Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue. Methods:Fourty eight rats were randomly divided into four groups(n=12): sham operation group,30 min ischemia60 min reperfusion group,60 min ischemia60 min reperfusion group, and 120 min ischemia60 min reperfusion group.The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreasedBcl-2 expression, increasedBax expression, upregulated expression ofNF-κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.

  8. High-throughput sequencing of frozen and paraffin-embedded tumor and normal tissue

    Kerick, M; Timmermann, B; Schweiger, M.

    2010-01-01

    Until now high-throughput sequencing of tumor samples relied on DNA isolated from fresh frozen tissues, the preparation of which, however, is relatively laborious. The use of preserved material, i.e. from tissue banks, could help to avoid this limitation and would enable the reanalysis of diverse clinical trials. So far we have shown that formalin-fixed paraffin-embedded (FFPE) tissue samples can be used for genomic re-sequencing processes. FFPE samples are amply available from surgical tumor...

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

    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%.

  10. Methylation Profiling Defines an Extensive Field Defect in Histologically Normal Prostate Tissues Associated with Prostate Cancer12

    Yang, Bing; Bhusari, Sachin; Kueck, Jessica; Weeratunga, Pushpa; Wagner, Jennifer; Leverson, Glen; Huang, Wei; Jarrard, David F

    2013-01-01

    Prostate cancer (PCa) is typically found as a multifocal disease suggesting the potential for molecular defects within the morphologically normal tissue. The frequency and spatial extent of DNA methylation changes encompassing a potential field defect are unknown. A comparison of non-tumor-associated (NTA) prostate to histologically indistinguishable tumor-associated (TA) prostate tissues detected a distinct profile of DNA methylation alterations (0.2%) using genome-wide DNA arrays based on the Encyclopedia of DNA Elements 18 sequence that tile both gene-rich and poor regions. Hypomethylation (87%) occurred more frequently than hypermethylation (13%). Several of the most significantly altered loci (CAV1, EVX1, MCF2L, and FGF1) were then used as probes to map the extent of these DNA methylation changes in normal tissues from prostates containing cancer. In TA tissues, the extent of methylation was similar both adjacent (2 mm) and at a distance (>1 cm) from tumor foci. These loci were also able to distinguish NTA from TA tissues in a validation set of patient samples. These mapping studies indicate that a spatially widespread epigenetic defect occurs in the peripheral prostate tissues of men who have PCa that may be useful in the detection of this disease. PMID:23555185

  11. Correction of electrode polarization contributions to the dielectric properties of normal and cancerous breast tissues at audio/radiofrequencies

    Spurious contributions from electrode polarization (EP) are a major nuisance in dielectric measurements of biological tissues and hamper accurate determination of tissue properties in the audio/radiofrequencies. Various electrode geometries and/or treatments have been employed traditionally to reduce EP contributions, although none succeeded to completely remove EP from measurements on tissues for all practical frequency ranges. A method of correction for contributions of EP to the dielectric properties of tissues is proposed. The method is based on modeling the electrode impedance with suitable functions and on the observation that certain parameters are only dependent on electrodes properties and can thus be determined separately. The method is tested on various samples with known properties, and its usefulness is demonstrated with samples of normal and cancerous human female breast tissue. It is observed that the dielectric properties of the tissues over the frequency range 40 Hz-100 MHz are significantly different among different types of breast tissue. This observation is used further to demonstrate that, by scanning the tip of the measuring dielectric probe (with modest spatial resolution) across a sample of excised breast tissue, significant variations in the electrical properties are detected at a position where a tumor is located. This study shows that dielectric spectroscopy has the potential to offer a viable alternative to the current methods for detection of breast cancer in vivo

  12. Can fruits and vegetables be used as substitute phantoms for normal human brain tissues in magnetic resonance imaging?

    Various custom-made phantoms designed to optimize magnetic resonance imaging (MRI) sequences have been created and subsequently reported in Japanese Society of Radiological Technology (JSRT). However, custom-made phantoms that correctly match the T1-value and T2-values of human brain tissue (gray matter and white matter) cannot be made easily or quickly. The aim of this project was to search for alternative materials, such as fruits and vegetables, for optimizing MRI sequences. The following eight fruits and vegetables were investigated: apple, tomato, melon, apple mango (Mangifera indica), banana, avocado, peach, and eggplant. Their potential was studied for use in modeling phantoms of normal human brain tissues. MRI (T1- and T2-weighted sequences) was performed on the human brain and the fruits and vegetables using various concentrations of contrast medium (gadolinium) in the same size tubes as the custom-made phantom. The authors compared the signal intensity (SI) in human brain tissue (gray matter and white matter) with that of the fruits and the custom-made phantom. The T1 and T2 values were measured for banana tissue and compared with those for human brain tissue in the literature. Our results indicated that banana tissue is similar to human brain tissue (both gray matter and white matter). Banana tissue can thus be employed as an alternative phantom for the human brain for the purpose of MRI. (author)

  13. The role of insulin therapy and glucose normalization in patients with acute coronary syndrome

    J.A. Lipton; A. Can; S. Akoudad (Saloua); M.L. Simoons (Maarten)

    2011-01-01

    textabstractPatients with acute myocardial infarction (AMI) and diabetes mellitus, as well as patients admitted with elevated blood glucose without known diabetes, have impaired outcome. Therefore intensive glucose-lowering therapy with insulin (IGL) has been proposed in diabetic or hyperglycaemic p

  14. Normalization of gene expression measurement of tissue samples obtained by transurethral resection of bladder tumors

    Pop LA

    2016-06-01

    Full Text Available Laura A Pop,1,* Valentina Pileczki,1,2,* Roxana M Cojocneanu-Petric,1 Bogdan Petrut,3,4 Cornelia Braicu,1 Ancuta M Jurj,1 Rares Buiga,5 Patriciu Achimas-Cadariu,6,7 Ioana Berindan-Neagoe1,8 1The Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; 2Department of Analytical Chemistry, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; 3Department of Surgery II – Urology, The Oncology Institute “Prof Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania; 4Department of Urology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; 5Department of Pathology, The Oncology Institute “Prof. Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania; 6Department of Surgery, The Oncology Institute “Prof Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania; 7Department of Surgical Oncology and Gynecological Oncology, Iuliu Haţieganu University of Medicine and Pharmacy, 8Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania *These authors contributed equally to this work Background: Sample processing is a crucial step for all types of genomic studies. A major challenge for researchers is to understand and predict how RNA quality affects the identification of transcriptional differences (by introducing either false-positive or false-negative errors. Nanotechnologies help improve the quality and quantity control for gene expression studies. Patients and methods: The study was performed on 14 tumor and matched normal pairs of tissue from patients with bladder urothelial carcinomas. We assessed the RNA quantity by using the NanoDrop spectrophotometer and the quality by nano-microfluidic capillary electrophoresis technology provided by Agilent 2100 Bioanalyzer. We evaluated the amplification status of three

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

    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 (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. 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 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

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

    Moore, Kevin L., E-mail: kevinmoore@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Schmidt, Rachel [Department of Physics, Fort Hays State University, Hays, Kansas (United States); Moiseenko, Vitali [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Olsen, Lindsey A.; Tan, Jun [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri (United States); Xiao, Ying; Galvin, James [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Pugh, Stephanie [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Seider, Michael J. [Akron City Hospital, Akron, Ohio (United States); Dicker, Adam P. [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Bosch, Walter; Michalski, Jeff; Mutic, Sasa [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri (United States)

    2015-06-01

    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{sub 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{sub 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

  17. Normal tissue damage in radiotherapy development of a clinical audit tool

    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

  18. Expression profiles of inhibitor of growth protein 2 in normal and cancer tissues: An immunohistochemical screening analysis.

    Zhao, Shuang; Yang, Xue-Feng; Gou, Wen-Feng; Lu, Hang; Li, Hua; Zhu, Zhi-Tu; Sun, Hong-Zhi; Zheng, Hua-Chuan

    2016-02-01

    Inhibitor of growth protein 2 (ING2) has an important role in the regulation of chromatin remodeling, cell proliferation, cell‑cycle arrest, senescence and apoptosis. The present study performed an immunohistochemical analysis for expression profiling of ING2 protein in an array of tissues comprising normal mouse and human tissues, as well as human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung (n=192) carcinoma tissues. In mouse tissues, ING2 was detected in the nuclei and cytoplasm of the glandular epithelium of breast, hepatocytes, intestine, bronchium and alveoli, as well as the squamous epithelium of skin and glomeruli, and in myocardial cells, while it was located in the cytoplasm of renal tubules and striated muscle cells. ING2 protein was scattered in the brain and spleen. In human tissues, ING2 protein was principally distributed in the cytoplasm, while in it was present in the cytoplasm and nuclei in the stomach, intestine, cervix, endometrium trachea, breast and pancreas. The nuclear location of ING2 in the stomach was more prominent than that in the cytoplasm. High ING2 immunoreactivity was detected in the tongue, stomach, skin, pancreas, cervix and breast, whereas weakly in the brain stem, thymus, thyroid, lung, striated muscle, testis, bladder and ovary. In total, 617 out of 1,194 of the tested cancer tissues (51.7%) were ING2-positive. In most cases, ING2 expression was found to be restricted to the cytoplasm of all cancer tissues, while in certain cancer types, including renal clear cell, ovarian and colorectal carcinoma, it was occasionally present in the nuclei. Among the cancer tissues examined, ING2 was most frequently expressed in breast cancer (67.4%) and gynecological cancer types, including ovarian cancer (61.5%) and endometrial cancer (57.3%). Compared with

  19. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

    Ryan, James

    2011-01-01

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro.

  20. Simulation study of diffuse photon density waves traveling through normal and abnormal breast tissue

    Deng, Xiaoyuan; Xing, Da

    1999-09-01

    Diffuse Photon Density Waves (DPDW) is new concept and principle, which takes advantage of the difference of absorption and scattering coefficients of different tissues to study the law of photon density fluctuation during a modulated light traveling through the tissues, thus to explore the structure and function of tissues. With the combination of image reconstruction technology, we can directly `visualize' the tissues. As a non- invasive exam, it has highly extensive applied prospect in medical field and brain cognition study. In this paper, the behavior of DPDW traveling through simulated breast tissue is tentatively examined. Under various conditions, we observed the characteristics of DPDW. We observed the reasonability of the distribution of sources and detectors, the factors that influence the distortion of DPDW. Simulation results could be used as a good theoretical guideline for experiments.

  1. Cingulin, a specific protein component of tight junctions, is expressed in normal and neoplastic human epithelial tissues.

    Citi, S.; Amorosi, A.; Franconi, F.; Giotti, A.; Zampi, G.

    1991-01-01

    Cingulin is a 140-kd protein localized on the cytoplasmic face of avian tight junctions. The expression of cingulin in human normal and neoplastic colonic tissue has been investigated with an antiserum against chicken cingulin. Human cingulin shares its apparent molecular mass and localization with avian cingulin. In normal colonic epithelium, villous adenomas, and differentiated adenocarcinomas, cingulin staining is observed in the junctional region of the polarized cells lining the surface, the crypts, and the glandular lumina. In poorly differentiated adenocarcinomas, labeling also is observed at the interface between cancer tissue and stroma, or in clumps of malignant cells, forming a pattern that highlights the presence of small, compressed lumina. The cingulin content of four adenocarcinomas, estimated by immunoblotting and densitometry, was higher than that of the normal tissue (150% to 230%). Cingulin was detected in a metastasis from a colon adenocarcinoma but not in nonepithelial tissues and neoplasias, suggesting that cingulin may be a useful marker in the characterization of colonic and probably other epithelial neoplasias. Images Figure 1 Figure 2 Figure 3 PMID:2012170

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

    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.

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

    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

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

    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 90Y 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 99mTc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with 18F-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. 99mTc-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.)

  5. Study of normal/tumorous tissue fluorescence using a pH-dependent fluorescent probe in vivo

    Mordon, Serge R.; Maunoury, Vincent; Devoisselle, Jean-Marie; Abbas, Y.; Coustaut, Denise

    1992-04-01

    The pH of interstitial fluid of malignant tumors tends to be lower than that of normal tissue and depressed by glucose administration. This study aimed to evaluate the effectiveness of dual-wavelength ratio fluorometry using a pH-dependent indicator (5,6-carboxyfluorescein: 5,6-CF) for the characterization of normal and tumoral areas in vivo. 5,6-CF has two main characteristics: it has two wavelengths of maximum absorbance (465 and 490 nm) and its fluorescence emission (maximum at 515 nm) increases as a function of pH in the physiological 6 - 7.4 pH range. The experimental study was performed on 31 CDF mice bearing lymphoid leukaemia P388 grafted subcutaneously. The tissular pH values were evaluated from the ratio of the fluorescence intensities (I490/I465) on the basis of a calibration curve linking pH measurements performed intratissularly with a microelectrode and fluorescence intensities ratio values. The fluorescence intensity reached its maximum value at 60 min after 5,6-CF and glucose administration, followed by a plateau (90 min). The ratios remain constant at 1.79 +/- 0.06 for normal tissue and 1.61 +/- 0.07 (without glucose administration) for tumoral tissue. The tumoral tissue ratios decrease down to 1.35 +/- 0.04 after 6 g/kg glucose administration. These results were correlated to the pH measurements in accordance to the calibration curve. This study validates the relevance of dual-wavelength fluorometry using a pH-dependent indicator to characterize in-vivo normal and tumoral tissues after glucose administration.

  6. Case report of acute lymphoblastic leukemia with multiple soft tissue mass

    Jang, Jung Yong; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-06-15

    A 15-year-old patient, who had been diagnosed and treated as Burkitt cell type acute lymphoblastic leukemia (ALL-L3) already, visited our department. He complained of gingival enlargement and loosening teeth 1 month ago. The clinical examination revealed anterior open bite, gingival enlargement, and non tender swelling particularly in molar regions of both jaws. Deep periodontal pockets and severe mobility was shown on most of the teeth. The panoramic radiographs showed severe bone destruction and extrusion of the molars. The contrast enhanced CT showed multiple enhanced mass and bone marrow obliteration in both jaws. Chemotherapy was done the swelling was subsided at 1 month later. In conclusion, radiologic findings of leukemia with soft tissue mass, known as chloroma or granulocytic sarcoma, mimic those of lymphoma, so blood test may be needed for the final diagnosis.

  7. Clinical impact of MRI perfusion disturbances and normal diffusion in acute stroke patients

    Purpose: In acute ischemic stroke MR-imaging typically shows diffusion abnormalities surrounded by reduced perfusion signifying the so-called ischemic penumbra. Mismatch between diffusion and perfusion abnormalities gives indication for thrombolysis. But is there an indication for thrombolytic treatment, if there is no diffusion abnormality but pathologic perfusion combined with acute stroke symptoms?. Material and methods: MR-imaging of 1465 patients treated on our Stroke Unit between June 2004 and May 2007 retrospectively are analyzed. 6 patients met the inclusion criteria of severe neurological symptoms, large territorial perfusion disturbances, lack of diffusion abnormalities and complete neurological recovery after treatment. Results: In all six patients MTT measurements showed a significantly depressed perfusion in the symptomatic hemisphere (p < 0.02). Time-to-peak delay correlated with the mean transit time delay (0.949, p < 0.01). Indication for thrombolysis was based on perfusion abnormalities and clinical symptoms. Stroke symptoms could be reversed in all patients without any complication. Conclusion: Whereas diffusion imaging could not reveal any abnormality, perfusion analysis legitimated therapy with systemic thrombolysis in heavily affected patients. This work underlines the importance of multimodal MR imaging for guiding treatment decisions in acute stroke patients.

  8. Clinical impact of MRI perfusion disturbances and normal diffusion in acute stroke patients

    Blondin, D. [Institute of Diagnostic Radiology, University Hospital Duesseldorf (Germany)], E-mail: blondin@med.uni-duesseldorf.de; Seitz, R.J. [Department of Neurology, University Hospital Duesseldorf (Germany); Biomedical Research Centre, Heinrich-Heine-Universitaet Duesseldorf (Germany); Brain Imaging Centre, Research Centre Julich (Germany); Rusch, O.; Janssen, H.; Andersen, K.; Wittsack, H.-J.; Turowski, B. [Institute of Diagnostic Radiology, University Hospital Duesseldorf (Germany)

    2009-07-15

    Purpose: In acute ischemic stroke MR-imaging typically shows diffusion abnormalities surrounded by reduced perfusion signifying the so-called ischemic penumbra. Mismatch between diffusion and perfusion abnormalities gives indication for thrombolysis. But is there an indication for thrombolytic treatment, if there is no diffusion abnormality but pathologic perfusion combined with acute stroke symptoms?. Material and methods: MR-imaging of 1465 patients treated on our Stroke Unit between June 2004 and May 2007 retrospectively are analyzed. 6 patients met the inclusion criteria of severe neurological symptoms, large territorial perfusion disturbances, lack of diffusion abnormalities and complete neurological recovery after treatment. Results: In all six patients MTT measurements showed a significantly depressed perfusion in the symptomatic hemisphere (p < 0.02). Time-to-peak delay correlated with the mean transit time delay (0.949, p < 0.01). Indication for thrombolysis was based on perfusion abnormalities and clinical symptoms. Stroke symptoms could be reversed in all patients without any complication. Conclusion: Whereas diffusion imaging could not reveal any abnormality, perfusion analysis legitimated therapy with systemic thrombolysis in heavily affected patients. This work underlines the importance of multimodal MR imaging for guiding treatment decisions in acute stroke patients.

  9. Diagnostic Role of Hyperechoic Fatty Tissue at Ultrasonography in Women with Acute Pelvic Pain

    The aim of this study was to determine whether hyperechoic fatty tissue (HFT) at transabdominal and transvaginal ultrasonography in women with acute pelvic pain has a diagnostic role. We studied 201 women (mean age, 32 years) with acute pelvic and lower abdominal pain; we performed ultrasonography (US) in all them. Of the 201, 94 with gynecological problems were included., They were divided into two groups: with pelvic inflammatory disease (PID: n = 45) and without PID (n = 49). We evaluated the presence and distribution of HFT and its role in differential diagnosis between PID and non-PID groups. We found, using US, HFT in 36/45 (80%) patients with PID by US. Of the 36, single-center HFT was observed in 12/36 (33.3%) patients and multicentric HFT was detected in 24/36 (66.7%). HFT was present adjacent to inflammatory foci, tuboovarian abscesses or inflamed salpinx in 30 women: HFT was present outside the pelvic cavity in 24. Among the latter 24, HFT was present only in the lower abdomen, and not in the pelvic cavity in 6. In the non-PID group, HFT was found in the lower abdomen and pelvic cavity in 7 women. Four of the seven were misdiagnosed with PID. One of seven women with a hemorrhagic corpus luteal cyst rupture with underlying PID and two with ectopic pregnancy with HFT were correctly diagnosed. The presence of HFT may be a reliable US finding for the diagnosis of PID. HFT distinguishes PID from other acute gynecological problems

  10. The relationship between hyperuricemia and the risk of contrast-induced acute kidney injury after percutaneous coronary intervention in patients with relatively normal serum creatinine

    Yong Liu; Ning Tan; Jiyan Chen; Yingling Zhou; Liling Chen; Shiqun Chen; Zhujun Chen; Liwen Li

    2013-01-01

    OBJECTIVES: Hyperuricemia is a risk factor for contrast-induced acute kidney injury in patients with chronic kidney disease. This study evaluated the value of hyperuricemia for predicting the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine who were undergoing percutaneous coronary interventions. METHODS AND RESULTS: A total of 788 patients with relatively normal baseline serum creatinine (7 mg/ dL in males and >6 mg/dL in females. The incidence...

  11. Glucose-stimulated calcium dynamics in islets of Langerhans in acute mouse pancreas tissue slices.

    Andraž Stožer

    Full Text Available In endocrine cells within islets of Langerhans calcium ions couple cell stimulation to hormone secretion. Since the advent of modern fluorimetry, numerous in vitro studies employing primarily isolated mouse islets have investigated the effects of various secretagogues on cytoplasmic calcium, predominantly in insulin-secreting beta cells. Due to technical limitations, insights of these studies are inherently limited to a rather small subpopulation of outermost cells. The results also seem to depend on various factors, like culture conditions and duration, and are not always easily reconcilable with findings in vivo. The main controversies regard the types of calcium oscillations, presence of calcium waves, and the level of synchronized activity. Here, we set out to combine the in situ acute mouse pancreas tissue slice preparation with noninvasive fluorescent calcium labeling and subsequent confocal laser scanning microscopy to shed new light on the existing controversies utilizing an innovative approach enabling the characterization of responses in many cells from all layers of islets. Our experiments reproducibly showed stable fast calcium oscillations on a sustained plateau rather than slow oscillations as the predominant type of response in acute tissue slices, and that calcium waves are the mechanistic substrate for synchronization of oscillations. We also found indirect evidence that even a large amplitude calcium signal was not sufficient and that metabolic activation was necessary to ensure cell synchronization upon stimulation with glucose. Our novel method helped resolve existing controversies and showed the potential to help answer important physiological questions, making it one of the methods of choice for the foreseeable future.

  12. Alternative promoter usage and mRNA splicing pathways for parathyroid hormone-related protein in normal tissues and tumours.

    Southby, J.; O'Keeffe, L. M.; Martin, T.J.; Gillespie, M T

    1995-01-01

    The parathyroid hormone-related protein (PTHrP) gene consists of nine exons and allows the production of multiple PTHrP mRNA species via the use of three promoters and 5' and 3' alternative splicing; as a result of 3' alternative splicing one of three protein isoforms may be produced. This organisation has potential for tissue-specific splicing patterns. We examined PTHrP mRNA expression and splicing patterns in a series of tumours and normal tissues, using the sensitive reverse transcription...

  13. Determination and correlation of spatial distribution of trace elements in normal and neoplastic breast tissues evaluated by {mu}-XRF

    Silva, M.P.; Oliveira, M.A.; Poletti, M.E. [Universidade de Sao Paulo (USP),Ribeirao Preto, SP (Brazil)

    2012-07-01

    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 {mu}-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 {mu}m 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 {mu}m 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

  14. Brain-derived neurotrophic factor expression is higher in brain tissue from patients with refractory epilepsy than in normal controls

    Yudan Lv; Jiqing Qiu; Zan Wang; Li Cui; Hongmei Meng; Weihong Lin

    2011-01-01

    The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obtained from the seizure foci of 24 patients with temporal epilepsy. We found that epileptic tissue showed neuronal degeneration, glial cell proliferation, nuclear vacuolization, and neural cell tropism. Immunoelectron microscopy and immunohistochemistry showed that brain-derived neurotrophic factor was expressed at significantly higher levels in patients with refractory temporal epilepsy compared with normal controls, demonstrating that the pathological changes within seizure foci in patients with refractory epilepsy are associated with brain-derived neurotrophic factor expression alterations.

  15. p53 expression in human rectal tissue after radiotherapy: upregulation in normal mucosa versus functional loss in rectal carcinomas

    Purpose: In vitro, ionizing radiation of epithelial cells leads to upregulation of wild-type p53 and subsequent induction of p21waf1. The effect of radiotherapy (RT) on the expression of these proteins in patients is unknown. We assessed the influence of RT on the expression of p53 and p21waf1 in normal mucosa and rectal carcinomas in vivo. Methods: Tumor and normal tissue samples were derived from rectal cancer patients randomized in a clinical trial in which the value of preoperative RT was evaluated. p53 and p21waf1 expression was determined in 51 irradiated and 52 nonirradiated patients using immunohistochemistry. Results: In normal mucosa, both p53 and p21waf1 were strongly upregulated after RT compared with the expression in unirradiated normal tissue (p waf1 was found in the irradiated vs. nonirradiated group. In the few rectal tumors with wild-type p53, induction of p53 after RT did not necessarily lead to upregulation of p21waf1. Conclusion: These findings demonstrate that in normal mucosa, a functional p53-p21waf1 pathway is present, whereas in tumor cells it is defective in almost all cases because of either p53 mutation or down- or upstream disruption in tumors with wild-type p53. Therefore, we believe that the role of p53 expression as a single prognostic marker in rectal cancer needs reconsideration

  16. Correlation between the serum and tissue levels of oxidative stress markers and the extent of inflammation in acute appendicitis

    Ersin Gürkan Dumlu

    2014-12-01

    Full Text Available OBJECTIVES: To determine the serum and tissue levels of markers of impaired oxidative metabolism and correlate these levels with the histopathology and Alvarado score of acute appendicitis patients. METHOD: Sixty-five acute appendicitis patients (mean age, 31.4±12.06 years; male/female, 30/35 and 30 healthy control subjects were studied. The Alvarado score was recorded. Serum samples were obtained before surgery and 12 hours postoperatively to examine the total antioxidant status, total oxidant status, paraoxonase, stimulated paraoxonase, arylesterase, catalase, myeloperoxidase, ceruloplasmin, oxidative stress markers (advanced oxidized protein products and total thiol level and ischemia-modified albumin. Surgical specimens were also evaluated. RESULTS: The diagnoses were acute appendicitis (n = 37, perforated appendicitis (n = 8, phlegmonous appendicitis (n = 12, perforated+phlegmonous appendicitis (n = 4, or no appendicitis (n = 4. The Alvarado score of the acute appendicitis group was significantly lower than that of the perforated+phlegmonous appendicitis group (p = 0.004. The serum total antioxidant status, total thiol level, advanced oxidized protein products, total oxidant status, catalase, arylesterase, and ischemia-modified albumin levels were significantly different between the acute appendicitis and control groups. There was no correlation between the pathological extent of acute appendicitis and the tissue levels of the markers; additionally, there was no correlation between the tissue and serum levels of any of the parameters. CONCLUSIONS: The imbalance of oxidant/antioxidant systems plays a role in the pathogenesis acute appendicitis. The Alvarado score can successfully predict the presence and extent of acute appendicitis.

  17. Detection of metabolic differences between normal and cancerous prostate tissues with in-vitro hydrogen MR spectroscopy

    High-resolution in vitro hydrogen spectroscopy of perchloric acid extracts of human prostate cell lines prepared from radical prostatectomy specimens was performed at 360 MHz. Epithelial cell strains representing normal peripheral zone, normal central zone, carcinoma of varying Gleason grades, and benign prostatic hypertrophy were evaluated. The spectral peak assignments for metabolities, including lactate, citrate, and various amino acids, were determined from the literature, reference standards, gas chromatography-mass spectroscopy. Inferences as to the possibility of differentiating various types of prostatic tissues based on hydrogen spectral signatures are discussed

  18. Modulation of antioxidant enzymes as radioprotector mechanism of oligo elements and lachesis muta in normal tissues

    The therapeutic use of the ionizing radiations (IR) it has acquired great relevance in the last decades although their effects are not selective and they are also manifested on the normal tissues. In previous works we demonstrate the radioprotector effect that the combination of oligo elements Zinc, Selenium and Manganese associated to the snake poison Lachesis muta (O-LM) it exercises on the small intestine and the bone marrow of irradiated mouse. The objective of this work was to study the molecular mechanisms, and particularly the paper of the anti-oxidant superoxide dismutases enzymes (MnSOD and Cu/ZnSOD), Catalase (CAT), and Glutathione Peroxidase (GPx), in the radioprotector action that exercises the combination O-LM. Four groups of mice were used: A) control; B) treated with O-LM; C) irradiated; D) irradiated and treated with O-LM. The two treated groups were injected daily via s.c. with 0,1 ml of O-LM from 30 days before the irradiation and until to 4 days later. The two irradiated groups received 10 Gy in whole body the day 30. The day 35 all the animals were sacrificed. The histological intestinal cuts of the mucous one were evaluated by tint with hematoxyline-eosin; the presence of apoptotic cells it was determined by the Tunel method (Apoptag kit); the expression of PCNA (nuclear antigen of proliferating cells), MnSOD, CuZnSOD, CAT and GPx, by immunohistochemistry. The results demonstrated that in the lot D it was preserved totally the histology of the intestinal mucous. In the control A it was observed PCNA expression in the crypts, of MnSOD in the hairiness and CuZnSOD, CAT and Gpx in both. The change produced by O-LM (group B) it was the increase of PCNA, of CAT and the appearance of MnSOD in the crypts. On the other hand, the irradiation (C) it produced a marked descent in the GPx, the complete disappearance of PCNA and an increase of the apoptotic cells. The group D showed that O-LM it reverted totally the effect of the RI on the expression of PCNA

  19. Abdominal Adipose Tissue was Associated with Glomerular Hyperfiltration among Non- Diabetic and Normotensive Adults with a Normal Body Mass Index.

    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

  20. Proteomic Analysis of Lung Tissue in a Rat Acute Lung Injury Model: Identification of PRDX1 as a Promoter of Inflammation

    Dongdong Liu

    2014-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α, whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.

  1. Recent progress in defining mechanisms and potential targets for prevention of normal tissue injury after radiation therapy

    The ability to optimize treatments for cancer on the basis of relative risks for normal tissue injury has important implications in oncology, because higher doses of radiation might, in some diseases, improve both local control and survival. To achieve this goal, a thorough understanding of the molecular mechanisms responsible for radiation-induced toxicity will be essential. Recent research has demonstrated that ionizing radiation triggers a series of genetic and molecular events, which might lead to chronic persistent alterations in the microenvironment and an aberrant wound-healing response. Disrupted epithelial-stromal cell communication might also be important. With the application of a better understanding of fundamental biology to clinical practice, new approaches to treating and preventing normal tissue injury can focus on correcting these disturbed molecular processes

  2. Personalized identification of altered pathways in cancer using accumulated normal tissue data

    Ahn, TaeJin; Lee, Eunjin; Huh, Nam; Park, Taesung

    2014-01-01

    Motivation: Identifying altered pathways in an individual is important for understanding disease mechanisms and for the future application of custom therapeutic decisions. Existing pathway analysis techniques are mainly focused on discovering altered pathways between normal and cancer groups and are not suitable for identifying the pathway aberrance that may occur in an individual sample. A simple way to identify individual’s pathway aberrance is to compare normal and tumor data from the same...

  3. The relationship between decorrelation time and sample thickness in acute rat brain tissue slices (Conference Presentation)

    Brake, Joshua; Jang, Mooseok; Yang, Changhuei

    2016-03-01

    The optical opacity of biological tissue has long been a challenge in biomedical optics due to the strong scattering nature of tissue in the optical regime. While most conventional optical techniques attempt to gate out multiply scattered light and use only unscattered light, new approaches in the field of wavefront shaping exploit the time reversible symmetry of optical scattering in order to focus light inside or through scattering media. While these approaches have been demonstrated effectively on static samples, it has proven difficult to apply them to dynamic biological samples since even small changes in the relative positions of the scatterers within will cause the time symmetry that wavefront shaping relies upon to decorrelate. In this paper we investigate the decorrelation curves of acute rat brain slices for thicknesses in the range 1-3 mm (1/e decorrelation time on the order of seconds) using multi-speckle diffusing wave spectroscopy (MSDWS) and compare the results with theoretical predictions. The results of this study demonstrate that the 1/L^2 relationship between decorrelation time and thickness predicted by diffusing wave spectroscopy provides a good rule of thumb for estimating how the decorrelation of a sample will change with increasing thickness. Understanding this relationship will provide insight to guide the future development of biophotonic wavefront shaping tools by giving an estimate of how fast wavefront shaping systems need to operate to overcome the dynamic nature of biological samples.

  4. Characterization of Transgenic Gfrp Knock-In Mice: Implications for Tetrahydrobiopterin in Modulation of Normal Tissue Radiation Responses

    Pathak, Rupak; Pawar, Snehalata A.; Fu, Qiang; Gupta, Prem K.; Berbée, Maaike; Garg, Sarita; Sridharan, Vijayalakshmi; Wang, Wenze; Biju, Prabath G.; Krager, Kimberly J; Boerma, Marjan; Ghosh, Sanchita P.; Amrita K Cheema; Hendrickson, Howard P.; Aykin-Burns, Nukhet

    2014-01-01

    Aims: The free radical scavenger and nitric oxide synthase cofactor, 5,6,7,8-tetrahydrobiopterin (BH4), plays a well-documented role in many disorders associated with oxidative stress, including normal tissue radiation responses. Radiation exposure is associated with decreased BH4 levels, while BH4 supplementation attenuates aspects of radiation toxicity. The endogenous synthesis of BH4 is catalyzed by the enzyme guanosine triphosphate cyclohydrolase I (GTPCH1), which is regulated by the inhi...

  5. Radiotherapy of large target volumes in Hodgkin's lymphoma: normal tissue sparing capability of forward IMRT versus conventional techniques

    Conson Manuel; Magliulo Mario; Liuzzi Raffaele; Cella Laura; Camera Luigi; Salvatore Marco; Pacelli Roberto

    2010-01-01

    Abstract Background This paper analyses normal tissue sparing capability of radiation treatment techniques in Hodgkin's lymphoma with large treatment volume. Methods 10 patients with supradiaphragmatic Hodgkin's lymphoma and planning target volume (PTV) larger than 900 cm3 were evaluated. Two plans were simulated for each patient using 6 MV X-rays: a conventional multi-leaf (MLC) parallel-opposed (AP-PA) plan, and the same plan with additional MLC shaped segments (forward planned intensity mo...

  6. Dose reduction to normal tissues as compared to the gross tumor by using intensity modulated radiotherapy in thoracic malignancies

    Bhalla NK; Garg C; Sinha SN; Rawat Sheh; Kataria Tejinder; Negi PS

    2006-01-01

    Abstract Background and purpose Intensity modulated radiotherapy (IMRT) is a powerful tool, which might go a long way in reducing radiation doses to critical structures and thereby reduce long term morbidities. The purpose of this paper is to evaluate the impact of IMRT in reducing the dose to the critical normal tissues while maintaining the desired dose to the volume of interest for thoracic malignancies. Materials and methods During the period January 2002 to March 2004, 12 patients of var...

  7. Expression of a plant-associated human cancer antigen in normal,premalignant and malignant esophageal tissues

    Jun Fu; Ping Qu; Mo Li; Hai-Mei Tian; Zhen-Hai Zheng; Xin-Wen Zheng; Wei Zhang

    2003-01-01

    AIM: To study the relationship between the expression profiles of a plant-associated human cancer antigen and carcinogenesis of esophagus and its significance. METHODS: We analyzed expression of a plant-associated human cancer antigen in biopsy specimens of normal (n=29),mildly hyperplastic (n=29), mildly (n=30), moderately (n=27)and severely dysplastic (n=29) and malignant esophageal (n=30) tissues by immunohistochemistry. RESULTS: The plant-associated human cancer antigen was mainly confined to the cytoplasm and showed diffuse type of staining. Positive staining was absent or weak in normal (0/30) and mildly hyperplastic tissue samples (2/29), while strong staining was observed in severe dysplasia (23/29) and carcinoma in situ (24/30). There was significant difference of its expression between normal mucosa and severely dysplastic tissues (P<0.001) or carcinoma in situ (P<0.001). Significant difference was also observed between mild dysplasia and severe dysplasia (P<0.001) or carcinomain situ (P<0.001). An overall trend toward increased staining intensity with increasing grade of dysplasia was found. There was a linear correlation between grade of lesions and staining intensity (r=0.794,P<0.001). Samples from esophageal cancer showed no higher levels of expression than those in severely dysplastic lesions (P>0.05). CONCLUSION: The abnormal expression of this plantassociated human cancer antigen in esophageal lesions is a frequent and early finding in the normal-dysplasiacarcinoma sequence in esophageal carcinogenesis. It might contribute to the carcinogenesis of esophageal cancer. The abnormal expression of this plant-associated human cancer antigen in esophageal lesion tissues may serve as a potential new biomarker for early identification of esophageal cancer.

  8. Effects of carbon ion irradiation on inflammatory processes and normal tissue damage in the endothelium and the rat lung

    Dettmering, Till

    2013-01-01

    Ionizing radiation is able to elicit an anti-inflammatory, as well as a pro-inflammatory response. The anti-inflammatory effect of low radiation doses is successfully used within the scope of radon therapy to treat chronic inflammatory conditions such as Morbus Bechterew. In contrast, high radiation doses elicit a pro-inflammatory response which plays a role in normal tissue injury occurring after tumor therapy. The mechanisms underlying those differential effects are not fully understood and...

  9. Clinical Study of Ultrasonic Tissue Characterization with Integrated Backscatter and Echo Intensity in the Diagnosis of Acute Myocardial Infarction

    王志刚; 冉海涛; 黄晶; 陈庆伟; 邹建中; 苏海兵; 蒲世玉; 凌智瑜; 陈永新; 何明菊

    2001-01-01

    Objectives The purpose of this study was to determine if the ultrasonic integrated backscatter and echo intensity could be used in clinical diagnosis of acute myocardial infarction. Methods and Results Within 2 weeks after acute myocardial infarction, 35 patients underwent ultrasonic tissue characterization from the papillary short- axis view.The cyclic variation of integrated backscatter and echo intensity of three different myocardial regions perfused by left anterior descending coronary artery, left cir cumflex coronary and right coronary were measured .The value of cyclic variation of integrated backscatter and integrated backscatter and echo intensity ≤ half of the highest value of three different myocardial regions on a same view were define as the criteria for diag nosing acute myocardial infarction , and the results were compared with coronary angiography. The sensitivity of diagnosing acute myocardial infarction by both Ultrasonic tissue characterization with integrated backscatter and echo intensity were 91.43 % . The location of myocardial infarction detected by this technique corresponded with the damaged myocardial region determined by coronary angiography. Conclusions Ultrasonic tissue characterization with integrated backscatter and echo intensity could clinically be used as a noninvasive approach in the diagnosis of acute myocardial infarction.

  10. Differences in the effects of anaesthesia on hypoxia in normal tissues

    A study has been made of the effect of anaesthesia with sodium pentobarbitone on the mean skin reaction of mouse-tails 12 to 85 days after X-irradiation (0 to 7.5 krad). Anaesthetized mice were irradiated while breathing air or oxygen, or after the tails were clamped and nitrogen passed over the tails. The dose response curves showed that anaesthesia increased the radiosensitivity of the tissue. This increase can be ascribed to the suppression of the animal's temperature control mechanism by the anaesthetic, resulting is vasodilation of the blood vessels in the tail, and increase in oxygenation of the tissue. The effect is in contrast to that in many other tissues of the mouse. (U.K.)

  11. Tumor and normal tissue dosimetry changes during MR-guided pulsed-dose-rate (PDR) brachytherapy for cervical cancer

    Background and purpose: To analyze systematic changes in tumor and normal tissue anatomy and dosimetry using serial MR imaging during pulsed dose rate brachytherapy (PDR BT) for cervical cancer. Material and methods: Forty-three patients with cervical cancer underwent MR-guided PDR BT using an intrauterine applicator alone after external beam radiotherapy. MR imaging was repeated on days 2 and 3 of treatment and the day 1 plan was applied to the re-contoured volumes. Results: The mean uterine volume and mean HR CTV increased during treatment. This resulted in a decrease in the mean HR CTV D90 relative to the day 1 planned dose. There was no change in the mean bladder volume during treatment but the mean rectal volume increased. This correlated with an increase in the mean rectal dose. There were four local recurrences. There was no apparent relationship between either the planned or the delivered HR CTV D90 and local recurrence. There was only one case of late bladder toxicity but nine patients developed late rectal toxicity. The cumulative rectal dose during treatment was a better predictor of late rectal toxicity than the planned dose. Conclusions: Significant changes in tumor and normal tissue anatomy and dosimetry can occur during PDR BT and should be tracked and corrected using serial imaging and plan adaptation, especially when the day 1 tumor or normal tissue doses are close to the planning constraints

  12. Classification of mass and normal breast tissue: A convolution neural network classifier with spatial domain and texture images

    The authors investigated the classification of regions of interest (ROI's) on mammograms as either mass or normal tissue using a convolution neural network (CNN). A CNN is a back-propagation neural network with two-dimensional (2-D) weight kernels that operate on images. A generalized, fast and stable implementation of the CNN was developed. The input images to the CNN were obtained form the ROI's using two techniques. The first technique employed averaging and subsampling. The second technique employed texture feature extraction methods applied to small subregions inside the ROI. Features computed over different subregions were arranged as texture images, which were subsequently used as CNN inputs. The effects of CNN architecture and texture feature parameters on classification accuracy were studied. Receiver operating characteristic (ROC) methodology was used to evaluate the classification accuracy. A data set consisting of 168 ROI's containing biopsy-proven masses and 504 ROI's containing normal breast tissue was extracted from 168 mammograms by radiologists experienced in mammography. This data set was used for training and testing the CNN. With the best combination of CNN architecture and texture feature parameters, the area under the test ROC curve reached 0.87, which corresponded to a true-positive fraction of 90% at a false positive fraction of 31%. The results demonstrate the feasibility of using a CNN for classification of masses and normal tissue on mammograms

  13. Simultaneous and sequential hyperthermia and radiation treatment of an experimental tumor and its surrounding normal tissue in vivo

    In order to optimize the therapeutic effect of a combined hyperthermia-radiation treatment, the influence of sequence and interval between the two modalities on local tumor control and normal tissue damage was studied during variation of heating time and temperature. A C3H mouse mammary carcinoma transplanted into the feet of C3D2F1 mice was used as a model. Local hyperthermia was given to unanesthetized mice by immersion of the tumor-bearing foot into a water bath. Radiation was given either before, during or after heating. After simultaneous treatment an increasing thermal enhancement ratio (TER) was observed with increasing temperatures and/or increasing heating time. In all simultaneous treatment schedules, the TER values were almost similar in tumor and normal tissue. Different results were obtained by using an interval between the two modalities. An increased therapeutic ratio could be obtained if radiation was given before heat and an interval of 4 hours or more was allowed. This improved therapeutic ratio was dependent on the temperature and ranged from about 1.1 at 41.50 C to 2.1 at 43.50C given for one hour. These data indicate that if both tumor and normal tissue are heated, the optimal tumore effect may not be a hyperthermic radiosensitization, but rather a direct heat killing of radioresistant tumor cells

  14. A new variable for SRS plan quality evaluation based on normal tissue sparing: The Effect of Prescription Isodose Levels

    Zhang, Q; Lei, Y; Morgan, B; Driewer, J; Zhang, M; Li, S; Zhou, S; Zhen, W; Thompson, R; Wahl, A; Lin, C; Enke, C

    2014-01-01

    Objectives: A new dosimetric variable, dose dropping speed (DDS), was proposed and used to evaluate normal tissue sparing among stereotactic radiosurgery (SRS) plans with different prescription isodose lines. Methods: Forty plans were generated for 8 intracranial SRS cases, prescribing to isodose levels (IDLs) ranging from 50% to 90% in 10% increments. Whilst maintaining similar coverage and conformity, plans at different IDLs were evaluated in terms of normal tissue sparing using the proposed DDS. The DDS was defined as the greater decay coefficient in a double exponential decay fit of the dose drop-off outside the PTV, which models the steep portion of the drop-off. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. Results: Among all plans, the DDS was found the lowest for the prescription at 90% IDL and the highest for the prescription at 60% or 70%. Beam profile slope change in penumbra and its field size dependence were explored and given as t...

  15. EMPLOYMENT OF A «SIDE POPULATION» APPROACH TO STEM CELL ISOLATION IN NORMAL AND TUMOR TISSUES

    O. R. Tsinkalovsky

    2008-01-01

    Full Text Available Abstract. A combination of fluorescent staining with Hoechst 33342 dye, and flow cytometry of murine bone marrow cells may be used for separation of a side population (SP, which is highly enriched for hematopoietic stem cells capable of long-term hematopoietic reconstitution in lethally irradiated recipients. Recently, this approach was also applied to analysis of SP cells in several types of non-hematopoietic tissues, and malignant tumours. In spite of yet poor definition of phenotype and functional potency of SP cells from various tissues, the method of SP isolation may be a useful tool for analysis and pre-enrichment of stem cell-like cells of different origin. Present review article presents a brief description of Hoechst 33342-staining approach, and of recent reports concerning SP studies in various normal and malignant tissues. (Med. Immunol., vol. 10, N 4-5, pp 319-326.

  16. Proteomic Comparison of Two-Dimensional Gel Electrophoresis Pro files from Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Tissues

    Cui Li; Ping Chen; Jingyun Xie; Songping Liang; Xianquan Zhan; Maoyu Li; Xiaoying Wu; Feng Li; Jianling Li; Zhiqiang Xiao; Zhuchu Chen; Xueping Feng

    2003-01-01

    Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The results showed that well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-ug protein-load. The average deviation of spot position was 0.733+0.101 mm in IEF direction, and 0.925+0.207 mm in SDS-PAGE direction. For tumor tissue, a total of 1241±88 spots were detected, 987±65 spots were matched with an average matching rate of 79.5%. For control, a total of 1190+72 spots were detected, and 875±48 spots were matched with an average matching rate of 73.5%. A total of 864±34 spots were matched between tumors and controls.Forty-three differential proteins were characterized: some proteins were related to oncogenes, and others involved in the regulation of cell cycle and signal transduction. It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis.These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.

  17. Reduced Genetic Diversity in Lymphoid and Central Nervous System Tissues and Selection-Induced Tissue-Specific Compartmentalization of Neuropathogenic SIVsmmFGb during Acute Infection

    Reeve, Aaron B.; Patel, Kalpana; Pearce, Nicholas C.; Augustus, Katherine V.; Domingues, Heber G.; O'Neil, Shawn P.; Novembre, Francis J.

    2009-01-01

    The simian lentivirus strain SIVsmmFGb is a viral swarm population inducing neuropathology in over 90% of infected pigtailed macaques and serves as a reliable model for HIV neuropathogenesis. However, little is understood about the genetic diversity of this virus, how said diversity influences the initial seeding of the central nervous system and lymph nodes, or whether the virus forms distinct genetic compartments between tissues during acute infection. In this study, we establish that our S...

  18. Determination of optical properties of normal and adenomatous human colon tissues in vitro using integrating sphere techniques

    Hua-Jiang Wei; Da Xing; Jian-Jun Lu; Huai-Min Gu; Guo-Yong Wu; Ying Jin

    2005-01-01

    AIM: The purpose of the present study is to compare the optical properties of normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion in vitro at 476.5, 488, 496.5, 514.5 and 532 nm. We believe these differences in optical properties should help differential diagnosis of human colon tissues by using optical methods.METHODS: In vitro optical properties were investigated for four kinds of tissues: normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion. Tissue samples were taken from 13 human colons (13 adenomatous, 13 normal). From the normal human colons a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion), and from the adenomatous human bladders a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion). The measurements were performed using a double-integratingsphere setup and the optical properties were assessed from these measurements using the adding-doubling method that was considered reliable.RESULTS: The results of measurement showed that there were significant differences in the absorption coefficients and scattering coefficients between normal and adenomatous human colon mucosa/submucosa at the same wavelength,and there were also significant differences in the two optical parameters between both colon muscle layer/chorion at the same wavelength. And there were large differences in the anisotropy factors between both colon mucosa/submucosa at the same wavelength, there were also large differences in the anisotropy factors between both colon muscle layer/chorion at the same wavelength.There were large differences in the value ranges of the absorption coefficients, scattering coefficients and anisotropy factors between both colon mucosa/submucosa,and there

  19. Evaluation of discoidin domain receptor-2 (DDR2) expression level in normal, benign, and malignant human prostate tissues.

    Azemikhah, Mitra; Ashtiani, Hamidreza Ahmadi; Aghaei, Mahmoud; Rastegar, Hosein

    2015-01-01

    Discoidin domain receptor (DDR) is a new member of the receptor tyrosine kinase family. There are two isoforms of discoidin domain receptor (DDR), DDR1 and DDR2. These receptors play a major role in the adhesion, motility and cell proliferation. Due to the important role of DDR2 in the development of tumor extension, this receptor is pivotal in the field of carcinogenesis. The aim of this study was to investigate the mRNA and protein expression of DDR2, in the malignant, benign prostatic hyperplasia (BPH) and normal tissues of patients with prostate cancer. In this study the gene and protein expression of DDR2 in adjacent normal (n=40), BPH (n=40), and malignant (n=40) prostate tissue were measured using real-time PCR and Western blotting. Then, the correlation of DDR2 gene and protein expression with prognostic factors such as age, tumor grade, tumor stage, lymph node involvement, and serum prostate-specific antigen (PSA) concentration were evaluated. The relative mRNA and protein expression level of DDR2 in malignant and benign prostate tissue was significantly higher than those of adjacent normal tissues (P<0.01). This expression was found to increase approximately 3.5 and 2.1 fold for mRNA and protein levels, respectively. Spearman test indicated a significant correlation between DDR2 mRNA and protein expression with prognostic factors such as tumor grade, stage, lymph node involvement, and serum PSA concentration. However, significant correlation with age was not observed. These findings suggest that DDR2 is a cancer-related gene associated with the aggressive progression of prostate cancer patients. PMID:26600862

  20. Evaluation of discoidin domain receptor-2 (DDR2) expression level in normal, benign, and malignant human prostate tissues

    Azemikhah, Mitra; Ashtiani, Hamidreza Ahmadi; Aghaei, Mahmoud; Rastegar, Hosein

    2015-01-01

    Discoidin domain receptor (DDR) is a new member of the receptor tyrosine kinase family. There are two isoforms of discoidin domain receptor (DDR), DDR1 and DDR2. These receptors play a major role in the adhesion, motility and cell proliferation. Due to the important role of DDR2 in the development of tumor extension, this receptor is pivotal in the field of carcinogenesis. The aim of this study was to investigate the mRNA and protein expression of DDR2, in the malignant, benign prostatic hyperplasia (BPH) and normal tissues of patients with prostate cancer. In this study the gene and protein expression of DDR2 in adjacent normal (n=40), BPH (n=40), and malignant (n=40) prostate tissue were measured using real-time PCR and Western blotting. Then, the correlation of DDR2 gene and protein expression with prognostic factors such as age, tumor grade, tumor stage, lymph node involvement, and serum prostate-specific antigen (PSA) concentration were evaluated. The relative mRNA and protein expression level of DDR2 in malignant and benign prostate tissue was significantly higher than those of adjacent normal tissues (P<0.01). This expression was found to increase approximately 3.5 and 2.1 fold for mRNA and protein levels, respectively. Spearman test indicated a significant correlation between DDR2 mRNA and protein expression with prognostic factors such as tumor grade, stage, lymph node involvement, and serum PSA concentration. However, significant correlation with age was not observed. These findings suggest that DDR2 is a cancer-related gene associated with the aggressive progression of prostate cancer patients. PMID:26600862

  1. New Tetrachromic VOF Stain (Type III-G.S) for Normal and Pathological Fish Tissues

    Sarasquete, C.; Gutiérrez, M.

    2005-01-01

    A new VOF Type III-G.S stain was applied to histological sections of different organs and tissues of healthy and pathological larvae, juvenile and adult fish species (Solea senegalensis; Sparus aurata; Diplodus sargo; Pagrus auriga; Argyrosomus regius and Halobatrachus didactylus). In comparison to the original Gutiérrez VOF stain, more acid dyes of contrasting colours and polychromatic/metachromatic properties were incorporated as essential constituents of the tetrachromic VOF stain. This fa...

  2. GENETIC VARIABILITY OF CULTURED PLANT TISSUES UNDER NORMAL CONDITIONS AND UNDER STRESS

    Dolgikh Yu.I.; E.S. Osipova; A.I. Solov’eva; E. A. Lysenko; O.N. Vysotskaya

    2012-01-01

    The genetic variability induced by in vitro conditions known as somaclonal variation is of practical interest due to its potential uses in plant breeding but, on the other hand, if clonal propagation or transformation is main goal, it becomes an unwelcome phenomenon. Thus, it is important to know frequency, the genomic distribution, the mechanisms and factors influencing somaclonal variation. We studied variability of PCR-based DNA markers of cultured tissues and regenerated plants of maize a...

  3. Automated characterization of normal and pathologic lung tissue by topological texture analysis of multidetector CT

    Boehm, H. F.; Fink, C.; Becker, C.; Reiser, M.

    2007-03-01

    Reliable and accurate methods for objective quantitative assessment of parenchymal alterations in the lung are necessary for diagnosis, treatment and follow-up of pulmonary diseases. Two major types of alterations are pulmonary emphysema and fibrosis, emphysema being characterized by abnormal enlargement of the air spaces distal to the terminal, nonrespiratory bronchiole, accompanied by destructive changes of the alveolar walls. The main characteristic of fibrosis is coursening of the interstitial fibers and compaction of the pulmonary tissue. With the ability to display anatomy free from superimposing structures and greater visual clarity, Multi-Detector-CT has shown to be more sensitive than the chest radiograph in identifying alterations of lung parenchyma. In automated evaluation of pulmonary CT-scans, quantitative image processing techniques are applied for objective evaluation of the data. A number of methods have been proposed in the past, most of which utilize simple densitometric tissue features based on the mean X-ray attenuation coefficients expressed in terms of Hounsfield Units [HU]. Due to partial volume effects, most of the density-based methodologies tend to fail, namely in cases, where emphysema and fibrosis occur within narrow spatial limits. In this study, we propose a methodology based upon the topological assessment of graylevel distribution in the 3D image data of lung tissue which provides a way of improving quantitative CT evaluation. Results are compared to the more established density-based methods.

  4. Acute effect of nano-copper on liver tissue and function in rat

    Miron Doudi

    2014-10-01

    Full Text Available Objective(s: This paper reports on the toxicity of CuO NPs on hepatic enzymes and liver and lung histology. Materials and Methods: To assess the toxicity of copper nanoparticles (10-15 nm in vivo, pathological examinations and blood biochemical indexes including serum glutamate oxaloacetate transaminase (SGOT and serum glutamate pyruvate transaminase (SGPT at various time points (2, 7 and 14 dayswere studied. Thirty two Wistar rats were randomly divided into four groups. Treatment groups (group 1, 2, 3 received CuO NP solution containing 5, 10 and 100 mg/kg, respectively. Control group received 0.5 mL of normal saline via ip injection for 7 consecutive days. After 14 days, the tissue of liver and lung were collected and investigated for their histological problems. Results:The histology of the hepatic tissues showed vasculature in central veins and portal triad vessels in all three treatment groups. Histology of lungs showed air sac wall thickening and increased fibrous tissue in all three groups. Biochemical results of the hepatic enzymes showed that the SGOT levels in groups 1 and 2 were significantly higher than the control group two days after the intervention. Conclusion: Results of this study indicated that all concentration of copper nanoparticles [with 10-15 nm diameters, spherical shape, purity of 99.9%, mineral in nature, and wet synthesis method in liquid phase (alternation] induce toxicity and changes of histo-pathological changes in liver and lung tissues of rats. It is evident that these nanoparticles cannot be used for human purposes because of their toxicity.

  5. Analysis of the Effects of Normal Walking on Ankle Joint Contact Characteristics After Acute Inversion Ankle Sprain.

    Bae, Ji Yong; Park, Kyung Soon; Seon, Jong Keun; Jeon, Insu

    2015-12-01

    To show the causal relationship between normal walking after various lateral ankle ligament (LAL) injuries caused by acute inversion ankle sprains and alterations in ankle joint contact characteristics, finite element simulations of normal walking were carried out using an intact ankle joint model and LAL injury models. A walking experiment using a volunteer with a normal ankle joint was performed to obtain the boundary conditions for the simulations and to support the appropriateness of the simulation results. Contact pressure and strain on the talus articular cartilage and anteroposterior and mediolateral translations of the talus were calculated. Ankles with ruptured anterior talofibular ligaments (ATFLs) had a higher likelihood of experiencing increased ankle joint contact pressures, strains and translations than ATFL-deficient ankles. In particular, ankles with ruptured ATFL + calcaneofibular ligaments and all ruptured ankles had a similar likelihood as the ATFL-ruptured ankles. The push off stance phase was the most likely situation for increased ankle joint contact pressures, strains and translations in LAL-injured ankles. PMID:26077988

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

    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)

  7. Role of nitric oxide radicals in tumor and normal tissue responses against heavy ion-beams

    The purpose of this study was to investigate whether radioadaptive responses were induced after irradiation with accelerated ion beams. To investigate whether apoptosis was induced in the unirradiated tissues by radiation-induced bystander responses after irradiation of mice with accelerated ion beams. Human non-small cell lung carcinoma cells transfected with wild-type p53 (H1299/wtp53 cells) were used. The cells were irradiated with accelerated neon (400 MeV/u, 31 keV/μm), carbon (290 MeV/u, 70 keV/μm), or iron (500 MeV/u, 200 keV/μm) ion beams. Then, the cells were allowed forming colonies. ICR male mice (Jcl: ICR) were used. The mice were irradiated on 2 days with accelerated carbon ion beams (290 MeV/u, 13 keV/μm) or argon ion beams (500 MeV/u, 90 keV/μm). The intestine and testis were excised 2 days after the last irradiation. These excised tissues were fixed, embedded in paraffin and made of thin-sections on slide glasses. Then the thin-sections of tissues were stained by the TUNEL method. A significant radioresistance of cells was observed when the cells were challengingly irradiated after the priming irradiation with accelerate neon or iron ion beams. These responses were mimicked by the treatment with nitric oxide generator, ISDN. A significant reduction of mutation rate of the hprt gene was observed when the cells were challengingly irradiated after the priming irradiation with accelerate neon or iron ion beams. This reduction was partially suppressed by NO radical scavenger, carboxy-PTIO. The apoptotic cells were obviously observed in unirradiated intestine and testis when mice were irradiated with carbon or argon ion beams across the upper body. The apoptosis as bystander response were partially suppressed by carboxy-PTIO into the peritoneal cavity. (author)

  8. Comparison of multiple assays for detecting human antibodies directed against antigens on normal and malignant tissue culture cells

    Four separate assays of human antibody reactivity to four separate normal and malignant human tissue culture cells lines from two patients have been evaluated using a single highly-reactive allogeneic serum. The visual end-point cytolysis assay and the chromium-51 release assay were equally sensitive in measuring complement mediated antibody cytotoxicity and both were far more sensitive than a trypan blue dye exclusion assay. The assay of antibody reactivity by hemadsorption technique was about 10 times more sensitive than any of the cytotoxicity assays. This latter assay measures only IgG antibody however. These assays showed that cell lines from different patients may differ greatly in 'reactivity' to an allogeneic serum and emphasized the importance of utilizing tumor and normal cells from the same patient when using tissue culture cells to search for tumor specific reactivity. These observations emphasize the importance of utilizing multiple assays against paired normal and malignant cells from the same patient to be certain of the specificity and magnitude of the measured antibody

  9. Incidence and significance of FLT3-ITD and NPM1 mutations in patients with normal karyotype acute myeloid leukaemia.

    Haslam, K

    2012-02-01

    BACKGROUND: Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haematopoietic progenitor cells. Approximately half of all adult AML patients have a normal karyotype (NK-AML) and an intermediate risk prognosis. AIMS: To determine the incidence and prognostic significance of NPM1 and FLT3-ITD mutations in a population of patients with NK-AML. METHODS: FLT3-ITD and NPM1 mutation status was retrospectively sought in presentation samples from 44 NK-AML patients. RESULTS: FLT3-ITD and NPM1 mutations were detected in 45.5 and 54.5% of patients, respectively, allowing stratification according to genotype. CONCLUSIONS: FLT3-ITD and NPM1 mutation status can be defined in NK-AML. Prospective screening for these mutations is advocated in all NK-AML patients, as the genotype is of clinical importance when considering treatment options including stem cell transplantation.

  10. Normal tissue complication probability (NTCP) parameters for breast fibrosis: Pooled results from two randomised trials

    Introduction: The dose–volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy. Materials and methods: We pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n = 1410) were used to test the predicted models. Results: 26.8% patients in the Cambridge trial (5 years) and 20.7% patients in the EORTC trial (10 years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD3(50) = 136.4 Gy, γ50 = 0.9 and n = 0.011 for the Niemierko model and BEUD3(50) = 132 Gy, m = 0.35 and n = 0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates. Conclusions: This large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter ‘n’ does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosis

  11. The indications for ablating normal thyroid tissue with 131I in differentiated thyroid cancer

    Consideration of the behaviour of differentiated thyroid tumours and retrospective analysis of patients who have been treated with 131I and followed up for a long time provide information which can be used to formulate a rational policy with regard to 131I therapy after thyroidectomy. There is a good case for ablating any residual thyroid tissue with 131I in patients with follicular tumours because these tumours are potentially functioning and some of them may already have metastasized by the time the patients seek medical advice. The arguments in favour of 131I therapy in patients with papillary tumours are less cogent. The prognosis for these patients is good provided they are under age of 40, but the recurrence rate is not insignificant and recurrences when they do occur are likely to be located in the remaining thyroid tissue. It would seem reasonable to recommend 131I ablation for all patients over the age of 40 and to consider ablation for those patients whose tumours contain a substantial follicular component. Young patients with papillary tumours showing little or no follicular structure probably require no treatment other than surgery. (author)

  12. Early detection of colorectal cancer relapse by infrared spectroscopy in ``normal'' anastomosis tissue

    Salman, Ahmad; Sebbag, Gilbert; Argov, Shmuel; Mordechai, Shaul; Sahu, Ranjit K.

    2015-07-01

    Colorectal cancer is one of the most aggressive cancers usually occurring in people above the age of 50 years. In the United States, colorectal cancer is the third most diagnosed cancer. The American Cancer Society has estimated 96,830 new cases of colon cancer and 40,000 new cases of rectal cancer in 2014 in the United States. According to the literature, up to 55% of colorectal cancer patients experience a recurrence within five years from the time of surgery. Relapse of colorectal cancer has a deep influence on the quality of patient life. Infrared (IR) spectroscopy has been widely used in medicine. It is a noninvasive, nondestructive technique that can detect changes in cells and tissues that are caused by different disorders, such as cancer. Abnormalities in the colonic crypts, which are not detectable using standard histopathological methods, could be determined using IR spectroscopic methods. The IR measurements were performed on formalin-fixed, paraffin-embedded colorectal tissues from eight patients (one control, four local recurrences, three distant recurrences). A total of 128 crypts were measured. Our results showed the possibility of differentiating among control, local, and distant recurrence crypts with more than a 92% success rate using spectra measured from the crypts' middle sites.

  13. Optimal Normal Tissue Sparing in Craniospinal Axis Irradiation Using IMRT With Daily Intrafractionally Modulated Junction(s)

    Purpose: To develop a treatment technique for craniospinal irradiation using intensity-modulated radiotherapy (IMRT) with improved dose homogeneity at the field junction(s), increased target volume conformity, and minimized dose to the organs at risk (OARs). Methods and Materials: Five patients with high-risk medulloblastoma underwent CT simulation in supine position. For each patient, an IMRT plan with daily intrafractionally modulated junction(s) was generated, as well as a treatment plan based on conventional three-dimensional planning (3DCRT). A dose of 39.6 Gy in 22 daily fractions of 1.8 Gy was prescribed. Dose–volume parameters for target volumes and OARs were compared for the two techniques. Results: The maximum dose with IMRT was and V>107 were 3 for IMRT compared with 3–9 cm3 for the craniospinal and 26–43 cm3 for the spinal–spinal junction with 3DCRT. These observations corresponded with a lower homogeneity index and a higher conformity index for the spinal planning target volume with IMRT. IMRT provided considerable sparing of acute and late reacting tissues. V75 for the esophagus, gastroesophageal junction, and intestine was 81%, 81%, and 22% with 3DCRT versus 5%, 0%, and 1% with IMRT, respectively. V75 for the heart and thyroid was 42% and 32% vs. 0% with IMRT. Conclusion: IMRT with daily intrafractionally modulated junction results in a superior target coverage and junction homogeneity compared with 3DCRT. A significant dose reduction can be obtained for acute as well as late-reacting tissues.

  14. Optimal Normal Tissue Sparing in Craniospinal Axis Irradiation Using IMRT With Daily Intrafractionally Modulated Junction(s)

    Kusters, Johannes M.A.M.; Louwe, Rob J.W.; Kollenburg, Peter G.M. van; Kunze-Busch, Martina C. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Gidding, Corrie E.M. [Department of Pediatric Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Lindert, Erik J. van [Department of Neurosurgery, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Kaanders, Johannes H.A.M. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Janssens, Geert O.R.J., E-mail: g.janssens@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2011-12-01

    Purpose: To develop a treatment technique for craniospinal irradiation using intensity-modulated radiotherapy (IMRT) with improved dose homogeneity at the field junction(s), increased target volume conformity, and minimized dose to the organs at risk (OARs). Methods and Materials: Five patients with high-risk medulloblastoma underwent CT simulation in supine position. For each patient, an IMRT plan with daily intrafractionally modulated junction(s) was generated, as well as a treatment plan based on conventional three-dimensional planning (3DCRT). A dose of 39.6 Gy in 22 daily fractions of 1.8 Gy was prescribed. Dose-volume parameters for target volumes and OARs were compared for the two techniques. Results: The maximum dose with IMRT was <107% in all patients. V{sub <95} and V{sub >107} were <1 cm{sup 3} for IMRT compared with 3-9 cm{sup 3} for the craniospinal and 26-43 cm{sup 3} for the spinal-spinal junction with 3DCRT. These observations corresponded with a lower homogeneity index and a higher conformity index for the spinal planning target volume with IMRT. IMRT provided considerable sparing of acute and late reacting tissues. V{sub 75} for the esophagus, gastroesophageal junction, and intestine was 81%, 81%, and 22% with 3DCRT versus 5%, 0%, and 1% with IMRT, respectively. V{sub 75} for the heart and thyroid was 42% and 32% vs. 0% with IMRT. Conclusion: IMRT with daily intrafractionally modulated junction results in a superior target coverage and junction homogeneity compared with 3DCRT. A significant dose reduction can be obtained for acute as well as late-reacting tissues.

  15. Differential expression profiling between the relative normal and dystrophic muscle tissues from the same LGMD patient

    Yang Wei

    2006-12-01

    Full Text Available Abstract Background Limb-girdle muscular dystrophy (LGMD is a group of heterogeneous muscular disorders with autosomal dominant and recessive inheritance, in which the pelvic or shoulder girdle musculature is predominantly or primarily involved. Although analysis of the defective proteins has shed some light onto their functions implicated in the etiology of LGMD, our understanding of the molecular mechanisms underlying muscular dystrophy remains incomplete. Methods To give insight into the molecular mechanisms of AR-LGMD, we have examined the differentially expressed gene profiling between the relative normal and pathological skeletal muscles from the same AR-LGMD patient with the differential display RT-PCR approach. The research subjects came from a Chinese AR-LGMD family with three affected sisters. Results In this report, we have identified 31 known genes and 12 unknown ESTs, which were differentially expressed between the relative normal and dystrophic muscle from the same LGMD patient. The expression of many genes encoding structural proteins of skeletal muscle fibers (such as titin, myosin heavy and light chains, and nebulin were dramatically down-regulated in dystrophic muscles compared to the relative normal muscles. The genes, reticulocalbin 1, kinectin 1, fatty acid desaturase 1, insulin-like growth factor binding protein 5 (IGFBP5, Nedd4 family interacting protein 1 (NDFIP1, SMARCA2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2, encoding the proteins involved in signal transduction and gene expression regulation were up-regulated in the dystrophic muscles. Conclusion The functional analysis of these expression-altered genes in the pathogenesis of LGMD could provide additional information for understanding possible molecular mechanisms of LGMD development.

  16. Myeloid tissue factor does not modulate lung inflammation or permeability during experimental acute lung injury.

    Shaver, Ciara M; Grove, Brandon S; Clune, Jennifer K; Mackman, Nigel; Ware, Lorraine B; Bastarache, Julie A

    2016-01-01

    Tissue factor (TF) is a critical mediator of direct acute lung injury (ALI) with global TF deficiency resulting in increased airspace inflammation, alveolar-capillary permeability, and alveolar hemorrhage after intra-tracheal lipopolysaccharide (LPS). In the lung, TF is expressed diffusely on the lung epithelium and intensely on cells of the myeloid lineage. We recently reported that TF on the lung epithelium, but not on myeloid cells, was the major source of TF during intra-tracheal LPS-induced ALI. Because of a growing body of literature demonstrating important pathophysiologic differences between ALI caused by different etiologies, we hypothesized that TF on myeloid cells may have distinct contributions to airspace inflammation and permeability between direct and indirect causes of ALI. To test this, we compared mice lacking TF on myeloid cells (TF(∆mye), LysM.Cre(+/-)TF(flox/flox)) to littermate controls during direct (bacterial pneumonia, ventilator-induced ALI, bleomycin-induced ALI) and indirect ALI (systemic LPS, cecal ligation and puncture). ALI was quantified by weight loss, bronchoalveolar lavage (BAL) inflammatory cell number, cytokine concentration, protein concentration, and BAL procoagulant activity. There was no significant contribution of TF on myeloid cells in multiple models of experimental ALI, leading to the conclusion that TF in myeloid cells is not a major contributor to experimental ALI. PMID:26924425

  17. Timing of tissue plasminogen activator for acute ischemic stroke: outcomes-based recommendations for practice.

    Hanselman, Carol J

    2014-12-01

    Acute ischemic stroke (AIS) is a major cause of death and disability in the United States. Tissue plasminogen activator (t-PA) is an intravenously administered therapy that can prevent death and disability for patients presenting within early onset of AIS. There has been a debate around the exact time parameters for administration, because very few patients present to the hospital within the initial 0- to 3-hour window of time. Not all of the current national guidelines for timing of AIS in the United States are in agreement with regards to this issue. To the nurse caring for patients with neurologic illnesses, this topic is of utmost importance. Nurse are not only involved in determining the time of stroke symptom onset, but nurses also hold responsibility for a working knowledge of the latest eligibility and exclusion criteria for t-PA administration. This article examines the central body of research related to the timing of t-PA and makes recommendations for eligible candidates based on this literature. PMID:25365047

  18. Genome-wide effects of acute progressive feed restriction in liver and white adipose tissue

    Acute progressive feed restriction (APFR) represents a specific form of caloric restriction in which feed availability is increasingly curtailed over a period of a few days to a few weeks. It is often used for control animals in toxicological and pharmacological studies on compounds causing body weight loss to equalize weight changes between experimental and control groups and thereby, intuitively, to also set their metabolic states to the same phase. However, scientific justification for this procedure is lacking. In the present study, we analyzed by microarrays the impact on hepatic gene expression in rats of two APFR regimens that caused identical diminution of body weight (19%) but differed slightly in duration (4 vs. 10 days). In addition, white adipose tissue (WAT) was also subjected to the transcriptomic analysis on day-4. The data revealed that the two regimens led to distinct patterns of differentially expressed genes in liver, albeit some major pathways of energy metabolism were similarly affected (particularly fatty acid and amino acid catabolism). The reason for the divergence appeared to be entrainment by the longer APFR protocol of peripheral oscillator genes, which resulted in derailment of circadian rhythms and consequent interaction of altered diurnal fluctuations with metabolic adjustments in gene expression activities. WAT proved to be highly unresponsive to the 4-day APFR as only 17 mRNA levels were influenced by the treatment. This study demonstrates that body weight is a poor proxy of metabolic state and that the customary protocols of feed restriction can lead to rhythm entrainment

  19. Acute Effects of Hemodialysis on Left and Right Ventricular Function: A Doppler Tissue Imaging Study

    Tansel Erol

    2012-08-01

    Full Text Available Purpose: Doppler tissue imaging (DTI allows noninvasive assessment of both left ventricular (LV and right ventricular (RV function. The aim of this study was to evaluate the effect of hemodialysis (HD on LV and RV function using DTI. Method: Our study group included 30 patients on chronic HD program (mean age 45 15 years. Myocardial (Sm, Em, Am and annular velocities (Ea, Aa were measured in several cardiac territories before and after HD. Results: After HD, Ea significantly reduced from 10.8 3.4 cm/s to 9.6 2.4 cm/s (p = 0.029. Patients exhibited a lower Em following HD in all measured territories. Em/Am ratio was also reduced for each LV wall investigated after HD in all measured territories. At the RV segments, Sm, Em, and Am decreased significantly in all measured territories. Em of the anterior wall was positively related to ultrafiltration volume (r = 0.25, p = 0.006, whereas the decrease of Sm of RV basal segment correlated with a decrease of diastolic blood pressure (r = 0.23, p < 0.01. Conclusion: Our data indicate that a single HD session is associated with acute changes of systolic and diastolic parameters of LV and RV. [Cukurova Med J 2012; 37(4.000: 215-222

  20. Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats

    Tucker, B. J.; Anderson, C. M.; Thies, R. S.; Collins, R. C.; Blantz, R. C.

    1992-01-01

    Treatment of insulin dependent diabetes invariably requires exogenous insulin to control blood glucose. Insulin treatment, independent of other factors associated with insulin dependent diabetes, may induce changes that affect glomerular function. Due to exogenous delivery of insulin in insulin dependent diabetes entering systemic circulation prior to the portal vein, plasma levels of insulin are often in excess of that observed in non-diabetics. The specific effects of hyperinsulinemia on glomerular hemodynamics have not been previously examined. Micropuncture studies were performed in control (non-diabetic), untreated diabetic and insulin-treated diabetic rats 7 to 10 days after administration of 65 mg/kg body weight streptozotocin. After the first period micropuncture measurements were obtained, 5 U of regular insulin (Humulin-R) was infused i.v., and glucose clamped at euglycemic values (80 to 120 mg/dl). Blood glucose concentration in non-diabetic controls was 99 +/- 6 mg/dl. In control rats, insulin infusion and glucose clamp increased nephron filtration rate due to decreases in both afferent and efferent arteriolar resistance (afferent greater than efferent) resulting in increased plasma flow and increased glomerular hydrostatic pressure gradient. However, insulin infusion and glucose clamp produced the opposite effect in both untreated and insulin-treated diabetic rats with afferent arteriolar vasoconstriction resulting in decreases in plasma flow, glomerular hydrostatic pressure gradient and nephron filtration rate. Thromboxane A2 (TX) synthetase inhibition partially decreased the vasoconstrictive response due to acute insulin infusion in diabetic rats preventing the decrease in nephron filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS).

  1. Normal formation of a vertebrate body plan and loss of tissue maintenance in the absence of ezh2.

    San, Bilge; Chrispijn, Naomi D; Wittkopp, Nadine; van Heeringen, Simon J; Lagendijk, Anne K; Aben, Marco; Bakkers, Jeroen; Ketting, René F; Kamminga, Leonie M

    2016-01-01

    Polycomb group (PcG) proteins are transcriptional repressors of numerous genes, many of which regulate cell cycle progression or developmental processes. We used zebrafish to study Enhancer of zeste homolog 2 (Ezh2), the PcG protein responsible for placing the transcriptional repressive H3K27me3 mark. We identified a nonsense mutant of ezh2 and generated maternal zygotic (MZ) ezh2 mutant embryos. In contrast to knockout mice for PcG proteins, MZezh2 mutant embryos gastrulate seemingly normal, but die around 2 days post fertilization displaying pleiotropic phenotypes. Expression analyses indicated that genes important for early development are not turned off properly, revealing a regulatory role for Ezh2 during zygotic gene expression. In addition, we suggest that Ezh2 regulates maternal mRNA loading of zygotes. Analyses of tissues arising later in development, such as heart, liver, and pancreas, indicated that Ezh2 is required for maintenance of differentiated cell fates. Our data imply that the primary role of Ezh2 is to maintain tissues after tissue specification. Furthermore, our work indicates that Ezh2 is essential to sustain tissue integrity and to set up proper maternal mRNA contribution, and presents a novel and powerful tool to study how PcG proteins contribute to early vertebrate development. PMID:27145952

  2. Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue.

    Drakaki, E; Kaselouris, E; Makropoulou, M; Serafetinides, A A; Tsenga, A; Stratigos, A J; Katsambas, A D; Antoniou, C

    2009-01-01

    The object of this study was to investigate whether laser-induced skin autofluorescence (LIF) and/or light reflectance spectra could provide a useful contrast between basal cell carcinoma (BCC) tissues and the surrounding healthy skin. Unstained human skin samples, excised from humans undergoing biopsy examination, were irradiated with a nitrogen laser (lambda = 337 nm) for excitation of autofluorescence and a tungsten halogen lamp for the reflectance measurements. The ex vivo spectroscopic results were correlated with the histopathology images to distinguish the areas of BCC from those of the surrounding health skin. A simple spectral analysis technique was also applied for better skin diagnosis. In conclusion, it seems that LIF and reflectance spectra could be used to differentiate neoplastic from normal skin tissue using an appropriate classification model analysis. PMID:19365155

  3. Laser and Non-Coherent Light Effect on Peripheral Blood Normal and Acute Lymphoblastic Leukemic Cells by Using Different Types of Photosensitizers

    El Batanouny, Mohamed H.; Khorshid, Amira M.; Arsanyos, Sonya F.; Shaheen, Hesham M.; Abdel Wahab, Nahed; Amin, Sherif N.; El Rouby, Mahmoud N.; Morsy, Mona I.

    2010-04-01

    Photodynamic therapy (PDT) is a novel treatment modality of cancer and non-cancerous conditions that are generally characterized by an overgrowth of unwanted or abnormal cells. Irradiation of photosensitizer loaded cells or tissues leads via the photochemical reactions of excited photosensitizer molecules to the production of singlet oxygen and free radicals, which initiate cell death. Many types of compounds have been tested as photosensitizers, such as methylene blue (MB) and photopherin seemed to be very promising. This study involved 26 cases of acute lymphoblastic leukemia and 15 normal volunteers as a control group. The cell viability was measured by Light microscope and flowcytometer. Mode of cell death was detected by flowcytometer and electron microscope in selected cases. The viability percentage of normal peripheral blood mononuclear cells (PBMC) incubated with methylene blue (MB) alone or combined with photo irradiation with diode laser (as measured by light microscope) was significantly lower than that of untreated cases either measured after 1 hour (p<0.001) or 24 hours (p<0.001) post incubation. There was a significantly lower viability percentage of normal cells incubated with MB and photoirradiated with diode laser compared to normal cells treated with MB alone for either measured after 1 hour (p<0.001) or 24 hours (p<0.001) post incubation. The decrease in viability was more enhanced with increasing the incubation time. For normal cells incubated with photopherin either for 1/2 an hour or 1 hour, there was a weak cytotoxic effect compared to the effect on untreated cells. There was a significant decrease in viability percentage of cells incubated with photopherin either for 1/2 an hour or 1 hour and photoirradiated with He:Ne laser compared to normal untreated cells. The decrease in the cell viability percentage was significantly lower with the use of PDT (photopherin and He:Ne laser ) compared to either photopherin alone or He:Ne laser alone. The

  4. Risk Factors and Markers for Acute Myocardial Infarction With Angiographically Normal Coronary Arteries.

    Daniel, Maria; Ekenbäck, Christina; Agewall, Stefan; Brolin, Elin B; Caidahl, Kenneth; Cederlund, Kerstin; Collste, Olov; Eurenius, Lars; Frick, Mats; Younis-Hassan, Shams; Henareh, Loghman; Jernberg, Tomas; Malmqvist, Karin; Spaak, Jonas; Sörensson, Peder; Hofman-Bang, Claes; Tornvall, Per

    2015-09-15

    Myocardial Infarction with normal coronary arteries (MINCA) is common with a prevalence of 1% to 12% of all myocardial infarctions. The pathogenic mechanisms of MINCA are still unknown, but endothelial dysfunction has been suggested as a possible cause. To investigate risk factors and markers for MINCA, we conducted a case-control study. Considering the reported low prevalence of classical risk factors for coronary heart disease (CHD) in some but not all studies, our hypothesis was that endothelial function and intima-media thickness (IMT) were better, respectively lower, than CHD controls. One hundred patients with MINCA fulfilling diagnostic criteria according to the European Society of Cardiology/American Collage of Cardiology/American Heart Association universal definition of myocardial infarction with myocarditis excluded by cardiac magnetic resonance imaging were investigated. Risk factors, endothelial function (EndoPAT), and IMT were compared to gender- and age-matched patients with myocardial infarction and CHD, respectively healthy controls. Smoking, hypertension, impaired glucose tolerance and diabetes mellitus, inflammatory disease, and psychiatric disorders were more common in patients with MINCA than in healthy controls. In contrast to patients with CHD, the lipid profile was antiatherogenic with low low-density lipoprotein and high high-density lipoprotein cholesterol. There were no major differences between the groups regarding endothelial function and IMT that were in the normal range. In conclusion, the present study showed that MINCA was associated with many established cardiovascular risk factors without major differences in atherosclerosis markers. MINCA patients recalled a high prevalence of emotional stress before admission that together with previous psychiatric vulnerability and female gender speaks strongly in favor of Takotsubo syndrome being an important cause of MINCA. PMID:26251000

  5. Tissue reactions in lambs and kids vaccinated with irradiated and normal amphistome metacercariae (Cercariae indicae XXVI)

    The intensity of gross and histopathological changes were inversely related to the dose of irradiation. Severe catarrhal enteritis was noticed with non-irradiated metacercariae while with increased irradiation doses the intensity of changes were in decreasing order, however, with 3 Krad dose no severe change was seen. The severe changes of gastro-enteritic lesions were seen from the challenge dose of normal metacercariae in the lambs and kids previously vaccinated with non-irradiated metacercariae. The moderate catarrhal enteritis, mild necrotic lesions and absence of severe lesions produced by the challenge dose of normal metacercariae in the lambs and kids previously vaccinated with 2, 2.5 and 3 Krad level of irradiated metacercariae suggested that the lesions produced by challenge doses were in order of reduced intensity as the dose of irradiation for initial vaccination increased. The cellular infiltration with round cells, plasma cells and macrophages in the mucosa of the small intestine was more in lambs and kids vaccinated with irradiated metacercariae and the order of increase was in correspondent with the level of irradiation. The present study showed that the optimal dose of irradiation for amphistome metacercariae was 3 Krad, where maximum immunological response could be obtained. This also suggests the possibility of immunizing lambs and kids against intestinal amphistomiasis with 3 Krad irradiated metacercariae. (author)

  6. Rhodamine 123 inhibits protein synthesis in mitochondria isolated from normal and cancer tissues

    The dye rhodamine 123 (Rho 123) is well known to specifically stain mitochrondria in living cells. Its accumulation in these organelles is associated with certain toxic effects where the dye is found to inhibit bioenergetic function in normal and cancer mitochondria. Since mitochondria appear to be a target for Rho 123 interaction, the authors investigated its effects on mitochondrial protein synthesis (PS) in rat liver, and in both erythroleukemia and chloroleukemia tumors. L-(14C) leucine incorporation into mitochondria protein was used to determine the rate of PS. While the specific activity of leucine incorporation was much higher in tumor as compared to liver mitochondria, the addition of 10 μg Rho 123/ml in all tested mitochondria resulted in 75-80% inhibition. Similar results were obtained with 10 μg/ml of chloramphenicol, the specific inhibitor for mitochondrial PS. PS inhibition in the three types of mitochondria was Rho 123 concentration-dependent being about 50% at 5 μg/ml and with total inhibition at 15-20 μg/ml. Moreover, the addition of Rho 123 to mitochondria under PS condition did not trigger any ATPase activity. If present, such activity would compete for ATP which is the energy source of PS. These results demonstrate that the mitochondrial probe Rho 123 has a potent inhibitory effect on PS in both normal and cancer mitochondria

  7. Type I collagen degradation during tissue repair: comparison of mechanisms following fracture and acute coronary syndromes.

    Stansfield, Rachel; Gossiel, Fatma; Morton, Allison; Newman, Christopher; Eastell, Richard

    2014-12-01

    There is turnover of type I collagen during tissue repair. The degradation of type I collagen by matrix metalloproteinases (MMPs) is reflected by serum ICTP and that by cathepsins by CTX-I. There is evidence for increases in ICTP after acute coronary syndromes (ACS) and in CTX-I during fracture repair. The involvement of the MMP pathway in fracture repair and cathepsins after myocardial infarction is unclear. We studied 74 men; 22 were admitted to the hospital on the day of their ACS (ST or non-ST elevation myocardial infarction) (mean age 56 years, range 39 to 82) and 9 attended hospital on the day of their tibial shaft fracture (mean age 33 years, range 21 to 79); we had 43 age-matched controls (mean age 54 years, range 20 to 82). Subjects with ACS and tibial shaft fracture were followed up for up to one year; control subjects were used to establish a reference interval. We measured serum ICTP by ELISA (reference interval 1.1 to 17.6 ng/mL) and CTX-I by chemiluminescence (reference interval 0.094 to 0.991 ng/mL). After ACS, the mean ICTP increased from 5.41 to 6.60 ng/mL within one day of admission (p<0.05); the mean CTX-I increased from 0.263 to 0.414 ng/mL (p<0.05). In two cases, the CTX increased to above the reference interval. After tibial shaft fracture, the mean ICTP increased from 5.51 to maximum of 8.71 ng/mL within 28 days of admission (p<0.01); the mean CTX increased from 0.200 to 0.374 ng/mL (p<0.001). In four cases, the CTX increased to above the reference interval. We conclude that the MMP and cathepsin pathways are both implicated in tissue repair in the bone and heart. This may have clinical implications; drugs that block either pathway (TIMPs, cathepsin K inhibitors) may affect the repair of both tissues. PMID:25193029

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

    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.

  9. Proteomic Comparison of Two—Dimensional Gel Electrophoresis Profiles from Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Tissues

    CuiLi; XianquanZhan; MaoyuLi; XiaoyingWu; FengLi; JianlingLi; ZhiqiangXiao; ZhuchuChen; XuepingFeng; PingChen; JingyunXie; SongpingLiang

    2003-01-01

    Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis(2-D PAGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS).The results showed that well-resolved,reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-mg protein-load.The average deviation of spot position was 0.733±0.101 mm in IEF direction,and 0.925±0.207mm in SDS-PAGE direction.For tumor tissue,a total of 1241±88 spots were detected,987±65 spots were matched with an average matching rate of 79.5%.For control,a total of 1190±72 spots were detected,and 875±48 spots were matched with an average matching rate of 73.5%.A total of 864±34 spots were matched between tumors and controls.Forth-three differential proteins were characterized:some proteins were related to oncogenes,and others involved in the regulation of cell cycle and signal transduction.It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis.These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.

  10. Pentobarbital anesthesia and the response of tumor and normal tissue in the C3Hf/SED mouse to radiation

    Experiments have been performed to assess the effect of sodium pentobarbital (NaPb) on the response of MCaIV, FSaII, and SCCVII using TCD50 and acute reaction of normal skin as end points. The TCD50 was lower or unchanged in the anesthetized than in the conscious mouse. There was no effect of NaPb on the acute reaction of skin. The ERs for NaPb on the TCD50 (ν = 1) for air breathing condition was essentially 1.0 for all three tumors. For the FSaII and SCCVII pentobarbital enhancement ratios were 1.29 and 1.34 for O/sub 2/3ATA conditions. For two dose (ν=2) irradiations ERs for the O/sub 2/3ATA were 1.46, 1.72 and 2.21 for MCaIV, FSaII and SCCVII respectively. For ν = 15, temperature 350C ERs for O/sub 2/3ATA were 1.08 and 1.09 for MCaIV and FSaII but 1.22 for SCCVII

  11. Consequences of dose response curves for tumor control and normal tissue injury on the precision necessary in patient management

    This paper is concerned with an analysis of the relationship between dose response curves, treatment precision, and treatment outcome. The approach that is taken is first to define the term ''treatment precision'' as it is used in this paper and then to compare the expected treatment outcomes for two treatment systems with different levels of precision. The treatment outcomes will be calculated using assumed dose response curves for tumor control and for severe normal tissue injury. This approach is admittedly theoretical and is not intended to provide any quantitative conclusions concerning the treatment of patients. The approach will, however, provide valuable insight into the relationship between treatment precision and outcome

  12. Expression of aminopeptidase-n (CD 13) in normal tissues and malignant neoplasms of epithelial and lymphoid origin.

    Dixon, J.; Kaklamanis, L.; Turley, H; Hickson, I D; Leek, R. D.; Harris, A. L.; Gatter, K C

    1994-01-01

    AIMS--To provide a detailed knowledge of the distribution of the CD13 molecule, also known as the protease aminopeptidase-N, on both normal tissues and malignant neoplasms of epithelial and lymphoid origin. METHODS--CD13 antigen was examined by immunocytochemistry, using a recently produced antibody (VS5E) alongside a commercially available anti-CD13 monoclonal antibody. The VS5E recognising CD13 was produced by immunising a doxorubicin resistant breast cancer cell line (MCF-7-ADr). A strikin...

  13. Elemental analysis of tissue pellets for the differentiation of epidermal lesion and normal skin by laser-induced breakdown spectroscopy.

    Moon, Youngmin; Han, Jung Hyun; Shin, Sungho; Kim, Yong-Chul; Jeong, Sungho

    2016-05-01

    By laser induced breakdown spectroscopy (LIBS) analysis of epidermal lesion and dermis tissue pellets of hairless mouse, it is shown that Ca intensity in the epidermal lesion is higher than that in dermis, whereas Na and K intensities have an opposite tendency. It is demonstrated that epidermal lesion and normal dermis can be differentiated with high selectivity either by univariate or multivariate analysis of LIBS spectra with an intensity ratio difference by factor of 8 or classification accuracy over 0.995, respectively. PMID:27231610

  14. External validation of a normal tissue complication probability model for radiation-induced hypothyroidism in an independent cohort

    Rønjom, Marianne F; Brink, Carsten; Bentzen, Søren M;

    2015-01-01

    BACKGROUND: A normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism (RIHT) was previously derived in patients with squamous cell carcinoma of the head and neck (HNSCC) discerning thyroid volume (Vthyroid), mean thyroid dose (Dmean), and latency as predictive...... TSH > 4.0 mU/l from blood samples obtained during follow-up. A new mixture NTCP model was developed from the validation cohort after multivariable analysis. Due to only one follow-up TSH assessment in the validation cohort, the time factor derived from the original cohort was fixed in a mixture model...

  15. Experimental and clinical study of dose-reducing effect of normal tissues in intestinal radiotherapy of tongue carcinoma

    A spacer is used to reduce radiation doses in normal tissue in interstitial radiation therapy for tongue carcinoma. Experimental and clinical studies were performed to examine dose-reducing effects of the spacer. In an experimental study, both radium and iridium sources were used. Resin and silicon impressions were used as materials. Both types of materials had more dose-reducing effects than air; and the effects were greater in silicon materials than resin materials. Doses of radium and iridium needles were 30% and 40%, respectively, when the materials were one cm in thickness; the dose-reducing effects were greater for radium than iridium. (N.K.)

  16. Desferal (DFO) induced Ga-67 washout from normal tissue, tumor and abscess in experimental animals

    In the experimental animal, desferal (DFO) given intravenously washes out Ga-67 from all tissues. This effect is not uniform: blood activity is reduced very markedly, while liver activity is less affected. Maximal effect of DFO occurs if given close to the Ga-67 injection. When the time interval between the two is increased, the absolute amount of Ga-67 excreted in the urine in excess of the spontaneous excretion is reduced. Administration of DFO does not effect Ga-67 gastrointestinal excretion. In three animal tumor models (EMT-6 sarcoma in Balb/c mice, spontaneous adenocarcinoma in mice, and spontaneous adenocarcinoma in the rabbit) and in sterile abscess-bearing rats, the administration of DFO 24 hrs after Ga-67-citrate improves significantly the target-to-nontarget ratio. Animals given 50 mg/kg DFO I.V. after Ga-67 citrate showed a significant reduction in the whole-body activity as seen in a one-week follow up

  17. Some biochemical effects of Aloe vera leaves on tissues in normal mice

    S. A. Al-Ameen

    2010-01-01

    Full Text Available This research was carried out mainly to investigate the effects of the aqueous extract and proteinous fractions of Aloe veraleaves on cholesterol, acetycholinesterase in brain, glycogen, glutathione in liver and malonaldehyde levels in heart in normalmale albino mice. The antioxidant properties and inhibition of acetylcholine-sterase in tissue were detected. Intraperitonealadministration of Aloe vera extract in concentration of 400 mg/kg significantly decreased the levels of AchE in brain by (-88.27% and glutathione content in liver by (-35.48%, and increased the levels of glycogen in liver and malonaldehyde inheart by (22.60%, 85.50% respectively. At a concentration of 300 mg/kg Aloe vera extract significantly increased the level ofcholesterol in brain by (24.39%. These results clearly show the antioxidant property of the extract of Aloe vera leaves.

  18. Effects of experimental radiotherapy and hyperthermia on tumors and normal tissues in small animals

    Experiments on responses of tumors, implanted subcutaneously in the leg, to irradiation alone or combined with heat are reported. The influence of factors modifying the fraction of hypoxic cells (e.g. anesthesia of the animal and tumor volume) is also discussed. The radiosensitivity of developing lung tumors was examined for spontaneous as well as for artificial lung metastases. Both experimental tumor models were compared with regard to their value in experimental radiotherapy. Data obtained on the response of artificial metastases and lung tissue to combined treatment with irradiation and several drugs are presented. Data on damage of the mouse foot, as a result of heat and/or irradiation treatments are presented. In particular the influence of thermotolerance on thermal enhancement of the radiation induced skin reaction was studied. Tolerance of the skin of previously irradiated mice to retreatment with irradiation, to hyperthermia alone and combined with X-rays was assessed. (Auth.)

  19. Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC

    Hirsch, Pierre; Tang, Ruoping; Marzac, Christophe; Perrot, Jean-Yves; FAVA, FANNY; Bernard, Chantal; Jeziorowska, Dorota; MARIE, JEAN PIERRE; Legrand, Ollivier

    2012-01-01

    ATP-binding cassette transporter (and specially P-glycoprotein) activity is a well known prognostic factor in acute myeloid leukemia, but when compared to other molecular markers its prognostic value has not been well studied. Here we study relationships between this activity, fms-like tyro-sine kinase 3(FLT3/ITD), nucleophosmin(NPM1), CAAT-enhancer binding protein alpha(CEBPα), and brain and acute leukemia cytoplasmic protein (BAALC), in 111 patients with normal cytogenetics who underwent th...

  20. Site-specific differences of insulin action in adipose tissue derived from normal prepubertal children

    Body fat distribution determines obesity-related morbidity in adults but little is known of the aetiology or pathophysiology in children. This study investigates differences in insulin-mediated metabolism in primary cell cultures of subcutaneous and visceral preadipocytes derived from prepubertal children. The impact of differentiation and responses to TNFα exposure was also investigated. Proliferation rates were greater in subcutaneous versus visceral preadipocytes (41 h(3) versus 69 h(4); P = 0.008). Insulin caused a dose-dependent increase in GSK-3 phosphorylation and an increase in MAPK phosphorylation over time, with increased sensitivity in subcutaneous preadipocytes. Post-differentiation, dose-dependent increases in GSK-3 phosphorylation were maintained, while MAPK phosphorylation was identical in both subtypes. No changes were observed in insulin receptor abundance pre-/post-differentiation. GLUT4 abundance was significantly increased in visceral versus subcutaneous adipocytes by 76(4)%; P = 0.03), coincidental with increased insulin-stimulated 2-deoxy-glucose transport (+150(26)% versus +79(10)%; P = 0.014) and further elevated by acute exposure to TNFα (+230(52)%; P = 0.019 versus +123(24)%; P = 0.025, respectively). TNFα also significantly increased basal glucose transport rates (+44(14)%; P = 0.006 versus +34(11)%; P = 0.007) and GLUT1 localisation to the plasma membrane. These data establish site-specific differences in subcutaneous and visceral fat cells from children. Responses to insulin varied with differentiation and TNFα exposure in the two depots, consistent with parallel changes in GLUT1/4 abundance and localisation

  1. Identification of valid reference genes for the normalization of RT qPCR gene expression data in human brain tissue

    Ravid Rivka

    2008-05-01

    Full Text Available Abstract Background Studies of gene expression in post mortem human brain can contribute to understanding of the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD, Parkinson's disease (PD and dementia with Lewy bodies (DLB. Quantitative real-time PCR (RT qPCR is often used to analyse gene expression. The validity of results obtained using RT qPCR is reliant on accurate data normalization. Reference genes are generally used to normalize RT qPCR data. Given that expression of some commonly used reference genes is altered in certain conditions, this study aimed to establish which reference genes were stably expressed in post mortem brain tissue from individuals with AD, PD or DLB. Results The present study investigated the expression stability of 8 candidate reference genes, (ubiquitin C [UBC], tyrosine-3-monooxygenase [YWHAZ], RNA polymerase II polypeptide [RP II], hydroxymethylbilane synthase [HMBS], TATA box binding protein [TBP], β-2-microglobulin [B2M], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], and succinate dehydrogenase complex-subunit A, [SDHA] in cerebellum and medial temporal gyrus of 6 AD, 6 PD, 6 DLB subjects, along with 5 matched controls using RT qPCR (TaqMan® Gene Expression Assays. Gene expression stability was analysed using geNorm to rank the candidate genes in order of decreasing stability in each disease group. The optimal number of genes recommended for accurate data normalization in each disease state was determined by pairwise variation analysis. Conclusion This study identified validated sets of mRNAs which would be appropriate for the normalization of RT qPCR data when studying gene expression in brain tissue of AD, PD, DLB and control subjects.

  2. Isolation and genome-wide expression and methylation characterization of CD31+ cells from normal and malignant human prostate tissue

    Luo, Wei; Hu, Qiang; Wang, Dan; Deeb, Kristin K.; Ma, Yingyu; Morrison, Carl D.; Liu, Song; Johnson, Candace S.; Trump, Donald L.

    2013-01-01

    Endothelial cells (ECs) are an important component involved in the angiogenesis. Little is known about the global gene expression and epigenetic regulation in tumor endothelial cells. The identification of gene expression and epigenetic difference between human prostate tumor-derived endothelial cells (TdECs) and those in normal tissues may uncover unique biological features of TdEC and facilitate the discovery of new anti-angiogenic targets. We established a method for isolation of CD31+ endothelial cells from malignant and normal prostate tissues obtained at prostatectomy. TdECs and normal-derived ECs (NdECs) showed >90% enrichment in primary culture and demonstrated microvascular endothelial cell characteristics such as cobblestone morphology in monolayer culture, diI-acetyl-LDL uptake and capillary-tube like formation in Matrigel®. In vitro primary cultures of ECs maintained expression of endothelial markers such as CD31, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2. We then conducted a pilot study of transcriptome and methylome analysis of TdECs and matched NdECs from patients with prostate cancer. We observed a wide spectrum of differences in gene expression and methylation patterns in endothelial cells, between malignant and normal prostate tissues. Array-based expression and methylation data were validated by qRT-PCR and bisulfite DNA pyrosequencing. Further analysis of transcriptome and methylome data revealed a number of differentially expressed genes with loci whose methylation change is accompanied by an inverse change in gene expression. Our study demonstrates the feasibility of isolation of ECs from histologically normal prostate and prostate cancer via CD31+ selection. The data, although preliminary, indicates that there exist widespread differences in methylation and transcription between TdECs and NdECs. Interestingly, only a small

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

    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%

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

    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%.

  5. Expression of hypoxia-inducible factor 1α in human normal, benign, and malignant prostate tissue

    都镇先; 藤山千里; 陈永昕; 真崎善二郎

    2003-01-01

    Objective To investigate hypoxia-inducible factor 1α (HIF-1α) protein expression in normal prostates (NP), benign prostatic glandular hyperplasia (BPH), and prostate adenocarcinoma (Pca).Methods HIF-1α protein expression was determined by immunohistochemistry in formalin-fixed and paraffin-embedded specimens obtained from 13 cases of NP, 28 cases of BPH, and 34 cases of Pca. In cases of Pca, the relationship between HIF-1α protein expression and certain clinicopathological factors, such as clinicopathologic stage and Gleason score, was evaluated.Results NP manifested no immunoreactivity, whereas Pca and BPH showed significantly increased HIF-1α protein expression. A significantly higher expression was observed in Pca specimens compared with BPH samples. In Pca, no significant relationship between HIF-1α protein expression and clinicopathological factors was found.Conclusion Our findings of increased HIF-1α protein expression in BPH and Pca specimens suggests the potential role of this protein in BPH and Pca.

  6. Distinguishing human normal or cancerous esophagus tissue ex vivo using multiphoton microscopy

    Application of multiphoton microscopy (MPM) to clinical cancer research has greatly developed over the last few years. In this paper, we mainly focus on two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) for investigating esophageal cancer. We chiefly discuss the SHG/TPEF image and spectral characteristics of normal and cancerous esophagus submucosa with the combined multi-channel imaging mode and Lambda mode of a multiphoton microscope (LSM 510 META). Great differences can be detected, such as collagen content and morphology, glandular-shaped cancer cells, TPEF/SHG intensity ratio, and so on, which demonstrate that the multiphoton imaging technique has the potential ability for minimally-invasive early cancer diagnosis. (paper)

  7. Radiolocalization of human small cell lung cancer and antigen-positive normal tissues using monoclonal antibody LS2D617

    The murine monoclonal antibody LS2D617, which reacts with an antigen associated with human small cell lung carcinoma (SCLC), was tested in preclinical models to assess its potential for specific targeting of tumors in human SCLC cancer patients. LS2D617 detects a cell antigen on the surface of cultured SCLC and neuroblastoma cell lines. Scatchard analysis of the binding of LS2D617 to NCIH69 SCLC cells indicates an affinity constant of about 1 x 10(8) M-1 and an epitope expression level of approximately 2 x 10(6) antigenic sites/cell. Molecular weight analysis of the target antigen and antibody competition experiments showed that LS2D617 should be classified as a SCLC Cluster 1 antibody. LS2D617 was labeled with 111In and tested for biodistribution (4, 24, 48, 72, and 96 h postinjection) in nude mice bearing the human SCLC NCIH69 tumor. Tumor values peaked at about 35% injected dose/g (Day 3) compared with about 8% injected dose/g for an irrelevant IgG1 antibody while normal tissue accumulation for both antibodies was about 2-8% injected dose/g. Immunohistochemical studies demonstrated that LS2D617 reacts with the central nervous system, peripheral nerves, endocrine tissues, and heart tissue of rabbits as it does in human tissues. The ability of LS2D617 to accumulate in vivo in normal tissues that express the specific target antigen was tested in rabbits. Rabbits given i.v. injections of 111In-LS2D617 or control labeled antibody were sacrificed at 48 h and tissues were examined by gamma well counting, autoradiography, and immunohistochemical staining for murine immunoglobulin. Specific uptake was seen in all sites defined as antigen positive by immunohistology (i.e., heart, liver bile duct, peripheral nerves, pituitary, adrenal), except the central nervous system (brain and spinal cord) which was inaccessible to antibody because of the blood brain barrier

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

    Ao Huilan; Xing Da; Wei Huajiang; Gu Huaimin [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, ina Normal University, Guangzhou 510631 (China); Wu Guoyong; Lu Jianjun [Department of Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China)], E-mail: xingda@scnu.edu.cn

    2008-04-21

    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.

  9. Acute effects of ethanol and acetate on glucose kinetics in normal subjects

    The authors compared the effects of two ethanol doses on glucose kinetics and assessed the role of acetate as a mediator of ethanol-induced insulin resistance. Ten normal males were studied on four occasions, during which either a low or moderate ethanol, acetate, or saline dose was administered. Both ethanol doses similarly inhibited basal glucose production. The decrease in Ra was matched by a comparable decrease in glucose utilization (Rd), resulting in maintenance of normoglycemia. During hyperinsulinemia glucose disposal was lower in the moderate than the low-dose ethanol or saline studies. During acetate infusion, the blood acetate level was comparable with those in the ethanol studies. Acetate had no effect on glucose kinetics. In conclusion, (1) in overnight fasted subjects, ethanol does not cause hypoglycemia because its inhibitory effect on Ra is counterbalanced by equal inhibition of Rd; (2) basal Ra and Rd are maximally inhibited already by small ethanol doses, whereas inhibition of insulin-stimulated glucose disposal requires a moderate ethanol dose; and (3) acetate is not the mediator of ethanol-induced insulin resistance

  10. Acute effects of ethanol and acetate on glucose kinetics in normal subjects

    Yki-Jaervinen, H.; Koivisto, V.A.; Ylikahri, R.; Taskinen, M.R. (Helsinki Univ. and Research Labs. of the Finnish State Alcohol Co. (Finland))

    1988-02-01

    The authors compared the effects of two ethanol doses on glucose kinetics and assessed the role of acetate as a mediator of ethanol-induced insulin resistance. Ten normal males were studied on four occasions, during which either a low or moderate ethanol, acetate, or saline dose was administered. Both ethanol doses similarly inhibited basal glucose production. The decrease in R{sub a} was matched by a comparable decrease in glucose utilization (R{sub d}), resulting in maintenance of normoglycemia. During hyperinsulinemia glucose disposal was lower in the moderate than the low-dose ethanol or saline studies. During acetate infusion, the blood acetate level was comparable with those in the ethanol studies. Acetate had no effect on glucose kinetics. In conclusion, (1) in overnight fasted subjects, ethanol does not cause hypoglycemia because its inhibitory effect on R{sub a} is counterbalanced by equal inhibition of R{sub d}; (2) basal R{sub a} and R{sub d} are maximally inhibited already by small ethanol doses, whereas inhibition of insulin-stimulated glucose disposal requires a moderate ethanol dose; and (3) acetate is not the mediator of ethanol-induced insulin resistance.

  11. Efficacy of recombinant tissue-type plasminogen activator thrombolysis and primary coronary stenting after acute myocardial infarction

    陈步星; 王伟民; 赵红; 胡大一; 徐成斌; 赵明中; 卢明瑜; 刘健; 吴淳

    2003-01-01

    Objective To compare the efficacy of low dose recombinant tissue-type plasminogen activator (rt-PA) thrombolysis with primary coronary stenting after acute myocardial infarction.Methods Of 261 patients with first acute myocardial infarction, 131 were given low dose rt-PA intravenous thrombolysis, and 130 primary coronary stenting.Results The age, time from onset of chest pain to hospital presentation and infarct location between these two groups were comparable. The patency rate of the infarct-related artery (IRA) in patients in the thrombolysis group was significantly lower than that of patients in the primary stenting group (P0.05).Conclusion Comparing with low dose rt-PA thrombolytic therapy after acute myocardial infarction, primary coronary stenting has a higher patency rate of the IRA, better cardiac function and shorter hospitalization time.

  12. Two-dimensional electrophoretogram of acute brain injury-associated proteins Comparison between Injured and normal cerebral cortex

    Xuejun Li; Xianrui Yuan; Cui Li; Zefeng Peng; Dun Yuan

    2008-01-01

    BACKGROUND:To this date,specific molecular markers for early diagnosis and prognosis monitoring ofcraniocerebral injury in clinical medicine do not exist.Therefore,differential detection of specific proteinsmight play an important role in diagnosis and treatment of this type of brain injury.OBJECTIVE:To compare differential cerebral cortical protein expression of craniocerebral injury patientsand normal subjects through the use of proteomics.DESIGN:Contrast observation.SETTING:Department of Neurosurgery,Xiangya Hospital of Central South University.PARTICIPANTS:Ten patients(6 males and 4 females,20-58 years old),with severe craniocerebral injury,were selected at the Department of Neurosurgery,Xiangya Hospital of Central South University,from June2004 to December 2006.All patients were diagnosed with CT test and Glasgow test(scores <8).Surgery was performed 4-12 hours after craniocerebral injury,and injured cortical tissues of the frontal and temporal lobes were resected for sampling.At the same time,control cortical tissues were collected from frontal and temporal lobes of 2 epileptic patients who underwent hippocampus-nucleus amygdala resection,and 2 lateral ventricular tumor patients who underwent tumor resection.The participants and their relatives provided confirmed consent,and this study received confirmed consent from the local ethics committee. METHODS:Ten samples from injured patients and 4 normal samples were compared through the use of proteomics.Total protein was separated by using two-dimensional electrophoresis with immobilized pH gradients,and the differential protein expressions were compared using image analysis after blue-sliver staining. Differential protein spot expressions were analyzed with a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI/TOF MS) and electrospray ionization-quadrupole time of flight mass spectrometry(ESI-Qq TOF MS).MAIN OUTCOME MEASURES: ①Two-dimensional electrophoresis of protein from

  13. Dosimetry of 223Ra-chloride: dose to normal organs and tissues

    223Ra-Chloride (also called Alpharadin registered) targets bone metastases with short range alpha particles. In recent years several clinical trials have been carried out showing, in particular, the safety and efficacy of palliation of painful bone metastases in patients with castration-resistant prostate cancer using 223Ra-chloride. The purpose of this work was to provide a comprehensive dosimetric calculation of organ doses after intravenous administration of 223Ra-chloride according to the present International Commission on Radiological Protection (ICRP) model for radium. Absorbed doses were calculated for 25 organs or tissues. Bone endosteum and red bone marrow show the highest dose coefficients followed by liver, colon and intestines. After a treatment schedule of six intravenous injections with 0.05 MBq/kg of 223Ra-chloride each, corresponding to 21 MBq for a 70 kg patient, the absorbed alpha dose to the bone endosteal cells is about 16 Gy and the corresponding absorbed dose to the red bone marrow is approximately 1.5 Gy. The comprehensive list of dose coefficients presented in this work will assist in comparing and evaluating organ doses from various therapy modalities used in nuclear medicine and will provide a base for further development of patient-specific dosimetry. (orig.)

  14. The expression of Dicer and Drosha in matched normal tissues, tumours and lymph node metastases in triple negative breast cancer

    Breast cancer is the most common malignancy in women world-wide. Triple negative breast cancer (TNBC) is a highly aggressive subtype that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor 2; and is associated with a high propensity for metastatic spread. Several studies have identified critical roles for microRNAs in breast cancer, but the role of two critical enzymes involved in microRNA biogenesis, Dicer and Drosha, is not well understood, particularly with respect to metastatic progression in this subtype. We examined the expression of Dicer and Drosha in a series of invasive 35 TNBCs with matched normal adjacent tissues (n = 18) and lymph node metastases (n = 15) using semi-quantitative real time RT-PCR. The relationship of their expression with clinical features including age at diagnosis, lymph node positivity and tumour size was analysed. We report that Dicer was significantly decreased while Drosha was significantly increased in tumours when compared to normal adjacent tissues. While there was no difference in Drosha expression in lymph node metastases when compared to the primary tumour, Dicer was significantly increased. There was no correlation between the expression of either Dicer or Drosha to age at diagnosis, lymph node positivity and tumour size. In conclusion, Dicer and Drosha are dysregulated in TNBC and matched lymph node metastases however, the clinical relevance of this is still not known. The altered expression of Dicer and Drosha may serve as markers for disrupted miRNA biogenesis in TNBC

  15. Radiotherapy of large target volumes in Hodgkin's lymphoma: normal tissue sparing capability of forward IMRT versus conventional techniques

    Conson Manuel

    2010-05-01

    Full Text Available Abstract Background This paper analyses normal tissue sparing capability of radiation treatment techniques in Hodgkin's lymphoma with large treatment volume. Methods 10 patients with supradiaphragmatic Hodgkin's lymphoma and planning target volume (PTV larger than 900 cm3 were evaluated. Two plans were simulated for each patient using 6 MV X-rays: a conventional multi-leaf (MLC parallel-opposed (AP-PA plan, and the same plan with additional MLC shaped segments (forward planned intensity modulated radiation therapy, FPIMRT. In order to compare plans, dose-volume histograms (DVHs of PTV, lungs, heart, spinal cord, breast, and thyroid were analyzed. The Inhomogeneity Coefficient (IC, the PTV receiving 95% of the prescription dose (V95, the normal tissue complication probability (NTCP and dose-volume parameters for the OARs were determined. Results the PTV coverage was improved (mean V95AP-PA = 95.9 and ICAP-PA = 0.4 vs. V95FPIMRT = 96.8 and ICFPIMRT = 0.31, p ≤ 0.05 by the FPIMRT technique compared to the conventional one. At the same time, NTCPs of lung, spinal cord and thyroid, and the volume of lung and thyroid receiving ≥ 30 Gy resulted significantly reduced when using the FPIMRT technique. Conclusions The FPIMRT technique can represent a very useful and, at the same time, simple method for improving PTV conformity while saving critical organs when large fields are needed as in Hodgkin's lymphoma.

  16. Comparison of the acute effects of hemostatic agents on neural tissues in spine surgery: Histologic analysis in rat models

    Gokhan Meric; Omer Akcali; Serap Cilaker Micili; Alper Bagriyanik

    2016-01-01

    Objective: The most frightening and likely complication of chemical hemostatic agents is neurologic deficit. The histological basis of this potential complication is still unknown. The aim of this study is to observe the acute histologic effects of routinely used hemostatic agents on neural tissues in a rat model. Methods: Eighteen Winstar Albino rats were operated and same-level laminectomies were performed. The rats were divided into three groups. In group 1 (control group), surgical lay...

  17. Intravenous Recombinant Tissue Plasminogen Activator Thrombolysis in a Patient with Acute Ischemic Stroke Secondary to Aortic Dissection

    Hong, Keun-Sik; Park, So-Young; Whang, Seon-Il; Seo, So-Young; Lee, Dong-Ha; Kim, Han-Joon; Cho, Joong-Yang; Cho, Yong-Jin; Jang, Woo-Ik; Kim, Chang Young

    2008-01-01

    Background Acute ischemic stroke secondary to aortic dissection (AoD) is challenging in the era of thrombolysis owing to the diagnostic difficulty within a narrow time window and the high risk of complications. Case Report A 64-year-old woman with middle cerebral artery occlusion syndrome admitted to the emergency room within intravenous recombinant tissue plasminogen activator (rt-PA) time window. Her neurological symptoms improved during thrombolysis, but chest and abdominal pain developed....

  18. Organotypic tissue culture of adult rodent retina followed by particle-mediated acute gene transfer in vitro.

    Satoru Moritoh

    Full Text Available BACKGROUND: Organotypic tissue culture of adult rodent retina with an acute gene transfer that enables the efficient introduction of variable transgenes would greatly facilitate studies into retinas of adult rodents as animal models. However, it has been a difficult challenge to culture adult rodent retina. The purpose of this present study was to develop organotypic tissue culture of adult rodent retina followed by particle-mediated acute gene transfer in vitro. METHODOLOGY/PRINCIPAL FINDINGS: We established an interphase organotypic tissue culture for adult rat retinas (>P35 of age which was optimized from that used for adult rabbit retinas. We implemented three optimizations: a greater volume of Ames' medium (>26 mL per retina, a higher speed (constant 55 rpm of agitation by rotary shaker, and a greater concentration (10% of horse serum in the medium. We also successfully applied this method to adult mouse retina (>P35 of age. The organotypic tissue culture allowed us to keep adult rodent retina morphologically and structurally intact for at least 4 days. However, mouse retinas showed less viability after 4-day culture. Electrophysiologically, ganglion cells in cultured rat retina were able to generate action potentials, but exhibited less reliable light responses. After transfection of EGFP plasmids by particle-mediated acute gene transfer, we observed EGFP-expressing retinal ganglion cells as early as 1 day of culture. We also introduced polarized-targeting fusion proteins such as PSD95-GFP and melanopsin-EYFP (hOPN4-EYFP into rat retinal ganglion cells. These fusion proteins were successfully transferred into appropriate locations on individual retinal neurons. CONCLUSIONS/SIGNIFICANCE: This organotypic culture method is largely applicable to rat retinas, but it can be also applied to mouse retinas with a caveat regarding cell viability. This method is quite flexible for use in acute gene transfection in adult rodent retina, replacing

  19. Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas

    High serum levels of estradiol are associated with increased risk of postmenopausal breast cancer. Little is known about the gene expression in normal breast tissue in relation to levels of circulating serum estradiol. We compared whole genome expression data of breast tissue samples with serum hormone levels using data from 79 healthy women and 64 breast cancer patients. Significance analysis of microarrays (SAM) was used to identify differentially expressed genes and multivariate linear regression was used to identify independent associations. Six genes (SCGB3A1, RSPO1, TLN2, SLITRK4, DCLK1, PTGS1) were found differentially expressed according to serum estradiol levels (FDR = 0). Three of these independently predicted estradiol levels in a multivariate model, as SCGB3A1 (HIN1) and TLN2 were up-regulated and PTGS1 (COX1) was down-regulated in breast samples from women with high serum estradiol. Serum estradiol, but none of the differentially expressed genes were significantly associated with mammographic density, another strong breast cancer risk factor. In breast carcinomas, expression of GREB1 and AREG was associated with serum estradiol in all cancers and in the subgroup of estrogen receptor positive cases. We have identified genes associated with serum estradiol levels in normal breast tissue and in breast carcinomas. SCGB3A1 is a suggested tumor suppressor gene that inhibits cell growth and invasion and is methylated and down-regulated in many epithelial cancers. Our findings indicate this gene as an important inhibitor of breast cell proliferation in healthy women with high estradiol levels. In the breast, this gene is expressed in luminal cells only and is methylated in non-BRCA-related breast cancers. The possibility of a carcinogenic contribution of silencing of this gene for luminal, but not basal-like cancers should be further explored. PTGS1 induces prostaglandin E2 (PGE2) production which in turn stimulates aromatase expression and hence increases the

  20. GENETIC VARIABILITY OF CULTURED PLANT TISSUES UNDER NORMAL CONDITIONS AND UNDER STRESS

    Dolgikh Yu.I.

    2012-08-01

    Full Text Available The genetic variability induced by in vitro conditions known as somaclonal variation is of practical interest due to its potential uses in plant breeding but, on the other hand, if clonal propagation or transformation is main goal, it becomes an unwelcome phenomenon. Thus, it is important to know frequency, the genomic distribution, the mechanisms and factors influencing somaclonal variation. We studied variability of PCR-based DNA markers of cultured tissues and regenerated plants of maize and bread wheat. The original A188 line of maize and the somaclones obtained were tested using 38 RAPD and 10 ISSR primers. None of the A188 plants showed variation in the RAPD and ISSR spectra for any of the primers used. However, the PCR spectra obtained from the somaclones demonstrated some variations, i.e., 22 RAPD primers and 6 ISSR primers differentiated at least one somaclonal variant from the progenitor line. Six SCAR markers were developed based on several RAPD and ISSR fragments. The inheritance of these SCAR markers was verified in the selfing progeny of each somaclone in the R1–R4 generations and in the hybrids, with A188 as the parental line in the F1 and F2 generations. These markers were sequenced and bioinformatic searches were performed to understand the molecular events that may underlie the variability observed in the somaclones. All changes were found in noncoding sequences and were induced by different molecular events, such as the insertion of long terminal repeat transposon, precise miniature inverted repeat transposable element (MITE excision, microdeletion, recombination, and a change in the pool of mitochondrial DNA. In two groups of independently produced somaclones, the same features (morphological, molecular were variable, which confirms the theory of ‘hot spots’ occurring in the genome. The presence of the same molecular markers in the somaclones and in different non-somaclonal maize variants suggests that in some cases

  1. Changes of learning and memory ability associated with neuronal nitric oxide synthase in brain tissues of rats with acute alcoholism

    Shuang Li; Chunyang Xu; Dongliang Li; Xinjuan Li; Linyu Wei; Yuan Cheng

    2006-01-01

    BACKGROUD: Ethanol can influence neural development and the ability of learning and memory, but its mechanism of the neural toxicity is not clear till now. Endogenous nitric oxide (NO) as a gaseous messenger is proved to play an important role in the formation of synaptic plasticity, transference of neuronal information and the neural development, but excessive nitro oxide can result in neurotoxicity.OBJECTIVE: To observe the effects of acute alcoholism on the learning and memory ability and the content of neuronal nitric oxide synthase (nNOS) in brain tissue of rats.DESIGN: A randomized controlled animal experiment.SETTING: Department of Physiology, Xinxiang Medical College.MATERIALS; Eighteen male clean-degree SD rats of 18-22 weeks were raised adaptively for 2 days, and then randomly divided into control group (n = 8) and experimental group (n = 10). The nNOS immunohistochemical reagent was provided by Beijing Zhongshan Golden Bridge Biotechnology Co.,Ltd. Y-maze was produced by Suixi Zhenghua Apparatus Plant.METHODS: The experiment was carried out in the laboratory of the Department of Physiology, Xinxiang Medical College from June to October in 2005. ① Rats in the experimental group were intraperitoneally injected with ethanol (2.5 g/kg) which was dissolved in normal saline (20%). The loss of righting reflex and ataxia within 5 minutes indicated the successful model. Whereas rats in the control group were given saline of the same volume. ② Examinations of learning and memory ability: The Y-maze tests for learning and memory ability were performed at 6 hours after the models establishment. The rats were put into the Y-maze separately. The test was performed in a quiet and dark room. There was a lamp at the end of each of three pathways in Y-maze and the base of maze had electric net. All the lamps of the three pathways were turned on for 3 minutes and then turned off. One lamp was turned on randomly, and the other two delayed automatically. In 5 seconds

  2. Ultrastructural and tissue restructuring of the rat atrial myocardium under the influence of acute and chronic prenatal hypoxia

    Shevchenko K. M.

    2015-09-01

    Full Text Available Background. There are relatively few researches that focused on the study of the influence of hypoxia on atrial myocardium. However the results of previous researches are contradictory and fragmentary, that leades to the further study of this item. Objective. Purpose of the work was to determine the tissue, cellular and ultrastructural changes of the rat atrial myocardium during the stages of cardiogenesis under the conditions of acute and chronic prenatal hypoxia. Methods. Embryo hearts were investigated on 14th, 16th and 18th day of prenatal ontogenesis, newborn rat hearts and the hearts of rats on the 3rd, 14th and 30th day of postnatal ontogenesis. Animals were subdivided into three groups: first experimental group animals were exposed to acute prenatal hypoxia, second experimental group animals were exposed to chronic prenatal hypoxia and control group animals. Hypoxia modeling was conducted on pregnant females by injection of 1% sodium nitrite intraperitonealy in doses that lead to moderate hypoxia. During the work complex of histological, immunohistochemical and morphometric methods was used. Results and conclusion. Effect of acute hypoxia leads to stimulation of proliferative activity of fibroblasts and endothelial cells on the right atrium, which causes to increasing of the relative volume of connective tissue and blood vessels of microvasculature of myocardium. Relative volume of connective tissue of the atrial myocardium exceeds significantly the control level of newborn rats. Ultrastructural changes of the atrial cardiomyocytes in 3 days after the influence of acute prenatal hypoxia reveals on violation of mitochondrial structure, significant inhibition of myofibrils accumulation. Until the birth of most of morphometric parameters renewal and reach control levels, however changes of the degree of myofibrils orientation on the left atrium proves stability of hypoxic damages. Chronic prenatal hypoxia causes a significant increase of

  3. Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues

    Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels. A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS. The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02). Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next logical step is the assessment of whether the aluminum

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

    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)

  5. Evaluation of candidate reference genes for normalization of quantitative RT-PCR in soybean tissues under various abiotic stress conditions.

    Dung Tien Le

    Full Text Available Quantitative RT-PCR can be a very sensitive and powerful technique for measuring differential gene expression. Changes in gene expression induced by abiotic stresses are complex and multifaceted, which make determining stably expressed genes for data normalization difficult. To identify the most suitable reference genes for abiotic stress studies in soybean, 13 candidate genes collected from literature were evaluated for stability of expression under dehydration, high salinity, cold and ABA (abscisic acid treatments using delta CT and geNorm approaches. Validation of reference genes indicated that the best reference genes are tissue- and stress-dependent. With respect to dehydration treatment, the Fbox/ABC, Fbox/60s gene pairs were found to have the highest expression stability in the root and shoot tissues of soybean seedlings, respectively. Fbox and 60s genes are the most suitable reference genes across dehydrated root and shoot tissues. Under salt stress the ELF1b/IDE and Fbox/ELF1b are the most stably expressed gene pairs in roots and shoots, respectively, while 60s/Fbox is the best gene pair in both tissues. For studying cold stress in roots or shoots, IDE/60s and Fbox/Act27 are good reference gene pairs, respectively. With regard to gene expression analysis under ABA treatment in either roots, shoots or across these tissues, 60s/ELF1b, ELF1b/Fbox and 60s/ELF1b are the most suitable reference genes, respectively. The expression of ELF1b/60s, 60s/Fbox and 60s/Fbox genes was most stable in roots, shoots and both tissues, respectively, under various stresses studied. Among the genes tested, 60s was found to be the best reference gene in different tissues and under various stress conditions. The highly ranked reference genes identified from this study were proved to be capable of detecting subtle differences in expression rates that otherwise would be missed if a less stable reference gene was used.

  6. DNA demethylation in normal colon tissue predicts predisposition to multiple cancers.

    Kamiyama, H; Suzuki, K; Maeda, T; Koizumi, K; Miyaki, Y; Okada, S; Kawamura, Y J; Samuelsson, J K; Alonso, S; Konishi, F; Perucho, M

    2012-11-29

    Some colon cancer (CC) patients present synchronous cancers at diagnosis and others develop metachronous neoplasms, but the risk factors are unclear for non-hereditary CC. We showed previously that global DNA demethylation increased with aging and correlated with genomic damage in CC, and we show now that preferentially associates to CCs with wild-type p53. This study aimed to elucidate the extent of DNA hypomethylation in patients with single and multiple CC, its relationship with aging, and its potential as predictive tool. We compared by real-time methylation-specific PCR the relative demethylation level (RDL) of long interspersed nucleotide element-1 (LINE-1) sequences in matched cancer tissues and non-cancerous colonic mucosa (NCM) from patients with single and multiple right-sided CCs. Although no RDL difference was found in NCM from single CC patients and healthy volunteers (P=0.5), there was more demethylation (higher RDL) in NCM from synchronous cancer patients (P=1.1 × 10(-5)) multiple CCs also were more demethylated than single CCs (P=0.0014). High NCM demethylation was predictive for metachronous neoplasms (P=0.003). In multivariate logistic regression analyses RDL was the only independent predictor for metachronous (P=0.02) and multiple (P=4.9 × 10(-5)) tumors. The higher LINE-1 demethylation in NCM from patients with multiple (synchronous and metachronous) tumors (P=9.6 × 10(-7)) was also very significant in patients with tumors without (P=3.8 × 10(-6)), but not with (P=0.16) microsatellite instability. NCM demethylation increased with aging in patients with single tumors, but decreased in those with multiple tumors. Moreover, the demethylation difference between patients with single vs multiple tumors appeared higher in younger (P=3.6 × 10(-4)) than in older (P=0.0016) patients. These results predict that LINE-1 hypomethylation in NCM can be used as an epigenetic predictive biomarker for multiple CC risk. The stronger association of

  7. Protein Profiling of Isolated Leukocytes, Myofibroblasts, Epithelial, Basal, and Endothelial Cells from Normal, Hyperplastic, Cancerous, and Inflammatory Human Prostate Tissues

    Zahraa I. Khamis, Kenneth A. Iczkowski, Ziad J. Sahab, Qing-Xiang Amy Sang

    2010-01-01

    Full Text Available In situ neoplastic prostate cells are not lethal unless they become invasive and metastatic. For cells to become invasive, the prostate gland must undergo degradation of the basement membrane and disruption of the basal cell layer underneath the luminal epithelia. Although the roles of proteinases in breaking down the basement membrane have been well-studied, little is known about the factors that induce basal cell layer disruption, degeneration, and its eventual disappearance in invasive cancer. It is hypothesized that microenvironmental factors may affect the degradation of the basal cell layer, which if protected may prevent tumor progression and invasion. In this study, we have revealed differential protein expression patterns between epithelial and stromal cells isolated from different prostate pathologies and identified several important epithelial and stromal proteins that may contribute to inflammation and malignant transformation of human benign prostate tissues to cancerous tissues using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and proteomics methods. Cellular retinoic acid-binding protein 2 was downregulated in basal cells of benign prsotate. Caspase-1 and interleukin-18 receptor 1 were highly expressed in leukocytes of prostate cancer. Proto-oncogene Wnt-3 was downregulated in endothelial cells of prostatitis tissue and tyrosine phosphatase non receptor type 1 was only found in normal and benign endothelial cells. Poly ADP-ribose polymerase 14 was downregulated in myofibroblasts of prostatitis tissue. Interestingly, integrin alpha-6 was upregulated in epithelial cells but not detected in myofibroblasts of prostate cancer. Further validation of these proteins may generate new strategies for the prevention of basal cell layer disruption and subsequent cancer invasion.

  8. Computer treatment of the contents of some elements in the normal and pathologically altered human colon mucosa tissues obtained by INAA

    Draskovic, R.J.; Bozanic, M.; Bozanic, V.; Bohus, T. (Institut za Nuklearne Nauke Boris Kidric, Belgrade (Yugoslavia))

    1984-11-01

    Distribution of some elements (Cr, Fe, Co, Sb, Sc and Zn) in normal and pathologically altered human colon mucosa tissues were investigated by INAA. The following tissues were analyzed: normal colon mucosa, colitis chronica, colitis ulcerosa, adenoma tubulare and adenocarcinoma (diagnoses were previously confirmed clinically and histopathologically). The values of contents of the elements in these tissues (Csub(x) in nkg/g) are treated by specific computer functional programs. Regression functions of these parameters were found for the altered tissues in comparison to the normal, as well as specific functional correlations of the Csub(x)/Csub(y) relations for pairs of investigated elements. The functions which characterize these relations for the investigated colon mucosa tissue were also determined.

  9. The relationship between hyperuricemia and the risk of contrast-induced acute kidney injury after percutaneous coronary intervention in patients with relatively normal serum creatinine

    Yong Liu

    2013-01-01

    Full Text Available OBJECTIVES: Hyperuricemia is a risk factor for contrast-induced acute kidney injury in patients with chronic kidney disease. This study evaluated the value of hyperuricemia for predicting the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine who were undergoing percutaneous coronary interventions. METHODS AND RESULTS: A total of 788 patients with relatively normal baseline serum creatinine (7 mg/ dL in males and >6 mg/dL in females. The incidence of contrast-induced acute kidney injury was significantly higher in the hyperuricemic group than in the normouricemic group (8.1% vs. 1.4%, p75 years, emergent percutaneous coronary intervention, diuretic usage and the need for an intra-aortic balloon pump. CONCLUSION: Hyperuricemia was significantly associated with the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine after percutaneous coronary interventions. This observation will help to generate hypotheses for further prospective trials examining the effect of uric acid-lowering therapies for preventing contrast-induced acute kidney injury.

  10. Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke

    Olsen, T S; Larsen, B; Herning, M;

    1983-01-01

    infarcted territory. The brain tissue overlying the deep infarcts appeared normal on CT-scan and was supplied by collateral circulation. rCBF was measured in all within 72 hours after the stroke. The intra-carotid Xe-133 injection method and a 254 multidetector camera were used to study rCBF. Relatively...... ischemic low flow areas were a constant finding in the collaterally perfused tissue. In 6 of the patients, the collaterally perfused part of the brain had low flow values comparable to those of an "ischemic penumbra" (viable, but functionally depressed brain tissue due to inadequate perfusion...

  11. Comparison of Radiation-Induced Normal Lung Tissue Density Changes for Patients From Multiple Institutions Receiving Conventional or Hypofractionated Treatments

    Purpose: To quantitatively assess changes in computed tomography (CT)–defined normal lung tissue density after conventional and hypofractionated radiation therapy (RT). Methods and Materials: The pre-RT and post-RT CT scans from 118 and 111 patients receiving conventional and hypofractionated RT, respectively, at 3 institutions were registered to each other and to the 3-dimensional dose distribution to quantify dose-dependent changes in normal lung tissue density. Dose-response curves (DRC) for groups of patients receiving conventional and hypofractionated RT were generated for each institution, and the frequency of density changes >80 Hounsfield Units (HU) was modeled depending on the fractionation type using a Probit model for different follow-up times. Results: For the pooled data from all institutions, there were significant differences in the DRC between the conventional and hypofractionated groups; the respective doses resulting in 50% complication risk (TD50) were 62 Gy (95% confidence interval [CI] 57-67) versus 36 Gy (CI 33-39) at <6 months, 48 Gy (CI 46-51) versus 31 Gy (CI 28-33) at 6-12 months, and 47 Gy (CI 45-49) versus 35 Gy (32-37) at >12 months. The corresponding m values (slope of the DRC) were 0.52 (CI 0.46-0.59) versus 0.31 (CI 0.28-0.34) at <6 months, 0.46 (CI 0.42-0.51) versus 0.30 (CI 0.26-0.34) at 6-12 months, and 0.45 (CI 0.42-0.50) versus 0.31 (CI 0.27-0.35) at >12 months (P<.05 for all comparisons). Conclusion: Compared with conventional fractionation, hypofractionation has a lower TD50 and m value, both suggesting an increased degree of normal tissue density sensitivity with hypofractionation

  12. Doppler Tissue Imaging Assessment of Left Ventricular Systolic Dyssynchrony in Severe Heart Failure Patients With a Normal QRS Duration

    Xiaozhu Chen; Jieting Wang; Suyun Song; Juan Fu; Xinxia Zhang

    2008-01-01

    Objectives To assess the prevalence of systolic dyssynchrony of the left ventricular(LV)wails in patients of heart failure(HF)with a normal QRS duration by Doppler tissue imaging(DTI).Methods 20 patients of HF with a normal QRS duration and 20 healthy individuals were investigated with DTI to quantitatively analyze their pulsed-wave Doppler spectrum of basal and middle segments in six walls of left ventricle.The time between the onset of the QRS complex of the surface ECG and the onset of the systolic wave of pulsed-wave Doppler spectrum was measured(TS).LV systolic synchronization was assessed by the maximal difference(MD)in time of TS,the standard deviation(SD)and the coefficient of variation(CV)of TS in the all 12 LV segments.Results When a TS-MD of TS>53.08 ms,a TS-SD of TS>18.08 ms and a TS-CV of TS>0.91(+1.65 SD of normal controls) was used to define significant systolic dyssynchrony,the prevalence of systolic dyssynchrony was 55.0%,55.0% and 55.0%,respectively,in the HF patients group,significantly gher than those in the normai control and the locations of delayed contraction of these patients were different.Conclusions LV systolic dyssynchrony could be commonly demonstrated by DTI in HF patients with a normal QRS duration.This finding will support the view about the possibility that more HF patients could benefit from cardiac resynchronization therapy.

  13. Metabolism of cytokinins by tissue culture lines of oil palm (Elaeis guineensis Jacq.) producing normal and abnormal flowering palms

    The metabolism of cytokinins in tissue cultures of two oil palm clones previously known to regenerate palms ultimately manifesting normal and abnormal flowering was studied using radiolabeled benzyladenine and isopentenyladenosine, with particular regard to the kinetics of formation of the cytokinin 9-glucoside. Labeled products were separated by high performance liquid chromatography and identified by comparison of retention times with authentic cytokinin standards run immediately before or after the experimental sample. Using benzyladenine, which is insensitive to cytokinin oxidase, ribotide appeared rapidly and then declined. 6-Benzylaminopurine (BA) 9-glucoside quickly became the major soluble product with some formation of riboside. No other ethanol-soluble products were found. Over an incubation period of 24 h up to 30% of label appeared in the ethanol-insoluble fraction. The uptake of label was consistently faster in the normal than the abnormal clone. Dose-rate and time course experiments produced an in vivo asymptotic dose-response curve for the accumulation of BA 9-glucoside analogous to a Michaelis-Menten first-order reaction with a 'V(max)' of 3.5 nmol.g-1.h-1 (on a fresh weight basis) and a 'K(m)' of 0.12 mM. There were no differences between clones in the rate of synthesis. Using isopentenyladenosine, which is susceptible to cytokinin oxidase and cannot be glucosylated without prior deribosylation, a complex pattern of metabolism was seen, with much slower production of 9-glucoside. A number of transient unidentified compounds were seen, together with adenosine and adenine. Comparison of normal and abnormal flowering clones showed striking differences in the kinetics of production of a compound thought to be [9R]Z and in a transient compound eluting at 22 min which accounted for 42% of the radioactivity after a 7-h incubation in the abnormal line. By 17 h there was no difference between normal and abnormal lines in the

  14. Acute shoulder injury with a normal x-ray: a simple algorithm of patient assessment to guide the need for further imaging

    O’Rourke, S

    2012-09-20

    Purpose: Patients presenting to their General Practitioner or to the Emergency Department following an acute shoulder injury but a normal x-ray may have a significant underlying injury to the Rotator Cuff. Imaging (whether by ultrasound or MRI) is often indicated but available clinical evidence has yet to establish what group of patients benefit most from early imaging.\\r\

  15. Histological changes in the normal tissues of rat after local application of the holmium-166 chitosan complex attached to biodegradable solide material

    The aim of this study was to find out a clinically appliable method to insert a biodegradable solid material containing holmium 166-chitosan complex into the surgical field, and to evaluate the histological changes in the normal tissues after irradiation from holmium 166 according to the dose, period and type of tissues

  16. Is the planning dosimetry accurate to estimate the Normal Tissue Complication Probability (NTCP) in case of prostate cancer radiotherapy (RT)?

    The prediction of toxicity is crucial to manage prostate cancer radiotherapy. This prediction is classically based on the dose volume histogram (DVH) calculated at the planning time and using the mathematical Lyman NTCP (Normal Tissue Complication Probability) model. However, anatomical deformations occur during the 8 weeks of radiotherapy and consequently the planned dose does not correspond to the actual delivered dose, leading to uncertainties in NTCP calculation. The objective of this study was to compare the planned DVH-based rectal NTCP with a cumulative DVH-based rectal NTCP, in one case of prostate cancer radiotherapy. The average difference between planning DVH-based NTCP and cumulative-based DVH NTCP was 14% and the standard deviation 10.7%. We showed the impact of organ deformation on NTCP calculation, which leads to significant uncertainties in toxicity prediction. Cumulative DVH, being more representative of the actual received dose, should lead to a more reliable NTCP model

  17. Generation of benchmark DVH's for normal tissues in IMRT for base of tongue and tonsil cancer patients

    IMRT is the treatment of choice for treatment of prostate and H and N cancer treatment but it take quality of time to generate an optima