Immunolocalization of transforming growth factor alpha in normal human tissues

DEFF Research Database (Denmark)

Christensen, M E; Poulsen, Steen Seier

1996-01-01

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

Measurement of human normal tissue and tumour responses

International Nuclear Information System (INIS)

Ross, G.; Yarnold, J.R.

1988-01-01

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

Extravascular transport in normal and tumor tissues.

Science.gov (United States)

Jain, R K; Gerlowski, L E

1986-01-01

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

Computer modeling the boron compound factor in normal brain tissue

International Nuclear Information System (INIS)

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

1993-01-01

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

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

Directory of Open Access Journals (Sweden)

Thorsten Schlomm

2013-03-01

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

Differentiating cancerous from normal breast tissue by redox imaging

Science.gov (United States)

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

2015-02-01

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

T lymphocytes and normal tissue responses to radiation

International Nuclear Information System (INIS)

Schaue, Dörthe; McBride, William H.

2012-01-01

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

Role of endothelium in radiation-induced normal tissue damages

International Nuclear Information System (INIS)

Milliat, F.

2007-05-01

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

Human normal tissue reactions in radiotherapy

International Nuclear Information System (INIS)

Taniike, Keiko

1990-01-01

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

Analytical formulae in fractionated irradiation of normal tissue

International Nuclear Information System (INIS)

Kozubek, S.

1982-01-01

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

Comparative study of radiosensitivity of normal and regenerating tissues

International Nuclear Information System (INIS)

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

1983-01-01

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

Effects of pions on normal tissues

International Nuclear Information System (INIS)

Tokita, N.

1981-01-01

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

DNA Double-Strand Break Rejoining in Complex Normal Tissues

International Nuclear Information System (INIS)

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

2008-01-01

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

β class II tubulin predominates in normal and tumor breast tissues

International Nuclear Information System (INIS)

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

2003-01-01

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

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

Directory of Open Access Journals (Sweden)

Tozeren Aydin

2006-11-01

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

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

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

2015-10-15

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Radiosensitization effects of nicotinamide on malignant and normal mouse tissue

International Nuclear Information System (INIS)

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

1985-01-01

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

Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

International Nuclear Information System (INIS)

Bentzen, Soeren M.

1997-01-01

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 SF 2 . 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 SF 2 . 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

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

Science.gov (United States)

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

2014-01-01

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

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

Science.gov (United States)

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

2014-04-16

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

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

International Nuclear Information System (INIS)

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

2000-01-01

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

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

International Nuclear Information System (INIS)

Yeoh, E.K.

2011-01-01

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

Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

Science.gov (United States)

Li, Li; Xie, Wengming; Li, Hui

2012-12-01

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

Speech pattern improvement following gingivectomy of excess palatal tissue.

Science.gov (United States)

Holtzclaw, Dan; Toscano, Nicholas

2008-10-01

Speech disruption secondary to excessive gingival tissue has received scant attention in periodontal literature. Although a few articles have addressed the causes of this condition, documentation and scientific explanation of treatment outcomes are virtually non-existent. This case report describes speech pattern improvements secondary to periodontal surgery and provides a concise review of linguistic and phonetic literature pertinent to the case. A 21-year-old white female with a history of gingival abscesses secondary to excessive palatal tissue presented for treatment. Bilateral gingivectomies of palatal tissues were performed with inverse bevel incisions extending distally from teeth #5 and #12 to the maxillary tuberosities, and large wedges of epithelium/connective tissue were excised. Within the first month of the surgery, the patient noted "changes in the manner in which her tongue contacted the roof of her mouth" and "changes in her speech." Further anecdotal investigation revealed the patient's enunciation of sounds such as "s," "sh," and "k" was greatly improved following the gingivectomy procedure. Palatometric research clearly demonstrates that the tongue has intimate contact with the lateral aspects of the posterior palate during speech. Gingival excess in this and other palatal locations has the potential to alter linguopalatal contact patterns and disrupt normal speech patterns. Surgical correction of this condition via excisional procedures may improve linguopalatal contact patterns which, in turn, may lead to improved patient speech.

Statistical validation of normal tissue complication probability models

NARCIS (Netherlands)

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

2012-01-01

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

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

International Nuclear Information System (INIS)

Cohen, L.; Creditor, M.

1983-01-01

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

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

Science.gov (United States)

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

1998-01-01

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

Evaluation of normal tissue responses to high-LET radiations

International Nuclear Information System (INIS)

Halnan, K.E.

1979-01-01

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

MRI appearance of radiation-induced changes of normal cervical tissues

International Nuclear Information System (INIS)

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

2001-01-01

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

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

Science.gov (United States)

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

2011-12-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1996-08-01

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

High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

International Nuclear Information System (INIS)

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

2012-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1996-08-01

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

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

International Nuclear Information System (INIS)

Constine, L; Hodgson, D; Bentzen, S

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-06-15

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

Optical redox imaging indices discriminate human breast cancer from normal tissues

Science.gov (United States)

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

2016-01-01

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

Morphologic alterations in normal and neoplastic tissues following hyperthermia treatment

International Nuclear Information System (INIS)

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

1984-01-01

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

Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo

International Nuclear Information System (INIS)

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

2009-01-01

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

Modification of the biologic dose to normal tissue by daily fraction

Energy Technology Data Exchange (ETDEWEB)

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

1976-12-01

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

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

Directory of Open Access Journals (Sweden)

Ben-Zhou Feng

2016-04-01

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

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

Science.gov (United States)

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

2013-07-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-15

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

DEFF Research Database (Denmark)

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

2017-01-01

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

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

Science.gov (United States)

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

2013-04-23

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

Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

Energy Technology Data Exchange (ETDEWEB)

D. W. Nigg

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

Tumor blood vessel 'normalization' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

International Nuclear Information System (INIS)

Nigg, D.W.

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

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

International Nuclear Information System (INIS)

Ai, H; Zhang, H

2014-01-01

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

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

Directory of Open Access Journals (Sweden)

Jun Zhang

2015-01-01

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

Radioprotection of normal tissues in tumor-bearing mice by troxerutin

International Nuclear Information System (INIS)

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

2004-01-01

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

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

Science.gov (United States)

Hoffmann, Aswin L; Nahum, Alan E

2013-10-07

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

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

International Nuclear Information System (INIS)

Yap, YeeLeng; Zhang, XueWu; Ling, MT; Wang, XiangHong; Wong, YC; Danchin, Antoine

2004-01-01

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

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

International Nuclear Information System (INIS)

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

1984-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-07-15

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

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

Science.gov (United States)

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

2014-06-01

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

Radioprotection of normal tissues of the mouse by hypoxic breathing

International Nuclear Information System (INIS)

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

1989-01-01

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

Normal tissue complication probability for salivary glands

International Nuclear Information System (INIS)

Rana, B.S.

2008-01-01

The purpose of radiotherapy is to make a profitable balance between the morbidity (due to side effects of radiation) and cure of malignancy. To achieve this, one needs to know the relation between NTCP (normal tissue complication probability) and various treatment variables of a schedule viz. daily dose, duration of treatment, total dose and fractionation along with tissue conditions. Prospective studies require that a large number of patients be treated with varied schedule parameters and a statistically acceptable number of patients develop complications so that a true relation between NTCP and a particular variable is established. In this study Salivary Glands Complications have been considered. The cases treated in 60 Co teletherapy machine during the period 1994 to 2002 were analyzed and the clinicians judgement in ascertaining the end points was the only means of observations. The only end points were early and late xerestomia which were considered for NTCP evaluations for a period of 5 years

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

International Nuclear Information System (INIS)

Plevova, P.

2002-01-01

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

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

International Nuclear Information System (INIS)

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

1988-01-01

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

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

International Nuclear Information System (INIS)

Rahman, S.

2012-01-01

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

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

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

2013-01-01

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

Genetic markers for prediction of normal tissue toxicity after radiotherapy

DEFF Research Database (Denmark)

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

2008-01-01

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

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

International Nuclear Information System (INIS)

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

1978-01-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

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

International Nuclear Information System (INIS)

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

1982-01-01

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

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

International Nuclear Information System (INIS)

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

2003-01-01

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

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

Science.gov (United States)

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

2012-12-13

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

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Wenyan Hu

Full Text Available BACKGROUND: Pancreatic cancer is a lethal disease with a 5-year survival rate of only 1-5%. The acceleration of intraoperative histological examination would be beneficial for better management of pancreatic cancer, suggesting an improved survival. Nonlinear optical methods based on two-photon excited fluorescence (TPEF and second harmonic generation (SHG of intrinsic optical biomarkers show the ability to visualize the morphology of fresh tissues associated with histology, which is promising for real-time intraoperative evaluation of pancreatic cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate whether the nonlinear optical imaging methods have the ability to characterize pancreatic histology at cellular resolution, we studied different types of pancreatic tissues by using label-free TPEF and SHG. Compared with other routine methods for the preparation of specimens, fresh tissues without processing were found to be most suitable for nonlinear optical imaging of pancreatic tissues. The detailed morphology of the normal rat pancreas was observed and related with the standard histological images. Comparatively speaking, the preliminary images of a small number of chemical-induced pancreatic cancer tissues showed visible neoplastic differences in the morphology of cells and extracellular matrix. The subcutaneous pancreatic tumor xenografts were further observed using the nonlinear optical microscopy, showing that most cells are leucocytes at 5 days after implantation, the tumor cells begin to proliferate at 10 days after implantation, and the extracellular collagen fibers become disordered as the xenografts grow. CONCLUSIONS/SIGNIFICANCE: In this study, nonlinear optical imaging was used to characterize the morphological details of fresh pancreatic tissues for the first time. We demonstrate that it is possible to provide real-time histological evaluation of pancreatic cancer by the nonlinear optical methods, which present an

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

Science.gov (United States)

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

2014-04-01

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

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

Science.gov (United States)

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

2014-01-01

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

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

International Nuclear Information System (INIS)

Withers, H.R.

1975-01-01

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

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

International Nuclear Information System (INIS)

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

1997-01-01

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

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

NARCIS (Netherlands)

Broerse, J.J.

1974-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-11-15

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

Mathematical model of normal tissue injury in telegammatherapy

International Nuclear Information System (INIS)

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

1983-01-01

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

Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy

International Nuclear Information System (INIS)

Hendry, Jolyon H.

2001-01-01

, particularly gene polymorphisms, or other low penetrant gene mutations, contribute to the recognized spectrum of normal tissue radiosensitivity amongst cancer patients, or in the general population. Tests for such genetic modifications may help in the search for more accurate prognostic markers of response, which hopefully could be used in addition to other strategies to further improve the outcome for cancer patients given radiotherapy

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

International Nuclear Information System (INIS)

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

1983-01-01

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

Mathematical models of tumour and normal tissue response

International Nuclear Information System (INIS)

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

1999-01-01

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

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

International Nuclear Information System (INIS)

Maase, H. van der

1986-01-01

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-07-01

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

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

Science.gov (United States)

Samani, Abbas; Zubovits, Judit; Plewes, Donald

2007-03-01

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

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

International Nuclear Information System (INIS)

Samani, Abbas; Zubovits, Judit; Plewes, Donald

2007-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-03-21

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

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

Science.gov (United States)

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

2007-05-21

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

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Directory of Open Access Journals (Sweden)

Knüchel Ruth

2008-05-01

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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

Science.gov (United States)

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

2014-04-01

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

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

Science.gov (United States)

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

2014-01-01

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

Local stem cell depletion model for normal tissue damage

International Nuclear Information System (INIS)

Yaes, R.J.; Keland, A.

1987-01-01

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

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

Directory of Open Access Journals (Sweden)

Emara Marwan

2010-09-01

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

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

NARCIS (Netherlands)

van Oorschot, B.

2016-01-01

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

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

International Nuclear Information System (INIS)

Begnozzi, L.; Gentile, F.P.; Di Nallo, A.M.; Chiatti, L.; Zicari, C.; Consorti, R.; Benassi, M.

1994-01-01

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.) [de

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

International Nuclear Information System (INIS)

Barendsen, G.W.

1982-01-01

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

Science.gov (United States)

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

2007-01-01

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

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

International Nuclear Information System (INIS)

Suga, Kazuyoshi

1986-01-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Repair in normal tissues and the possible relevance to radiotherapy

International Nuclear Information System (INIS)

Field, S.B.; Hornsey, S.

1977-01-01

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

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

Science.gov (United States)

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

2012-06-01

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

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

Science.gov (United States)

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

2017-07-10

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

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

Directory of Open Access Journals (Sweden)

Michelle A.C. Reed

2017-03-01

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

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

International Nuclear Information System (INIS)

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

1991-01-01

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

Does bariatric surgery improve adipose tissue function?

Science.gov (United States)

Frikke-Schmidt, H.; O’Rourke, R. W.; Lumeng, C. N.; Sandoval, D. A.; Seeley, R. J.

2017-01-01

Summary Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. PMID:27272117

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-10-21

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

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

Science.gov (United States)

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

2007-10-01

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

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

International Nuclear Information System (INIS)

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

2000-01-01

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

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

Science.gov (United States)

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

2018-02-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

International Nuclear Information System (INIS)

Kagiya, Tsutomu

2006-01-01

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

The use of normal tissue complication probability to predict radiation hepatitis

International Nuclear Information System (INIS)

Keum, Ki Chang; Seong, Jin Sil; Suh, Chang Ok; Lee, Sang Wook; Chung, Eun Ji; Shin, Hyun Soo; Kim, Gwi Eon

2000-01-01

Although it has been known that the tolerance of the liver to external beam irradiation depends on the irradiated volume and dose, few data exist which quantify this dependence. However, recently, with the development of three dimensional (3-D) treatment planning, have the tools to quantify the relationships between dose, volume, and normal tissue complications become available. The objective of this study is to investigate the relationships between normal tissue complication probability (NTCP) and the risk of radiation hepatitis for patients who received variant dose partial liver irradiation. From March 1992 to December 1994, 10 patients with hepatoma and 10 patients with bile duct cancer were included in this study. Eighteen patients had normal hepatic function, but 2 patients (prothrombin time 73%, 68%) had mild liver cirrhosis before irradiation. Radiation therapy was delivered with 10MV linear accelerator, 180-200 cGy fraction per day. The total dose ranged from 3,960 cGy to 6,000 cGy (median dose 5,040 cGy). The normal tissue complication probability was calculated by using Lyman's model. Radiation hepatitis was defined as the development of anicteric elevation of alkaline phosphatase of at least two fold and non-malignant ascites in the absence of documented progressive. The calculated NTCP ranged from 0.001 to 0.840 (median 0.05). Three of the 20 patients developed radiation hepatitis. The NTCP of the patients with radiation hepatitis were 0.390, 0.528, 0.844 (median: O.58±0.23), but that of the patients without radiation hepatitis ranged from 0.001 to 0.308 (median: 0.09±0.09). When the NTCP was calculated by using the volume factor of 0.32, a radiation hepatitis was observed only in patients with the NTCP value more than 0.39. By contrast, clinical results of evolving radiation hepatitis were not well correlated with NTCP value calculated when the volume factor of 0.69 was applied. On the basis of these observations, volume factor of 0.32 was more

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-01-01

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

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

Science.gov (United States)

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 effect was improved cerebral tissue PtiO2 during acute hypoxia [11.4 (2.7) (hypoxia) to 16.5 (3.0) mmHg (hypoxia + acetazolamide), P 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. Copyright © 2015 the American Physiological Society.

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

Directory of Open Access Journals (Sweden)

Zora Djuric

2017-08-01

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

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

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

1993-04-01

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

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

Science.gov (United States)

Tong, Y; Lin, Y

2001-06-01

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

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

Directory of Open Access Journals (Sweden)

Ana Paula Cleto Marolla

2016-01-01

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

A method for normalizing pathology images to improve feature extraction for quantitative pathology

International Nuclear Information System (INIS)

Tam, Allison; Barker, Jocelyn; Rubin, Daniel

2016-01-01

Purpose: With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. Methods: To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology images by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. Results: The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. Conclusions: ICHE may be a useful preprocessing step a digital pathology image processing pipeline

A method for normalizing pathology images to improve feature extraction for quantitative pathology

Energy Technology Data Exchange (ETDEWEB)

Tam, Allison [Stanford Institutes of Medical Research Program, Stanford University School of Medicine, Stanford, California 94305 (United States); Barker, Jocelyn [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 (United States); Rubin, Daniel [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 and Department of Medicine (Biomedical Informatics Research), Stanford University School of Medicine, Stanford, California 94305 (United States)

2016-01-15

Purpose: With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. Methods: To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology images by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. Results: The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. Conclusions: ICHE may be a useful preprocessing step a digital pathology image processing pipeline.

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-07-15

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Mineral density volume gradients in normal and diseased human tissues.

Directory of Open Access Journals (Sweden)

Sabra I Djomehri

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

Mineral Density Volume Gradients in Normal and Diseased Human Tissues

Science.gov (United States)

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

2015-01-01

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

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

DEFF Research Database (Denmark)

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

2009-01-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Science.gov (United States)

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

2007-08-01

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

Statistical validation of normal tissue complication probability models.

Science.gov (United States)

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

2012-09-01

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. 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. 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. Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use. Copyright © 2012 Elsevier Inc. All rights reserved.

Statistical Validation of Normal Tissue Complication Probability Models

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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.

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

International Nuclear Information System (INIS)

Michalowski, A.S.

1994-01-01

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

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

International Nuclear Information System (INIS)

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

1998-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1998-08-01

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

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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

Science.gov (United States)

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

2011-01-01

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

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

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Adel Spotin

2012-04-01

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

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

1991-01-01

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

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

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

2015-06-15

improve predictions of normal tissue morbidity.

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

International Nuclear Information System (INIS)

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

2008-01-01

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

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

International Nuclear Information System (INIS)

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

1997-01-01

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

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

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

2015-01-01

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

Anatomy, normal variants, and basic biomechanics

International Nuclear Information System (INIS)

Berquist, T.H.; Johnson, K.A.

1989-01-01

This paper reports on the anatomy and basic functions of the foot and ankle important to physicians involved in imaging procedures, clinical medicine, and surgery. New radiographic techniques especially magnetic resonance imaging, provide more diagnostic information owing to improved tissue contrast and the ability to obtain multiple image planes (axial, sagittal, coronal, oblique). Therefore, a thorough knowledge of skeletal and soft tissue anatomy is even more essential. Normal variants must also be understood in order to distinguish normal from pathologic changes in the foot and ankle. A basic understanding of biomechanics is also essential for selecting the proper diagnostic techniques

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

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Arpita Chatterjee

2018-01-01

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

Immunohistochemical Expression of FXR1 in Canine Normal Tissues and Melanomas.

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

2018-04-01

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

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

International Nuclear Information System (INIS)

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

1988-01-01

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

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

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

2014-02-15

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

International Nuclear Information System (INIS)

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

1998-01-01

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

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

International Nuclear Information System (INIS)

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

2001-01-01

Purpose: Intensity-modulated radiotherapy (IMRT) is being evaluated in the management of head-and-neck cancers at several institutions, and a Radiation Therapy Oncology Group study of its utility in parotid sparing is under development. There is an inherent risk that the sharper dose gradients generated by IMRT amplify the potentially detrimental impact of setup uncertainty. The International Commission on Radiation Units and Measurements Report 62 (ICRU-62) defined planning organ-at-risk volume (PRV) to account for positional uncertainties for normal tissues. The purpose of this study is to quantify the dosimetric effect of employing PRV for the parotid gland and to evaluate the use of PRV on normal-tissue sparing in the setting of small clinical setup errors. Methods and Materials: The optimized nine-beam IMRT plans for three head-and-neck cancer patients participating in an institutional review board approved parotid-sparing protocol were used as reference plans. A second optimized plan was generated for each patient by adding a PRV of 5 mm for the contralateral parotid gland. The effect of these additions on the quality of the plans was quantified, in terms of both target coverage and normal-tissue sparing. To test the value of PRV in a worst-case scenario, systematic translational setup uncertainties were simulated by shifting the treatment isocenter 5 mm superiorly, inferiorly, left, right, anteriorly, and posteriorly, without altering optimized beam profiles. At each shifted isocenter, dose distributions were recalculated, producing a total of six shifted plans without PRV and six shifted plans with PRV for each patient. The effect of setup uncertainty on parotid sparing and the value of PRV in compensating for the uncertainty were evaluated. Results: The addition of the PRV and reoptimization did not significantly affect the dose to gross tumor volume, spinal cord, or brainstem. In contrast, without any shift, the PRV did increase parotid sparing and reduce

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

Institute of Scientific and Technical Information of China (English)

Ya-Fei Zhang

2015-01-01

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

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

Science.gov (United States)

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

2017-09-01

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

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

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Xiaoli Zhang

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

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

Science.gov (United States)

Nerlich, A

1995-01-01

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

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

Science.gov (United States)

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

2015-04-01

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

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

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

2016-09-01

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

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

International Nuclear Information System (INIS)

Mossman, K.L.

1982-01-01

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

68Ga-DOTATOC PET/CT and somatostatin receptor (sst1-sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax

International Nuclear Information System (INIS)

Boy, Christian; Poeppel, Thorsten D.; Jentzen, Walter; Brandau, Wolfgang; Bockisch, Andreas; Heusner, Till A.; Antoch, Gerald; Redmann-Bischofs, Anja; Unger, Nicole; Mann, Klaus; Petersenn, Stephan

2011-01-01

By targeting somatostatin receptors (sst) radiopeptides have been established for both diagnosis and therapy. For physiologically normal human tissues the study provides a normative database of maximum standardized uptake value (SUV max ) and sst mRNA. A total of 120 patients were subjected to diagnostic 68 Ga-DOTATOC positron emission tomography (PET)/CT (age range 19-83 years). SUV max values were measured in physiologically normal tissues defined by normal morphology, absence of surgical intervention and absence of metastatic spread during clinical follow-up. Expression of sst subtypes (sst1-sst5) was measured independently in pooled adult normal human tissue by real-time reverse transcriptase polymerase chain reaction (RT-PCR). SUV max revealed a region-specific pattern (e.g., mean ± SD, spleen 31.1 ± 10.9, kidney 16.9 ± 5.3, liver 12.8 ± 3.6, stomach 7.0 ± 3.1, head of pancreas 6.2 ± 2.3, small bowel 4.8 ± 1.8, thyroid 4.7 ± 2.2, bone 3.9 ± 1.3, large bowel 2.9 ± 0.8, muscle 2.1 ± 0.5, parotid gland 1.9 ± 0.6, axillary lymph node 0.8 ± 0.3 and lung 0.7 ± 0.3). SUV max was age independent. Gender differences were evident within the thyroid (female/male: 3.7 ± 1.6/5.5 ± 2.4, p max values exclusively correlated with sst2 expression (r = 0.846, p max with the expression of the other four subtypes. In normal human tissues 68 Ga-DOTATOC imaging has been related to the expression of sst2 at the level of mRNA. The novel normative database may improve diagnostics, monitoring and therapy of sst-expressing tumours or inflammation on a molecular basis. (orig.)

Polydeoxyribonucleotide Improves Peripheral Tissue Oxygenation and Accelerates Angiogenesis in Diabetic Foot Ulcers

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Seoyoung Kim

2017-11-01

Full Text Available Background Polydeoxyribonucleotide (PDRN is known to have anti-inflammatory and angiogenic effects and to accelerate wound healing. The aim of this study was to investigate whether PDRN could improve peripheral tissue oxygenation and angiogenesis in diabetic foot ulcers. Methods This was a prospective randomized controlled clinical trial. Twenty patients with a non-healing diabetic foot ulcer were randomly distributed into a control group (n=10 and a PDRN group (n=10. Initial surgical debridement and secondary surgical procedures such as a split-thickness skin graft, primary closure, or local flap were performed. Between the initial surgical debridement and secondary surgical procedures, 0.9% normal saline (3 mL or PDRN was injected for 2 weeks by the intramuscular (1 ampule, 3 mL, 5.625 mg, 5 days per week and perilesional routes (1 ampule, 3 mL, 5.625 mg, 2 days per week. Transcutaneous oxygen tension (TcPO2 was evaluated using the Periflux System 5000 with TcPO2/CO2 unit 5040 before the injections and on days 1, 3, 7, 14, and 28 after the start of the injections. A pathologic review (hematoxylin and eosin stain of the debrided specimens was conducted by a pathologist, and vessel density (average number of vessels per visual field was calculated. Results Compared with the control group, the PDRN-treated group showed improvements in peripheral tissue oxygenation on day 7 (P<0.01, day 14 (P<0.001, and day 28 (P<0.001. The pathologic review of the specimens from the PDRN group showed increased angiogenesis and improved inflammation compared with the control group. No statistically significant difference was found between the control group and the PDRN group in terms of vessel density (P=0.094. Complete healing was achieved in every patient. Conclusions In this study, PDRN improved peripheral tissue oxygenation. Moreover, PDRN is thought to be effective in improving inflammation and angiogenesis in diabetic foot ulcers.

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

Science.gov (United States)

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

2015-01-01

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

Differentiation of prostate cancer from normal prostate tissue in an animal model: conventional MRI and dynamic contrast-enhanced MRI

International Nuclear Information System (INIS)

Gemeinhardt, O.; Prochnow, D.; Taupitz, M.; Hamm, B.; Beyersdorff, D.; Luedemann, L.; Abramjuk, C.

2005-01-01

Purpose: to differentiate orthotopically implanted prostate cancer from normal prostate tissue using magnetic resonance imaging (MRI) and Gd-DTPA-BMA-enhanced dynamic MRI in the rat model. Material and methods: tumors were induced in 15 rats by orthotopic implantation of G subline Dunning rat prostatic tumor cells. MRI was performed 56 to 60 days after tumor cell implantation using T1-weighted spin-echo, T2-weighted turbo SE sequences, and a 2D FLASH sequence for the contrast medium based dynamic study. The interstitial leakage volume, normalized permeability and the permeability surface area product of tumor and healthy prostate were determined quantitatively using a pharmacokinetic model. The results were confirmed by histologic examination. Results: axial T2-weighted TSE images depicted low-intensity areas suspicious for tumor in all 15 animals. The mean tumor volume was 46.5 mm3. In the dynamic study, the suspicious areas in all animals displayed faster and more pronounced signal enhancement than surrounding prostate tissue. The interstitial volume and the permeability surface area product of the tumors increased significantly by 420% (p<0.001) and 424% (p<0.001), respectively, compared to normal prostate tissue, while no significant difference was seen for normalized permeability alone. Conclusion: the results of the present study demonstrate that quantitative analysis of contrast-enhanced dynamic MRI data enables differentiation of small, slowly growing orthotopic prostate cancer from normal prostate tissue in the rat model. (orig.)

The claudin gene family: expression in normal and neoplastic tissues

International Nuclear Information System (INIS)

Hewitt, Kyle J; Agarwal, Rachana; Morin, Patrice J

2006-01-01

The claudin (CLDN) genes encode a family of proteins important in tight junction formation and function. Recently, it has become apparent that CLDN gene expression is frequently altered in several human cancers. However, the exact patterns of CLDN expression in various cancers is unknown, as only a limited number of CLDN genes have been investigated in a few tumors. We identified all the human CLDN genes from Genbank and we used the large public SAGE database to ascertain the gene expression of all 21 CLDN in 266 normal and neoplastic tissues. Using real-time RT-PCR, we also surveyed a subset of 13 CLDN genes in 24 normal and 24 neoplastic tissues. We show that claudins represent a family of highly related proteins, with claudin-16, and -23 being the most different from the others. From in silico analysis and RT-PCR data, we find that most claudin genes appear decreased in cancer, while CLDN3, CLDN4, and CLDN7 are elevated in several malignancies such as those originating from the pancreas, bladder, thyroid, fallopian tubes, ovary, stomach, colon, breast, uterus, and the prostate. Interestingly, CLDN5 is highly expressed in vascular endothelial cells, providing a possible target for antiangiogenic therapy. CLDN18 might represent a biomarker for gastric cancer. Our study confirms previously known CLDN gene expression patterns and identifies new ones, which may have applications in the detection, prognosis and therapy of several human cancers. In particular we identify several malignancies that express CLDN3 and CLDN4. These cancers may represent ideal candidates for a novel therapy being developed based on CPE, a toxin that specifically binds claudin-3 and claudin-4

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

Energy Technology Data Exchange (ETDEWEB)

Rubin, Philip; Constine, Louis S. [Univ. Rochester Medical Center, NY (United States). Dept. of Radiation Oncology; Marks, Lawrence B. (ed.) [Univ. North Carolina and Lineberger, Comprehensive Cancer Center, Chapel Hill, NC (United States). Dept. of Radiation Oncology

2014-09-01

Comprehensively documents potential late effects in all the normal tissue sites in the human body. Considers in detail the detection, diagnosis, management and prevention of effects and discusses prognostic outcomes. Clearly presents radiation risk factors and interactions with chemotherapy effects. Provides the most current evidence-based medicine for cancer care survivorship guidelines. The literature on the late effects of cancer treatment is widely scattered in different journals since all major organ systems are affected and management is based on a variety of medical and surgical treatments. The aim of ALERT - Adverse Late Effects of Cancer Treatment is to offer a coherent multidisciplinary approach to the care of cancer survivors. The central paradigm is that cytotoxic multimodal therapy results in a perpetual cascade of events that affects each major organ system differently and is expressed continually over time. Essentially, radiation and chemotherapy are intense biologic modifiers that allow for cancer cure and cancer survivorship but accelerate senescence of normal tissues and increase the incidence of age-related diseases and second malignant tumors. Volume 2 of this two-volume work comprehensively documents potential late effects in all the normal tissue anatomic sites in the human body. The detection, diagnosis, management and prevention of effects are all considered in detail, and prognostic outcomes are discussed. Radiation risk factors and interactions with chemotherapy effects are clearly presented. The text is accompanied by numerous supportive illustrations and tables.

Apparent diffusion coefficient of breast cancer and normal fibroglandular tissue in diffusion-weighted imaging: the effects of menstrual cycle and menopausal status.

Science.gov (United States)

Kim, Jin You; Suh, Hie Bum; Kang, Hyun Jung; Shin, Jong Ki; Choo, Ki Seok; Nam, Kyung Jin; Lee, Seok Won; Jung, Young Lae; Bae, Young Tae

2016-05-01

The purpose of this study was to investigate prospectively whether the apparent diffusion coefficients (ADCs) of both breast cancer and normal fibroglandular tissue vary with the menstrual cycle and menopausal status. Institutional review board approval was obtained, and informed consent was obtained from each participant. Fifty-seven women (29 premenopausal, 28 postmenopausal) with newly diagnosed breast cancer underwent diffusion-weighted imaging twice (interval 12-20 days) before surgery. Two radiologists independently measured ADC of breast cancer and normal contralateral breast tissue, and we quantified the differences according to the phases of menstrual cycle and menopausal status. With normal fibroglandular tissue, ADC was significantly lower in postmenopausal than in premenopausal women (P = 0.035). In premenopausal women, ADC did not differ significantly between proliferative and secretory phases in either breast cancer or normal fibroglandular tissue (P = 0.969 and P = 0.519, respectively). In postmenopausal women, no significant differences were found between ADCs measured at different time intervals in either breast cancer or normal fibroglandular tissue (P = 0.948 and P = 0.961, respectively). The within-subject variability of the ADC measurements was quantified using the coefficient of variation (CV) and was small: the mean CVs of tumor ADC were 2.90 % (premenopausal) and 3.43 % (postmenopausal), and those of fibroglandular tissue ADC were 4.37 % (premenopausal) and 2.55 % (postmenopausal). Both intra- and interobserver agreements were excellent for ADC measurements, with intraclass correlation coefficients in the range of 0.834-0.974. In conclusion, the measured ADCs of breast cancer and normal fibroglandular tissue were not affected significantly by menstrual cycle, and the measurements were highly reproducible both within and between observers.

2-deoxyglucose tissue levels and insulin levels following tolazamide dosing in normal and obese mice

International Nuclear Information System (INIS)

Skillman, C.A.; Fletcher, H.P.

1986-01-01

The effect of tolazamide (TZ), a sulfonylurea, on 14 C-2-deoxyglucose ( 14 C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased 14 C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased 14 C-2DG levels in muscle and fat. The results demonstrate that the in vivo 14 C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated 14 C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing 14 C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on 14 C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable mice may be resistant to subchronic treatment with TZ. (author)

Human BLCAP transcript: new editing events in normal and cancerous tissues.

Science.gov (United States)

Galeano, Federica; Leroy, Anne; Rossetti, Claudia; Gromova, Irina; Gautier, Philippe; Keegan, Liam P; Massimi, Luca; Di Rocco, Concezio; O'Connell, Mary A; Gallo, Angela

2010-07-01

Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing events. Some of the new editing events alter the highly conserved amino terminus of the protein creating alternative protein isoforms by changing the genetically coded amino acids. We found that both ADAR1 and ADAR2-editing enzymes cooperate to edit this transcript and that different tissues displayed distinctive ratios of edited and unedited BLCAP transcripts. Moreover, we observed a general decrease in BLCAP-editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues. The newly identified editing events, found to be downregulated in cancers, could be useful for future studies as a diagnostic tool to distinguish malignancies or epigenetic changes in different tumors.

Identification of the boundary between normal breast tissue and invasive ductal carcinoma during breast-conserving surgery using multiphoton microscopy

Science.gov (United States)

Deng, Tongxin; Nie, Yuting; Lian, Yuane; Wu, Yan; Fu, Fangmeng; Wang, Chuan; Zhuo, Shuangmu; Chen, Jianxin

2014-11-01

Breast-conserving surgery has become an important way of surgical treatment for breast cancer worldwide nowadays. Multiphoton microscopy (MPM) has the ability to noninvasively visualize tissue architectures at the cellular level using intrinsic fluorescent molecules in biological tissues without the need for fluorescent dye. In this study, MPM is used to image the microstructures of terminal duct lobular unit (TDLU), invasive ductal carcinoma and the boundary region between normal and cancerous breast tissues. Our study demonstrates that MPM has the ability to not only reveal the morphological changes of the cuboidal epithelium, basement membrane and interlobular stroma but also identify the boundary between normal breast tissue and invasive ductal carcinoma, which correspond well to the Hematoxylin and Eosin (H and E) images. Predictably, MPM can monitor surgical margins in real time and provide considerable accuracy for resection of breast cancerous tissues intraoperatively. With the development of miniature, real-time MPM imaging technology, MPM should have great application prospects during breast-conserving surgery.

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

DEFF Research Database (Denmark)

Rønjom, Marianne Feen; Brink, Carsten; Bentzen, Søren

2013-01-01

To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors.......To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors....

Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa.

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Valeria Musella

Full Text Available BACKGROUND: Genome-wide gene expression analyses of tumors are a powerful tool to identify gene signatures associated with biologically and clinically relevant characteristics and for several tumor types are under clinical validation by prospective trials. However, handling and processing of clinical specimens may significantly affect the molecular data obtained from their analysis. We studied the effects of tissue handling time on gene expression in human normal and tumor colon tissues undergoing routine surgical procedures. METHODS: RNA extracted from specimens of 15 patients at four time points (for a total of 180 samples after surgery was analyzed for gene expression on high-density oligonucleotide microarrays. A mixed-effects model was used to identify probes with different expression means across the four different time points. The p-values of the model were adjusted with the Bonferroni method. RESULTS: Thirty-two probe sets associated with tissue handling time in the tumor specimens, and thirty-one in the normal tissues, were identified. Most genes exhibited moderate changes in expression over the time points analyzed; however four of them were oncogenes, and two confirmed the effect of tissue handling by independent validation. CONCLUSIONS: Our results suggest that a critical time point for tissue handling in colon seems to be 60 minutes at room temperature. Although the number of time-dependent genes we identified was low, the three genes that already showed changes at this time point in tumor samples were all oncogenes, hence recommending standardization of tissue-handling protocols and effort to reduce the time from specimen removal to snap freezing accounting for warm ischemia in this tumor type.

The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

International Nuclear Information System (INIS)

Lawton, P.A.

1995-01-01

Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author)

The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

Energy Technology Data Exchange (ETDEWEB)

Lawton, P.A.

1995-12-31

Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author).

Large animal normal tissue tolerance with boron neutron capture.

Science.gov (United States)

Gavin, P R; Kraft, S L; DeHaan, C E; Swartz, C D; Griebenow, M L

1994-03-30

Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA2B12H11SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood.

Large animal normal tissue tolerance with boron neutron capture

International Nuclear Information System (INIS)

Gavin, P.R.; Swartz, C.D.; Kraft, S.L.; Briebenow, M.L.; DeHaan, C.E.

1994-01-01

Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA 2 B 12 H 11 SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood. 23 refs., 6 figs., 2 tabs

Antiandrogenic actions of medroxyprogesterone acetate on epithelial cells within normal human breast tissues cultured ex vivo.

Science.gov (United States)

Ochnik, Aleksandra M; Moore, Nicole L; Jankovic-Karasoulos, Tanja; Bianco-Miotto, Tina; Ryan, Natalie K; Thomas, Mervyn R; Birrell, Stephen N; Butler, Lisa M; Tilley, Wayne D; Hickey, Theresa E

2014-01-01

Medroxyprogesterone acetate (MPA), a component of combined estrogen-progestin therapy (EPT), has been associated with increased breast cancer risk in EPT users. MPA can bind to the androgen receptor (AR), and AR signaling inhibits cell growth in breast tissues. Therefore, the aim of this study was to investigate the potential of MPA to disrupt AR signaling in an ex vivo culture model of normal human breast tissue. Histologically normal breast tissues from women undergoing breast surgical operation were cultured in the presence or in the absence of the native AR ligand 5α-dihydrotestosterone (DHT), MPA, or the AR antagonist bicalutamide. Ki67, bromodeoxyuridine, B-cell CLL/lymphoma 2 (BCL2), AR, estrogen receptor α, and progesterone receptor were detected by immunohistochemistry. DHT inhibited the proliferation of breast epithelial cells in an AR-dependent manner within tissues from postmenopausal women, and MPA significantly antagonized this androgenic effect. These hormonal responses were not commonly observed in cultured tissues from premenopausal women. In tissues from postmenopausal women, DHT either induced or repressed BCL2 expression, and the antiandrogenic effect of MPA on BCL2 was variable. MPA significantly opposed the positive effect of DHT on AR stabilization, but these hormones had no significant effect on estrogen receptor α or progesterone receptor levels. In a subset of postmenopausal women, MPA exerts an antiandrogenic effect on breast epithelial cells that is associated with increased proliferation and destabilization of AR protein. This activity may contribute mechanistically to the increased risk of breast cancer in women taking MPA-containing EPT.

Pesquisa da prevalência do papilomavírus humano em amostras de tecido endometrial normal e com carcinoma pela técnica de PCR Search for human papillomavirus in samples of normal endometrial tissue and tissue with carcinoma by the PCR technique

Directory of Open Access Journals (Sweden)

Edison Natal Fedrizzi

2004-05-01

tissue, and tissue with endometrial carcinoma of women submitted to surgical treatment (hysterectomy, or between endometrial carcinoma and benign disease, through the PCR technique. METHODS: this is an observational control-case study where 100 women (50 with endometrial carcinoma and 50 with normal endometrial tissue were analyzed for the detection of HPV DNA in samples of endometrial tissue kept in paraffin blocks by the PCR technique. The cases of endometrial carcinoma with uncertain primary site of the lesion as well as the cases with previous or current history of pre-neoplasic lesions or carcinoma of the lower genital tract were excluded. Variables as age, smoking habit, endometrial trophism, squamous differentiation and degree of tumor differentiation were also evaluated. RESULTS: the estimated relative risk of the presence of HPV in the endometrial carcinoma and in the normal endometrial tissue was the same. HPV was detected in 8% of the cases of carcinoma and 10% in the normal endometrial tissue. In spite of HPV having been 3.5 times more detected in women with smoking habit in the group without carcinoma, there was no statistical difference. The presence of HPV was also not correlated with the women's age, endometrial trophism, squamous differentiation and degree of tumor differentiation. The HPV types 16 (5 cases and 18 (4 cases were the viruses most frequently found both in the normal endometrial tissue or in the tissue with carcinoma. No oncogenic low risk virus was detected in the samples. CONCLUSION: The same proportion of HPV is present in the endometrial tissue of women with endometrial cancer and with normal endometrium. It could not be demonstrated a possible correlation of DNA of HPV with the development of endometrial carcinoma.

Normal tissue complication probabilities correlated with late effects in the rectum after prostate conformal radiotherapy

International Nuclear Information System (INIS)

Dale, Einar; Olsen, Dag R.; Fossa, Sophie D.

1999-01-01

Purpose: Radiation therapy of deep-sited tumours will always result in normal tissue doses to some extent. The aim of this study was to calculate different risk estimates of late effects in the rectum for a group of cancer prostate patients treated with conformal radiation therapy (CRT) and correlate these estimates with the occurrences of late effects. Since the rectum is a hollow organ, several ways of generating dose-volume distributions over the organ are possible, and we wanted to investigate two of them. Methods and Materials: A mathematical model, known as the Lyman-Kutcher model, conventionally used to estimate normal tissue complication probabilities (NTCP) associated with radiation therapy, was applied to a material of 52 cancer prostate patients. The patients were treated with a four field box technique, with the rectum as organ at risk. Dose-volume histograms (DVH) were generated for the whole rectum (including the cavity) and of the rectum wall. One to two years after the treatment, the patients completed a questionnaire concerning bowel (rectum) related morbidity quantifying the extent of late effects. Results: A correlation analysis using Spearman's rank correlation coefficient, for NTCP values calculated from the DVHs and the patients' scores, gave correlation coefficients which were not statistically significant at the p max , of the whole rectum, correlated better to observed late toxicity than D max derived from histograms of the rectum wall. Correlation coefficients from 'high-dose' measures were larger than those calculated from the NTCP values. Accordingly, as the volume parameter of the Lyman-Kutcher model was reduced, raising the impact of small high-dose volumes on the NTCP values, the correlation between observed effects and NTCP values became significant at p < 0.01 level. Conclusions: 1) High-dose levels corresponding to small volume fractions of the cumulative dose-volume histograms were best correlated with the occurrences of late

Determination and correlation of spatial distribution of trace elements in normal and neoplastic breast tissues evaluated by μ-XRF

International Nuclear Information System (INIS)

Silva, M.P.; Oliveira, M.A.; Poletti, M.E.

2012-01-01

Full text: Some trace elements, naturally present in breast tissues, participate in a large number of biological processes, which include among others, activation or inhibition of enzymatic reactions and changes on cell membranes permeability, suggesting that these elements may influence carcinogenic processes. Thus, knowledge of the amounts of these elements and their spatial distribution in normal and neoplastic tissues may help in understanding the role of these elements in the carcinogenic process and tumor progression of breast cancers. Concentrations of trace elements like Ca, Fe, Cu and Zn, previously studied at LNLS using TXRF and conventional XRF, were elevated in neoplastic breast tissues compared to normal tissues. In this study we determined the spatial distribution of these elements in normal and neoplastic breast tissues using μ-XRF technique. We analyzed 22 samples of normal and neoplastic breast tissues (malignant and benign) obtained from paraffin blocks available for study at the Department of Pathology HC-FMRP/USP. From the blocks, a small fraction of material was removed and subjected to histological sections of 60 μm thick made with a microtome. The slices where placed in holder samples and covered with ultralen film. Tissue samples were irradiated with a white beam of synchrotron radiation. The samples were positioned at 45 degrees with respect to the incident beam on a table with 3 freedom degrees (x, y and z), allowing independent positioning of the sample in these directions. The white beam was collimated by a 20 μm microcapillary and samples were fully scanned. At each step, a spectrum was detected for 10 s. The fluorescence emitted by elements present in the sample was detected by a Si (Li) detector with 165 eV at 5.9 keV energy resolution, placed at 90 deg with respect to the incident beam. Results reveal that trace elements Ca-Zn and Fe-Cu could to be correlated in malignant breast tissues. Quantitative results, achieved by Spearman

Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.

Science.gov (United States)

Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Gullu Amuran, Gokce; Ozmen, Tolga; Gulluoglu, Bahadır M; Kaya, Handan; Ozer, Ayse

2017-09-01

Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. Telomeres were shorter in tumor tissues compared to controls (Pbreast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association. © 2016 Wiley Periodicals, Inc.

Binding of (/sup 3/H) progesterone to normal and neoplastic tissue samples from tumour bearing breasts

Energy Technology Data Exchange (ETDEWEB)

Pollow, K; Sinnecker, R; Schmidt-Gollwitzer, M; Boquoi, E; Pollow, B [Institut fuer Molekularbiologie und Biochemie, Frauenklinik Charlottenburg der Freien Universitat, Berlin (G.F.R.)

1977-01-01

Macromolecular components of normal human mammary cytosol (obtained from 'non-malignant tissue samples' from cancer bearing breasts) which bind (/sup 3/H)progesterone in vitro were characterized by sucrose gradient centrifugation, gel filtration on Agarose, ion exchange chromatography, isoelectric focusing, competition studies and kinetic parameters. The size of the cytoplasmic binding components vary with the concentration of KCl. In the absence of KCl, the major components are characterized by sedimentation coefficients of about 4 S and 8 S. In solutions containing 0.3M KCl, the cytoplasmic components sediment at 4 S in sucrose gradient. The corticosteroid-binding component of normal human mammary cytosol both sediment at about the same rate in the presence of 0.3M KCl and chromatograph as a single component on Agarose. The isoelectric point of the progesterone-binding component of normal human mammary cytosol was located around pH 5.0. The progesterone-binding component was more thermo-labile than serum CBG. CBG was inactivated at temperatures above 45 deg C but temperature above 20 deg C destroyed specific progesterone receptor binding. Progesterone receptor concentrations in normal mammary cytosol of premenopausal women depended on the menstrual cycle. The binding of progesterone was highest around the time of ovulation. In breast tumor tissue samples the progesterone receptor concentration was lower than in the normal mammary cytosol (obtained in each case from the same tumor-bearing breast). In 5 out of 37 breast tumor samples progesterone binding activity could not be detected.

Normal Values of Tissue-Muscle Perfusion Indexes of Lower Limbs Obtained with a Scintigraphic Method.

Science.gov (United States)

Manevska, Nevena; Stojanoski, Sinisa; Pop Gjorceva, Daniela; Todorovska, Lidija; Miladinova, Daniela; Zafirova, Beti

2017-09-01

Introduction Muscle perfusion is a physiologic process that can undergo quantitative assessment and thus define the range of normal values of perfusion indexes and perfusion reserve. The investigation of the microcirculation has a crucial role in determining the muscle perfusion. Materials and method The study included 30 examinees, 24-74 years of age, without a history of confirmed peripheral artery disease and all had normal findings on Doppler ultrasonography and pedo-brachial index of lower extremity (PBI). 99mTc-MIBI tissue muscle perfusion scintigraphy of lower limbs evaluates tissue perfusion in resting condition "rest study" and after workload "stress study", through quantitative parameters: Inter-extremity index (for both studies), left thigh/right thigh (LT/RT) left calf/right calf (LC/RC) and perfusion reserve (PR) for both thighs and calves. Results In our investigated group we assessed the normal values of quantitative parameters of perfusion indexes. Indexes ranged for LT/RT in rest study 0.91-1.05, in stress study 0.92-1.04. LC/RC in rest 0.93-1.07 and in stress study 0.93-1.09. The examinees older than 50 years had insignificantly lower perfusion reserve of these parameters compared with those younger than 50, LC (p=0.98), and RC (p=0.6). Conclusion This non-invasive scintigraphic method allows in individuals without peripheral artery disease to determine the range of normal values of muscle perfusion at rest and stress condition and to clinically implement them in evaluation of patients with peripheral artery disease for differentiating patients with normal from those with impaired lower limbs circulation.

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-06-01

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

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

NARCIS (Netherlands)

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

2012-01-01

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

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

Energy Technology Data Exchange (ETDEWEB)

Milliat, F

2007-05-15

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

The composition of engineered cartilage at the time of implantation determines the likelihood of regenerating tissue with a normal collagen architecture.

Science.gov (United States)

Nagel, Thomas; Kelly, Daniel J

2013-04-01

The biomechanical functionality of articular cartilage is derived from both its biochemical composition and the architecture of the collagen network. Failure to replicate this normal Benninghoff architecture in regenerating articular cartilage may in turn predispose the tissue to failure. In this article, the influence of the maturity (or functionality) of a tissue-engineered construct at the time of implantation into a tibial chondral defect on the likelihood of recapitulating a normal Benninghoff architecture was investigated using a computational model featuring a collagen remodeling algorithm. Such a normal tissue architecture was predicted to form in the intact tibial plateau due to the interplay between the depth-dependent extracellular matrix properties, foremost swelling pressures, and external mechanical loading. In the presence of even small empty defects in the articular surface, the collagen architecture in the surrounding cartilage was predicted to deviate significantly from the native state, indicating a possible predisposition for osteoarthritic changes. These negative alterations were alleviated by the implantation of tissue-engineered cartilage, where a mature implant was predicted to result in the formation of a more native-like collagen architecture than immature implants. The results of this study highlight the importance of cartilage graft functionality to maintain and/or re-establish joint function and suggest that engineering a tissue with a native depth-dependent composition may facilitate the establishment of a normal Benninghoff collagen architecture after implantation into load-bearing defects.

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-10-01

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

DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing.

Science.gov (United States)

Rübe, Claudia E; Grudzenski, Saskia; Kühne, Martin; Dong, Xiaorong; Rief, Nicole; Löbrich, Markus; Rübe, Christian

2008-10-15

Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced radiosensitivity. Using a preclinical mouse model, the highly sensitive gammaH2AX-foci approach was tested to verify even subtle, genetically determined DSB repair deficiencies known to be associated with increased normal tissue radiosensitivity. By enumerating gammaH2AX-foci in blood lymphocytes and normal tissues (brain, lung, heart, and intestine), the induction and repair of DSBs after irradiation with therapeutic doses (0.1-2 Gy) was investigated in repair-proficient and repair-deficient mouse strains in vivo and blood samples irradiated ex vivo. gammaH2AX-foci analysis allowed to verify the different DSB repair deficiencies; even slight impairments caused by single polymorphisms were detected similarly in both blood lymphocytes and solid tissues, indicating that DSB repair measured in lymphocytes is valid for different and complex organs. Moreover, gammaH2AX-foci analysis of blood samples irradiated ex vivo was found to reflect repair kinetics measured in vivo and, thus, give reliable information about the individual DSB repair capacity. gammaH2AX analysis of blood and tissue samples allows to detect even minor genetically defined DSB repair deficiencies, affecting normal tissue radiosensitivity. Future studies will have to evaluate the clinical potential to identify patients more susceptible to radiation toxicities before radiotherapy.

Improved Root Normal Size Distributions for Liquid Atomization

Science.gov (United States)

2015-11-01

ANSI Std. Z39.18 j CONVERSION TABLE Conversion Factors for U.S. Customary to metric (SI) units of measurement. MULTIPLY BY TO...Gray (Gy) coulomb /kilogram (C/kg) second (s) kilogram (kg) kilo pascal (kPa) 1 Improved Root Normal Size Distributions for Liquid

Systematic bias in genomic classification due to contaminating non-neoplastic tissue in breast tumor samples.

Science.gov (United States)

Elloumi, Fathi; Hu, Zhiyuan; Li, Yan; Parker, Joel S; Gulley, Margaret L; Amos, Keith D; Troester, Melissa A

2011-06-30

Genomic tests are available to predict breast cancer recurrence and to guide clinical decision making. These predictors provide recurrence risk scores along with a measure of uncertainty, usually a confidence interval. The confidence interval conveys random error and not systematic bias. Standard tumor sampling methods make this problematic, as it is common to have a substantial proportion (typically 30-50%) of a tumor sample comprised of histologically benign tissue. This "normal" tissue could represent a source of non-random error or systematic bias in genomic classification. To assess the performance characteristics of genomic classification to systematic error from normal contamination, we collected 55 tumor samples and paired tumor-adjacent normal tissue. Using genomic signatures from the tumor and paired normal, we evaluated how increasing normal contamination altered recurrence risk scores for various genomic predictors. Simulations of normal tissue contamination caused misclassification of tumors in all predictors evaluated, but different breast cancer predictors showed different types of vulnerability to normal tissue bias. While two predictors had unpredictable direction of bias (either higher or lower risk of relapse resulted from normal contamination), one signature showed predictable direction of normal tissue effects. Due to this predictable direction of effect, this signature (the PAM50) was adjusted for normal tissue contamination and these corrections improved sensitivity and negative predictive value. For all three assays quality control standards and/or appropriate bias adjustment strategies can be used to improve assay reliability. Normal tissue sampled concurrently with tumor is an important source of bias in breast genomic predictors. All genomic predictors show some sensitivity to normal tissue contamination and ideal strategies for mitigating this bias vary depending upon the particular genes and computational methods used in the predictor.

Comparison of normal tissue pharmacokinetics with 111In/9Y monoclonal antibody m170 for breast and prostate cancer

International Nuclear Information System (INIS)

Lehmann, Joerg; DeNardo, Gerald L.; Yuan, Aina; Shen Sui; O'Donnell, Robert T.; Richman, Carol M.; De Nardo, Sally J.

2006-01-01

Purpose: Radioactivity deposition in normal tissues limits the dose deliverable by radiopharmaceuticals (RP) in radioimmunotherapy (RIT). This study investigated the absorbed radiation dose in normal tissues for prostate cancer patients in comparison to breast cancer patients for 2 RPs using the monoclonal antibody (MAb) m170. Methods and Materials: 111 In-DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine amide (GGGF)-m170 and 111 In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) 2-iminothiolane (2IT)-m170, representing the same MAb and chelate with and without a cleavable linkage, were studied in 13 breast cancer and 26 prostate cancer patients. Dosimetry for 9 Y was calculated using 111 In MAb pharmacokinetics from the initial imaging study for each patient, using reference man- and patient-specific masses. Results: The reference man-specific radiation doses (cGy/MBq) were not significantly different for the breast and the prostate cancer patients for both RPs in all but one tissue-RP combination (liver, DOTA-2IT). The patient-specific doses had differences between the groups most of which can be related to weight differences. Conclusions: Similar normal tissue doses were calculated for two groups of patients having different cancers and genders. This similarity combined with continued careful analysis of the imaging data might allow the use of higher starting doses in early phase RIT studies

Dynamic contrast-enhanced magnetic resonance imaging: a non-invasive method to evaluate significant differences between malignant and normal tissue

International Nuclear Information System (INIS)

Rudisch, Ansgar; Kremser, Christian; Judmaier, Werner; Zunterer, Hildegard; DeVries, Alexander F.

2005-01-01

Purpose: An ever recurring challenge in diagnostic radiology is the differentiation between non-malignant and malignant tissue. Based on evidence that microcirculation of normal, non-malignant tissue differs from that of malignant tissue, the goal of this study was to assess the reliability of dynamic contrast-enhanced Magnetic Resonance Imaging (dcMRI) for differentiating these two entities. Materials and methods: DcMRI data of rectum carcinoma and gluteus maximus muscles were acquired in 41 patients. Using an fast T1-mapping sequence on a 1.5-T whole body scanner, T1-maps were dynamically retrieved before, during and after constant rate i.v. infusion of a contrast medium (CM). On the basis of the acquired data sets, PI-values were calculated on a pixel-by-pixel basis. The relevance of spatial heterogeneities of microcirculation was investigated by relative frequency histograms of the PI-values. Results: A statistically significant difference between malignant and normal tissue was found for the mean PI-value (P < 0.001; 8.95 ml/min/100 g ± 2.45 versus 3.56 ml/min/100 g ± 1.20). Additionally relative frequency distributions of PI-values with equal class intervals of 2.5 ml/min/100 g revealed significant differences between the histograms of muscles and rectum carcinoma. Conclusion: We could show that microcirculation differences between malignant and normal, non-malignant tissue can be reliably assessed by non-invasive dcMRI. Therefore, dcMRI holds great promise in the aid of cancer assessment, especially in patients where biopsy is contraindicated

Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

Energy Technology Data Exchange (ETDEWEB)

Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian [Department of Radiation Oncology, Royal North Shore Hospital, St Leonards, New South Wales (Australia)

2015-09-15

We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D{sub 105%} and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.

Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

International Nuclear Information System (INIS)

Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian

2015-01-01

We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D 105% and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT

Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

Directory of Open Access Journals (Sweden)

Johan W.E. Jocken

2014-10-01

Full Text Available With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocytes. Recent evidence suggests involvement of several hormones, membrane receptors, and intracellular signalling cascades, which has added complexity to the regulation of cytosolic lipolysis. Interestingly, a specific form of autophagy, called lipophagy, has been implicated as alternative lipolytic pathway. Defective regulation of cytosolic lipolysis and lipophagy might have substantial effects on lipid metabolism, thereby contributing to adipose tissue dysfunction, insulin resistance, and related cardiometabolic (cMet diseases. This review will discuss recent advances in our understanding of classical lipolysis and lipophagy in adipocyte lipid metabolism under normal and pathological conditions. Furthermore, the question of whether modulation of adipocyte lipolysis and lipophagy might be a potential therapeutic target to combat cMet disorders will be addressed.

Non-invasive characterization of normal and pathological tissues through dynamic infrared imaging in the hamster cheek pouch oral cancer model

Science.gov (United States)

Herrera, María. S.; Monti Hughes, Andrea; Salva, Natalia; Padra, Claudio; Schwint, Amanda; Santa Cruz, Gustavo A.

2017-05-01

Biomedical infrared thermography, a non-invasive and functional imaging method, provides information on the normal and abnormal status and response of tissues in terms of spatial and temporal variations in body infrared radiance. It is especially attractive in cancer research due to the hypervascular and hypermetabolic activity of solid tumors. Moreover, healthy tissues like skin or mucosa exposed to radiation can be examined since inflammation, changes in water content, exudation, desquamation, erosion and necrosis, between others, are factors that modify their thermal properties. In this work we performed Dynamic Infrared Imaging (DIRI) to contribute to the understanding and evaluation of normal tissue, tumor and precancerous tissue response and radiotoxicity in an in vivo model, the hamster cheek pouch, exposed to Boron Neutron Capture Therapy. In this study, we particularly focused on the observation of temperature changes under forced transient conditions associated with mass moisture transfer in the tissue-air interface, in each tissue with or without treatment. We proposed a simple mathematical procedure that considerers the heat transfer from tissue to ambient through convection and evaporation to model the transient (exponential decay o recover) thermal study. The data was fitted to determined the characteristic decay and recovery time constants of the temperature as a function of time. Also this model allowed to explore the mass flux of moisture, as a degree of evaporation occurring on the tissue surface. Tissue thermal responses under provocation tests could be used as a non-invasive method to characterize tissue physiology.

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

International Nuclear Information System (INIS)

Abderrahmani, R.

2010-01-01

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

ECM Decorated Electrospun Nanofiber for Improving Bone Tissue Regeneration

Directory of Open Access Journals (Sweden)

Yong Fu

2018-03-01

Full Text Available Optimization of nanofiber surface properties can lead to enhanced tissue regeneration outcomes in the context of bone tissue engineering. Herein, we developed a facile strategy to decorate elctrospun nanofibers using extracellular matrix (ECM in order to improve their performance for bone tissue engineering. Electrospun PLLA nanofibers (PLLA NF were seeded with MC3T3-E1 cells and allowed to grow for two weeks in order to harvest a layer of ECM on nanofiber surface. After decellularization, we found that ECM was successfully preserved on nanofiber surface while maintaining the nanostructure of electrospun fibers. ECM decorated on PLLA NF is biologically active, as evidenced by its ability to enhance mouse bone marrow stromal cells (mBMSCs adhesion, support cell proliferation and promote early stage osteogenic differentiation of mBMSCs. Compared to PLLA NF without ECM, mBMSCs grown on ECM/PLLA NF exhibited a healthier morphology, faster proliferation profile, and more robust osteogenic differentiation. Therefore, our study suggests that ECM decoration on electrospun nanofibers could serve as an efficient approach to improving their performance for bone tissue engineering.

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

Directory of Open Access Journals (Sweden)

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.

Mechanical stimulation improves tissue-engineered human skeletal muscle

Science.gov (United States)

Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

2002-01-01

Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

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

Directory of Open Access Journals (Sweden)

Jeonghwan Lee

Full Text Available Glomerular hyperfiltration is recognized as an early marker of progressive kidney dysfunction in the obese population. This study aimed to identify the relationship between glomerular hyperfiltration and body fat distribution measured by computed tomography (CT in healthy Korean adults. The study population included individuals aged 20-64 years who went a routine health check-up including an abdominal CT scan. We selected 4,378 individuals without diabetes and hypertension. Glomerular filtration rate was estimated using the CKD-EPI equation, and glomerular hyperfiltration was defined as the highest quintile of glomerular filtration rate. Abdominal adipose tissue areas were measured at the level of the umbilicus using a 16-detector CT scanner, and the cross-sectional area was calculated using Rapidia 2.8 CT software. The prevalence of glomerular hyperfiltration increased significantly according to the subcutaneous adipose tissue area in men (OR = 1.74 (1.16-2.61, P for trend 0.016, for the comparisons of lowest vs. highest quartile and visceral adipose tissue area in women (OR = 2.34 (1.46-3.75, P for trend < 0.001 in multivariate analysis. After stratification by body mass index (normal < 23 kg/m2, overweight ≥ 23 kg/m2, male subjects with greater subcutaneous adipose tissue, even those in the normal BMI group, had a higher prevalence of glomerular hyperfiltration (OR = 2.11 (1.17-3.80, P for trend = 0.009. Among women, the significance of visceral adipose tissue area on glomerular hyperfiltration resulted from the normal BMI group (OR = 2.14 (1.31-3.49, P for trend = 0.002. After menopause, the odds ratio of the association of glomerular hyperfiltration with subcutaneous abdominal adipose tissue increased (OR = 2.96 (1.21-7.25, P for trend = 0.013. Subcutaneous adipose tissue areas and visceral adipose tissue areas are positively associated with glomerular hyperfiltration in healthy Korean adult men and women, respectively. In post

Improved resolution by mounting of tissue sections for laser microdissection.

Science.gov (United States)

van Dijk, M C R F; Rombout, P D M; Dijkman, H B P M; Ruiter, D J; Bernsen, M R

2003-08-01

Laser microbeam microdissection has greatly facilitated the procurement of specific cell populations from tissue sections. However, the fact that a coverslip is not used means that the morphology of the tissue sections is often poor. To develop a mounting method that greatly improves the morphological quality of tissue sections for laser microbeam microdissection purposes so that the identification of target cells can be facilitated. Fresh frozen tissue and formalin fixed, paraffin wax embedded tissue specimens were used to test the morphological quality of mounted and unmounted tissue. The mounting solution consisted of an adhesive gum and blue ink diluted in water. Interference of the mounting solution with DNA quality was analysed by the polymerase chain reaction using 10-2000 cells isolated by microdissection from mounted and unmounted tissue. The mounting solution greatly improved the morphology of tissue sections for laser microdissection purposes and had no detrimental effects on the isolation and efficiency of amplification of DNA. One disadvantage was that the mounting solution reduced the cutting efficiency of the ultraviolet laser. To minimise this effect, the mounting solution should be diluted as much as possible. Furthermore, the addition of blue ink to the mounting medium restores the cutting efficiency of the laser. The mounting solution is easy to prepare and apply and can be combined with various staining methods without compromising the quality of the DNA extracted.

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

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Milliat, F

2007-05-15

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

Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer

International Nuclear Information System (INIS)

Barber, J.B.P.; Burrill, W.; Spreadborough, A.R.; Levine, E.; Warren, C.; Scott, D.; Kiltie, A.E.; Roberts, S.A.

2000-01-01

There is a need for rapid and reliable tests for the prediction of normal tissue responses to radiotherapy, as this could lead to individualization of patient radiotherapy schedules and thus improvements in the therapeutic ratio. Because the use of cultured fibroblasts is too slow to be practicable in a clinical setting, we evaluated the predictive role of assays of lymphocyte chromosomal radiosensitivity in patients having radiotherapy for breast cancer. Radiosensitivity was assessed using a macronucleus (MN) assay at high dose rate (HDR) and low dose rate (LDR) on lymphocytes irradiated in the G 0 phase of the cell cycle (Scott D, Barber JB, Levine EL, Burril W, Roberts SA. Radiation-induced micronucleus induction in lymphocytes identifies a frequency of radiosensitive cases among breast cancer patients: a test for predisposition? Br. J. Cancer 1998;77;614-620) and an assay of G 2 phase chromatid radiosensitivity ('G 2 assay') (Scott D, Spreadborough A, Levine E, Roberts SA. Genetic predisposition in breast cancer. Lancet 1994; 344: 1444). In a study of acute reactions, blood samples were taken from breast cancer patients before the start of radiotherapy, and the skin reaction documented. 116 patients were tested with the HDR MN assay, 73 with the LDR MN assay and 123 with the G 2 assay. In a study of late reactions, samples were taken from a series of breast cancer patients 8-14 years after radiotherapy and the patients assessed for the severity of late effects according to the 'LENT SOMA' scales. 47 were tested with the HDR assay, 26 with the LDR assay and 19 with the G 2 assay. For each clinical endpoint, patients were classified as being normal reactors or 'highly radiosensitive patients' (HR patients (Burnet NG. Johansen J, Turesson I, Nyman J. Describing patients' normal tissue reactions: Concerning the possibility of individualising radiotherapy dose prescriptions based on potential predictive assays of normal tissue radiosensitivity. Int. J. Cancer 1998

Mammary stem cell and macrophage markers are enriched in normal tissue adjacent to inflammatory breast cancer.

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Reddy, Jay P; Atkinson, Rachel L; Larson, Richard; Burks, Jared K; Smith, Daniel; Debeb, Bisrat G; Ruffell, Brian; Creighton, Chad J; Bambhroliya, Arvind; Reuben, James M; Van Laere, Steven J; Krishnamurthy, Savitri; Symmans, William F; Brewster, Abenaa M; Woodward, Wendy A

2018-06-01

We hypothesized that breast tissue not involved by tumor in inflammatory breast cancer (IBC) patients contains intrinsic differences, including increased mammary stem cells and macrophage infiltration, which may promote the IBC phenotype. Normal breast parenchyma ≥ 5 cm away from primary tumors was obtained from mastectomy specimens. This included an initial cohort of 8 IBC patients and 60 non-IBC patients followed by a validation cohort of 19 IBC patients and 25 non-IBC patients. Samples were immunostained for either CD44 + CD49f + CD133/2 + mammary stem cell markers or the CD68 macrophage marker and correlated with IBC status. Quantitation of positive cells was determined using inForm software from PerkinElmer. We also examined the association between IBC status and previously published tumorigenic stem cell and IBC tumor signatures in the validation cohort samples. 8 of 8 IBC samples expressed isolated CD44 + CD49f + CD133/2 + stem cell marked cells in the initial cohort as opposed to 0/60 non-IBC samples (p = 0.001). Similarly, the median number of CD44 + CD49f + CD133/2 + cells was significantly higher in the IBC validation cohort as opposed to the non-IBC validation cohort (25.7 vs. 14.2, p = 0.007). 7 of 8 IBC samples expressed CD68 + histologically confirmed macrophages in initial cohort as opposed to 12/48 non-IBC samples (p = 0.001). In the validation cohort, the median number of CD68 + cells in IBC was 3.7 versus 1.0 in the non-IBC cohort (p = 0.06). IBC normal tissue was positively associated with a tumorigenic stem cell signature (p = 0.02) and with a 79-gene IBC signature (p stem cell signature and IBC-specific tumor signature. Collectively, these data suggest that IBC normal tissue differs from non-IBC tissue. Whether these changes occur before the tumor develops or is induced by tumor warrants further investigation.

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

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Liu, T; Yang, X; Curran, W; Torres, M [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States)

2014-06-15

that ultrasound imaging may be used to improve early detection of normal-tissue toxicity in breast-cancer RT.

Hypoxyradiotherapy: lack of experimental evidence for a preferential radioprotective effect on normal versus tumor tissue as shown by direct oxygenation measurements in experimental sarcomas

International Nuclear Information System (INIS)

Kelleher, Debra K.; Thews, Oliver; Vaupel, Peter

1997-01-01

Aim: In order to investigate possible pathophysiological mechanisms underlying the postulated preferential protective effect of hypoxia on normal tissue during radiotherapy, the impact of acute respiratory hypoxia (8.2% O 2 + 91.8% N 2 ) on tissue oxygenation was assessed. Methods: Tumor and normal tissue oxygenation was directly determined using O 2 -sensitive electrodes in two experimental rat tumors (DS and Yoshida sarcomas) and in the normal subcutis of the hind foot dorsum. Results: During respiratory hypoxia, arterial blood O 2 tension (pO 2 ), oxyhemoglobin saturation and mean arterial blood pressure decreased. Changes in the arterial blood gas status were accompanied by a reflex hyperventilation leading to hypocapnia and respiratory alkalosis. In the subcutis, tissue oxygenation worsened during acute hypoxia, with decreases in the mean and median pO 2 . Significant increases in the hypoxic fractions were, however, not seen. In tumor tissues, oxygenation also worsened upon hypoxic hypoxia with significant decreases in the mean and median pO 2 and increases in the size of the hypoxic fractions for both sarcomas. Conclusion: These results suggest that during respiratory hypoxia, radiobiologically relevant reductions in the oxygenation (and a subsequent selective radioprotection) of normal tissue may not be achieved. In addition, in the tumor models studied, a worsening of tumor oxygenation was seen which could result in an increased radioresistance

Incorporation of tritiated thymidine and uridine in normal and endopolyploid nuclei of differentiated tissue

International Nuclear Information System (INIS)

Bansal, Y.K.; Sen, Sumitra

1987-01-01

Rate of replication and transcription between normal and giant endopolyploid nuclei of differentiated tissue of Hordeum vulgare L. (2n=14) roots and Phlox drummondii Hook. (2n=14) and Zea mays L. (2n=20) endosperms were studied by labelling experiments with tritiated thymidine and uridine. The incorporation of thymidine and uridine was identical in both diploid and giant endopolyploid nuclei of the roots of H. vulgare. The endosperm cells of P. drummondii and Z. mays, however, exhibit markedly different labelling pattern in normal (i.e. triploid) and endopolyploid nuclei where both replication and transcription were rather high. The nutritive function of the endosperm is probably responsible for this high degree of activity. (author). 14 refs., 10 figs., 3 tables

Comparison of radiosensitivity between tumor and normal tissue in terms of cell population kinetics

International Nuclear Information System (INIS)

Sugahara, Tsutomu; Utsumi, Hiroshi

1975-01-01

Puck and Marcus in 1956 established the in vitro colony formation of mammalian cells and demonstrated a dose-survival curve of mammalian cells well fitted to the target theory. Since then almost all of the work on the radiosensitivity of malignant and normal cells has been based on the reproductive integrity of cells. However, in the author's laboratory, a recent work was done on the effect of ionizing radiation on the differentiative trait, using clonal cell cultures developed by Coon (1966) in chick embryonic cartilage cells. This work demonstrated clearly that the differentiative trait is more radiosensitive than is reproduction. Based on this finding a new compartment model is proposed for a cell renewal system which demonstrates the difference between normal and malignant tissue. (author)

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

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Kim, Woo Hyoung; Kim, Chang Guhn; Kim, Dae Weung [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of)

2012-09-15

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 {sup 18}F 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 (LBM{sup CT1}-3). Five PEs were used for comparison (LBM{sup PE1}-5). Tissue SUV normalized by LBM (SUL) was calculated using LBM from each method (SUL{sup CT1}-3, SUL{sup PE1}-5). Agreement between methods was assessed by Bland Altman analysis. Percentage difference and percentage error were also calculated. For all liver SUL{sup CTS} vs. liver SUL{sup PES} except liver SUL{sup PE3}, 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 SUL{sup CTs} vs. liver SUL{sup PE3}, 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 SUL{sup CT1}-3 and liver SUL{sup PE1}-5. The results of spleen and aorta SUL{sup CTs} and SUL{sup PEs} comparison were almost identical to those for liver. The present study demonstrated substantial errors in individual SUL{sup PEs} compared with SUL{sup CTs} 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 SUL{sup PEs}.

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

International Nuclear Information System (INIS)

Kim, Woo Hyoung; Kim, Chang Guhn; Kim, Dae Weung

2012-01-01

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 18 F 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 (LBM CT1 -3). Five PEs were used for comparison (LBM PE1 -5). Tissue SUV normalized by LBM (SUL) was calculated using LBM from each method (SUL CT1 -3, SUL PE1 -5). Agreement between methods was assessed by Bland Altman analysis. Percentage difference and percentage error were also calculated. For all liver SUL CTS vs. liver SUL PES except liver SUL PE3 , 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 SUL CTs vs. liver SUL PE3 , 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 SUL CT1 -3 and liver SUL PE1 -5. The results of spleen and aorta SUL CTs and SUL PEs comparison were almost identical to those for liver. The present study demonstrated substantial errors in individual SUL PEs compared with SUL CTs 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 SUL PEs

Classification of mass and normal breast tissue: A convolution neural network classifier with spatial domain and texture images

International Nuclear Information System (INIS)

Sahiner, B.; Chan, H.P.; Petrick, N.; Helvie, M.A.; Adler, D.D.; Goodsitt, M.M.; Wei, D.

1996-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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)

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

International Nuclear Information System (INIS)

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

2003-01-01

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

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

International Nuclear Information System (INIS)

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

1997-01-01

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)

Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

Science.gov (United States)

Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

2015-10-10

Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of multiple assays for detecting human antibodies directed against antigens on normal and malignant tissue culture cells

International Nuclear Information System (INIS)

Rosenberg, S.A.; Schwarz, S.; Anding, H.; Hyatt, C.; Williams, G.M.; Johns Hopkins Univ., Baltimore, Md.

1977-01-01

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

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

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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)

Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel: Comparisons with the normal articular cartilage

Directory of Open Access Journals (Sweden)

Kurokawa Takayuki

2011-09-01

Full Text Available Abstract Background We have recently found a phenomenon that spontaneous regeneration of a hyaline cartilage-like tissue can be induced in a large osteochondral defect by implanting a double-network (DN hydrogel plug, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid and poly-(N, N'-Dimetyl acrylamide, at the bottom of the defect. The purpose of this study was to clarify gene expression profile of the regenerated tissue in comparison with that of the normal articular cartilage. Methods We created a cylindrical osteochondral defect in the rabbit femoral grooves. Then, we implanted the DN gel plug at the bottom of the defect. At 2 and 4 weeks after surgery, the regenerated tissue was analyzed using DNA microarray and immunohistochemical examinations. Results The gene expression profiles of the regenerated tissues were macroscopically similar to the normal cartilage, but showed some minor differences. The expression degree of COL2A1, COL1A2, COL10A1, DCN, FMOD, SPARC, FLOD2, CHAD, CTGF, and COMP genes was greater in the regenerated tissue than in the normal cartilage. The top 30 genes that expressed 5 times or more in the regenerated tissue as compared with the normal cartilage included type-2 collagen, type-10 collagen, FN, vimentin, COMP, EF1alpha, TFCP2, and GAPDH genes. Conclusions The tissue regenerated by using the DN gel was genetically similar but not completely identical to articular cartilage. The genetic data shown in this study are useful for future studies to identify specific genes involved in spontaneous cartilage regeneration.

Radiation therapy and late reactions in normal tissues

International Nuclear Information System (INIS)

Aoyama, Takashi; Kuroda, Yasumasa

1998-01-01

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

Normal liver tissue sparing by intensity-modulated proton stereotactic body radiotherapy for solitary liver tumours

International Nuclear Information System (INIS)

Petersen, Joergen B. B.; Hansen, Anders T.; Lassen, Yasmin; Grau, Cai; Hoeyer, Morten; Muren, Ludvig P.

2011-01-01

Background. Stereotactic body radiotherapy (SBRT) is often the preferred treatment for the advanced liver tumours which owing to tumour distribution, size and multi-focality are out of range of surgical resection or radiofrequency ablation. However, only a minority of patients with liver tumours may be candidates for conventional SBRT because of the limited radiation tolerance of normal liver, intestine and other normal tissues. Due to the favourable depth-dose characteristics of protons, intensity-modulated proton therapy (IMPT) may be a superior alternative to photon-based SBRT. The purpose of this treatment planning study was therefore to investigate the potential sparing of normal liver by IMPT compared to photon-based intensity-modulated radiotherapy (IMRT) for solitary liver tumours. Material and methods. Ten patients with solitary liver metastasis treated at our institution with multi-field SBRT were retrospectively re-planned with IMRT and proton pencil beam scanning techniques. For the proton plans, two to three coplanar fields were used in contrast to five to six coplanar and non-coplanar photon fields. The same planning objectives were used for both techniques. A risk adapted dose prescription to the PTV surface of 12.5-16.75 Gy x 3 was used. Results. The spared liver volume for IMPT was higher compared to IMRT in all 10 patients. At the highest prescription dose level, the median liver volume receiving less than 15 Gy was 1411 cm 3 for IMPT and 955 cm 3 for IMRT (p D 15 Gy > 700 cm 3 constraint. For the D mean = 15 Gy constraint, nine of 10 cases could be treated at the highest dose level using IMPT whereas with IMRT, only two cases met this constraint at the highest dose level and six at the lowest dose level. Conclusion. A considerable sparing of normal liver tissue can be obtained using proton-based SBRT for solitary liver tumours

B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue

OpenAIRE

Carlsen, H S; Baekkevold, E S; Johansen, F-E; Haraldsen, G; Brandtzaeg, P

2002-01-01

Background and aims: In mice, the B lymphocyte chemoattractant (BLC) CXC chemokine ligand 13 (CXCL13) is sufficient to induce a series of events leading to the formation of organised lymphoid tissue. Its receptor, CXCR5, is required for normal development of secondary lymphoid tissue. However, the human counterpart, B cell attracting chemokine 1 (BCA-1) has only been detected in the stomach and appendix and not in other parts of normal or diseased gut. Hence to elucidate the potential role of...

Quantification of Estrogen Receptor Expression in Normal Breast Tissue in Postmenopausal Women With Breast Cancer and Association With Tumor Subtypes.

Science.gov (United States)

Gulbahce, H Evin; Blair, Cindy K; Sweeney, Carol; Salama, Mohamed E

2017-09-01

Estrogen exposure is important in the pathogenesis of breast cancer and is a contributing risk factor. In this study we quantified estrogen receptor (ER) alpha expression in normal breast epithelium (NBR) in women with breast cancer and correlated it with breast cancer subtypes. Tissue microarrays were constructed from 204 breast cancer patients for whom normal breast tissue away from tumor was available. Slides stained with ER were scanned and expression in normal terminal duct lobular epithelium was quantitated using computer-assisted image analysis. ER expression in normal terminal duct lobular epithelium of postmenopausal women with breast cancer was significantly associated with estrogen and triple (estrogen, progesterone receptors, and HER2) negative phenotypes. Also increased age at diagnosis was significantly associated with ER expression in NBR. ER positivity in normal epithelium did not vary by tumor size, lymph node status, tumor grade, or stage. On the basis of quantitative image analysis, we confirm that ER expression in NBR increases with age in women with breast cancer, and report for the first time, a significant association between ER expression in NBR with ER-negative and triple-negative cancers in postmenopausal women.

Collagen tissue treated with chitosan solutions in carbonic acid for improved biological prosthetic heart valves

Energy Technology Data Exchange (ETDEWEB)

Gallyamov, Marat O., E-mail: glm@spm.phys.msu.ru [Faculty of Physics, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation); Chaschin, Ivan S. [Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation); Khokhlova, Marina A. [Faculty of Physics, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Grigorev, Timofey E. [Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation); Bakuleva, Natalia P.; Lyutova, Irina G.; Kondratenko, Janna E. [Bakulev Scientific Center for Cardiovascular Surgery of the Russian Academy of Medical Sciences, Roublyevskoe Sh. 135, Moscow 121552 (Russian Federation); Badun, Gennadii A.; Chernysheva, Maria G. [Radiochemistry Division, Faculty of Chemistry, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Khokhlov, Alexei R. [Faculty of Physics, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation)

2014-04-01

Calcification of bovine pericardium dramatically shortens typical lifetimes of biological prosthetic heart valves and thus precludes their choice for younger patients. The aim of the present work is to demonstrate that the calcification is to be mitigated by means of treatment of bovine pericardium in solutions of chitosan in carbonic acid, i.e. water saturated with carbon dioxide at high pressure. This acidic aqueous fluid unusually combines antimicrobial properties with absolute biocompatibility as far as at normal pressure it decomposes spontaneously and completely into H{sub 2}O and CO{sub 2}. Yet, at high pressures it can protonate and dissolve chitosan materials with different degrees of acetylation (in the range of 16–33%, at least) without any further pretreatment. Even exposure of the bovine pericardium in pure carbonic acid solution without chitosan already favours certain reduction in calcification, somewhat improved mechanical properties, complete biocompatibility and evident antimicrobial activity of the treated collagen tissue. The reason may be due to high extraction ability of this peculiar compressed fluidic mixture. Moreover, exposure of the bovine pericardium in solutions of chitosan in carbonic acid introduces even better mechanical properties and highly pronounced antimicrobial activity of the modified collagen tissue against adherence and biofilm formation of relevant Gram-positive and Gram-negative strains. Yet, the most important achievement is the detected dramatic reduction in calcification for such modified collagen tissues in spite of the fact that the amount of the thus introduced chitosan is rather small (typically ca. 1 wt.%), which has been reliably detected using original tritium labelling method. We believe that these improved properties are achieved due to particularly deep and uniform impregnation of the collagen matrix with chitosan from its pressurised solutions in carbonic acid. - Highlights: • Treatment of GA

Collagen tissue treated with chitosan solutions in carbonic acid for improved biological prosthetic heart valves

International Nuclear Information System (INIS)

Gallyamov, Marat O.; Chaschin, Ivan S.; Khokhlova, Marina A.; Grigorev, Timofey E.; Bakuleva, Natalia P.; Lyutova, Irina G.; Kondratenko, Janna E.; Badun, Gennadii A.; Chernysheva, Maria G.; Khokhlov, Alexei R.

2014-01-01

Calcification of bovine pericardium dramatically shortens typical lifetimes of biological prosthetic heart valves and thus precludes their choice for younger patients. The aim of the present work is to demonstrate that the calcification is to be mitigated by means of treatment of bovine pericardium in solutions of chitosan in carbonic acid, i.e. water saturated with carbon dioxide at high pressure. This acidic aqueous fluid unusually combines antimicrobial properties with absolute biocompatibility as far as at normal pressure it decomposes spontaneously and completely into H 2 O and CO 2 . Yet, at high pressures it can protonate and dissolve chitosan materials with different degrees of acetylation (in the range of 16–33%, at least) without any further pretreatment. Even exposure of the bovine pericardium in pure carbonic acid solution without chitosan already favours certain reduction in calcification, somewhat improved mechanical properties, complete biocompatibility and evident antimicrobial activity of the treated collagen tissue. The reason may be due to high extraction ability of this peculiar compressed fluidic mixture. Moreover, exposure of the bovine pericardium in solutions of chitosan in carbonic acid introduces even better mechanical properties and highly pronounced antimicrobial activity of the modified collagen tissue against adherence and biofilm formation of relevant Gram-positive and Gram-negative strains. Yet, the most important achievement is the detected dramatic reduction in calcification for such modified collagen tissues in spite of the fact that the amount of the thus introduced chitosan is rather small (typically ca. 1 wt.%), which has been reliably detected using original tritium labelling method. We believe that these improved properties are achieved due to particularly deep and uniform impregnation of the collagen matrix with chitosan from its pressurised solutions in carbonic acid. - Highlights: • Treatment of GA-stabilised bovine

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

International Nuclear Information System (INIS)

Niemierko, Andrzej; Goitein, Michael

1991-01-01

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

Influence of low-energy laser radiation on normal skin and certain tumor tissues

Energy Technology Data Exchange (ETDEWEB)

Pletnev, S.D.; Karpenko, O.M.

For some years, the authors' Institute has studied the influence of various types of low-energy laser radiation on normal tissue and the growth of tumors. Radiation at 3 and 30 J/cm/sup 2/ causes an increase in biological activity of various cell elements, manifested as an increase in mitotic activity of the cells in the basal layer of the epidermis, conglomeration of chromatin in the cell nuclei and an increase in degranulation of fat cells in the process of their migration to the reticular layer. Also noted was an increase in content of fibroblastic and lymphohistocytic elements in the dermis, as well as an increase in collagenization of connective tissue. It was found that irradiation of the skin by helium-neon, cadmium-helium and nitrogen lasers before and after grafting of the cells of various tumors modifies the course of the tumor process. This effect is apparently related to the fact that systematic irradiation results in changes creating a favorable background for survival and proliferation of tumor cells in the skin tissue medium. The changes facilitate an increase in survival and growth of both pigmented and nonpigmented tumors. Low power radiation stimulates the activity of the cells or cell structures; medium power stimulates their activity; high power suppresses activity.

Sarcoglycans in the normal and pathological breast tissue of humans: an immunohistochemical and molecular study.

Science.gov (United States)

Arco, Alba; Favaloro, Angelo; Gioffrè, Mara; Santoro, Giuseppe; Speciale, Francesco; Vermiglio, Giovanna; Cutroneo, Giuseppina

2012-01-01

The sarcoglycan complex, consisting of α-, β-, γ-, δ- and ε-sarcoglycans, is a multimember transmembrane system providing a mechanosignaling connection from the cytoskeleton to the extracellular matrix. Whereas the expression of α- and γ-sarcoglycan is restricted to striated muscle, other sarcoglycans are widely expressed. Although many studies have investigated sarcoglycans in all muscle types, insufficient data are available on the distribution of the sarcoglycan complex in nonmuscle tissue. On this basis, we used immunohistochemical and RT-PCR techniques to study preliminarily the sarcoglycans in normal glandular breast tissue (which has never been studied in the literature on these proteins) to verify the effective wider distribution of this complex. Moreover, to understand the role of sarcoglycans, we also tested samples obtained from patients affected by fibrocystic mastopathy and breast fibroadenoma. Our data showed, for the first time, that all sarcoglycans are always detectable in all normal samples both in epithelial and myoepithelial cells; in pathological breast tissue, all sarcoglycans appeared severely reduced. These data demonstrated that all sarcoglycans, not only β-, δ-, and ε-sarcoglycans, have a wider distribution, implying a new unknown role for these proteins. Moreover, in breast diseases, sarcoglycans containing cadherin domain homologs could provoke a loss of strong adhesion between epithelial cells, permitting and facilitating the degeneration of these benign breast tumors into malignant tumors. Consequently, sarcoglycans could play an important and intriguing role in many breast diseases and in particular in tumor progression from benign to malignant. Copyright © 2011 S. Karger AG, Basel.

Glucose diffusion in colorectal mucosa—a comparative study between normal and cancer tissues

Science.gov (United States)

Carvalho, Sónia; Gueiral, Nuno; Nogueira, Elisabete; Henrique, Rui; Oliveira, Luís; Tuchin, Valery V.

2017-09-01

Colorectal carcinoma is a major health concern worldwide and its high incidence and mortality require accurate screening methods. Following endoscopic examination, polyps must be removed for histopathological characterization. Aiming to contribute to the improvement of current endoscopy methods of colorectal carcinoma screening or even for future development of laser treatment procedures, we studied the diffusion properties of glucose and water in colorectal healthy and pathological mucosa. These parameters characterize the tissue dehydration and the refractive index matching mechanisms of optical clearing (OC). We used ex vivo tissues to measure the collimated transmittance spectra and thickness during treatments with OC solutions containing glucose in different concentrations. These time dependencies allowed for estimating the diffusion time and diffusion coefficient values of glucose and water in both types of tissues. The measured diffusion times for glucose in healthy and pathological mucosa samples were 299.2±4.7 s and 320.6±10.6 s for 40% and 35% glucose concentrations, respectively. Such a difference indicates a slower glucose diffusion in cancer tissues, which originate from their ability to trap far more glucose than healthy tissues. We have also found a higher free water content in cancerous tissue that is estimated as 64.4% instead of 59.4% for healthy mucosa.

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

International Nuclear Information System (INIS)

Ahmad, S.

2004-01-01

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

Human Colors-The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

Science.gov (United States)

Piña-Oviedo, Sergio; Ortiz-Hidalgo, Carlos; Ayala, Alberto G

2017-03-01

- Colors are important to all living organisms because they are crucial for camouflage and protection, metabolism, sexual behavior, and communication. Human organs obviously have color, but the underlying biologic processes that dictate the specific colors of organs and tissues are not completely understood. A literature search on the determinants of color in human organs yielded scant information. - To address 2 specific questions: (1) why do human organs have color, and (2) what gives normal and pathologic tissues their distinctive colors? - Endogenous colors are the result of complex biochemical reactions that produce biologic pigments: red-brown cytochromes and porphyrins (blood, liver, spleen, kidneys, striated muscle), brown-black melanins (skin, appendages, brain nuclei), dark-brown lipochromes (aging organs), and colors that result from tissue structure (tendons, aponeurosis, muscles). Yellow-orange carotenes that deposit in lipid-rich tissues are only produced by plants and are acquired from the diet. However, there is lack of information about the cause of color in other organs, such as the gray and white matter, neuroendocrine organs, and white tissues (epithelia, soft tissues). Neoplastic tissues usually retain the color of their nonneoplastic counterpart. - Most available information on the function of pigments comes from studies in plants, microorganisms, cephalopods, and vertebrates, not humans. Biologic pigments have antioxidant and cytoprotective properties and should be considered as potential future therapies for disease and cancer. We discuss the bioproducts that may be responsible for organ coloration and invite pathologists and pathology residents to look at a "routine grossing day" with a different perspective.

Automated Spatial Brain Normalization and Hindbrain White Matter Reference Tissue Give Improved [(18)F]-Florbetaben PET Quantitation in Alzheimer's Model Mice.

Science.gov (United States)

Overhoff, Felix; Brendel, Matthias; Jaworska, Anna; Korzhova, Viktoria; Delker, Andreas; Probst, Federico; Focke, Carola; Gildehaus, Franz-Josef; Carlsen, Janette; Baumann, Karlheinz; Haass, Christian; Bartenstein, Peter; Herms, Jochen; Rominger, Axel

2016-01-01

Preclinical PET studies of β-amyloid (Aβ) accumulation are of growing importance, but comparisons between research sites require standardized and optimized methods for quantitation. Therefore, we aimed to evaluate systematically the (1) impact of an automated algorithm for spatial brain normalization, and (2) intensity scaling methods of different reference regions for Aβ-PET in a large dataset of transgenic mice. PS2APP mice in a 6 week longitudinal setting (N = 37) and another set of PS2APP mice at a histologically assessed narrow range of Aβ burden (N = 40) were investigated by [(18)F]-florbetaben PET. Manual spatial normalization by three readers at different training levels was performed prior to application of an automated brain spatial normalization and inter-reader agreement was assessed by Fleiss Kappa (κ). For this method the impact of templates at different pathology stages was investigated. Four different reference regions on brain uptake normalization were used to calculate frontal cortical standardized uptake value ratios (SUVRCTX∕REF), relative to raw SUVCTX. Results were compared on the basis of longitudinal stability (Cohen's d), and in reference to gold standard histopathological quantitation (Pearson's R). Application of an automated brain spatial normalization resulted in nearly perfect agreement (all κ≥0.99) between different readers, with constant or improved correlation with histology. Templates based on inappropriate pathology stage resulted in up to 2.9% systematic bias for SUVRCTX∕REF. All SUVRCTX∕REF methods performed better than SUVCTX both with regard to longitudinal stability (d≥1.21 vs. d = 0.23) and histological gold standard agreement (R≥0.66 vs. R≥0.31). Voxel-wise analysis suggested a physiologically implausible longitudinal decrease by global mean scaling. The hindbrain white matter reference (R mean = 0.75) was slightly superior to the brainstem (R mean = 0.74) and the cerebellum (R mean = 0.73). Automated

Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity.

Science.gov (United States)

Monceau, Virginie; Pasinetti, Nadia; Schupp, Charlotte; Pouzoulet, Fred; Opolon, Paule; Vozenin, Marie-Catherine

2010-11-01

The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established

Far-Infrared Radiation Thermotherapy Improves Tissue Fibrosis in Chronic Extremity Lymphedema.

Science.gov (United States)

Li, Ke; Zhang, Zheng; Liu, Ning Fei; Sadigh, Parviz; Evans, Verity Joyce; Zhou, Huihong; Gao, Weiqing; Zhang, Yi Xin

2017-09-29

Fibrosis can enhance the exacerbation of lymphedema, which becomes obvious in late stage II-III lymphedema. However, whether far-infrared radiation thermotherapy (FIRT) can cure lymphedema fibrosis is still lack of research. This research was to investigate the therapeutic effect of FIRT on tissue fibrosis in the treatment of Late stage II-III lymphedema. Patients accepted only FIRT for a total of 20 sessions. The treatment session duration was 2 hours, and a stable machine temperature of 42°C was maintained throughout treatments. Clinical evaluation and laboratory evaluation were conducted before and after FIRT. Clinical outcome measures included circumference of affected extremity, skin elasticity, ultrasound, patients' subjective assessment, and quality of life (QOL). Laboratory outcome measures included serum and local lymphedema tissue fluid concentrations of fibrosis associated cytokines, tissue growth factor beta-1 (TGF-β1), interleukin (IL)-1β, IL-4, IL-18, and caspase-1. Between 2015 and 2016, clinical evaluation of 64 patients with late stage II-III lymphedema was conducted. From this group, 12 cases (18.75%) underwent simultaneous laboratory evaluation. Circumferences of affected extremities improved significantly following treatment (p pain, discomfort, and numbness (p effective treatment for lymphedema tissue fibrosis; it reduces the concentration of fibrosis cytokines in local lymphedema tissues. Consequently, this treatment can reduce the density of fibrosed tissue in the affected extremity, increase skin elasticity, significantly improve clinical symptoms, and improve QOL of patients.

Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas

International Nuclear Information System (INIS)

Haakensen, Vilde D; Børresen-Dale, Anne-Lise; Helland, Åslaug; Bjøro, Trine; Lüders, Torben; Riis, Margit; Bukholm, Ida K; Kristensen, Vessela N; Troester, Melissa A; Homen, Marit M; Ursin, Giske

2011-01-01

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

CT-based patient modeling for head and neck hyperthermia treatment planning: manual versus automatic normal-tissue-segmentation.

Science.gov (United States)

Verhaart, René F; Fortunati, Valerio; Verduijn, Gerda M; van Walsum, Theo; Veenland, Jifke F; Paulides, Margarethus M

2014-04-01

Clinical trials have shown that hyperthermia, as adjuvant to radiotherapy and/or chemotherapy, improves treatment of patients with locally advanced or recurrent head and neck (H&N) carcinoma. Hyperthermia treatment planning (HTP) guided H&N hyperthermia is being investigated, which requires patient specific 3D patient models derived from Computed Tomography (CT)-images. To decide whether a recently developed automatic-segmentation algorithm can be introduced in the clinic, we compared the impact of manual- and automatic normal-tissue-segmentation variations on HTP quality. CT images of seven patients were segmented automatically and manually by four observers, to study inter-observer and intra-observer geometrical variation. To determine the impact of this variation on HTP quality, HTP was performed using the automatic and manual segmentation of each observer, for each patient. This impact was compared to other sources of patient model uncertainties, i.e. varying gridsizes and dielectric tissue properties. Despite geometrical variations, manual and automatic generated 3D patient models resulted in an equal, i.e. 1%, variation in HTP quality. This variation was minor with respect to the total of other sources of patient model uncertainties, i.e. 11.7%. Automatically generated 3D patient models can be introduced in the clinic for H&N HTP. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

CT-based patient modeling for head and neck hyperthermia treatment planning: Manual versus automatic normal-tissue-segmentation

International Nuclear Information System (INIS)

Verhaart, René F.; Fortunati, Valerio; Verduijn, Gerda M.; Walsum, Theo van; Veenland, Jifke F.; Paulides, Margarethus M.

2014-01-01

Background and purpose: Clinical trials have shown that hyperthermia, as adjuvant to radiotherapy and/or chemotherapy, improves treatment of patients with locally advanced or recurrent head and neck (H and N) carcinoma. Hyperthermia treatment planning (HTP) guided H and N hyperthermia is being investigated, which requires patient specific 3D patient models derived from Computed Tomography (CT)-images. To decide whether a recently developed automatic-segmentation algorithm can be introduced in the clinic, we compared the impact of manual- and automatic normal-tissue-segmentation variations on HTP quality. Material and methods: CT images of seven patients were segmented automatically and manually by four observers, to study inter-observer and intra-observer geometrical variation. To determine the impact of this variation on HTP quality, HTP was performed using the automatic and manual segmentation of each observer, for each patient. This impact was compared to other sources of patient model uncertainties, i.e. varying gridsizes and dielectric tissue properties. Results: Despite geometrical variations, manual and automatic generated 3D patient models resulted in an equal, i.e. 1%, variation in HTP quality. This variation was minor with respect to the total of other sources of patient model uncertainties, i.e. 11.7%. Conclusions: Automatically generated 3D patient models can be introduced in the clinic for H and N HTP

Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

Science.gov (United States)

Chen, Qun; Shetty, Sugandh D.; Heads, Larry; Bolin, Frank; Wilson, Brian C.; Patterson, Michael S.; Sirls, Larry T., II; Schultz, Daniel; Cerny, Joseph C.; Hetzel, Fred W.

1993-06-01

The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

IMPROVEMENT IN HANDWRITTEN NUMERAL STRING RECOGNITION BY SLANT NORMALIZATION AND CONTEXTUAL INFORMATION

NARCIS (Netherlands)

Britto jr., A. de S.; Sabourin, R.; Lethelier, E.; Bortolozzi, F.; Suen, C.Y.

2004-01-01

This work describes a way of enhancing handwritten numeral string recognition by considering slant normalization and contextual information to train an implicit segmentation­based system. A word slant normalization method is modified in order to improve the results for handwritten numeral strings.

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

Energy Technology Data Exchange (ETDEWEB)

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

2008-09-15

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

Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure.

Science.gov (United States)

Massie, Isobel; Dale, Sarah B; Daniels, Julie T

2015-06-01

Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE- RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP.

Expression of IL-18, IL-18 Binding Protein, and IL-18 Receptor by Normal and Cancerous Human Ovarian Tissues: Possible Implication of IL-18 in the Pathogenesis of Ovarian Carcinoma

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Liat Medina

2014-01-01

Full Text Available Proinflammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. The aim of the study was to examine the levels and cellular origin of IL-18, IL-18 binding protein, and IL-18 receptor in normal and cancerous ovarian tissues. Ovarian tissue samples were examined by immunohistochemical staining for IL-18, IL-18BP, and IL-18R and mRNA of these cytokines was analyzed with semiquantitative PT-PCR. IL-18 levels were significantly higher in cancerous ovarian tissues (P=0.0007, IL-18BP levels were significantly higher in normal ovarian tissues (P=0.04, and the ratio of IL-18/IL-18BP was significantly higher in cancerous ovarian tissues (P=0.036. Cancerous ovarian tissues expressed significantly higher IL-18 mRNA levels (P=0.025, while there was no difference in the expression of IL-18BP mRNA and IL-18R mRNA between cancerous and normal ovarian tissues. IL-18 and IL-18BP were expressed dominantly in the epithelial cells of both cancerous and normal ovarian tissues, while IL-18R was expressed dominantly in the epithelial cells of cancerous ovarian tissues but expressed similarly in the epithelial and stromal cells of normal cancerous tissues. This study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma.

Differentiating the two main histologic categories of fibroadenoma tissue from normal breast tissue by using multiphoton microscopy.

Science.gov (United States)

Nie, Y T; Wu, Y; Fu, F M; Lian, Y E; Zhuo, S M; Wang, C; Chen, J X

2015-04-01

Multiphoton microscopy has become a novel biological imaging technique that allows cellular and subcellular microstructure imaging based on two-photon excited fluorescence and second harmonic generation. In this work, we used multiphoton microscopy to obtain the high-contrast images of human normal breast tissue and two main histologic types of fibroadenoma (intracanalicular, pericanalicular). Moreover, quantitative image analysis was performed to characterize the changes of collagen morphology (collagen content, collagen orientation). The results show that multiphoton microscopy combined with quantitative method has the ability to identify the characteristics of fibroadenoma including changes of the duct architecture and collagen morphology in stroma. With the advancement of multiphoton microscopy, we believe that the technique has great potential to be a real-time histopathological diagnostic tool for intraoperative detection of fibroadenoma in the future. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

International Nuclear Information System (INIS)

Bujak, Emil; Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah; Neri, Dario

2014-01-01

There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

Energy Technology Data Exchange (ETDEWEB)

Bujak, Emil [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland); Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah [Philochem AG, Libernstrasse 3, CH-8112 Otelfingen (Switzerland); Neri, Dario, E-mail: neri@pharma.ethz.ch [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland)

2014-09-10

There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

Enhancement technology improves palatability of normal and callipyge lambs.

Science.gov (United States)

Everts, A K R; Wulf, D M; Wheeler, T L; Everts, A J; Weaver, A D; Daniel, J A

2010-12-01

The objective of this research was to determine if BPI Processing Technology (BPT) improved palatability of normal (NN) and callipyge (CN) lamb meat and to determine the mechanism by which palatability was improved. Ten ewe and 10 wether lambs of each phenotype were slaughtered, and carcass traits were assessed by a trained evaluator. The LM was removed at 2 d postmortem. Alternating sides served as controls (CON) or were treated with BPT. Muscles designated BPT were injected to a target 120% by weight with a patented solution containing water, ammonium hydroxide, carbon monoxide, and salt. Muscle pH, cooking loss, Warner-Bratzler shear force (WBS), sarcomere length, cooked moisture retention, and desmin degradation were measured. A trained sensory panel and a take-home consumer panel evaluated LM chops. Callipyge had a heavier BW and HCW, less adjusted fat thickness, reduced yield grades, and greater conformation scores than NN (P cooked moisture retention, smaller WBS values, greater juiciness ratings, less off-flavors, and greater consumer ratings for raw characteristics (like of portion size, like of color, overall like of appearance) and eating characteristics (like of juiciness, like of flavor) than CON (P lamb by increasing cooked moisture retention, improving consumer acceptability of CN to near-normal levels.

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

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Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D [M.D. Anderson Cancer Center, Houston, TX (United States)

2015-06-15

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

International Nuclear Information System (INIS)

Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D

2015-01-01

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted

Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

Energy Technology Data Exchange (ETDEWEB)

Nichols, Romaine C., E-mail: rnichols@floridaproton.org [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Huh, Soon N. [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Prado, Karl L.; Yi, Byong Y.; Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States); Ho, Meng W.; Hoppe, Bradford S.; Mendenhall, Nancy P.; Li, Zuofeng [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States)

2012-05-01

Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

On Predicting lung cancer subtypes using ‘omic’ data from tumor and tumor-adjacent histologically-normal tissue

International Nuclear Information System (INIS)

Pineda, Arturo López; Ogoe, Henry Ato; Balasubramanian, Jeya Balaji; Rangel Escareño, Claudia; Visweswaran, Shyam; Herman, James Gordon; Gopalakrishnan, Vanathi

2016-01-01

Adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the most prevalent histological types among lung cancers. Distinguishing between these subtypes is critically important because they have different implications for prognosis and treatment. Normally, histopathological analyses are used to distinguish between the two, where the tissue samples are collected based on small endoscopic samples or needle aspirations. However, the lack of cell architecture in these small tissue samples hampers the process of distinguishing between the two subtypes. Molecular profiling can also be used to discriminate between the two lung cancer subtypes, on condition that the biopsy is composed of at least 50 % of tumor cells. However, for some cases, the tissue composition of a biopsy might be a mix of tumor and tumor-adjacent histologically normal tissue (TAHN). When this happens, a new biopsy is required, with associated cost, risks and discomfort to the patient. To avoid this problem, we hypothesize that a computational method can distinguish between lung cancer subtypes given tumor and TAHN tissue. Using publicly available datasets for gene expression and DNA methylation, we applied four classification tasks, depending on the possible combinations of tumor and TAHN tissue. First, we used a feature selector (ReliefF/Limma) to select relevant variables, which were then used to build a simple naïve Bayes classification model. Then, we evaluated the classification performance of our models by measuring the area under the receiver operating characteristic curve (AUC). Finally, we analyzed the relevance of the selected genes using hierarchical clustering and IPA® software for gene functional analysis. All Bayesian models achieved high classification performance (AUC > 0.94), which were confirmed by hierarchical cluster analysis. From the genes selected, 25 (93 %) were found to be related to cancer (19 were associated with ADC or SCC), confirming the biological relevance of our

THE PRESENCE OF ENDOGENOUS PYROGEN IN NORMAL RABBIT TISSUES.

Science.gov (United States)

SNELL, E S; ATKINS, E

1965-06-01

Saline extracts of homogenized, uninfected, rabbit tissues produced febrile responses when injected intravenously into rabbits. Extracts of muscle, lung, and heart evoked fevers that were similar to those induced by leucocyte pyrogen; extracts of spleen, liver, and kidney caused more sustained fevers. The minimal pyrogenic dose appeared to be between 1.5 and 3 gm wet weight of tissue. Evidence is presented that neither Gram-negative bacterial endotoxin nor polymorphonuclear leucocytes (circulating or sequestered in the tissues) can be implicated as the source of pyrogen in tissue extracts. It seems likely, therefore, that a pyrogenic material of truly endogenous origin is widely distributed in tissues. Tissue pyrogen appears to be a large molecule which is relatively resistant to treatment with acid but not with alkali. Possible pathological roles for this endogenous agent (or agents) are briefly indicated.

Activity of pyrimidine degradation enzymes in normal tissues

NARCIS (Netherlands)

van Kuilenburg, A. B. P.; van Lenthe, H.; van Gennip, A. H.

2006-01-01

In this study, we measured the activity of dihydropyrimidine dehydrogenase (DPD), dihydropyrimidinase (DHP) and beta-ureidopropionase (beta-UP), using radiolabeled substrates, in 16 different tissues obtained at autopsy from a single patient. The activity of DPD could be detected in all tissues

Radiosensitization of tumors and normal tissues by combined treatment with misonidazole and heat

International Nuclear Information System (INIS)

Hofer, K.G.; MacKinnon, A.R.; Schubert, A.L.; Lehr, J.E.; Grimmett, E.V.

1981-01-01

Combination treatment of mice with misonidazole (0.5 mg/g body wt.) and hyperthermia (41.5/sup o/C for 45 mins.) produced dramatic radiosensitization in hypoxic BP-8 murine sarcoma cells. The dose modifying factor (DMF: 4.3) was such that hypoxic BP-8 cells subjected to combination therapy became more radiosensitive than untreated, fully oxygenated cell populations. In contrast, radiosensitization by combination treatment was comparatively minor or completely absent in normal body tissues such as skin (DMF: 1.57), intestine (DMF: 1.0), and bone marrow (DMF: 1.0). These results suggest that simultaneous administration of misonidazole and hyperthermia may prove an effective adjuvant to conventional clinical radiation therapy

Differentiation between chronic hepatitis and normal liver of grayscale ultrasound tissue quantification using adobe photoshop(5.0)

International Nuclear Information System (INIS)

Choi, Jong Cheol; Oh, Jong Young; Lim, Jong Uk; Nam, Kyung Jin

2001-01-01

To evaluate whether was any difference in the brightness of echogenicity on gray scale ultrasound imaging between the liver with chronic hepatitis and the normal liver using Adobe photoshop 5.0 Seventy-five patients with pathologically proven chronic hepatitis and twenty normal volunteers were included in this study. Adobe photoshop 5.0 histogram was used to measure the brightness of image. The measured brightness of the liver was divided by the brightness of the kidney, and the radio was calculated and compared between patients with chronic hepatitis and the normal control groups. In addition, the degree of fibrosis was also evaluated. The difference in brightness between the normal liver and live with chronic hepatitis was statistically significant, but no statistically significant difference was observed between the brightness of the liver and the degree of fibrosis in the liver. Tissue echo quantification using Adobe Photoshop 5.0 may be a helpful diagnostic methods for the patients with chronic hepatitis.

Correlation of in vitro lymphocyte radiosensitivity and gene expression with late normal tissue reactions following curative radiotherapy for breast cancer

International Nuclear Information System (INIS)

Finnon, Paul; Kabacik, Sylwia; MacKay, Alan; Raffy, Claudine; A’Hern, Roger; Owen, Roger; Badie, Christophe; Yarnold, John; Bouffler, Simon

2012-01-01

Background and purpose: Identification of mechanisms of late normal tissue responses to curative radiotherapy that discriminate individuals with marked or mild responses would aid response prediction. This study aimed to identify differences in gene expression, apoptosis, residual DNA double strand breaks and chromosomal damage after in vitro irradiation of lymphocytes in a series of patients with marked (31 cases) or mild (28 controls) late adverse reaction to adjuvant breast radiotherapy. Materials and methods: Gene expression arrays, residual γH2AX, apoptosis, G2 chromosomal radiosensitivity and G0 micronucleus assay were used to compare case and control lymphocyte radiation responses. Results: Five hundred and thirty genes were up-regulated and 819 down-regulated by ionising radiation. Irradiated samples were identified with an overall cross-validated error rate of 3.4%. Prediction analyses to classify cases and controls using unirradiated (0 Gy), irradiated (4 Gy) or radiation response (4–0 Gy) expression profiles correctly identified samples with, respectively, 25%, 22% or 18.5% error rates. Significant inter-sample variation was observed for all cellular endpoints but cases and controls could not be distinguished. Conclusions: Variation in lymphocyte radiosensitivity does not necessarily correlate with normal tissue response to radiotherapy. Gene expression analysis can predict of radiation exposure and may in the future help prediction of normal tissue radiosensitivity.

Numerical study of water diffusion in biological tissues using an improved finite difference method

International Nuclear Information System (INIS)

Xu Junzhong; Does, Mark D; Gore, John C

2007-01-01

An improved finite difference (FD) method has been developed in order to calculate the behaviour of the nuclear magnetic resonance signal variations caused by water diffusion in biological tissues more accurately and efficiently. The algorithm converts the conventional image-based finite difference method into a convenient matrix-based approach and includes a revised periodic boundary condition which eliminates the edge effects caused by artificial boundaries in conventional FD methods. Simulated results for some modelled tissues are consistent with analytical solutions for commonly used diffusion-weighted pulse sequences, whereas the improved FD method shows improved efficiency and accuracy. A tightly coupled parallel computing approach was also developed to implement the FD methods to enable large-scale simulations of realistic biological tissues. The potential applications of the improved FD method for understanding diffusion in tissues are also discussed. (note)

A Protocol for the Comprehensive Flow Cytometric Analysis of Immune Cells in Normal and Inflamed Murine Non-Lymphoid Tissues

Science.gov (United States)

Yu, Yen-Rei A.; O’Koren, Emily G.; Hotten, Danielle F.; Kan, Matthew J.; Kopin, David; Nelson, Erik R.; Que, Loretta; Gunn, Michael D.

2016-01-01

Flow cytometry is used extensively to examine immune cells in non-lymphoid tissues. However, a method of flow cytometric analysis that is both comprehensive and widely applicable has not been described. We developed a protocol for the flow cytometric analysis of non-lymphoid tissues, including methods of tissue preparation, a 10-fluorochrome panel for cell staining, and a standardized gating strategy, that allows the simultaneous identification and quantification of all major immune cell types in a variety of normal and inflamed non-lymphoid tissues. We demonstrate that our basic protocol minimizes cell loss, reliably distinguishes macrophages from dendritic cells (DC), and identifies all major granulocytic and mononuclear phagocytic cell types. This protocol is able to accurately quantify 11 distinct immune cell types, including T cells, B cells, NK cells, neutrophils, eosinophils, inflammatory monocytes, resident monocytes, alveolar macrophages, resident/interstitial macrophages, CD11b- DC, and CD11b+ DC, in normal lung, heart, liver, kidney, intestine, skin, eyes, and mammary gland. We also characterized the expression patterns of several commonly used myeloid and macrophage markers. This basic protocol can be expanded to identify additional cell types such as mast cells, basophils, and plasmacytoid DC, or perform detailed phenotyping of specific cell types. In examining models of primary and metastatic mammary tumors, this protocol allowed the identification of several distinct tumor associated macrophage phenotypes, the appearance of which was highly specific to individual tumor cell lines. This protocol provides a valuable tool to examine immune cell repertoires and follow immune responses in a wide variety of tissues and experimental conditions. PMID:26938654

Corrugated round fibers to improve cell adhesion and proliferation in tissue engineering scaffolds

NARCIS (Netherlands)

Bettahalli Narasimha, M.S.; Arkesteijn, I.T.M.; Wessling, Matthias; Poot, Andreas A.; Stamatialis, Dimitrios

2013-01-01

Optimal cell interaction with biomaterial scaffolds is one of the important requirements for the development of successful in vitro tissue-engineered tissues. Fast, efficient and spatially uniform cell adhesion can improve the clinical potential of engineered tissue. Three-dimensional (3-D) solid

Modulation of the ρ/rock pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity

International Nuclear Information System (INIS)

Monceau, V.; Pasinetti, N.; Schupp, C.; Pouzoulet, F.; Opolon, P.; Vozenin, M.C.

2010-01-01

The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibro-genic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardio-myocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibro-genic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibro-genic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of

Canine tumor and normal tissue response to heat and radiation

International Nuclear Information System (INIS)

Gillette, E.L.; McChesney, S.L.

1985-01-01

Oral squamous cell carcinomas of dogs were treated with either irradiation alone or combined with hyperthermia. Tumor control was assessed as no evidence of disease one year following treatment. Dogs were randomized to variable radiation doses which were given in ten fractions three times a week for three weeks. Heat was given three hours after the first and third radiation dose each week for seven treatments. The attempt was made to achieve a minimum tumor temperature of 42 0 C for thirty minutes with a maximum normal tissue temperature of 40 0 C. It was usually possible to selectively heat tumors. The TCD 50 for irradiation alone was about 400 rads greater than for heat plus irradiation. The dose response curve for heat plus radiation was much steeper than for radiation alone indicating less heterogeneity of tumor response. That also implies a much greater effectiveness of radiation combined with heat at higher tumor control probabilities. Early necrosis caused by heating healed with conservative management. No increase in late radiation necrosis was observed

Acute and late effects of multimodal therapy on normal tissues

International Nuclear Information System (INIS)

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

1977-01-01

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

Radiotherapy. Non-standard fractionated regimens improving cancer treatment. Part II. Response of normal tissues to fractionated irradiation

International Nuclear Information System (INIS)

Villar, A.; Hernandez, M.; Pera, J.; Cambray, M.; Villa, S.; Arnaiz, M.D.

1988-01-01

The phenomena participating in the response of tissues to fractionated irradiation are analyzed with special emphasis on the most relevant points influencing the design of non-standard fractionated regimens. (Author)

Suberoylanilide hydroxamic acid affects γH2AX expression in osteosarcoma, atypical teratoid rhabdoid tumor and normal tissue cell lines after irradiation

International Nuclear Information System (INIS)

Blattmann, C.; Oertel, S.; Thiemann, M.; Weber, K.J.; Schmezer, P.; Zelezny, O.; Lopez Perez, R.; Kulozik, A.E.; Debus, J.; Ehemann, V.

2012-01-01

Osteosarcoma and atypical teratoid rhabdoid tumors are tumor entities with varying response to common standard therapy protocols. Histone acetylation affects chromatin structure and gene expression which are considered to influence radiation sensitivity. The aim of this study was to investigate the effect of the combination therapy with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and irradiation on atypical teratoid rhabdoid tumors and osteosarcoma compared to normal tissue cell lines. Clonogenic assay was used to determine cell survival. DNA double-strand breaks (DSB) were examined by pulsed-field electrophoresis (PFGE) as well as by γH2AX immunostaining involving flow cytometry, fluorescence microscopy, and immunoblot analysis. SAHA lead to an increased radiosensitivity in tumor but not in normal tissue cell lines. γH2AX expression as an indicator for DSB was significantly increased when SAHA was applied 24 h before irradiation to the sarcoma cell cultures. In contrast, γH2AX expression in the normal tissue cell lines was significantly reduced when irradiation was combined with SAHA. Analysis of initial DNA fragmentation and fragment rejoining by PFGE, however, did not reveal differences in response to the SAHA pretreatment for either cell type. SAHA increases radiosensitivity in tumor but not normal tissue cell lines. The increased H2AX phosphorylation status of the SAHA-treated tumor cells post irradiation likely reflects its delayed dephosphorylation within the DNA damage signal decay rather than chromatin acetylation-dependent differences in the overall efficacy of DSB induction and rejoining. The results support the hypothesis that combining SAHA with irradiation may provide a promising strategy in the treatment of solid tumors. (orig.)

Computed tomography of the normal sternum

International Nuclear Information System (INIS)

Goodman, L.R.; Teplick, S.K.; Kay, H.

1983-01-01

The normal CT anatomy of the sternum was studied in 35 patients. In addition to the normal appearance of the sternum, normal variants that may mimic desease were often noted. In the manubrium, part of the posterior cortical margin was unsharp and irregular in 34 of 35 patients. Part of the anterior cortical margin was indistinct in 20 of the 35 patients. Angulation of the CT gantry to a position more nearly perpendicular to the manubrium improved the definition of the cortical margins. The body of the sternum was ovoid to rectangular and usually had sharp cortical margins. Sections through the manubriosternal joint and xyphoid often demonstrated irregular mottled calcifications and indistinct margins again simulating bony lesions. The rib insertions, sternal clavicular joints, and adjacent soft-tissue appearance also were evaluated

In-vivo tissue uptake and retention of Sn-117m(4+)DTPA in a human subject with metastatic bone pain and in normal mice

International Nuclear Information System (INIS)

Swailem, Fayez M.; Krishnamurthy, Gerbail T.; Srivastava, Suresh C.; Aguirre, Maria L.; Ellerson, Dawn L.; Walsh, T. Kent; Simpson, Laura

1998-01-01

Organ and tissue uptake and retention of Sn-117m(4+)DTPA were studied in a human subject treated for metastatic bone pain, and the results were compared with the biodistribution studies in five normal mice. The explanted organs from a patient who received a therapy dose of 18.6 mCi (688.2 MBq) Sn-117m(4+)DTPA and who died 47 days later were imaged with a γ-camera, and tissue samples were counted and also autoradiographed. Bone, muscle, liver, fat, lungs, kidneys, spleen, heart and pancreas tissue samples were assayed in a well counter for radioactivity. Regions of interest were drawn over bone and major organs to calculate and quantify clearance times using three in vivo Sn-117m(4+)DTPA whole-body scintigrams acquired at 1, 24 and 168 h after injection. Five normal mice injected with the same batch of Sn-117m(4+)DTPA as used for the human subject were sacrificed at 24 h, and tissue samples were collected and assayed for radioactivity for comparison with the human data. For the human subject, whole-body retention at 47 days postinjection was 81% of the injected dose, and the rest (19%) was excreted in urine. Of the whole-body retained activity at 47 days, 82.4% was in bone, 7.8% in the muscle and 1.5% in the liver, and the rest was distributed among other tissues. γ-Ray scintigrams and electron autoradiographs of coronal slices of the thoracolumbar vertebral body showed heterogenous metastatic involvement with normal bone between metastatic lesions. There was nonuniform distribution of radioactivity even within a single vertebral body, indicating normal bone between metastatic lesions. Lesion-to-nonlesion ratios ranged from 3 to 5. However, the osteoid-to-marrow cavity deposition ratio, from the microautoradiographs, was 11:1. The peak uptake in the human bone was seen at 137 h with no biological clearance. Soft tissues showed peak uptake at 1 h and exhibited three compartmental clearance components. Whole-body retention in normal mice was 38.7% of the injected

Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics.

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Maryna Perepelyuk

Full Text Available Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G' and G" and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver.

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

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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.

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

Science.gov (United States)

Dhanapal, Raghu; Ranganathan, K; Kondaiah, Paturu; Devi, R Uma; Joshua, Elizabeth; Saraswathi, T R

2015-01-01

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. 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. 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. 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.

Relaxation time of normal breast tissues. Changes with age and variations during the menstrual cycle

International Nuclear Information System (INIS)

Dean, K.I.; Majurin, M.L.; Komu, M.

1994-01-01

The influence of age on the relaxation times of normal breast parenchyma and its surrounding fatty tissue were evaluated, and the variations during a normal menstrual cycle were analyzed using an ultra low field 0.02 T imager. Thirty-nine healthy volunteers aged 21 to 59 years were examined to determine T1 and T2 relaxation times, and 8 of these volunteers were studied once weekly during one menstrual cycle. The only significant trend was an increase in the T2 of breast parenchyma with increasing age. During the menstrual cycle there was a slight but insignificant (p=0.10) increase in T1 of the breast parenchyma values during the latter half of the menstrual cycle, and a corresponding increase in T2 values between the 2nd and 3rd weeks of the menstrual cycle, which was significant. (orig.)

Relaxation time of normal breast tissues. Changes with age and variations during the menstrual cycle

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Dean, K.I. (University Central Hospital, Turku (Finland). Dept. of Diagnostic Radiology); Majurin, M.L. (University Central Hospital, Turku (Finland). Dept. of Diagnostic Radiology); Komu, M. (University Central Hospital, Turku (Finland). Dept. of Diagnostic Radiology)

1994-05-01

The influence of age on the relaxation times of normal breast parenchyma and its surrounding fatty tissue were evaluated, and the variations during a normal menstrual cycle were analyzed using an ultra low field 0.02 T imager. Thirty-nine healthy volunteers aged 21 to 59 years were examined to determine T1 and T2 relaxation times, and 8 of these volunteers were studied once weekly during one menstrual cycle. The only significant trend was an increase in the T2 of breast parenchyma with increasing age. During the menstrual cycle there was a slight but insignificant (p=0.10) increase in T1 of the breast parenchyma values during the latter half of the menstrual cycle, and a corresponding increase in T2 values between the 2nd and 3rd weeks of the menstrual cycle, which was significant. (orig.).

Darkfield illumination improves microscopic detection of metals in Timm's stained tissue

DEFF Research Database (Denmark)

Baatrup, E; Frederickson, C J

1989-01-01

Deposits of trace or toxic metals can be quickly identified by light microscopical surveys of tissue sections stained for metals by variants of Timm's silver enhancement method. The present work shows that the small, isolated silver grains that label isolated deposits of metal in tissue are undet...... are undetectable in brightfield light microscopy but are easily detected in darkfield microscopy. Darkfield illumination is therefore recommended for improving the detection of trace or toxic metals in tissue. Udgivelsesdato: 1989-Aug......Deposits of trace or toxic metals can be quickly identified by light microscopical surveys of tissue sections stained for metals by variants of Timm's silver enhancement method. The present work shows that the small, isolated silver grains that label isolated deposits of metal in tissue...

of the stomach (ID 345), neutralisation of gastric acid (ID 345), contribution to normal formation of collagen and connective tissue (ID 287, 288, 333, 334, 335, 1405, 1652, 1718, 1719, 1945), maintenance of normal bone (ID 287, 335, 1652, 1718, 1945), maintenance of normal joints (ID 1405, 1652, 1945

DEFF Research Database (Denmark)

Tetens, Inge

claims in relation to silicon and protection against aluminium accumulation in the brain, cardiovascular health, forming a protective coat on the mucous membrane of the stomach, neutralisation of gastric acid, contribution to normal formation of collagen and connective tissue, maintenance of normal bone...

Discrimination of prostate cancer from normal peripheral zone and central gland tissue by using dynamic contrast-enhanced MR imaging

NARCIS (Netherlands)

Engelbrecht, Marc R.; Huisman, Henkjan J.; Laheij, Robert J. F.; Jager, Gerrit J.; van Leenders, Geert J. L. H.; Hulsbergen-van de Kaa, Christina A.; de La Rosette, Jean J. M. C. H.; Blickman, Johan G.; Barentsz, Jelle O.

2003-01-01

PURPOSE: To evaluate which parameters of dynamic magnetic resonance (MR) imaging and T2 relaxation rate would result in optimal discrimination of prostatic carcinoma from normal peripheral zone (PZ) and central gland (CG) tissues and to correlate these parameters with tumor stage, Gleason score,

Irbesartan increased PPARγ activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

International Nuclear Information System (INIS)

Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo; Horiuchi, Masatsugu

2011-01-01

Research highlights: → Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. → Irbesartan decreased white adipose tissue weight without affecting body weight. → DNA-binding for PPARγ was increased in white adipose tissue in vivo by irbesartan. → Irbesartan increased adipocyte number in white adipose tissue. → Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPARγ agonistic action of an AT 1 receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPARγ in white adipose tissue and the DNA-binding activity of PPARγ in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPARγ and improved adipose tissue dysfunction including insulin resistance.

Is NAA reduction in normal contralateral cerebral tissue in stroke patients dependent on underlying risk factors?

Science.gov (United States)

Walker, P M; Ben Salem, D; Giroud, M; Brunotte, F

2006-05-01

This retrospective study investigated the dependence of N-acetyl aspartate (NAA) ratios on risk factors for cerebral vasculopathy such as sex, age, hypertension, diabetes mellitus, carotid stenosis, and dyslipidaemia, which may have affected brain vessels and induced metabolic brain abnormalities prior to stroke. We hypothesise that in stroke patients metabolic alterations in the apparently normal contralateral brain are dependent on the presence or not of such risk factors. Fifty nine patients (31 male, 28 female: 58.8+/-16.1 years old) with cortical middle cerebral artery (MCA) territory infarction were included. Long echo time chemical shift imaging spectroscopy was carried out on a Siemens 1.5 T Magnetom Vision scanner using a multi-voxel PRESS technique. Metabolite ratios (NAA/choline, NAA/creatine, lactate/choline, etc) were studied using uni- and multivariate analyses with respect to common risk factors. The influence of age, stroke lesion size, and time since stroke was studied using a linear regression approach. Age, sex, and hypertension all appeared to individually influence metabolite ratios, although only hypertension was significant after multivariate analysis. In both basal ganglia and periventricular white matter regions in apparently normal contralateral brain, the NAA/choline ratio was significantly lower in hypertensive (1.37+/-0.16 and 1.50+/-0.19, respectively) than in normotensive patients (1.72+/-0.19 and 1.85+/-0.15, respectively). Regarding MCA infarction, contralateral tissue remote from the lesion behaves abnormally in the presence of hypertension, the NAA ratios in hypertensive patients being significantly lower. These data suggest that hypertension may compromise the use of contralateral tissue data as a reference for comparison with ischaemic tissue.

Detection of cancerous kidney tissue areas by means of infrared spectroscopy of intercellular fluid

Science.gov (United States)

Urboniene, V.; Jankevicius, F.; Zelvys, A.; Steiner, G.; Sablinskas, V.

2014-03-01

In this work the infrared absorption spectra of intercellular fluid of normal and tumor kidney tissue were recorded and analyzed. The samples were prepared by stamping freshly resected tissue onto a CaF2 substrate. FT-IR spectra obtained from intracellular fluid of tumor tissue exhibit stronger absorption bands in the spectral region from 1000-1200 cm-1 and around 1750 cm-1 than those obtained from normal tissue. It is likely the spectra of extracellular matrix of kidney tumor tissue with large increases in the intensities of these bands represent a higher concentration of fatty acids and glycerol. Amide I and amide II bands are stronger in spectra of normal tissue indicating a higher level of proteins. The results demonstrate that FT-IR spectroscopy of intercellular fluids is a novel approach for a quick diagnosis during surgical resection, which can improve the therapy of kidney tumors.

Normalization with Corresponding Naïve Tissue Minimizes Bias Caused by Commercial Reverse Transcription Kits on Quantitative Real-Time PCR Results.

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Andreas Garcia-Bardon

Full Text Available Real-time reverse transcription polymerase chain reaction (PCR is the gold standard for expression analysis. Designed to improve reproducibility and sensitivity, commercial kits are commonly used for the critical step of cDNA synthesis. The present study was designed to determine the impact of these kits. mRNA from mouse brains were pooled to create serial dilutions ranging from 0.0625 μg to 2 μg, which were transcribed into cDNA using four different commercial reverse-transcription kits. Next, we transcribed mRNA from brain tissue after acute brain injury and naïve mice into cDNA for qPCR. Depending on tested genes, some kits failed to show linear results in dilution series and revealed strong variations in cDNA yield. Absolute expression data in naïve and trauma settings varied substantially between these kits. Normalization with a housekeeping gene failed to reduce kit-dependent variations, whereas normalization eliminated differences when naïve samples from the same region were used. The study shows strong evidence that choice of commercial cDNA synthesis kit has a major impact on PCR results and, consequently, on comparability between studies. Additionally, it provides a solution to overcome this limitation by normalization with data from naïve samples. This simple step helps to compare mRNA expression data between different studies and groups.

Diode laser soft-tissue surgery: advancements aimed at consistent cutting, improved clinical outcomes.

Science.gov (United States)

Romanos, Georgios E

2013-01-01

Laser dentistry and soft-tissue surgery, in particular, have become widely adopted in recent years. Significant cost reductions for dental lasers and the increasing popularity of CADCAM, among other factors, have contributed to a substantial increase in the installed base of dental lasers, especially soft-tissue lasers. New development in soft-tissue surgery, based on the modern understanding of laser-tissue interactions and contact soft-tissue surgery mechanisms, will bring a higher quality and consistency level to laser soft-tissue surgery. Recently introduced diode-laser technology enables enhanced control of side effects that result from tissue overheating and may improve soft-tissue surgical outcomes.

SU-F-T-150: Comparing Normal Tissue Irradiated Volumes for Proton Vs. Photon Treatment Plans On Lung Patients

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Liu, A; Mohan, R; Liao, Z [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: The aim of this work is to compare the “irradiated volume” (IRV) of normal tissues receiving 5, 20, 50, 80 and 90% or higher of the prescription dose with passively scattered proton therapy (PSPT) vs. IMRT of lung cancer patients. The overall goal of this research is to understand the factors affecting outcomes of a randomized PSPT vs. IMRT lung trial. Methods: Thirteen lung cancer patients, selected randomly, were analyzed. Each patient had PSPT and IMRT 74 Gy (RBE) plans meeting the same normal tissue constraints generated. IRVs were created for pairs of IMRT and PSPT plans on each patient. The volume of iGTV, (respiratory motion-incorporated GTV) was subtracted from each IRV to create normal tissue irradiated volume IRVNT. The average of IRVNT DVHs over all patients was also calculated for both modalities and inter-compared as were the selected dose-volume indices. Probability (p value) curves were calculated based on the Wilcoxon matched-paired signed-rank test to determine the dose regions where the statistically significant differences existed. Results: As expected, the average 5, 20 and 50% IRVNT’s for PSPT was found to be significantly smaller than for IMRT (p < 0.001, 0.01, and 0.001 respectively). However, the average 90% IRVNT for PSPT was greater than for IMRT (p = 0.003) presumably due to larger penumbra of protons and the long range of protons in lower density media. The 80% IRVNT for PSPT was also larger but not statistically distinguishable (p = .224). Conclusion: PSPT modality has smaller irradiated volume at lower doses, but larger volume at high doses. A larger cohort of lung patients will be analyzed in the future and IRVNT of patients treated with PSPT and IMRT will be compared to determine if the irradiated volumes (the magnitude of “dose bath”) correlate with outcomes.

Normal tissue tolerance to external beam radiation therapy: Brain and hypophysis

International Nuclear Information System (INIS)

Haberer, S.; Assouline, A.; Mazeron, J.J.

2010-01-01

Anticancer treatments-induced central nervous system neurotoxicity has become a major problem in recent years. Real advances in therapeutic results for cancer treatments have improved patients survival. Nowadays, central nervous system radiation therapy is widely prescribed, both for palliative and curative treatments in the management of malignant or benign tumors. Recent data on tolerance of normal central nervous system to radiation therapy are reviewed here, early and delayed radiation-induced effects are described and dose recommendations are suggested for clinical practice. (authors)

Fibrochondrogenic potential of synoviocytes from osteoarthritic and normal joints cultured as tensioned bioscaffolds for meniscal tissue engineering in dogs

Directory of Open Access Journals (Sweden)

Jennifer J. Warnock

2014-09-01

Full Text Available Meniscal tears are a common cause of stifle lameness in dogs. Use of autologous synoviocytes from the affected stifle is an attractive cell source for tissue engineering replacement fibrocartilage. However, the diseased state of these cells may impede in vitro fibrocartilage formation. Synoviocytes from 12 osteoarthritic (“oaTSB” and 6 normal joints (“nTSB” were cultured as tensioned bioscaffolds and compared for their ability to synthesize fibrocartilage sheets. Gene expression of collagens type I and II were higher and expression of interleukin-6 was lower in oaTSB versus nTSB. Compared with nTSB, oaTSB had more glycosaminoglycan and alpha smooth muscle staining and less collagen I and II staining on histologic analysis, whereas collagen and glycosaminoglycan quantities were similar. In conclusion, osteoarthritic joint—origin synoviocytes can produce extracellular matrix components of meniscal fibrocartilage at similar levels to normal joint—origin synoviocytes, which makes them a potential cell source for canine meniscal tissue engineering.

Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

Science.gov (United States)

Yang, Tao; Liu, Shan; Zheng, Tian-Hui; Tao, Yan-Yan; Liu, Cheng-Hai

2015-05-26

Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (Pdistribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (Pdistribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Isolation and genome-wide expression and methylation characterization of CD31+ cells from normal and malignant human prostate tissue

Science.gov (United States)

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

Accuracy of real-time shear wave elastography in the assessment of normal liver tissue in the guinea pig (cavia porcellus).

Science.gov (United States)

Glińska-Suchocka, K; Kubiak, K; Spużak, J; Jankowski, M; Borusewicz, P

2017-03-28

Shear wave elastography is a novel technique enabling real-time measurement of the elasticity of liver tissue. The color map is superimposed on the classic ultrasound image of the assessed tissue, which enables a precise evaluation of the stiffness of the liver tissue. The aim of the study was to assess the stiffness of normal liver tissue in the guinea pig using shear wave elastography. The study was carried out on 36 guinea pigs using the SuperSonic Imagine Aixplorer scanner, and a 1 to 6 MH convex SC6-1 transducer. An ultrasound guided Try-Cut liver core needle biopsy was carried out in all the studied animals and the collected samples were examined to exclude pathological lesions. The mean liver tissue stiffness ranged from 0.89 to 5.40 kPa. We found that shear wave elastography is an easy, non-invasive technique that can be used to assess the stiffness of liver tissue. The obtained results can be used in future studies to assess the types and changes of liver tissue in the course of various types of liver disease.

Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

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Saurabh Chattopadhyay

Full Text Available Angiotensin-converting enzyme (ACE regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS. Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

Science.gov (United States)

Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

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

International Nuclear Information System (INIS)

Teramoto, Daisuke; Ushioda, Yuichi; Sasaki, Ayaka; Sakurai Yuki; Nagahama, Hiroshi; Nakamura, Manami; Sugimori, Hiroyuki; Sakata, Motomichi

2013-01-01

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 T 1 -value and T 2 -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 (T 1 - and T 2 -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 T 1 and T 2 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)

Spiral wave classification using normalized compression distance: Towards atrial tissue spatiotemporal electrophysiological behavior characterization.

Science.gov (United States)

Alagoz, Celal; Guez, Allon; Cohen, Andrew; Bullinga, John R

2015-08-01

Analysis of electrical activation patterns such as re-entries during atrial fibrillation (Afib) is crucial in understanding arrhythmic mechanisms and assessment of diagnostic measures. Spiral waves are a phenomena that provide intuitive basis for re-entries occurring in cardiac tissue. Distinct spiral wave behaviors such as stable spiral waves, meandering spiral waves, and spiral wave break-up may have distinct electrogram manifestations on a mapping catheter. Hence, it is desirable to have an automated classification of spiral wave behavior based on catheter recordings for a qualitative characterization of spatiotemporal electrophysiological activity on atrial tissue. In this study, we propose a method for classification of spatiotemporal characteristics of simulated atrial activation patterns in terms of distinct spiral wave behaviors during Afib using two different techniques: normalized compressed distance (NCD) and normalized FFT (NFFTD). We use a phenomenological model for cardiac electrical propagation to produce various simulated spiral wave behaviors on a 2D grid and labeled them as stable, meandering, or breakup. By mimicking commonly used catheter types, a star shaped and a circular shaped both of which do the local readings from atrial wall, monopolar and bipolar intracardiac electrograms are simulated. Virtual catheters are positioned at different locations on the grid. The classification performance for different catheter locations, types and for monopolar or bipolar readings were also compared. We observed that the performance for each case differed slightly. However, we found that NCD performance is superior to NFFTD. Through the simulation study, we showed the theoretical validation of the proposed method. Our findings suggest that a qualitative wavefront activation pattern can be assessed during Afib without the need for highly invasive mapping techniques such as multisite simultaneous electrogram recordings.

Comparison of radiosensitivities of human autologous normal and neoplastic thyroid epithelial cells

International Nuclear Information System (INIS)

Miller, R.C.; Kopecky, K.J.; Hiraoka, T.; Ezaki, H.; Clifton, K.H.

1986-01-01

Studies were conducted to examine differences between the radiosensitivities of normal and neoplastic epithelial cells of the human thyroid. Freshly excised thyroid tissues from the tumours of eight patients with papillary carcinoma (PC) and five with follicular adenoma (FA) were cultured in vitro separately from normal thyroid tissue obtained from the surgical margins of the same patients. Plating efficiency of unirradiated control tissue was lower, on average for tumour tissue compared with normal tissue. Radiosensitivity, measured by the 37% inactivation dose D 0 , was greater for carcinoma tissue than for normal tissue in seven out of eight PC cases. Adenomatous tissue was less radiosensitive than normal tissue in four out of five FA cases. This is the first report comparing the radiosensitivity of autologous normal and abnormal epithelial tissue from the human thyroid. (author)

The dynamic DNA methylation landscape of the mutL homolog 1 shore is altered by MLH1-93G>A polymorphism in normal tissues and colorectal cancer.

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Savio, Andrea J; Mrkonjic, Miralem; Lemire, Mathieu; Gallinger, Steven; Knight, Julia A; Bapat, Bharat

2017-01-01

Colorectal cancers (CRCs) undergo distinct genetic and epigenetic alterations. Expression of mutL homolog 1 ( MLH1 ), a mismatch repair gene that corrects DNA replication errors, is lost in up to 15% of sporadic tumours due to mutation or, more commonly, due to DNA methylation of its promoter CpG island. A single nucleotide polymorphism (SNP) in the CpG island of MLH1 ( MLH1 -93G>A or rs1800734) is associated with CpG island hypermethylation and decreased MLH1 expression in CRC tumours. Further, in peripheral blood mononuclear cell (PBMC) DNA of both CRC cases and non-cancer controls, the variant allele of rs1800734 is associated with hypomethylation at the MLH1 shore, a region upstream of its CpG island that is less dense in CpG sites . To determine whether this genotype-epigenotype association is present in other tissue types, including colorectal tumours, we assessed DNA methylation in matched normal colorectal tissue, tumour, and PBMC DNA from 349 population-based CRC cases recruited from the Ontario Familial Colorectal Cancer Registry. Using the semi-quantitative real-time PCR-based MethyLight assay, MLH1 shore methylation was significantly higher in tumour tissue than normal colon or PBMCs ( P  MLH1 was not associated with MSI status or promoter CpG island hypermethylation, regardless of genotype. To confirm these results, bisulfite sequencing was performed in matched tumour and normal colorectal specimens from six CRC cases, including two cases per genotype (wildtype, heterozygous, and homozygous variant). Bisulfite sequencing results corroborated the methylation patterns found by MethyLight, with significant hypomethylation in normal colorectal tissue of variant SNP allele carriers. These results indicate that the normal tissue types tested (colorectum and PBMC) experience dynamic genotype-associated epigenetic alterations at the MLH1 shore, whereas tumour DNA incurs aberrant hypermethylation compared to normal DNA.

Voluntary exercise improves murine dermal connective tissue status in high-fat diet-induced obesity.

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Lőrincz, Kende; Haluszka, Dóra; Kiss, Norbert; Gyöngyösi, Nóra; Bánvölgyi, András; Szipőcs, Róbert; Wikonkál, Norbert M

2017-04-01

Obesity is a risk factor for several cardiovascular and metabolic diseases. Its influence on the skin is less obvious, yet certain negative effects of adipose tissue inflammation on the dermis have been suggested. Excess weight is closely associated with sedentary behavior, so any increase in physical activity is considered beneficial against obesity. To investigate the effects of obesity and physical exercise on the skin, we established a mouse model in which mice were kept either on a high-fat diet or received standard chow. After the two groups achieved a significant weight difference, physical exercise was introduced to both. Animals were given the opportunity to perform voluntary exercise for 40 min daily in a hamster wheel for a period of 8 weeks. We evaluated the status of the dermis at the beginning and at the end of the exercise period by in vivo nonlinear microscopy. Obese mice kept on high-fat diet lost weight steadily after they started to exercise. In the high-fat diet group, we could detect significantly larger adipocytes and a thicker layer of subcutaneous tissue; both changes started to normalize after exercise. Nonlinear microscopy revealed an impaired collagen structure in obese mice that improved considerably after physical activity was introduced. With the ability to detect damage on collagen structure, we set out to address the question whether this process is reversible. With the use of a novel imaging method, we were able to show the reversibility of connective tissue deterioration as a benefit of physical exercise.

Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy.

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Schadler, Keri L; Thomas, Nicholas J; Galie, Peter A; Bhang, Dong Ha; Roby, Kerry C; Addai, Prince; Till, Jacob E; Sturgeon, Kathleen; Zaslavsky, Alexander; Chen, Christopher S; Ryeom, Sandra

2016-10-04

Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical stimuli exerted on endothelial cells by blood flow, modulates vascular integrity. Increasing vascular shear stress through aerobic exercise can alter and remodel blood vessels in normal tissues. Our data in mouse models indicate that activation of calcineurin-NFAT-TSP1 signaling in endothelial cells plays a critical role in exercise-induced shear stress mediated tumor vessel remodeling. We show that moderate aerobic exercise with chemotherapy caused a significantly greater decrease in tumor growth than chemotherapy alone through improved chemotherapy delivery after tumor vascular normalization. Our work suggests that the vascular normalizing effects of aerobic exercise can be an effective chemotherapy adjuvant.

Immersion radiography for enhancement of soft tissue contrast - experimental study and clinical application -

International Nuclear Information System (INIS)

Lee, Kyung Soo; Kang, Heung Sik; Kim, Chu Wan

1986-01-01

Detection and evaluation of early soft tissue changes are important in rheumatoid arthritis or other joint diseases. The most important factors for radiologic demonstration of soft tissue changes are resolving power and the optimization of contrast differences between structures representing skin and subcutaneous tissue densities. Phantom study was done by using combination of immersion technique and mammography to get the most reliable method for improvement of soft tissue contrast without deterioration of resolution. Clinical application was also done in 5 normal volunteers and 5 rheumatoid patients. The results indicate that soft tissue contrast, especially between skin and subcutaneous tissues can be significantly improved with combination of immersion technique and mammography with 50% ethanol in both phantom and clinical study.

Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells.

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Pistone Creydt, Virginia; Fletcher, Sabrina Johanna; Giudice, Jimena; Bruzzone, Ariana; Chasseing, Norma Alejandra; Gonzalez, Eduardo Gustavo; Sacca, Paula Alejandra; Calvo, Juan Carlos

2013-02-01

Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines. Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed. Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs. We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.

A hybrid electron and photon IMRT planning technique that lowers normal tissue integral patient dose using standard hardware.

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Rosca, Florin

2012-06-01

To present a mixed electron and photon IMRT planning technique using electron beams with an energy range of 6-22 MeV and standard hardware that minimizes integral dose to patients for targets as deep as 7.5 cm. Ten brain cases, two lung, a thyroid, an abdominal, and a parotid case were planned using two planning techniques: a photon-only IMRT (IMRT) versus a mixed modality treatment (E+IMRT) that includes an enface electron beam and a photon IMRT portion that ensures a uniform target coverage. The electron beam is delivered using a regular cutout placed in an electron cone. The electron energy was chosen to provide a good trade-off between minimizing integral dose and generating a uniform, deliverable plan. The authors choose electron energies that cover the deepest part of PTV with the 65%-70% isodose line. The normal tissue integral dose, the dose for ring structures around the PTV, and the volumes of the 75%, 50%, and 25% isosurfaces were used to compare the dose distributions generated by the two planning techniques. The normal tissue integral dose was lowered by about 20% by the E+IMRT plans compared to the photon-only IMRT ones for most studied cases. With the exception of lungs, the dose reduction associated to the E+IMRT plans was more pronounced further away from the target. The average dose ratio delivered to the 0-2 cm and the 2-4 cm ring structures for brain patients for the two planning techniques were 89.6% and 70.8%, respectively. The enhanced dose sparing away from the target for the brain patients can also be observed in the ratio of the 75%, 50%, and 25% isodose line volumes for the two techniques, which decreases from 85.5% to 72.6% and further to 65.1%, respectively. For lungs, the lateral electron beams used in the E+IMRT plans were perpendicular to the mostly anterior/posterior photon beams, generating much more conformal plans. The authors proved that even using the existing electron delivery hardware, a mixed electron/photon planning

Cell kinetical aspect of normal tissue damages in relation to radiosensitivity of cells, especially from the points of LQ model

International Nuclear Information System (INIS)

Tsubouchi, Susumu; Oohara, Hiroshi.

1989-01-01

Several points on the early and late radiation induced-normal tissue damages in terms of LQ model in multifractionation experiments of isoeffect were discussed from two fractors, (1) dose-responses of cell survivals or of tissue damages and (2) principles of the model. Application of the model to the both early and late tissue damages was fairly difficult in several tissues and several experimental conditions. In early damages, cell survival curve of single irradiation did not always fit to LQ model and further more incomlete repair as well as repopulation in multifractionation experiment contradicted the model especially in low dose fractionation. In late damages, the damages themselves did not express directly cell survival but probably indicate the degree of functional cell damage at the level of 10 -1 . As most isoeffects in early damages were taken at the level of 10 -3 , the comparison of two results from early and late tissue damages indicated the lack of coordinations both conceptionally and experimentally. (author)

Trace element load in cancer and normal lung tissue

International Nuclear Information System (INIS)

Kubala-Kukus, A.; Braziewicz, J.; Banas, D.; Majewska, U.; Gozdz, S.; Urbaniak, A.

1999-01-01

Samples of malignant and benign human lung tissues were analysed by two complementary methods, i.e., particle induced X-ray emission (PIXE) and total reflection X-ray fluorescence (TRXRF). The concentration of trace elements of P, S, K, Ca, Ti, Cr, Mn, Fe, Cu, Zn, Se, Sr, Hg and Pb was determined in squamous cancer of lung tissue from 65 people and in the benign lung tumour tissue from 5 people. Several elements shows enhancement in cancerous lung tissue of women in comparison to men, i.e., titanium show maximum enhancement by 48% followed by Cr (20%) and Mn (36%). At the same time trace element concentration of Sr and Pb are declaimed by 30% and 20% in women population. Physical basis of used analytical methods, experimental set-up and the procedure of sample preparation are described

Approaches to improve angiogenesis in tissue-engineered skin.

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Sahota, Parbinder S; Burn, J Lance; Brown, Nicola J; MacNeil, Sheila

2004-01-01

A problem with tissue-engineered skin is clinical failure due to delays in vascularization. The aim of this study was to explore a number of simple strategies to improve angiogenesis/vascularization using a tissue-engineered model of skin to which small vessel human dermal microvascular endothelial cells were added. For the majority of these studies, a modified Guirguis chamber was used, which allowed the investigation of several variables within the same experiment using the same human dermis; cell type, angiogenic growth factors, the influence of keratinocytes and fibroblasts, mechanical penetration of the human dermis, the site of endothelial cell addition, and the influence of hypoxia were all examined. A qualitative scoring system was used to assess the impact of these factors on the penetration of endothelial cells throughout the dermis. Similar results were achieved using freshly isolated small vessel human dermal microvascular endothelial cells or an endothelial cell line and a minimum cell seeding density was identified. Cell penetration was not influenced by the addition of angiogenic growth factors (vascular endothelial growth factor and basic fibroblast growth factor); similarly, including epidermal keratinocytes or dermal fibroblasts did not encourage endothelial cell entry, and neither did mechanical introduction of holes throughout the dermis. Two factors were identified that significantly enhanced endothelial cell penetration into the dermis: hypoxia and the site of endothelial cell addition. Endothelial cells added from the papillary surface entered into the dermis much more effectively than when cells were added to the reticular surface of the dermis. We conclude that this model is valuable in improving our understanding of how to enhance vascularization of tissue-engineered grafts.

Mechanically Reinforced Catechol-Containing Hydrogels with Improved Tissue Gluing Performance

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Jun Feng

2017-11-01

Full Text Available In situ forming hydrogels with catechol groups as tissue reactive functionalities are interesting bioinspired materials for tissue adhesion. Poly(ethylene glycol (PEG–catechol tissue glues have been intensively investigated for this purpose. Different cross-linking mechanisms (oxidative or metal complexation and cross-linking conditions (pH, oxidant concentration, etc. have been studied in order to optimize the curing kinetics and final cross-linking degree of the system. However, reported systems still show limited mechanical stability, as expected from a PEG network, and this fact limits their potential application to load bearing tissues. Here, we describe mechanically reinforced PEG–catechol adhesives showing excellent and tunable cohesive properties and adhesive performance to tissue in the presence of blood. We used collagen/PEG mixtures, eventually filled with hydroxyapatite nanoparticles. The composite hydrogels show far better mechanical performance than the individual components. It is noteworthy that the adhesion strength measured on skin covered with blood was >40 kPa, largely surpassing (>6 fold the performance of cyanoacrylate, fibrin, and PEG–catechol systems. Moreover, the mechanical and interfacial properties could be easily tuned by slight changes in the composition of the glue to adapt them to the particular properties of the tissue. The reported adhesive compositions can tune and improve cohesive and adhesive properties of PEG–catechol-based tissue glues for load-bearing surgery applications.

Normal bone and soft tissue distribution of fluorine-18-sodium fluoride and artifacts on 18F-NaF PET/CT bone scan: a pictorial review.

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Sarikaya, Ismet; Elgazzar, Abdelhamid H; Sarikaya, Ali; Alfeeli, Mahmoud

2017-10-01

Fluorine-18-sodium fluoride (F-NaF) PET/CT is a relatively new and high-resolution bone imaging modality. Since the use of F-NaF PET/CT has been increasing, it is important to accurately assess the images and be aware of normal distribution and major artifacts. In this pictorial review article, we will describe the normal uptake patterns of F-NaF in the bone tissues, particularly in complex structures, as well as its physiologic soft tissue distribution and certain artifacts seen on F-NaF PET/CT images.

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

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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.

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

International Nuclear Information System (INIS)

Wendler, J. J.; Porsch, M.; Hühne, S.; Baumunk, D.; Buhtz, P.; Fischbach, F.; Pech, M.; Mahnkopf, D.; Kropf, S.; Roessner, A.; Ricke, J.; Schostak, M.; Liehr, U.-B.

2013-01-01

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.

An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues.

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Corces, M Ryan; Trevino, Alexandro E; Hamilton, Emily G; Greenside, Peyton G; Sinnott-Armstrong, Nicholas A; Vesuna, Sam; Satpathy, Ansuman T; Rubin, Adam J; Montine, Kathleen S; Wu, Beijing; Kathiria, Arwa; Cho, Seung Woo; Mumbach, Maxwell R; Carter, Ava C; Kasowski, Maya; Orloff, Lisa A; Risca, Viviana I; Kundaje, Anshul; Khavari, Paul A; Montine, Thomas J; Greenleaf, William J; Chang, Howard Y

2017-10-01

We present Omni-ATAC, an improved ATAC-seq protocol for chromatin accessibility profiling that works across multiple applications with substantial improvement of signal-to-background ratio and information content. The Omni-ATAC protocol generates chromatin accessibility profiles from archival frozen tissue samples and 50-μm sections, revealing the activities of disease-associated DNA elements in distinct human brain structures. The Omni-ATAC protocol enables the interrogation of personal regulomes in tissue context and translational studies.

Normal foot and ankle

International Nuclear Information System (INIS)

Weissman, S.D.

1989-01-01

The foot may be thought of as a bag of bones tied tightly together and functioning as a unit. The bones re expected to maintain their alignment without causing symptomatology to the patient. The author discusses a normal radiograph. The bones must have normal shape and normal alignment. The density of the soft tissues should be normal and there should be no fractures, tumors, or foreign bodies

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

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

2018-01-01

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

Motion Normalized Proportional Control for Improved Pattern Recognition-Based Myoelectric Control.

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Scheme, Erik; Lock, Blair; Hargrove, Levi; Hill, Wendy; Kuruganti, Usha; Englehart, Kevin

2014-01-01

This paper describes two novel proportional control algorithms for use with pattern recognition-based myoelectric control. The systems were designed to provide automatic configuration of motion-specific gains and to normalize the control space to the user's usable dynamic range. Class-specific normalization parameters were calculated using data collected during classifier training and require no additional user action or configuration. The new control schemes were compared to the standard method of deriving proportional control using a one degree of freedom Fitts' law test for each of the wrist flexion/extension, wrist pronation/supination and hand close/open degrees of freedom. Performance was evaluated using the Fitts' law throughput value as well as more descriptive metrics including path efficiency, overshoot, stopping distance and completion rate. The proposed normalization methods significantly outperformed the incumbent method in every performance category for able bodied subjects (p < 0.001) and nearly every category for amputee subjects. Furthermore, one proposed method significantly outperformed both other methods in throughput (p < 0.0001), yielding 21% and 40% improvement over the incumbent method for amputee and able bodied subjects, respectively. The proposed control schemes represent a computationally simple method of fundamentally improving myoelectric control users' ability to elicit robust, and controlled, proportional velocity commands.

Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis.

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Yu-Zhe Song

Full Text Available The X-ray repair cross-complementing group 3 (XRCC3 protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs with corresponding 95% confidence intervals (CIs were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539 polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31-3.01, P = 0.001. A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97-1.68, P = 0.08. In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49-3.89, p = 0.0003 and breast irradiation (OR = 1.41, 95%CI: 1.02-1.95, p = 0.04, whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26-0.86, P = 0.01. Well-designed large-scale clinical studies are required to further validate our results.

Normal-tissue radioprotection by overexpression of the copper-zinc and manganese superoxide dismutase genes

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Veldwijk, Marlon R. [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Herskind, Carsten; Wenz, Frederik [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Sellner, Leopold; Zeller, W. Jens [Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Radujkovic, Aleksandar [Dept. of Internal Medicine V, Univ. of Heidelberg (Germany); Laufs, Stephanie [Dept. of Experimental Surgery, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Molecular Oncology of Solid Tumors (G360), German Cancer Research Center, Heidelberg (Germany); Fruehauf, Stefan [Center for Tumor Diagnostic and Therapy, Paracelsus-Klinik, Osnabrueck (Germany)

2009-08-15

Background and Purpose: Protection of normal tissue against radiation-induced damage may increase the therapeutic ratio of radiotherapy. A promising strategy for testing this approach is gene therapy-mediated overexpression of the copper-zinc (CuZnSOD) or manganese superoxide dismutase (MnSOD) using recombinant adeno-associated viral (rAAV2) vectors. The purpose of this study was to test the modulating effects of the SOD genes on human primary lung fibroblasts (HPLF) after irradiation. Material and Methods: HPLF were transduced with rAAV2 vectors containing cDNA for the CuZnSOD, MnSOD or a control gene. The cells were irradiated (1-6 Gy), and gene transfer efficiency, apoptosis, protein expression/activity, and radiosensitivity measured by the colony-forming assay determined. Results: After transduction, 90.0% {+-} 6.4% of the cells expressed the transgene. A significant fivefold overexpression of both SOD was confirmed by an SOD activity assay (control: 21.1 {+-} 12.6, CuZnSOD: 95.1 {+-} 17.1, MnSOD: 108.5 {+-} 36.0 U SOD/mg protein) and immunohistochemistry. CuZnSOD and MnSOD overexpression resulted in a significant radioprotection of HPLF compared to controls (surviving fraction [SF] ratio SOD/control > 1): CuZnSOD: 1.18-fold (95% confidence interval [CI]: 1.06-1.32; p = 0.005), MnSOD: 1.23-fold (95% CI: 1.07-1.43; p = 0.01). Conclusion: Overexpression of CuZnSOD and MnSOD in HPLF mediated an increase in clonogenic survival after irradiation compared to controls. In previous works, a lack of radioprotection in SOD-overexpressing tumor cells was observed. Therefore, the present results suggest that rAAV2 vectors are promising tools for the delivery of radioprotective genes in normal tissue. (orig.)

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

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Shyam Mohan Srinivas

2014-10-01

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

Rectification of pulsatile stress on soft tissues: a mechanism for normal-pressure hydrocephalus

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Jalikop, Shreyas; Hilgenfeldt, Sascha

2011-11-01

Hydrocephalus is a pathological condition of the brain that occurs when cerebrospinal fluid (CSF) accumulates excessively in the brain cavities, resulting in compression of the brain parenchyma. Counter-intuitively, normal-pressure hydrocephalus (NPH) does not show elevated pressure differences across the compressed parenchyma. We investigate the effects of nonlinear tissue mechanics and periodic driving in this system. The latter is due to the cardiac cycle, which provides significant intracranial pressure and volume flow rate fluctuations. Nonlinear rectification of the periodic driving within a model of fluid flow in poroelastic material can lead to compression or expansion of the parenchyma, and this effect does not rely on changes in the mean intracranial pressure. The rectification effects can occur gradually over several days, in agreement with clinical studies of NPH.

Calculation of neutron kerma in tissues

International Nuclear Information System (INIS)

Vega C, H.R.; Manzanares A, E.

2004-01-01

Neutron kerma of normal and tumor tissues has been calculated using the tissues elemental concentration. A program developed in Math cad contains the kerma factors of C, H, O, N, Na, Mg, P, S, Cl, K, etc. that are in normal and tumor human tissues. Having the elemental composition of any human tissue the neutron kerma can be calculated. The program was tested using the elemental composition of tumor tissues such as sarcoma, melanoma, carcinoma and adenoid cystic, also neutron kerma for adipose and muscle tissue for normal adult was calculated. The results are in agreement with those published in literature. The neutron kerma for water was also calculated because in some dosimetric calculations water is used to describe normal and tumor tissues. From this comparison was found that at larger energies kerma factors are approximately the same, but energies less than 100 eV the differences are large. (Author)

Complete solubilization of formalin-fixed, paraffin-embedded tissue may improve proteomic studies.

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Shi, Shan-Rong; Taylor, Clive R; Fowler, Carol B; Mason, Jeffrey T

2013-04-01

Tissue-based proteomic approaches (tissue proteomics) are essential for discovering and evaluating biomarkers for personalized medicine. In any proteomics study, the most critical issue is sample extraction and preparation. This problem is especially difficult when recovering proteins from formalin-fixed, paraffin-embedded (FFPE) tissue sections. However, improving and standardizing protein extraction from FFPE tissue is a critical need because of the millions of archival FFPE tissues available in tissue banks worldwide. Recent progress in the application of heat-induced antigen retrieval principles for protein extraction from FFPE tissue has resulted in a number of published FFPE tissue proteomics studies. However, there is currently no consensus on the optimal protocol for protein extraction from FFPE tissue or accepted standards for quantitative evaluation of the extracts. Standardization is critical to ensure the accurate evaluation of FFPE protein extracts by proteomic methods such as reverse phase protein arrays, which is now in clinical use. In our view, complete solubilization of FFPE tissue samples is the best way to achieve the goal of standardizing the recovery of proteins from FFPE tissues. However, further studies are recommended to develop standardized protein extraction methods to ensure quantitative and qualitative reproducibility in the recovery of proteins from FFPE tissues. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

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Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

2016-12-01

Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tissue physiology and the response to heat

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Horsman, Michael Robert

2006-01-01

physiological effects should occur in normal tissues, such combination therapies must be carefully applied. Heating tumours to higher temperatures typically causes a transient increase in perfusion during heating, followed by vascular collapse which if sufficient will increase tumour necrosis. The speed...... and degree of vascular collapse is dependent on heating time, temperature and tumour model used. Such vascular collapse generally occurs at temperatures that cause a substantial blood flow increase in certain normal tissues, thus preferential anti-tumour effects can be achieved. The tumour vascular supply...... can also be exploited to improve the response to heat. Decreasing blood flow, using transient physiological modifiers or longer acting vascular disrupting agents prior to the initiation of heating, can both increase the accumulation of physical heat in the tumour, as well as increase heat sensitivity...

The Differential Expression of Aqueous Soluble Proteins in Breast Normal and Cancerous Tissues in Relation to Ethnicity of the Patients; Chinese, Malay and Indian

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Seng Liang

2010-01-01

Full Text Available Female breast cancer is one of the leading causes of female mortality worldwide. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of the women in Malaysia, the Chinese have the highest number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC. A proteomic approach was applied in this study to identify changes in the protein profile of cancerous tissues compared with normal tissues from 18 patients; 8 Chinese, 6 Malay and 4 Indian were analysed. Twenty-four differentially expressed hydrophilic proteins were identified. We evaluated the potential of these proteins as biomarkers for infiltrating ductal carcinoma based on their ethnic-specific expressions. Three of the upregulated proteins, calreticulin, 14-3-3 protein zeta and 14-3-3 protein eta, were found to be expressed at a significantly higher level in the cancerous breast tissues when compared with the normal tissues in cases of infiltrating ductal carcinoma. The upregulation in expression was particularly dominant in the Malay cohort.

Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

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Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

2011-03-04

Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

Comparative tissue distribution profiles of five major bio-active components in normal and blood deficiency rats after oral administration of Danggui Buxue Decoction by UPLC-TQ/MS.

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Shi, Xuqin; Tang, Yuping; Zhu, Huaxu; Li, Weixia; Li, Zhenhao; Li, Wei; Duan, Jin-ao

2014-01-01

Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) were frequently combined and used in China as herbal pair called as Danggui Buxue Decoction (DBD) for treatment of blood deficiency syndrome, such as women's ailments. This study is to investigate the tissue distribution profiles of five major bio-active constituents (ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV) in DBD after oral administration of DBD in blood deficiency rats, and to compare the difference between normal and blood deficiency rats. The blood deficiency rats were induced by bleeding from orbit at the dosages of 5.0mLkg(-1) every day, and the experimental period was 12 days. At the finally day of experimental period, both normal and blood deficiency rats were orally administrated with DBD, and then the tissues samples were collected at different time points. Ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV in different tissues were detected simultaneously by UPLC-TQ/MS, and the histograms were drawn. The results showed that the overall trend was CLiver>CKidney>CHeart>CSpleen>CLung, CC-30min>CM-30min>CM-60min>CC-5min>CM-5min>CC-60min>CM-240min>CC-240min. The contents of the detected compounds in liver were more than that in other tissues no matter in normal or blood deficiency rats. Compared to normal rats, partial contents of the compounds in blood deficiency rats' tissues at different time points had significant difference (Pdistribution investigation in blood deficiency animals which is conducted by bleeding. And the results demonstrated that the five DBD components in normal and blood deficiency rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in blood deficiency animals. Copyright © 2013 Elsevier B.V. All rights reserved.

Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues

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Rodrigues-Peres, Raquel Mary; Cadore, Solange; Febraio, Stefanny; Heinrich, Juliana Karina; Serra, Katia Piton; Derchain, Sophie F M; Vassallo, Jose; Sarian, Luis Otavio

2013-01-01

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

UPLC-MS method for quantification of pterostilbene and its application to comparative study of bioavailability and tissue distribution in normal and Lewis lung carcinoma bearing mice.

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Deng, Li; Li, Yongzhi; Zhang, Xinshi; Chen, Bo; Deng, Yulin; Li, Yujuan

2015-10-10

A UPLC-MS method was developed for determination of pterostilbene (PTS) in plasma and tissues of mice. PTS was separated on Agilent Zorbax XDB-C18 column (50 × 2.1 mm, 1.8 μm) with gradient mobile phase at the flow rate of 0.2 ml/min. The detection was performed by negative ion electrospray ionization in multiple reaction monitoring mode. The linear calibration curve of PTS in mouse plasma and tissues ranged from 1.0 to 5000 and 0.50 to 500 ng/ml (r(2)>0.9979), respectively, with lowest limits of quantification (LLOQ) were between 0.5 and 2.0 ng/ml, respectively. The accuracy and precision of the assay were satisfactory. The validated method was applied to the study of bioavailability and tissue distribution of PTS in normal and Lewis lung carcinoma (LLC) bearing mice. The bioavailability of PTS (dose 14, 28 and 56 mg/kg) in normal mice were 11.9%, 13.9% and 26.4%, respectively; and the maximum level (82.1 ± 14.2 μg/g) was found in stomach (dose 28 mg/kg). The bioavailability, peak concentration (Cmax), time to peak concentration (Tmax) of PTS in LLC mice was increased compared with normal mice. The results indicated the UPLC-MS method is reliable and bioavailability and tissue distribution of PTS in normal and LLC mice were dramatically different. Copyright © 2015 Elsevier B.V. All rights reserved.

Intra-operative on-line discrimination of kidney cancer from normal tissue by IR ATR spectroscopy of extracellular fluid

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Urboniene, V.; Velicka, M.; Ceponkus, J.; Pucetaite, M.; Jankevicius, F.; Sablinskas, V.; Steiner, G.

2016-03-01

Determination of cancerous and normal kidney tissues during partial, simple or radical nephrectomy surgery was performed by using differences in the IR absorption spectra of extracellular fluid taken from the corresponding tissue areas. The samples were prepared by stamping of the kidney tissue on ATR diamond crystal. The spectral measurements were performed directly in the OR during surgery for 58 patients. It was found that intensities of characteristic spectral bands of glycogen (880-1200 cm-1) in extracellular fluid are sensitive to the type of the tissue and can be used as spectral markers of tumours. Characteristic spectral band of lactic acid (1730 cm-1) - product of the anaerobic glycolysis, taking place in the cancer cells is not suitable for use as a spectral marker of cancerous tissue, since it overlaps with the band of carbonyl stretch in phospholipids and fatty acids. Results of hierarchical cluster analysis of the spectra show that the spectra of healthy and tumour tissue films can be reliably separated into two groups. On the other hand, possibility to differentiate between tumours of different types and grades remains in question. While the fluid from highly malignant G3 tumour tissue contains highly pronounced glycogen spectral bands and can be well separated from benign and G1 tumours by principal component analysis, the variations between spectra from sample to sample prevent from obtaining conclusive results about the grouping between different tumour types and grades. The proposed method is instant and can be used in situ and even in vivo.

Identification of valid reference genes for the normalization of RT qPCR gene expression data in human brain tissue

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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.

High intensity interval training improves liver and adipose tissue insulin sensitivity

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Katarina Marcinko

2015-12-01

Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

Brightness-normalized Partial Least Squares Regression for hyperspectral data

International Nuclear Information System (INIS)

Feilhauer, Hannes; Asner, Gregory P.; Martin, Roberta E.; Schmidtlein, Sebastian

2010-01-01

Developed in the field of chemometrics, Partial Least Squares Regression (PLSR) has become an established technique in vegetation remote sensing. PLSR was primarily designed for laboratory analysis of prepared material samples. Under field conditions in vegetation remote sensing, the performance of the technique may be negatively affected by differences in brightness due to amount and orientation of plant tissues in canopies or the observing conditions. To minimize these effects, we introduced brightness normalization to the PLSR approach and tested whether this modification improves the performance under changing canopy and observing conditions. This test was carried out using high-fidelity spectral data (400-2510 nm) to model observed leaf chemistry. The spectral data was combined with a canopy radiative transfer model to simulate effects of varying canopy structure and viewing geometry. Brightness normalization enhanced the performance of PLSR by dampening the effects of canopy shade, thus providing a significant improvement in predictions of leaf chemistry (up to 3.6% additional explained variance in validation) compared to conventional PLSR. Little improvement was made on effects due to variable leaf area index, while minor improvement (mostly not significant) was observed for effects of variable viewing geometry. In general, brightness normalization increased the stability of model fits and regression coefficients for all canopy scenarios. Brightness-normalized PLSR is thus a promising approach for application on airborne and space-based imaging spectrometer data.

A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts

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Max Nobis

2017-10-01

Full Text Available The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time.

ADENOSINE RECEPTOR STIMULATION BY POLYDEOXYRIBONUCLEOTIDE IMPROVES TISSUE REPAIR AND SYMPTOMOLOGY IN EXPERIMENTAL COLITIS.

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Giovanni Pallio

2016-08-01

Full Text Available Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodelling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodelling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN, to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitro-benzene-sulfonic acid (DNBS, 25mg diluted in 0.8ml 50% ethanol. After 6 hrs, animals were randomized to receive either PDRN (8mg/kg/i.p., or PDRN + the A2A antagonist (DMPX; 10mg/kg/i.p., or vehicle (0.8 ml saline solution daily. In the second model, dextran sodium sulphate (DSS was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 hrs animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxydase activity, and malondialdheyde. All these effects were abolished by the concomitant administration of the A2a antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.

The SOD Mimic, MnTE-2-PyP, Protects from Chronic Fibrosis and Inflammation in Irradiated Normal Pelvic Tissues

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Shashank Shrishrimal

2017-11-01

Full Text Available Pelvic radiation for cancer therapy can damage a variety of normal tissues. In this study, we demonstrate that radiation causes acute changes to pelvic fibroblasts such as the transformation to myofibroblasts and the induction of senescence, which persist months after radiation. The addition of the manganese porphyrin, MnTE-2-PyP, resulted in protection of these acute changes in fibroblasts and this protection persisted months following radiation exposure. Specifically, at two months post-radiation, MnTE-2-PyP inhibited the number of α-smooth muscle actin positive fibroblasts induced by radiation and at six months post-radiation, MnTE-2-PyP significantly reduced collagen deposition (fibrosis in the skin and bladder tissues of irradiated mice. Radiation also resulted in changes to T cells. At two months post-radiation, there was a reduction of Th1-producing splenocytes, which resulted in reduced Th1:Th2 ratios. MnTE-2-PyP maintained Th1:Th2 ratios similar to unirradiated mice. At six months post-radiation, increased T cells were observed in the adipose tissues. MnTE-2-PyP treatment inhibited this increase. Thus, MnTE-2-PyP treatment maintains normal fibroblast function and T cell immunity months after radiation exposure. We believe that one of the reasons MnTE-2-PyP is a potent radioprotector is due to its protection of multiple cell types from radiation damage.

Ultrasound evaluation of normal and abnormal fetuses: comparison of conventional, tissue harmonic, and pulse- inversion harmonic imaging techniques

International Nuclear Information System (INIS)

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

2003-01-01

To determine the usefulness of tissue harmonic imaging (THI) and pulse-inversion harmonic imaging (PIHI) in the evaluation of normal and abnormal fetuses. 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 conspicuity and the definition of borders and internal structures. For the brain, heart, abdomen and face, overall conspicuity at THI and PIHI was significantly better than at CUS (p < 0.05). There was, though, no significant difference between THI and PIHI. Affected organs in abnormal fetuses were more clearly depicted at THI and PIHI than at CUS. Both THI and PIHI appear to be superior to CUS for the evaluation of normal or abnormal structures, particularly the brain, heart, abdomen and face

Improved normal tissue sparing in head and neck radiotherapy using biological cost function based-IMRT.

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Anderson, N; Lawford, C; Khoo, V; Rolfo, M; Joon, D L; Wada, M

2011-12-01

Intensity-modulated radiotherapy (IMRT) has reduced the impact of acute and late toxicities associated with head and neck radiotherapy. Treatment planning system (TPS) advances in biological cost function based optimization (BBO) and improved segmentation techniques have increased organ at risk (OAR) sparing compared to conventional dose-based optimization (DBO). A planning study was undertaken to compare OAR avoidance in DBO and BBO treatment planning. Simultaneous integrated boost treatment plans were produced for 10 head and neck patients using both planning systems. Plans were compared for tar get coverage and OAR avoidance. Comparisons were made using the BBO TPS Monte Carlo dose engine to eliminate differences due to inherent algorithms. Target coverage (V95%) was maintained for both solutions. BBO produced lower OAR doses, with statistically significant improvement to left (12.3%, p = 0.005) and right parotid mean dose (16.9%, p = 0.004), larynx V50_Gy (71.0%, p = 0.005), spinal cord (21.9%, p < 0.001) and brain stem dose maximums (31.5%, p = 0.002). This study observed improved OAR avoidance with BBO planning. Further investigations will be undertaken to review any clinical benefit of this improved planned dosimetry.

ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

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Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

2016-05-01

ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. © 2016 Federation of European Biochemical Societies.

Transcriptome profiling of the cancer, adjacent non-tumor and distant normal tissues from a colorectal cancer patient by deep sequencing.

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Yan'an Wu

Full Text Available Colorectal cancer (CRC is one of the most commonly diagnosed cancers in the world. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into the molecular basis of CRC initiation and progression. Compared with microarray technology, which is commonly used to identify transcriptional changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing, novel transcripts or gene fusion. In this study, we performed high-throughput transcriptome sequencing at ~50× coverage on CRC, adjacent non-tumor and distant normal tissue. The results revealed cancer-specific, differentially expressed genes and differential alternative splicing, suggesting that the extracellular matrix and metabolic pathways are activated and the genes related to cell homeostasis are suppressed in CRC. In addition, one tumor-restricted gene fusion, PRTEN-NOTCH2, was also detected and experimentally confirmed. This study reveals some common features in tumor invasion and provides a comprehensive survey of the CRC transcriptome, which provides better insight into the complexity of regulatory changes during tumorigenesis.

Classification of Laser Induced Fluorescence Spectra from Normal and Malignant bladder tissues using Learning Vector Quantization Neural Network in Bladder Cancer Diagnosis

DEFF Research Database (Denmark)

Karemore, Gopal Raghunath; Mascarenhas, Kim Komal; Patil, Choudhary

2008-01-01

In the present work we discuss the potential of recently developed classification algorithm, Learning Vector Quantization (LVQ), for the analysis of Laser Induced Fluorescence (LIF) Spectra, recorded from normal and malignant bladder tissue samples. The algorithm is prototype based and inherently...

The immune cell composition in Barrett's metaplastic tissue resembles that in normal duodenal tissue.

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Alexandra Lind

Full Text Available BACKGROUND AND OBJECTIVE: Barrett's esophagus (BE is characterized by the transition of squamous epithelium into columnar epithelium with intestinal metaplasia. The increased number and types of immune cells in BE have been indicated to be due to a Th2-type inflammatory process. We tested the alternative hypothesis that the abundance of T-cells in BE is caused by a homing mechanism that is found in the duodenum. PATIENTS AND METHODS: Biopsies from BE and duodenal tissue from 30 BE patients and duodenal tissue from 18 controls were characterized by immmunohistochemistry for the presence of T-cells and eosinophils(eos. Ex vivo expanded T-cells were further phenotyped by multicolor analysis using flowcytometry. RESULTS: The high percentage of CD4(+-T cells (69±3% (mean±SEM/n = 17, by flowcytometry, measured by flowcytometry and immunohistochemistry, and the presence of non-activated eosinophils found in BE by immunohistochemical staining, were not different from that found in duodenal tissue. Expanded lymphocytes from these tissues had a similar phenotype, characterized by a comparable but low percentage of αE(CD103 positive CD4(+cells (44±5% in BE, 43±4% in duodenum of BE and 34±7% in duodenum of controls and a similar percentage of granzyme-B(+CD8(+ cells(44±5% in BE, 33±6% in duodenum of BE and 36±7% in duodenum of controls. In addition, a similar percentage of α4β7(+ T-lymphocytes (63±5% in BE, 58±5% in duodenum of BE and 62±8% in duodenum of controls was found. Finally, mRNA expression of the ligand for α4β7, MAdCAM-1, was also similar in BE and duodenal tissue. No evidence for a Th2-response was found as almost no IL-4(+-T-cells were seen. CONCLUSION: The immune cell composition (lymphocytes and eosinophils and expression of intestinal adhesion molecule MAdCAM-1 is similar in BE and duodenum. This supports the hypothesis that homing of lymphocytes to BE tissue is mainly caused by intestinal homing signals rather than to an

The clinical significance of normal mammograms and normal sonograms in patients with palpable abnormalities of the breast

International Nuclear Information System (INIS)

Lee, Jin Hwa; Yoon, Seong Kuk; Choi, Sun Seob; Nam, Kyung Jin; Cho, Se Heon; Kim, Dae Cheol; Kim, Jung Il; Kim, Eun Kyung

2006-01-01

We wanted to evaluate the clinical significance of normal mammograms and normal sonograms in patients with palpable abnormalities of the breast. From Apr 2003 to Feb 2005, 107 patients with 113 palpable abnormalities who had combined normal sonographic and normal mammographic findings were retrospectively studied. The evaluated parameters included age of the patients, the clinical referrals, the distribution of the locations of the palpable abnormalities, whether there was a past surgical history, the mammographic densities and the sonographic echo patterns (purely hyperechoic fibrous tissue, mixed fibroglandular breast tissue, predominantly isoechoic glandular tissue and isoechoic subcutaneous fat tissue) at the sites of clinical concern, whether there was a change in imaging and/or the physical examination results at follow-up, and whether there were biopsy results. This study period was chosen to allow a follow-up period of at least 12 months. The patients' ages ranged from 22 to 66 years (mean age: 48.8 years) and 62 (58%) of the 107 patients were between 41 and 50 years old (58%). The most common location of the palpable abnormalities was the upper outer portion of the breast (45%) and most of the mammographic densities were dense patterns (BI-RADS Type 3 or 4: 91%). Our cases showed similar distribution for all the types of sonographic echo patterns. 23 patients underwent biopsy; all the biopsy specimens were benign. For the 84 patients with 90 palpable abnormalities who were followed, there was no interval development of breast cancer in the areas of clinical concern. Our results suggest that we can follow up and prevent unnecessary biopsies in women with palpable abnormalities when both the mammography and ultrasonography show normal tissue, but this study was limited by its small sample size. Therefore, a larger study will be needed to better define the negative predictive value of combined normal sonographic and mammographic findings

Relative expression of rRNA transcripts and 45S rDNA promoter methylation status are dysregulated in tumors in comparison with matched-normal tissues in breast cancer.

Science.gov (United States)

Karahan, Gurbet; Sayar, Nilufer; Gozum, Gokcen; Bozkurt, Betul; Konu, Ozlen; Yulug, Isik G

2015-06-01

Ribosomal RNA (rRNA) expression, one of the most important factors regulating ribosome production, is primarily controlled by a CG-rich 45 S rDNA promoter. However, the DNA methylation state of the 45 S rDNA promoter, as well as its effect on rRNA gene expression in types of human cancers is controversial. In the present study we analyzed the methylation status of the rDNA promoter (-380 to +53 bp) as well as associated rRNA expression levels in breast cancer cell lines and breast tumor-normal tissue pairs. We found that the aforementioned regulatory region was extensively methylated (74-96%) in all cell lines and in 68% (13/19 tumor-normal pairs) of the tumors. Expression levels of rRNA transcripts 18 S, 28 S, 5.8 S and 45 S external transcribed spacer (45 S ETS) greatly varied in the breast cancer cell lines regardless of their methylation status. Analyses of rRNA transcript expression levels in the breast tumor and normal matched tissues showed no significant difference when normalized with TBP. On the other hand, using the geometric mean of the rRNA expression values (GM-rRNA) as reference enabled us to identify significant changes in the relative expression of rRNAs in the tissue samples. We propose GM-rRNA normalization as a novel strategy to analyze expression differences between rRNA transcripts. Accordingly, the 18S rRNA/GM-rRNA ratio was significantly higher whereas the 5.8S rRNA/GM-rRNA ratio was significantly lower in breast tumor samples than this ratio in the matched normal samples. Moreover, the 18S rRNA/GM-rRNA ratio was negatively correlated with the 45 S rDNA promoter methylation level in the normal breast tissue samples, yet not in the breast tumors. Significant correlations observed between the expression levels of rRNA transcripts in the normal samples were lost in the tumor samples. We showed that the expression of rRNA transcripts may not be based solely on promoter methylation. Carcinogenesis may cause dysregulation of the correlation

Extracellular Matrix, Nuclear and Chromatin Structure and GeneExpression in Normal Tissues and Malignant Tumors: A Work inProgress

Energy Technology Data Exchange (ETDEWEB)

Spencer, Virginia A.; Xu, Ren; Bissell, Mina J.

2006-08-01

Almost three decades ago, we presented a model where theextracellular matrix (ECM) was postulated to influence gene expressionand tissue-specificity through the action of ECM receptors and thecytoskeleton. This hypothesis implied that ECM molecules could signal tothe nucleus and that the unit of function in higher organisms was not thecell alone, but the cell plus its microenvironment. We now know that ECMinvokes changes in tissue and organ architecture and that tissue, cell,nuclear, and chromatin structure are changed profoundly as a result ofand during malignant progression. Whereas some evidence has beengenerated for a link between ECM-induced alterations in tissuearchitecture and changes in both nuclear and chromatin organization, themanner by which these changes actively induce or repress gene expressionin normal and malignant cells is a topic in need of further attention.Here, we will discuss some key findings that may provide insights intomechanisms through which ECM could influence gene transcription and howtumor cells acquire the ability to overcome these levels ofcontrol.

Changes in the rate of proliferation in normal tissues after irradiation

International Nuclear Information System (INIS)

Denekamp, J.

1975-01-01

In tissues where reproductive cell death is known to cause the functional tissue damage (e.g., intestine and skin), repopulation becomes important only after the death of the radiation-damaged cells. Since these tissues have a fairly rapid turnover, this can occur within a short period of time and can assist in the healing of tissues during fractionated therapy. However, in tissues which express their damage late, such as the lung, it is very unlikely that repopulation will be stimulated before cell death is manifested and this does not occur during the period over which fractionated radiotherapy is administered. Although repopulation may be of no importance in these tissues, e.g., lungs and kidneys, there appears to be some other ''repair'' process which requires additional radiation dose to be administered to achieve the same endpoint if the overall time is increased

A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD).

Science.gov (United States)

Luxton, Gary; Keall, Paul J; King, Christopher R

2008-01-07

To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within approximately 0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD(50), and conversely m and TD(50) are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d(ref), n, v(eff) and the Niemierko equivalent uniform dose (EUD), where d(ref) and v(eff) are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data.

A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD)

International Nuclear Information System (INIS)

Luxton, Gary; Keall, Paul J; King, Christopher R

2008-01-01

To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within ∼0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD 50 , and conversely m and TD 50 are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d ref , n, v eff and the Niemierko equivalent uniform dose (EUD), where d ref and v eff are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data

Gene expression profiling of histologically normal breast tissue in females with human epidermal growth factor receptor 2‑positive breast cancer.

Science.gov (United States)

Zubor, Pavol; Hatok, Jozef; Moricova, Petra; Kapustova, Ivana; Kajo, Karol; Mendelova, Andrea; Sivonova, Monika Kmetova; Danko, Jan

2015-02-01

Gene expression profile‑based taxonomy of breast cancer (BC) has been described as a significant breakthrough in comprehending the differences in the origin and behavior of cancer to allow individually tailored therapeutic approaches. In line with this, we hypothesized that the gene expression profile of histologically normal epithelium (HNEpi) could harbor certain genetic abnormalities predisposing breast tissue cells to develop human epidermal growth factor receptor 2 (HER2)‑positive BC. Thus, the aim of the present study was to assess gene expression in normal and BC tissue (BCTis) from patients with BC in order to establish its value as a potential diagnostic marker for cancer development. An array study evaluating a panel of 84 pathway‑ and disease‑specific genes in HER2‑positive BC and tumor‑adjacent HNEpi was performed using quantitative polymerase chain reaction in 12 patients using microdissected samples from frozen tissue. Common prognostic and predictive parameters of BC were assessed by immunohistochemistry and in situ hybridization. In the BCTis and HNEpi samples of 12 HER2‑positive subjects with BC, the expression of 2,016 genes was assessed. A total of 39.3% of genes were deregulated at a minimal two‑fold deregulation rate and 10.7% at a five‑fold deregulation rate in samples of HNEpi or BCTis. Significant differences in gene expression between BCTis and HNEpi samples were revealed for BCL2L2, CD44, CTSD, EGFR, ERBB2, ITGA6, NGFB, RPL27, SCBG2A1 and SCGB1D2 genes (Pbreast tissue revealed gene expression abnormalities that may represent potential markers of increased risk for HER2‑positive malignant transformation of breast tissue, and may be able to be employed as predictors of prognosis.

Diagnosis of breast cancer by tissue analysis

Institute of Scientific and Technical Information of China (English)

Debnath Bhattacharyya; Samir Kumar Bandyopadhyay; Tai-hoon Kim

2013-01-01

In this paper,we propose a technique to locate abnormal growth of cells in breast tissue and suggest further pathological test,when require.We compare normal breast tissue with malignant invasive breast tissue by a series of image processing steps.Normal ductal epithelial cells and ductal/lobular invasive carcinogenic cells also consider for comparison here in this paper.In fact,features of cancerous breast tissue (invasive) are extracted and analyses with normal breast tissue.We also suggest the breast cancer recognition technique through image processing and prevention by controlling p53 gene mutation to some extent.

Effect of hormonal variation on in vivo high wavenumber Raman spectra improves cervical precancer detection

Science.gov (United States)

Duraipandian, Shiyamala; Zheng, Wei; Ng, Joseph; Low, Jeffrey J. H.; Ilancheran, A.; Huang, Zhiwei

2012-03-01

Raman spectroscopy is a unique analytical probe for molecular vibration and is capable of providing specific spectroscopic fingerprints of molecular compositions and structures of biological tissues. The aim of this study is to improve the classification accuracy of cervical precancer by characterizing the variations in the normal high wavenumber (HW - 2800-3700cm-1) Raman spectra arising from the menopausal status of the cervix. A rapidacquisition near-infrared (NIR) Raman spectroscopic system was used for in vivo tissue Raman measurements at 785 nm excitation. Individual HW Raman spectrum was measured with a 5s exposure time from both normal and precancer tissue sites of 15 patients recruited. The acquired Raman spectra were stratified based on the menopausal status of the cervix before the data analysis. Significant differences were noticed in Raman intensities of prominent band at 2924 cm-1 (CH3 stretching of proteins) and the broad water Raman band (in the 3100-3700 cm-1 range) with a peak at 3390 cm-1 in normal and dysplasia cervical tissue sites. Multivariate diagnostic decision algorithm based on principal component analysis (PCA) and linear discriminant analysis (LDA) was utilized to successfully differentiate the normal and precancer cervical tissue sites. By considering the variations in the Raman spectra of normal cervix due to the hormonal or menopausal status of women, the diagnostic accuracy was improved from 71 to 91%. By incorporating these variations prior to tissue classification, we can significantly improve the accuracy of cervical precancer detection using HW Raman spectroscopy.

Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues

Science.gov (United States)

2013-01-01

Background 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. Methods 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. Results 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). Conclusions 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

Inhibition of collagen production in scleroderma fibroblast cultures by a connective tissue glycoprotein extracted from normal dermis

International Nuclear Information System (INIS)

Maquart, F.X.; Bellon, G.; Cornillet-Stoupy, J.; Randoux, A.; Triller, R.; Kalis, B.; Borel, J.P.

1985-01-01

It was shown in a previous paper that a connective tissue glycoprotein (CTGP) extracted from normal rabbit dermis was able to inhibit total protein and collagen syntheses by normal dermis fibroblast cultures. In the present study, the effects of CTGP on scleroderma fibroblasts were investigated. [ 14 C]Proline incorporation into total proteins of the supernatant was not significantly different from that found in controls. By contrast, the amount of collagen, expressed as percentage of total secreted protein, was far higher in scleroderma cultures than in normal ones (14.4% +/- 6.0% vs 4.6% +/- 0.9%). Addition of CTGP to the medium induced a concentration-dependent inhibition of [ 14 C]proline incorporation into proteins from both control and scleroderma cells. In control cultures, no significant decrease of the percentage of collagen was observed, but over 60 micrograms/ml, both cytotoxic effects and inhibition of protein synthesis occurred. In scleroderma cultures, the inhibition was twice as effective on collagen as on noncollagen protein synthesis. The inhibition of collagen secretion was not related either to changes in collagen hydroxylation or to the intracellular catabolism of newly synthesized procollagen

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

International Nuclear Information System (INIS)

Hauer-Jensen, M.

2003-01-01

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

Effect of vanadium treatment on tissue distribution of biotrace elements in normal and streptozotocin-induced diabetic rats. Simultaneous analysis of V and Zn using radioactive multitracer

International Nuclear Information System (INIS)

Yasui, Hiroyuki; Takino, Toshikazu; Fugono, Jun; Sakurai, Hiromu; Hirunuma, Rieko; Enomoto, Shuichi

2001-01-01

Because vanadium ions such as vanadyl (VO 2+ ) and vanadate (VO 3- ) ions were demonstrated to normalize blood glucose levels of diabetic animals and patients, the action mechanism of vanadium treatment has been of interest. In this study, we focused on understanding interactions among trace elements in diabetic rats, in which a multitracer technique was used. The effects of vanadyl sulfate (VS)-treatment on the tissue distribution of trace vanadium ( 48 V) and zinc ( 65 Zn) in normal and streptozotocin (STZ)-induced diabetic rats were examined, and were evaluated in terms of the uptake ratio. The uptake ratio of both elements in tissues significantly changed between STZ-rats and those treated with VS. These results indicated that vanadium treatment in STZ-rats alters the tissue distribution of endogenous elements, suggesting the importance of the relationship between biotrace elements and pathophysiology. (author)

Enhancing the radiation response of tumors but not early or late responding normal tissues using a vascular disrupting agent

DEFF Research Database (Denmark)

Horsman, Michael R

2017-01-01

INTRODUCTION: Vascular disrupting agents (VDAs) damage tumor vasculature and enhance tumor radiation response. In this pre-clinical study, we combined radiation with the leading VDA in clinical development, combretastatin A-4 phosphate (CA4P), and compared the effects seen in tumors and relevant...... normal tissues. MATERIAL AND METHODS: Radiation was applied locally to tissues in CDF1 mice to produce full radiation dose-response curves. CA4P (250 mg/kg) was intraperitoneally (i.p.) injected within 30 minutes after irradiating. Response of 200 mm3 foot implanted C3H mammary carcinomas was assessed......% increase in ventilation rate measured by plethysmography within 9 months). A Chi-squared test was used for statistical comparisons (significance level of p 4P. The radiation...

The use of laser microdissection in the identification of suitable reference genes for normalization of quantitative real-time PCR in human FFPE epithelial ovarian tissue samples.

Science.gov (United States)

Cai, Jing; Li, Tao; Huang, Bangxing; Cheng, Henghui; Ding, Hui; Dong, Weihong; Xiao, Man; Liu, Ling; Wang, Zehua

2014-01-01

Quantitative real-time PCR (qPCR) is a powerful and reproducible method of gene expression analysis in which expression levels are quantified by normalization against reference genes. Therefore, to investigate the potential biomarkers and therapeutic targets for epithelial ovarian cancer by qPCR, it is critical to identify stable reference genes. In this study, twelve housekeeping genes (ACTB, GAPDH, 18S rRNA, GUSB, PPIA, PBGD, PUM1, TBP, HRPT1, RPLP0, RPL13A, and B2M) were analyzed in 50 ovarian samples from normal, benign, borderline, and malignant tissues. For reliable results, laser microdissection (LMD), an effective technique used to prepare homogeneous starting material, was utilized to precisely excise target tissues or cells. One-way analysis of variance (ANOVA) and nonparametric (Kruskal-Wallis) tests were used to compare the expression differences. NormFinder and geNorm software were employed to further validate the suitability and stability of the candidate genes. Results showed that epithelial cells occupied a small percentage of the normal ovary indeed. The expression of ACTB, PPIA, RPL13A, RPLP0, and TBP were stable independent of the disease progression. In addition, NormFinder and geNorm identified the most stable combination (ACTB, PPIA, RPLP0, and TBP) and the relatively unstable reference gene GAPDH from the twelve commonly used housekeeping genes. Our results highlight the use of homogeneous ovarian tissues and multiple-reference normalization strategy, e.g. the combination of ACTB, PPIA, RPLP0, and TBP, for qPCR in epithelial ovarian tissues, whereas GAPDH, the most commonly used reference gene, is not recommended, especially as a single reference gene.

The use of laser microdissection in the identification of suitable reference genes for normalization of quantitative real-time PCR in human FFPE epithelial ovarian tissue samples.

Directory of Open Access Journals (Sweden)

Jing Cai

Full Text Available Quantitative real-time PCR (qPCR is a powerful and reproducible method of gene expression analysis in which expression levels are quantified by normalization against reference genes. Therefore, to investigate the potential biomarkers and therapeutic targets for epithelial ovarian cancer by qPCR, it is critical to identify stable reference genes. In this study, twelve housekeeping genes (ACTB, GAPDH, 18S rRNA, GUSB, PPIA, PBGD, PUM1, TBP, HRPT1, RPLP0, RPL13A, and B2M were analyzed in 50 ovarian samples from normal, benign, borderline, and malignant tissues. For reliable results, laser microdissection (LMD, an effective technique used to prepare homogeneous starting material, was utilized to precisely excise target tissues or cells. One-way analysis of variance (ANOVA and nonparametric (Kruskal-Wallis tests were used to compare the expression differences. NormFinder and geNorm software were employed to further validate the suitability and stability of the candidate genes. Results showed that epithelial cells occupied a small percentage of the normal ovary indeed. The expression of ACTB, PPIA, RPL13A, RPLP0, and TBP were stable independent of the disease progression. In addition, NormFinder and geNorm identified the most stable combination (ACTB, PPIA, RPLP0, and TBP and the relatively unstable reference gene GAPDH from the twelve commonly used housekeeping genes. Our results highlight the use of homogeneous ovarian tissues and multiple-reference normalization strategy, e.g. the combination of ACTB, PPIA, RPLP0, and TBP, for qPCR in epithelial ovarian tissues, whereas GAPDH, the most commonly used reference gene, is not recommended, especially as a single reference gene.

X-ray phase-contrast tomosynthesis for improved breast tissue discrimination

International Nuclear Information System (INIS)

Schleede, Simone; Bech, Martin; Grandl, Susanne; Sztrókay, Aniko; Herzen, Julia; Mayr, Doris; Stockmar, Marco; Potdevin, Guillaume

2014-01-01

Purpose: Attenuation-based tomosynthesis has proven to successfully resolve the glandular tissue overlap present in mammography. However, the ability of tomosynthesis to differentiate tumorous and glandular tissue remains limited, due to the small differences in X-ray attenuation in breast tissue. One possibility to overcome this limitation and to further increase the diagnostic value of tomosynthesis exams, is the application of recently developed grating-based phase-contrast methods, which provide complementary information on the phase shift and the local scattering power of the sample. In this study, we report on first phase-contrast breast tomosynthesis results of a mastectomy sample slice with an invasive ductal carcinoma. Material and methods: A slice of a mastectomy sample with histologically proven invasive ductal cancer was imaged at the synchrotron radiation source ESRF (Grenoble, France). We used a two-grating interferometer setup at the ninth fractional Talbot distance and with an X-ray energy of 23 keV. In grating interferometry absorption, differential phase, and scattering images are recorded simultaneously. The tomosynthesis scan comprises 61 projections. Multimodal tomosynthesis results were reconstructed using a standard filtered back-projection approach. Our findings are supported by a comparison of tomographic views to histopathology. Results: Phase-contrast tomosynthesis combines the advantage of improved soft-tissue discrimination in phase-contrast imaging with the ability of tomosynthesis to provide a third dimension so that improved feature visibility is not hampered by superposition artifacts. Our results indicate superior diagnostic value due to the depth resolution supplied in tomosynthesis imaging; a region of necrotic tissue that is obscured in a projection image can clearly be depicted in one single tomosynthesis slice. Compared to absorption tomosynthesis alone, soft tissue contrast is significantly enhanced in phase

X-ray phase-contrast tomosynthesis for improved breast tissue discrimination.

Science.gov (United States)

Schleede, Simone; Bech, Martin; Grandl, Susanne; Sztrókay, Aniko; Herzen, Julia; Mayr, Doris; Stockmar, Marco; Potdevin, Guillaume; Zanette, Irene; Rack, Alexander; Weitkamp, Timm; Pfeiffer, Franz

2014-03-01

Attenuation-based tomosynthesis has proven to successfully resolve the glandular tissue overlap present in mammography. However, the ability of tomosynthesis to differentiate tumorous and glandular tissue remains limited, due to the small differences in X-ray attenuation in breast tissue. One possibility to overcome this limitation and to further increase the diagnostic value of tomosynthesis exams, is the application of recently developed grating-based phase-contrast methods, which provide complementary information on the phase shift and the local scattering power of the sample. In this study, we report on first phase-contrast breast tomosynthesis results of a mastectomy sample slice with an invasive ductal carcinoma. A slice of a mastectomy sample with histologically proven invasive ductal cancer was imaged at the synchrotron radiation source ESRF (Grenoble, France). We used a two-grating interferometer setup at the ninth fractional Talbot distance and with an X-ray energy of 23 keV. In grating interferometry absorption, differential phase, and scattering images are recorded simultaneously. The tomosynthesis scan comprises 61 projections. Multimodal tomosynthesis results were reconstructed using a standard filtered back-projection approach. Our findings are supported by a comparison of tomographic views to histopathology. Phase-contrast tomosynthesis combines the advantage of improved soft-tissue discrimination in phase-contrast imaging with the ability of tomosynthesis to provide a third dimension so that improved feature visibility is not hampered by superposition artifacts. Our results indicate superior diagnostic value due to the depth resolution supplied in tomosynthesis imaging; a region of necrotic tissue that is obscured in a projection image can clearly be depicted in one single tomosynthesis slice. Compared to absorption tomosynthesis alone, soft tissue contrast is significantly enhanced in phase-contrast tomosynthesis views, where fibrous structures

Effects of adipose tissue distribution on maximum lipid oxidation rate during exercise in normal-weight women.

Science.gov (United States)

Isacco, L; Thivel, D; Duclos, M; Aucouturier, J; Boisseau, N

2014-06-01

Fat mass localization affects lipid metabolism differently at rest and during exercise in overweight and normal-weight subjects. The aim of this study was to investigate the impact of a low vs high ratio of abdominal to lower-body fat mass (index of adipose tissue distribution) on the exercise intensity (Lipox(max)) that elicits the maximum lipid oxidation rate in normal-weight women. Twenty-one normal-weight women (22.0 ± 0.6 years, 22.3 ± 0.1 kg.m(-2)) were separated into two groups of either a low or high abdominal to lower-body fat mass ratio [L-A/LB (n = 11) or H-A/LB (n = 10), respectively]. Lipox(max) and maximum lipid oxidation rate (MLOR) were determined during a submaximum incremental exercise test. Abdominal and lower-body fat mass were determined from DXA scans. The two groups did not differ in aerobic fitness, total fat mass, or total and localized fat-free mass. Lipox(max) and MLOR were significantly lower in H-A/LB vs L-A/LB women (43 ± 3% VO(2max) vs 54 ± 4% VO(2max), and 4.8 ± 0.6 mg min(-1)kg FFM(-1)vs 8.4 ± 0.9 mg min(-1)kg FFM(-1), respectively; P normal-weight women, a predominantly abdominal fat mass distribution compared with a predominantly peripheral fat mass distribution is associated with a lower capacity to maximize lipid oxidation during exercise, as evidenced by their lower Lipox(max) and MLOR. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

Science.gov (United States)

Goodwin, T. J.; McCarthy, M.; Lin, Y-H

2006-01-01

In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE 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 parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, 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.

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Soft tissue grafting to improve implant esthetics

Directory of Open Access Journals (Sweden)

Moawia M Kassab

2010-09-01

Full Text Available Moawia M KassabDivision of Periodontics, Marquette University, School of Dentistry, Milwaukee, WI, USAAbstract: Dental implants are becoming the treatment of choice to replace missing teeth, especially if the adjacent teeth are free of restorations. When minimal bone width is present, implant placement becomes a challenge and often resulting in recession and dehiscence around the implant that leads to subsequent gingival recession. To correct such defect, the author turned to soft tissue autografting and allografting to correct a buccal dehiscence around tooth #24 after a malpositioned implant placed by a different surgeon. A 25-year-old woman presented with the chief complaint of gingival recession and exposure of implant threads around tooth #24. The patient received three soft tissue grafting procedures to augment the gingival tissue. The first surgery included a connective tissue graft to increase the width of the keratinized gingival tissue. The second surgery included the use of autografting (connective tissue graft to coronally position the soft tissue and achieve implant coverage. The third and final surgery included the use of allografting material Alloderm to increase and mask the implant from showing through the gingiva. Healing period was uneventful for the patient. After three surgical procedures, it appears that soft tissue grafting has increased the width and height of the gingiva surrounding the implant. The accomplished thickness of gingival tissue appeared to mask the showing of implant threads through the gingival tissue and allowed for achieving the desired esthetic that the patient desired. The aim of the study is to present a clinical case with soft tissue grafting procedures.Keywords: case report, connective tissue, dental implants, allograft, coronally positioned flap

Mathematical modeling in wound healing, bone regeneration and tissue engineering.

Science.gov (United States)

Geris, Liesbet; Gerisch, Alf; Schugart, Richard C

2010-12-01

The processes of wound healing and bone regeneration and problems in tissue engineering have been an active area for mathematical modeling in the last decade. Here we review a selection of recent models which aim at deriving strategies for improved healing. In wound healing, the models have particularly focused on the inflammatory response in order to improve the healing of chronic wound. For bone regeneration, the mathematical models have been applied to design optimal and new treatment strategies for normal and specific cases of impaired fracture healing. For the field of tissue engineering, we focus on mathematical models that analyze the interplay between cells and their biochemical cues within the scaffold to ensure optimal nutrient transport and maximal tissue production. Finally, we briefly comment on numerical issues arising from simulations of these mathematical models.

Effect of radiation and other cytotoxic agents on the growth of cells cultured from normal and tumor tissues from the female genital tract

International Nuclear Information System (INIS)

Mothersill, C.; Seymour, C.B.; Bonnar, J.

1990-01-01

A technique is presented which allows the response of human gynecological tissue to radiation and cytotoxic drugs to be assessed using a tissue culture explant system. The technique is simple to use and gives results in line with those obtained for human tissues by more complex culture methods. Data are presented showing how the explant technique developed by the group for other tissues can be adapted to yield acceptable results for normal tissue response to radiation. The potential of the technique for use in predictive testing of individual tumor response is then assessed in five cases of gynecological malignancy. It is clear that variations in sensitivity to different radio- and chemotherapy agents and combinations can be detected. The results obtained require clinical validation and it is hoped that this will come over the next few years from evaluation of patient response to treatment using individually optimized, rather than empirical therapy

Effects on normal tissues during radiosensitization of Dalton's Lymphoma by the DNA ligand Hoechst 33342 in Balb/c mice

International Nuclear Information System (INIS)

Kalra, Namita; Sampath, Swapna; Adhikari, J.S.; Dwarakanath, B.S.

2014-01-01

Hoechst 33342 is a bisbenzimidazole derivative with AT specific minor groove DNA binding ability. Scavenging of free radicals and stabilization of macromolecular structure resulting in reduced induction of DNA damage contributes to radioprotection afforded by the ligand. Their ability to inhibit topoisomerases I and II, which play important roles in damage response pathways including DNA repair has been shown to sensitize tumor cells in vitro and in vivo. Due to its mutagenic and clastogenic potentials, damage to vital normal tissues are a matter of concern in deploying the ligand as adjuvant in radiotherapy. Therefore, we investigated the effects of the ligand in Dalton's Lymphoma (DL) bearing Balb/c mice by studying the local tumor control and animal survival, besides damage to normal tissues like bone marrow, kidney and testis. Hoechst 33342 (10 mg/kg b wt) was administered (i.v.) 1 h before focal irradiation (10 Gy) of the tumor (∼ 500 mm 3 ) grown on the hind leg of the mice. Partial response with a growth delay of 16 days (3 x initial volume) was seen following irradiation, while a complete response (cure; tumor-free survival) was observed in 88% mice following the combined treatment (Hoechst 33342+radiation); ligand alone had no significant effect. Although the ligand induced marginal degree of chromosomal aberrations in the bone marrow, it did not enhance aberrations induced by radiation further. In testes, the proportions of diploid, haploid and hypo-haploid cells as well as resting primary spermatocytes (RPS) were not significantly altered by either. In kidney, Hoechst 33342 alone or in combination with radiation did not cause significant damage to the proximal tubules and glomeruli. These observations suggest that radiosensitization of tumor by the DNA ligand Hoechst 33342 may not be associated with enhanced toxicity to bone marrow as well as proximal normal tissues. (author)

Realistic biological approaches for improving thermoradiotherapy

DEFF Research Database (Denmark)

Horsman, Michael R

2016-01-01

There is now definitive clinical evidence that hyperthermia can successfully improve the response of certain human tumour types to radiation therapy, but, there is still the need for improvement. From a biological standpoint this can be achieved by either targeting the cellular or vascular...... or radiation in preclinical models and clear benefits in tumour response observed. But few of these methods have actually been combined with thermoradiotherapy. Furthermore, very few combinations have been tested in relevant normal tissue studies, despite the fact that it is the normal tissue response...... that controls the maximal heat or radiation treatment that can be applied. Here we review the most clinically relevant biological approaches that have been shown to enhance thermoradiotherapy, or have the potential to be applied in this context, and suggest how these should be moved forward into the clinic....

Histologic Normalization Occurs in Ulcerative Colitis and Is Associated With Improved Clinical Outcomes.

Science.gov (United States)

Christensen, Britt; Hanauer, Stephen B; Erlich, Jonathan; Kassim, Olufemi; Gibson, Peter R; Turner, Jerrold R; Hart, John; Rubin, David T

2017-10-01

Mucosal healing, determined by histologic analysis, is a potential therapeutic target for patients with ulcerative colitis (UC). However, the histologic features of tissue normalization, as an outcome of treatment, have not been well described. We examined the prevalence and predictive values of normalization of the colonic mucosa, based on histologic analysis (histologic normalization) in patients with UC, and determined its association with risk of clinical relapse, compared with histologic disease quiescence and endoscopic mucosal healing. We performed a retrospective study of 646 patients with confirmed UC who underwent colonoscopy at a tertiary medical center from August 2005 through October 2013. We reviewed reports from pathology analyses of random mucosal biopsies from each colon segment, and categorized them into 3 groups based on histology findings: (1) normalization (completely normal mucosa with no features of chronicity present), (2) quiescence (crypt atrophy or branching without signs of active inflammation including erosions, abscesses, or focal neutrophil infiltration), or (3) active disease (epithelial infiltration by neutrophils, crypt abscesses, erosions, or ulceration). Histology findings were compared with clinical and endoscopic findings. We assessed variables associated with histology findings and, in patients in clinical remission (Simple Clinical Colitis Activity Index score ≤2 and subscore of ≤1 for stool frequency or rectal bleeding), predictive values for clinical relapse at follow-up evaluations 6 months later or more were calculated. Of the 646 patients included in the study, 60% had endoscopic mucosal healing, 40% had histologic quiescence, and 10% had histologic normalization. The level of agreement between mucosal and histologic activity was moderate (agreement for 68% of samples; κ = 0.50; P normalization (P = .002). Of 310 patients in clinical remission at initial review, 25% had a clinical relapse, after a median time

The tissue injury and repair in cancer radiotherapy. A concept of tissue architecture and radio sensitivity

Energy Technology Data Exchange (ETDEWEB)

Matsuzawa, T [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

1975-06-01

One of the difficulties in cancer radiotherapy arises from the fact that the tissue tolerance dose is much smaller than the tumor lethal dose. In our opinion the former depends upon the tolerance of the endothelial cell of the blood vessel in the normal tissue. In this introduction, a new concept regarding the estimation of tissue radiosensitivity was described, and the possible significance of the mode of radiation injury and the repair capability of normal tissue in the cancer radiotheraphy was discussed.

Effect of vanadium treatment on tissue distribution of biotrace elements in normal and streptozotocin-induced diabetic rats. Simultaneous analysis of V and Zn using radioactive multitracer

Energy Technology Data Exchange (ETDEWEB)

Yasui, Hiroyuki; Takino, Toshikazu; Fugono, Jun; Sakurai, Hiromu [Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto (Japan); Hirunuma, Rieko; Enomoto, Shuichi [Radioisotope Technology Division, Cyclotron Center, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama (Japan)

2001-05-01

Because vanadium ions such as vanadyl (VO{sup 2+}) and vanadate (VO{sup 3-}) ions were demonstrated to normalize blood glucose levels of diabetic animals and patients, the action mechanism of vanadium treatment has been of interest. In this study, we focused on understanding interactions among trace elements in diabetic rats, in which a multitracer technique was used. The effects of vanadyl sulfate (VS)-treatment on the tissue distribution of trace vanadium ({sup 48}V) and zinc ({sup 65}Zn) in normal and streptozotocin (STZ)-induced diabetic rats were examined, and were evaluated in terms of the uptake ratio. The uptake ratio of both elements in tissues significantly changed between STZ-rats and those treated with VS. These results indicated that vanadium treatment in STZ-rats alters the tissue distribution of endogenous elements, suggesting the importance of the relationship between biotrace elements and pathophysiology. (author)

Altering the swelling pressures within in vitro engineered cartilage is predicted to modulate the configuration of the collagen network and hence improve tissue mechanical properties.

Science.gov (United States)

Nagel, Thomas; Kelly, Daniel J

2013-06-01

Prestress in the collagen network has a significant impact on the material properties of cartilaginous tissues. It is closely related to the recruitment configuration of the collagen network which defines the transition from lax collagen fibres to uncrimped, load-bearing collagen fibres. This recruitment configuration can change in response to alterations in the external environmental conditions. In this study, the influence of changes in external salt concentration or sequential proteoglycan digestion on the configuration of the collagen network of tissue engineered cartilage is investigated using a previously developed computational model. Collagen synthesis and network assembly are assumed to occur in the tissue configuration present during in vitro culture. The model assumes that if this configuration is more compact due to changes in tissue swelling, the collagen network will adapt by lowering its recruitment stretch. When returned to normal physiological conditions, these tissues will then have a higher prestress in the collagen network. Based on these assumptions, the model demonstrates that proteoglycan digestion at discrete time points during culture as well as culture in a hypertonic medium can improve the functionality of tissue engineered cartilage, while culture in hypotonic solution is detrimental to the apparent mechanical properties of the graft. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improving the dictionary lookup approach for disease normalization using enhanced dictionary and query expansion

Science.gov (United States)

Jonnagaddala, Jitendra; Jue, Toni Rose; Chang, Nai-Wen; Dai, Hong-Jie

2016-01-01

The rapidly increasing biomedical literature calls for the need of an automatic approach in the recognition and normalization of disease mentions in order to increase the precision and effectivity of disease based information retrieval. A variety of methods have been proposed to deal with the problem of disease named entity recognition and normalization. Among all the proposed methods, conditional random fields (CRFs) and dictionary lookup method are widely used for named entity recognition and normalization respectively. We herein developed a CRF-based model to allow automated recognition of disease mentions, and studied the effect of various techniques in improving the normalization results based on the dictionary lookup approach. The dataset from the BioCreative V CDR track was used to report the performance of the developed normalization methods and compare with other existing dictionary lookup based normalization methods. The best configuration achieved an F-measure of 0.77 for the disease normalization, which outperformed the best dictionary lookup based baseline method studied in this work by an F-measure of 0.13. Database URL: https://github.com/TCRNBioinformatics/DiseaseExtract PMID:27504009

Three dimensional conformal radiation therapy may improve the therapeutic ratio of radiation therapy after pneumonectomy for lung cancer

Energy Technology Data Exchange (ETDEWEB)

Trouette, R; Causse, N; Elkhadri, M; Caudry, M; Maire, J P; Houlard, J P; Racaldini, L; Demeaux, H

1995-12-01

Three dimensional conformal radiation therapy would allow to decrease the normal tissue dose while maintaining the same target dose as standard treatment. To evaluate the feasibility of normal tissue dose reduction for ten patients with pneumonectomy for lung cancer, we determined the dose distribution to the normal tissue with 3-dimensional conformal radiation therapy (3-DCRT) and conventional treatment planning (CTP). Dose-volume histograms for target and normal tissue (lung, heart) were used for comparison of the different treatment planning. The mean percentages of lung and heart volumes which received 40 Gy with 3-DCRT were respectively 63% and 37% of the mean percentage of lung and volumes which received the same dose with CTP. These preliminary results suggest that conformal therapy may improve the therapeutic ratio by reducing risk to normal tissue.

Association of reproductive history with breast tissue characteristics and receptor status in the normal breast.

Science.gov (United States)

Gabrielson, Marike; Chiesa, Flaminia; Behmer, Catharina; Rönnow, Katarina; Czene, Kamila; Hall, Per

2018-03-30

Reproductive history has been associated with breast cancer risk, but more knowledge of the underlying biological mechanisms is needed. Because of limited data on normal breast tissue from healthy women, we examined associations of reproductive history and established breast cancer risk factors with breast tissue composition and markers of hormone receptors and proliferation in a nested study within the Karolinska Mammography project for risk prediction for breast cancer (Karma). Tissues from 153 women were obtained by ultrasound-guided core needle biopsy as part of the Karma project. Immunohistochemical staining was used to assessed histological composition of epithelial, stromal and adipose tissue, epithelial and stromal oestrogen receptor (ER) and progesterone receptor (PR) status, and Ki-67 proliferation status. An individualised reproductive score including parity, number of pregnancies without birth, number of births, age at first birth, and duration of breastfeeding, was calculated based on self-reported reproductive history at the time of the Karma study entry. All analyses were adjusted for age and BMI. Cumulated reproductive score was associated with increased total epithelial content and greater expression of epithelial ER. Parity was associated with greater epithelial area, increased epithelial-stromal ratio, greater epithelial ER expression and a lower extent of stromal proliferation. Increasing numbers of pregnancies and births were associated with a greater epithelial area in the entire study set, which remained significant among postmenopausal women. Increasing numbers of pregnancies and births were also associated with a greater expression of epithelial ER among postmenopausal women. Longer duration of breastfeeding was associated with greater epithelial area and greater expression of epithelial PR both in the entire study set and among postmenopausal women. Breastfeeding was also positively associated with greater epithelial ER expression among

IMPROVING QUALITY OF STATISTICAL PROCESS CONTROL BY DEALING WITH NON‐NORMAL DATA IN AUTOMOTIVE INDUSTRY

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