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Sample records for model pathological tumour

  1. Correlation of Ultrasound Shear Wave Elastography with Pathological Analysis in a Xenografic Tumour Model

    DEFF Research Database (Denmark)

    Elyas, Eli; Papaevangelou, Efthymia; Alles, Erwin J

    2017-01-01

    The objective of this study was to evaluate the potential value of ultrasound (US) shear wave elastography (SWE) in assessing the relative change in elastic modulus in colorectal adenocarcinoma xenograft models in vivo and investigate any correlation with histological analysis. We sought to test...... = 0.37, p = 0.008). Irinotecan administration caused significant delay in the tumour growth (p = 0.02) when compared to control, but no significant difference in elastic modulus was detected. Histological analysis revealed a significant correlation between tumour necrosis and elastic modulus (r = -0...

  2. Pancreatic neuroendocrine tumours: correlation between MSCT features and pathological classification

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Yanji; Dong, Zhi; Li, Zi-Ping; Feng, Shi-Ting [The First Affiliated Hospital, Sun Yat-Sen University, Department of Radiology, Guangzhou, Guangdong (China); Chen, Jie [The First Affiliated Hospital, Sun Yat-Sen University, Department of Gastroenterology, Guangzhou, Guangdong (China); Chan, Tao; Chen, Minhu [Union Hospital, Hong Kong, Medical Imaging Department, Shatin, N.T. (China); Lin, Yuan [The First Affiliated Hospital, Sun Yat-Sen University, Department of Pathology, Guangzhou, Guangdong (China)

    2014-11-15

    We aimed to evaluate the multi-slice computed tomography (MSCT) features of pancreatic neuroendocrine neoplasms (P-NENs) and analyse the correlation between the MSCT features and pathological classification of P-NENs. Forty-one patients, preoperatively investigated by MSCT and subsequently operated on with a histological diagnosis of P-NENs, were included. Various MSCT features of the primary tumour, lymph node, and distant metastasis were analysed. The relationship between MSCT features and pathologic classification of P-NENs was analysed with univariate and multivariate models. Contrast-enhanced images showed significant differences among the three grades of tumours in the absolute enhancement (P = 0.013) and relative enhancement (P = 0.025) at the arterial phase. Univariate analysis revealed statistically significant differences among the tumours of different grades (based on World Health Organization [WHO] 2010 classification) in tumour size (P = 0.001), tumour contour (P < 0.001), cystic necrosis (P = 0.001), tumour boundary (P = 0.003), dilatation of the main pancreatic duct (P = 0.001), peripancreatic tissue or vascular invasion (P < 0.001), lymphadenopathy (P = 0.011), and distant metastasis (P = 0.012). Multivariate analysis suggested that only peripancreatic tissue or vascular invasion (HR 3.934, 95 % CI, 0.426-7.442, P = 0.028) was significantly associated with WHO 2010 pathological classification. MSCT is helpful in evaluating the pathological classification of P-NENs. (orig.)

  3. Ovarian sex-cord stromal tumours and small cell tumours: Pathological, genetic and management aspects.

    Science.gov (United States)

    Boussios, Stergios; Moschetta, Michele; Zarkavelis, George; Papadaki, Alexandra; Kefas, Aristides; Tatsi, Konstantina

    2017-12-01

    Non-epithelial ovarian cancers (NEOC) constitute a group of uncommon malignancies and their treatment is still a challenging task. Collectively, these tumours account for about 10% of all ovarian cancers and occur in all age groups from childhood to old-age. They include malignancies of germ cell origin, sex cord-stromal cell origin, and a variety of extremely rare ovarian cancers, such as small-cell carcinomas and sarcomas. Each of these classifications encompasses multiple histologic subtypes. It is imperative that these rare tumours are managed with accurate diagnosis, staging, and treatment, to optimise the outcome. The aetiology and molecular origins of each sub-group of NEOC remain largely unresolved, and international cooperation to promote high quality translational research is crucial. Much effort has been made into researching the molecular mechanisms underlying epithelial ovarian cancers, but far less is known about the genetic changes in NEOC. In this article, it is provided an overview of the current knowledge on the incidence, clinical presentation, pathology, genetics, therapeutic interventions, survival and prognostic factors of adult and juvenile granulosa cell tumours (GrCT), Sertoli-Leydig Cell tumours (SLCT) and small cell carcinoma of the ovary. We also consider future potential therapeutic targets in these rare cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. New clinical, pathological and molecular prognostic models and calculators in patients with locally diagnosed anaplastic oligodendroglioma or oligoastrocytoma. A prognostic factor analysis of European Organisation for Research and Treatment of Cancer Brain Tumour Group Study 26951.

    Science.gov (United States)

    Gorlia, Thierry; Delattre, Jean-Yves; Brandes, Alba A; Kros, Johan M; Taphoorn, Martin J B; Kouwenhoven, Mathilde C M; Bernsen, H J J A; Frénay, Marc; Tijssen, Cees C; Lacombe, Denis; van den Bent, Martin J

    2013-11-01

    The prognosis of patients with anaplastic oligodendrogliomas (AOD) and oligoastrocytomas (AOA) is variable. Biomarkers might be helpful to identify more homogeneous disease subtypes and improve therapeutic index. The aim of this study is to develop new clinical, pathological and molecular prognostic models for locally diagnosed anaplastic gliomas with oligodendroglial features (AOD or AOA). Data from 368 patients with AOD or AOA recruited in The European Organisation for Research and Treatment of Cancer (EORTC) trial 26951 on adjuvant PCV (Procarbazine, CCNU, Vincristine) chemotherapy in anaplastic oligodendroglial tumours were used to develop multifactor models to predict progression free survival (PFS) and overall survival (OS). Different models were compared by their percentage of explained variation (PEV). Prognostic calculators were derived from these new models. Treatment (for PFS only), younger age, confirmed absence of residual tumour on imaging, frontal location, good World Health Organisation (WHO) performance status, absence of endothelial abnormalities and/or necrosis, 1p/19q codeletion and Isocitrate dehydrogenase 1 (IDH1) mutation were independent factors that predicted better PFS and OS. We identified important prognostic factors for AOD and AOA and showed that molecular markers added a major contribution to clinical and pathological factors in explaining PFS and OS. With a positive predictive value of 92% for PFS and 94% for OS, our models allow physicians to precisely identify high risk patients and aid in making therapeutic decisions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Direct sagittal CT scanning in the diagnosis of pituitary fossa tumours and posterior fossa pathology

    International Nuclear Information System (INIS)

    Podlas, H.

    1981-01-01

    Two independent methods are presented for multidirectional CT scanning of the brain using the Philips Tomoscan 300. The advantages in scanning pituitary fossa tumours and pathology of the posterior fossa are discussed. No additional software or modifications are required. Direct sagittal scanning is particularly advantageous for accurate assessment of the size of pituitary tumours and intrasellar lesions requiring surgical intervention or radiation therapy. (Auth.)

  6. Optical diagnostics of tumour cells at different stages of pathology development

    Science.gov (United States)

    Shcheglova, L. S.; Abramova, L. L.; Maryakhina, V. S.

    2013-11-01

    The differences in optical and biophysical properties between the cells of mammary gland tumour extracted from tumours of different diameter are described. It is shown that the spectral and spectrokinetic properties of fluorescent probes in the cells extracted from the tumours 1 - 3 cm in diameter are essentially different. Thus, the extinction coefficient of rhodamine 6G gradually increases with the pathology development. At the same time the rate of interaction of the triplet states of molecular probes with the oxygen, diluted in the tumour cells cytoplasm, decreases with the growth of the tumour capsule diameter. The observed regularities can be due to the changes in the cell structure, biochemical and biophysical properties. The reported data may be useful for developing optical methods of diagnostics of biotissue pathological conditions.

  7. [Protocol for the study of bone tumours and standardization of pathology reports].

    Science.gov (United States)

    Machado, Isidro; Pozo, José Juan; Marcilla, David; Cruz, Julia; Tardío, Juan C; Astudillo, Aurora; Bagué, Sílvia

    Primary bone neoplasms represent a rare and heterogeneous group of mesenchymal tumours. The prevalence of benign and malignant tumours varies; the latter (sarcomas) account for less than 0.2% of all malignant tumours. Primary bone neoplasms are usually diagnosed and classified according to the criteria established and published by the World Health Organization (WHO 2013). These criteria are a result of advances in molecular pathology, which complements the histopathological diagnosis. Bone tumours should be diagnosed and treated in referral centers by a multidisciplinary team including pathologists, radiologists, orthopedic surgeons and oncologists. We analyzed different national and international protocols in order to provide a guide of recommendations for the improvement of pathological evaluation and management of bone tumours. We include specific recommendations for the pre-analytical, analytical, and post-analytical phases, as well as protocols for gross and microscopic pathology. Copyright © 2016 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Tumour resistance to cisplatin: a modelling approach

    International Nuclear Information System (INIS)

    Marcu, L; Bezak, E; Olver, I; Doorn, T van

    2005-01-01

    Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure

  9. A rare pathological trinity: an appendiceal ectopic pregnancy, acute appendicitis and a carcinoid tumour.

    Science.gov (United States)

    Thompson, R J; Hawe, M J G

    2011-06-01

    We present a case of a 27-year-old woman who was found to have an appendiceal ectopic pregnancy, a carcinoid tumour of the appendix and acute appendicitis existing concurrently. This triad of pathology has never been reported previously. This case highlights the importance of performing a pregnancy test in all women of childbearing age presenting with acute abdominal pain and also the need to consider other diagnoses that may mimic or present concurrently with acute appendicitis.

  10. Which factors influence MRI-pathology concordance of tumour size measurements in breast cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Rominger, M.; Frauenfelder, T. [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Berg, D. [Urbankrankenhaus Berlin, Anesthesiology, Berlin (Germany); Ramaswamy, A. [University Hospital Marburg, Pathology, Marburg (Germany); Timmesfeld, N. [Philipps University Marburg, Institute for Medical Biometry and Epidemiology, Marburg (Germany)

    2016-05-15

    To assess MRI-pathology concordance and factors influencing tumour size measurement in breast cancer. MRI tumour size (greatest diameter in anatomical planes (MRI-In-Plane) and greatest diameter along main tumour axis (MRI-MPR)) of 115 consecutive breast lesions (59 invasive lobular carcinoma, 46 invasive ductal carcinoma, and 10 ductal carcinoma in situ) was retrospectively compared to size measured at histopathology (pT size (Path-TNM) and greatest tumour diameter as relevant for excision (Path-Diameter; reference standard)). Histopathological tumour types, preoperative palpability, surgical management, additional high-risk lesions, and BI-RADS lesion type (mass versus non-mass enhancements) were assessed as possible influencing factors. Systematic errors were most pronounced between MRI-MPR and Path-TNM (7.1 mm, limits of agreement (LoA) [-21.7; 35.9]), and were lowest between MRI-In-Plane and Path-Diameter (0.2 mm, LoA [-19.7; 20.1]). Concordance rate of MRI-In-Plane with Path-Diameter was 86 % (97/113), overestimation 9 % (10/113) and underestimation 5 % (6/113); BI-RADS mass lesions were overestimated in 7 % (6/81) versus 41 % (13/32) for non-mass enhancements. On multivariate analysis only BI-RADS lesion type significantly influenced MRI-pathology concordance (p < 0.001). 2/59 (3 %) ILC did not enhance. Concordance rate varies according to the execution of MRI and histopathological measurements. Beyond this only non-mass enhancement significantly predicted discordance. (orig.)

  11. CD117 immunoexpression in canine mast cell tumours: correlations with pathological variables and proliferation markers

    Directory of Open Access Journals (Sweden)

    Pires Maria A

    2007-08-01

    Full Text Available Abstract Background Cutaneous mast cell tumours are one of the most common neoplasms in dogs and show a highly variable biologic behaviour. Several prognosis tools have been proposed for canine mast cell tumours, including histological grading and cell proliferation markers. CD117 is a receptor tyrosine kinase thought to play a key role in human and canine mast cell neoplasms. Normal (membrane-associated and aberrant (cytoplasmic, focal or diffuse CD117 immunoexpression patterns have been identified in canine mast cell tumours. Cytoplasmic CD117 expression has been found to correlate with higher histological grade and with a worsened post-surgical prognosis. This study addresses the role of CD117 in canine mast cell tumours by studying the correlations between CD117 immunoexpression patterns, two proliferation markers (Ki67 and AgNORs histological grade, and several other pathological variables. Results Highly significant (p Conclusion These findings highlight the key role of CD117 in the biopathology of canine MCTs and confirm the relationship between aberrant CD117 expression and increased cell proliferation and higher histological grade. Further studies are needed to unravel the cellular mechanisms underlying focal and diffuse cytoplasmic CD117 staining patterns, and their respective biopathologic relevance.

  12. Small cell neuroendocrine tumour of the endometrium and the importance of pathologic diagnosis.

    Science.gov (United States)

    Estruch, Adriana; Minig, Lucas; Illueca, Carmen; Romero, Ignacio; Guinot, Jose Luis; Poveda, Andrés

    2016-01-01

    Small cell carcinoma of the endometrium is a very rare entity. They are very aggressive tumours, with a poor prognosis. They represent a clinical challenge because of a lack of a standardised treatment. We see here a case of a 67-year-old woman with a history of a lobular breast carcinoma, diagnosed in 2002. After presenting with postmenopausal vaginal bleeding in October 2014, she underwent a hysteroscopy-guided biopsy which revealed a metastasis of breast carcinoma. A hysterectomy and bilateral oophorectomy was performed because of uncontrolled uterine bleeding. The pathologic diagnosis was small cell carcinoma (SCC) of the endometrium. A surgical complete cytoreduction was achieved after the case being presented in a multidisciplinary tumour board. Pathologic results revealed metastasis from peritoneal implants of SCC on the endometrium, and metastasis in pelvic and para-aortic lymph nodes from serous carcinoma of the endometrium. A total of four cycles of adjuvant chemotherapy based on cisplatin (80mg/m² day one) and etoposide (100mg/m² day one, two, three) every 21 days was given. The patient experienced persistent disease and died 17 months after the diagnosis. SCC of the endometrium is a very rare and aggressive disease that requires an individualised multidisciplinary management.

  13. Staging primary breast cancer. Are there tumour pathological features that correlate with a false-negative axillary ultrasound?

    International Nuclear Information System (INIS)

    Johnson, S.; Brown, S.; Porter, G.; Steel, J.; Paisley, K.; Watkins, R.; Holgate, C.

    2011-01-01

    Aim: To investigate whether the histopathological characteristics of primary breast cancer tumours could predict the likelihood of false-negative axillary ultrasound. Materials and methods: Screening and symptomatic patients were identified from pathology records and imaging and pathology records reviewed. True and false-negative axillary staging ultrasound groups were compared statistically in terms of tumour size, pathological type and grade, lymphovascular invasion, and oestrogen receptor (ER) status. Results: Of 155 women with normal ultrasounds, 45 (29%) were node positive at axillary surgery. Breast tumour size was significantly different with the average size smaller in the true-negative group: 21 versus 30 mm (p < 0.02). The histological type varied significantly between the groups, with more lobular carcinomas in the false-negative group [6/110 (5%) versus 6/45 (13%), p < 0.001]. The false-negative group was also more likely to show lymphovascular invasion in the breast [6/110 (5%) versus 14/45 (31%), p < 0.001]. There was no significant difference in tumour grade or ER status. Conclusion: The present study has found significant differences in tumour characteristics between women with true-negative and false-negative axillary staging ultrasound in terms of size, primary tumour histological type and presence of lymphovascular invasion. In particular, axillary ultrasound in primary lobular carcinoma may be less accurate and a negative result is more likely to be spurious than with primary ductal carcinomas.

  14. Modelling and detecting tumour oxygenation levels.

    Directory of Open Access Journals (Sweden)

    Anne C Skeldon

    Full Text Available Tumours that are low in oxygen (hypoxic tend to be more aggressive and respond less well to treatment. Knowing the spatial distribution of oxygen within a tumour could therefore play an important role in treatment planning, enabling treatment to be targeted in such a way that higher doses of radiation are given to the more radioresistant tissue. Mapping the spatial distribution of oxygen in vivo is difficult. Radioactive tracers that are sensitive to different levels of oxygen are under development and in the early stages of clinical use. The concentration of these tracer chemicals can be detected via positron emission tomography resulting in a time dependent concentration profile known as a tissue activity curve (TAC. Pharmaco-kinetic models have then been used to deduce oxygen concentration from TACs. Some such models have included the fact that the spatial distribution of oxygen is often highly inhomogeneous and some have not. We show that the oxygen distribution has little impact on the form of a TAC; it is only the mean oxygen concentration that matters. This has significant consequences both in terms of the computational power needed, and in the amount of information that can be deduced from TACs.

  15. 3D Multiscale Modelling of Angiogenesis and Vascular Tumour Growth

    KAUST Repository

    Perfahl, H.

    2012-11-01

    We present a three-dimensional, multiscale model of vascular tumour growth, which couples nutrient/growth factor transport, blood flow, angiogenesis, vascular remodelling, movement of and interactions between normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. We present computational simulations which show how a vascular network may evolve and interact with tumour and healthy cells. We also demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.

  16. A reproducible brain tumour model established from human glioblastoma biopsies

    Directory of Open Access Journals (Sweden)

    Li Xingang

    2009-12-01

    Full Text Available Abstract Background Establishing clinically relevant animal models of glioblastoma multiforme (GBM remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. Methods In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. Results The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. Conclusions In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.

  17. Differential Equations Related to the Williams-Bjerknes Tumour Model

    Indian Academy of Sciences (India)

    Bjerknes tumour model for a cancer which spreads through an epithelial basal layer modeled on ⊂ 2. The solution of this problem is a family =(()), where each () could be considered as an approximation to the probability that the ...

  18. A mathematical model of tumour angiogenesis: growth, regression and regrowth.

    Science.gov (United States)

    Vilanova, Guillermo; Colominas, Ignasi; Gomez, Hector

    2017-01-01

    Cancerous tumours have the ability to recruit new blood vessels through a process called angiogenesis. By stimulating vascular growth, tumours get connected to the circulatory system, receive nutrients and open a way to colonize distant organs. Tumour-induced vascular networks become unstable in the absence of tumour angiogenic factors (TAFs). They may undergo alternating stages of growth, regression and regrowth. Following a phase-field methodology, we propose a model of tumour angiogenesis that reproduces the aforementioned features and highlights the importance of vascular regression and regrowth. In contrast with previous theories which focus on vessel remodelling due to the absence of flow, we model an alternative regression mechanism based on the dependency of tumour-induced vascular networks on TAFs. The model captures capillaries at full scale, the plastic dynamics of tumour-induced vessel networks at long time scales, and shows the key role played by filopodia during angiogenesis. The predictions of our model are in agreement with in vivo experiments and may prove useful for the design of antiangiogenic therapies. © 2017 The Author(s).

  19. Multiphase modelling of vascular tumour growth in two spatial dimensions

    KAUST Repository

    Hubbard, M.E.

    2013-01-01

    In this paper we present a continuum mathematical model of vascular tumour growth which is based on a multiphase framework in which the tissue is decomposed into four distinct phases and the principles of conservation of mass and momentum are applied to the normal/healthy cells, tumour cells, blood vessels and extracellular material. The inclusion of a diffusible nutrient, supplied by the blood vessels, allows the vasculature to have a nonlocal influence on the other phases. Two-dimensional computational simulations are carried out on unstructured, triangular meshes to allow a natural treatment of irregular geometries, and the tumour boundary is captured as a diffuse interface on this mesh, thereby obviating the need to explicitly track the (potentially highly irregular and ill-defined) tumour boundary. A hybrid finite volume/finite element algorithm is used to discretise the continuum model: the application of a conservative, upwind, finite volume scheme to the hyperbolic mass balance equations and a finite element scheme with a stable element pair to the generalised Stokes equations derived from momentum balance, leads to a robust algorithm which does not use any form of artificial stabilisation. The use of a matrix-free Newton iteration with a finite element scheme for the nutrient reaction-diffusion equations allows full nonlinearity in the source terms of the mathematical model.Numerical simulations reveal that this four-phase model reproduces the characteristic pattern of tumour growth in which a necrotic core forms behind an expanding rim of well-vascularised proliferating tumour cells. The simulations consistently predict linear tumour growth rates. The dependence of both the speed with which the tumour grows and the irregularity of the invading tumour front on the model parameters is investigated. © 2012 Elsevier Ltd.

  20. Beyond typing and grading: target analysis in individualized therapy as a new challenge for tumour pathology.

    Science.gov (United States)

    Kreipe, Hans H; von Wasielewski, Reinhard

    2007-01-01

    In order to bring about its beneficial effects in oncology, targeted therapy depends on accurate target analysis. Whether cells of a tumour will be sensitive to a specific treatment is predicted by the detection of appropriate targets in cancer tissue by immunohistochemistry or molecular methods. In most instances this is performed by histopathologists. Reliability and reproducibility of tissue-based target analysis in histopathology require novel measures of quality assurance by internal and external controls. As a model for external quality assurance in targeted therapy an annual inter-laboratory trial has been set up in Germany applying tissue arrays with up to 60 mammary cancer samples which are tested by participants for expression of HER2/neu and steroid hormone receptors.

  1. Central nervous system tumours and related intracranial pathologies in radium dial workers

    International Nuclear Information System (INIS)

    Stebbings, J.H.; Semkiw, W.

    1989-01-01

    Among female radiation workers in the radium dial industry there is no overall excess of fatal brain or central nervous system tumours. A significant excess did appear, in one of three major cohorts; the excess was not due to an excess of gliomas and cannot be ascribed with certainty to radium or external radiation. A significant proportional excess of tumours outside of the brain was observed, consistent with irradiation of nervous system tissue from adjacent bone. Excess tumours of the eye, pituitary or pineal did not occur. Early deaths from brain abscess or mastoiditis, coded as diseases of the nervous system and sense organs, were observed. (author)

  2. Tumours in white suckers from Lake Michigan tributaries: Pathology and prevalence

    Science.gov (United States)

    Blazer, Vicki; Walsh, H.L.; Braham, R.P.; Hahn, C. M.; Mazik, P.; McIntyre, P.B.

    2016-01-01

    The prevalence and histopathology of neoplastic lesions were assessed in white suckerCatostomus commersonii captured at two Lake Michigan Areas of Concern (AOCs), the Sheboygan River and Milwaukee Estuary. Findings were compared to those observed at two non-AOC sites, the Root and Kewaunee rivers. At each site, approximately 200 adult suckers were collected during their spawning migration. Raised skin lesions were observed at all sites and included discrete white spots, mucoid plaques on the body surface and fins and large papillomatous lesions on lips and body. Microscopically, hyperplasia, papilloma and squamous cell carcinoma were documented. Liver neoplasms were also observed at all sites and included both hepatocellular and biliary tumours. Based on land use, the Kewaunee River was the site least impacted by human activities previously associated with fish tumours and had significantly fewer liver neoplasms when compared to the other sites. The proportion of white suckers with liver tumours followed the same patterns as the proportion of urban land use in the watershed: the Milwaukee Estuary had the highest prevalence, followed by the Root, Sheboygan and Kewaunee rivers. The overall skin neoplasm (papilloma and carcinoma) prevalence did not follow the same pattern, although the percentage of white suckers with squamous cell carcinoma exhibited a similar relationship to land use. Testicular tumours (seminoma) were observed at both AOC sites but not at the non-AOC sites. Both skin and liver tumours were significantly and positively associated with age but not sex.

  3. Numerical resolution of a model of tumour growth.

    Science.gov (United States)

    Muñoz, Ana I

    2016-03-01

    We consider and solve numerically a mathematical model of tumour growth based on cancer stem cells (CSC) hypothesis with the aim of gaining some insight into the relation of different processes leading to exponential growth in solid tumours and into the evolution of different subpopulations of cells. The model consists of four hyperbolic equations of first order to describe the evolution of four subpopulations of cells. A fifth equation is introduced to model the evolution of the moving boundary. The coefficients of the model represent the rates at which reactions occur. In order to integrate numerically the four hyperbolic equations, a formulation in terms of the total derivatives is posed. A finite element discretization is applied to integrate the model equations in space. Our numerical results suggest the existence of a pseudo-equilibrium state reached at the early stage of the tumour, for which the fraction of CSC remains small. We include the study of the behaviour of the solutions for longer times and we obtain that the solutions to the system of partial differential equations stabilize to homogeneous steady states whose values depend only on the values of the parameters. We show that CSC may comprise different proportions of the tumour, becoming, in some cases, the predominant type of cells within the tumour. We also obtain that possible effective measure to detain tumour progression should combine the targeting of CSC with the targeting of progenitor cells. © The Authors 2015. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  4. Odontogenic Tumours of Jaw: A Prospective Study on Clinico-Pathological Profile and Their Management.

    Science.gov (United States)

    Mukherjee, Dwaipayan; Das, Chiranjib; Chatterjee, Pritam

    2017-06-01

    Odontogenic tumours are a group of heterogeneous diseases that range from hamartomatous or non-neoplastic tissue proliferations to benign neoplasms to malignant tumours with metastatic potential. They are rare, comprising about lesions and review of literature. The present study was conducted in the ENT department of a Government Medical College and Hospital, West Bengal, India, over the period of 5 years from January 2011 to December 2015. It included a total of 15 patients who were clinico-radiologically diagnosed as odontogenic tumours, and were given appropriate treatment. Their diagnostic and management approaches are discussed. Among 15 odontogenic tumours, 13 were benign and two were malignant. Male to female ratio was 2:3. Mandible to maxilla ratio was 1.8:1. The patients were in between 4 and 56 years of age with highest incidence in 3rd decade of life. All patients are doing well till date with a minimum follow-up of 1 year. Incisional biopsy is considered as gold standard for preoperative diagnosis but FNAC can offer clinicians a less invasive alternative. CT is the choice of investigation for study of lesion, analysis of its extension and surgical planning. The challenge to proper management lies in balancing between conservative and radical approach to reduce morbidity and recurrence both. Final diagnosis is made by post-operative histopathological examination.

  5. An optimized small animal tumour model for experimentation with low energy protons.

    Science.gov (United States)

    Beyreuther, Elke; Brüchner, Kerstin; Krause, Mechthild; Schmidt, Margret; Szabo, Rita; Pawelke, Jörg

    2017-01-01

    The long-term aim of developing laser based particle acceleration towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short and ultra-intensive particle beam pulses. After comprehensive cell studies a mouse ear tumour model was established allowing for the penetration of low energy protons (~20 MeV) currently available at laser driven accelerators. The model was successfully applied for a first tumour growth delay study with laser driven electrons, whereby the need of improvements crop out. To optimise the mouse ear tumour model with respect to a stable, high take rate and a lower number of secondary tumours, Matrigel was introduced for tumour cell injection. Different concentrations of two human tumour cell lines (FaDu, LN229) and Matrigel were evaluated for stable tumour growth and fulfilling the allocation criteria for irradiation experiments. The originally applied cell injection with PBS was performed for comparison and to assess the long-term stability of the model. Finally, the optimum suspension of cells and Matrigel was applied to determine applicable dose ranges for tumour growth delay studies by 200 kV X-ray irradiation. Both human tumour models showed a high take rate and exponential tumour growth starting at a volume of ~10 mm3. As disclosed by immunofluorescence analysis these small tumours already interact with the surrounding tissue and activate endothelial cells to form vessels. The formation of delimited, solid tumours at irradiation size was shown by standard H&E staining and a realistic dose range for inducing tumour growth delay without permanent tumour control was obtained for both tumour entities. The already established mouse ear tumour model was successfully upgraded now providing stable tumour growth with high take rate for two tumour entities (HNSCC, glioblastoma) that are of interest for future irradiation experiments at experimental

  6. An optimized small animal tumour model for experimentation with low energy protons.

    Directory of Open Access Journals (Sweden)

    Elke Beyreuther

    Full Text Available The long-term aim of developing laser based particle acceleration towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short and ultra-intensive particle beam pulses. After comprehensive cell studies a mouse ear tumour model was established allowing for the penetration of low energy protons (~20 MeV currently available at laser driven accelerators. The model was successfully applied for a first tumour growth delay study with laser driven electrons, whereby the need of improvements crop out.To optimise the mouse ear tumour model with respect to a stable, high take rate and a lower number of secondary tumours, Matrigel was introduced for tumour cell injection. Different concentrations of two human tumour cell lines (FaDu, LN229 and Matrigel were evaluated for stable tumour growth and fulfilling the allocation criteria for irradiation experiments. The originally applied cell injection with PBS was performed for comparison and to assess the long-term stability of the model. Finally, the optimum suspension of cells and Matrigel was applied to determine applicable dose ranges for tumour growth delay studies by 200 kV X-ray irradiation.Both human tumour models showed a high take rate and exponential tumour growth starting at a volume of ~10 mm3. As disclosed by immunofluorescence analysis these small tumours already interact with the surrounding tissue and activate endothelial cells to form vessels. The formation of delimited, solid tumours at irradiation size was shown by standard H&E staining and a realistic dose range for inducing tumour growth delay without permanent tumour control was obtained for both tumour entities.The already established mouse ear tumour model was successfully upgraded now providing stable tumour growth with high take rate for two tumour entities (HNSCC, glioblastoma that are of interest for future irradiation experiments at

  7. An imaging-based computational model for simulating angiogenesis and tumour oxygenation dynamics

    Science.gov (United States)

    Adhikarla, Vikram; Jeraj, Robert

    2016-05-01

    Tumour growth, angiogenesis and oxygenation vary substantially among tumours and significantly impact their treatment outcome. Imaging provides a unique means of investigating these tumour-specific characteristics. Here we propose a computational model to simulate tumour-specific oxygenation changes based on the molecular imaging data. Tumour oxygenation in the model is reflected by the perfused vessel density. Tumour growth depends on its doubling time (T d) and the imaged proliferation. Perfused vessel density recruitment rate depends on the perfused vessel density around the tumour (sMVDtissue) and the maximum VEGF concentration for complete vessel dysfunctionality (VEGFmax). The model parameters were benchmarked to reproduce the dynamics of tumour oxygenation over its entire lifecycle, which is the most challenging test. Tumour oxygenation dynamics were quantified using the peak pO2 (pO2peak) and the time to peak pO2 (t peak). Sensitivity of tumour oxygenation to model parameters was assessed by changing each parameter by 20%. t peak was found to be more sensitive to tumour cell line related doubling time (~30%) as compared to tissue vasculature density (~10%). On the other hand, pO2peak was found to be similarly influenced by the above tumour- and vasculature-associated parameters (~30-40%). Interestingly, both pO2peak and t peak were only marginally affected by VEGFmax (~5%). The development of a poorly oxygenated (hypoxic) core with tumour growth increased VEGF accumulation, thus disrupting the vessel perfusion as well as further increasing hypoxia with time. The model with its benchmarked parameters, is applied to hypoxia imaging data obtained using a [64Cu]Cu-ATSM PET scan of a mouse tumour and the temporal development of the vasculature and hypoxia maps are shown. The work underscores the importance of using tumour-specific input for analysing tumour evolution. An extended model incorporating therapeutic effects can serve as a powerful tool for analysing

  8. Tumour-cell killing by X-rays and immunity quantitated in a mouse model system

    International Nuclear Information System (INIS)

    Porteous, D.D.; Porteous, K.M.; Hughes, M.J.

    1979-01-01

    As part of an investigation of the interaction of X-rays and immune cytotoxicity in tumour control, an experimental mouse model system has been used in which quantitative anti-tumour immunity was raised in prospective recipients of tumour-cell suspensions exposed to varying doses of X-rays in vitro before injection. Findings reported here indicate that, whilst X-rays kill a proportion of cells, induced immunity deals with a fixed number dependent upon the immune status of the host, and that X-rays and anti-tumour immunity do not act synergistically in tumour-cell killing. The tumour used was the ascites sarcoma BP8. (author)

  9. Application of flexible endoscopy-based biopsy in the diagnosis of tumour pathologies in otorhinolaryngology.

    Science.gov (United States)

    Saga, Carlos; Olalde, Manuel; Larruskain, Ekhiñe; Álvarez, Leire; Altuna, Xabier

    Interventional endoscopy allows us to act on the pathology of the patient with minimal discomfort, low costs and high efficiency. We assessed the validity of flexible endoscopic biopsies in our hospital, in lesions suspected of malignancy in the rhino-pharyngo-laryngeal space. Retrospective study of patients with a pathology suspected of malignancy assessed between 2006-2016 in our centre. We evaluated the effectiveness, the tolerance and the number of complications. We calculated the cost reduction in comparison with direct laryngoscopy in the operating room. We compared our sample with others of similar characteristics described in the literature. Thirty patients were studied with a flexible endoscopic biopsy during that period. Nineteen patients obtained positive results which allowed them to start treatment for their pathology. Seven cases had no evidence of malignancy and required another biopsy under general anaesthesia, which confirmed the carcinoma diagnosis. Two samples ruled out malignancy which was confirmed by laryngeal microsurgery. One case showed inflammation and the lesion was cured after antibiotherapy. It was impossible to collect the sample in one case. Thus, we obtained sensitivity levels of 73% with a specificity of 100%. There were no complications. The cost reduction in our sample was above 80%. Flexible endoscopic biopsy has advantages over direct laryngoscopy that are relevant in the diagnosis of oncological pathology in otorhinolaryngology. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  10. Treatment of pathological gambling - integrative systemic model.

    Science.gov (United States)

    Mladenović, Ivica; Lažetić, Goran; Lečić-Toševski, Dušica; Dimitrijević, Ivan

    2015-03-01

    Pathological gambling was classified under impulse control disorders within the International Classification of Diseases (ICD-10) (WHO 1992), but the most recent Diagnostic and Statistical Manual, 5th edition (DSM-V), (APA 2013), has recognized pathological gambling as a first disorder within a new diagnostic category of behavioral addictions - Gambling disorder. Pathological gambling is a disorder in progression, and we hope that our experience in the treatment of pathological gambling in the Daily Hospital for Addictions at The Institute of Mental Health, through the original "Integrative - systemic model" would be of use to colleagues, dealing with this pathology. This model of treatment of pathological gambling is based on multi-systemic approach and it primarily represents an integration of family and cognitive-behavioral therapy, with traces of psychodynamic, existential and pharmacotherapy. The model is based on the book "Pathological gambling - with self-help manual" by Dr Mladenovic and Dr Lazetic, and has been designed in the form of a program that lasts 10 weeks in the intensive phase, and then continues for two years in the form of "extended treatment" ("After care"). The intensive phase is divided into three segments: educational, insight with initial changes and analysis of the achieved changes with the definition of plans and areas that need to be addressed in the extended treatment. "Extended treatment" lasts for two years in the form of group therapy, during which there is a second order change of the identified patient, but also of other family members. Pathological gambling has been treated in the form of systemic-family therapy for more than 10 years at the Institute of Mental Health (IMH), in Belgrade. For second year in a row the treatment is carried out by the modern "Integrative-systemic model". If abstinence from gambling witihin the period of one year after completion of the intensive phase of treatment is taken as the main criterion of

  11. Spatio-temporal tumour model for analysis and mechanism of action ...

    Indian Academy of Sciences (India)

    We have developed a one-dimensional tumour simulator to describe the biodistribution of chemotherapeutic drugs to a tumoral lesion and the tumour cell's response to therapy. A three-compartment model is used for drug dynamics within the tumour. The first compartment represents the extracellular space in which cells ...

  12. TRIM32 ubiquitin E3 ligase, one enzyme for several pathologies: From muscular dystrophy to tumours.

    Science.gov (United States)

    Lazzari, Elisa; Meroni, Germana

    2016-10-01

    TRIM32 is a member of the TRIpartite Motif family characterised by the presence of an N-terminal three-domain-module that includes a RING domain, which confers E3 ubiquitin ligase activity, one or two B-box domains and a Coiled-Coil region that mediates oligomerisation. Several TRIM32 substrates were identified including muscular proteins and proteins involved in cell cycle regulation and cell motility. As ubiquitination is a versatile post-translational modification that can affect target turnover, sub-cellular localisation or activity, it is likely that diverse substrates may be differentially affected by TRIM32-mediated ubiquitination, reflecting its multi-faceted roles in muscle physiology, cancer and immunity. With particular relevance for muscle physiology, mutations in TRIM32 are associated with autosomal recessive Limb-Girdle Muscular Dystrophy 2H, a muscle-wasting disease with variable clinical spectrum ranging from almost asymptomatic to wheelchair-bound patients. In this review, we will focus on the ability of TRIM32 to mark specific substrates for proteasomal degradation discussing how the TRIM32-proteasome axis may (i) be important for muscle homeostasis and for the pathogenesis of muscular dystrophy; and (ii) define either an oncogenic or tumour suppressive role for TRIM32 in the context of different types of cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Neuronal Models for Studying Tau Pathology

    Directory of Open Access Journals (Sweden)

    Thorsten Koechling

    2010-01-01

    Full Text Available Alzheimer's disease (AD is the most frequent neurodegenerative disorder leading to dementia in the aged human population. It is characterized by the presence of two main pathological hallmarks in the brain: senile plaques containing -amyloid peptide and neurofibrillary tangles (NFTs, consisting of fibrillar polymers of abnormally phosphorylated tau protein. Both of these histological characteristics of the disease have been simulated in genetically modified animals, which today include numerous mouse, fish, worm, and fly models of AD. The objective of this review is to present some of the main animal models that exist for reproducing symptoms of the disorder and their advantages and shortcomings as suitable models of the pathological processes. Moreover, we will discuss the results and conclusions which have been drawn from the use of these models so far and their contribution to the development of therapeutic applications for AD.

  14. Pathology of Mouse Models of Accelerated Aging.

    Science.gov (United States)

    Harkema, L; Youssef, S A; de Bruin, A

    2016-03-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience," which aims at elucidating the molecular mechanisms involved in aging. Progeroid mouse models are frequently used in geroscience as they provide insight into the molecular mechanisms that are involved in the highly complex process of natural aging. This review provides an overview of the most commonly reported nonneoplastic macroscopic and microscopic pathologic findings in progeroid mouse models (eg, osteoporosis, osteoarthritis, degenerative joint disease, intervertebral disc degeneration, kyphosis, sarcopenia, cutaneous atrophy, wound healing, hair loss, alopecia, lymphoid atrophy, cataract, corneal endothelial dystrophy, retinal degenerative diseases, and vascular remodeling). Furthermore, several shortcomings in pathologic analysis and descriptions of these models are discussed. Progeroid mouse models are valuable models for aging, but thorough knowledge of both the mouse strain background and the progeria-related phenotype is required to guide interpretation and translation of the pathology data. © The Author(s) 2016.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  16. 68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT.

    Science.gov (United States)

    Kroiss, A; Putzer, D; Decristoforo, C; Uprimny, C; Warwitz, B; Nilica, B; Gabriel, M; Kendler, D; Waitz, D; Widmann, G; Virgolini, I J

    2013-04-01

    We wanted to establish the range of (68)Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). In 249 patients, 390 (68)Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). SUVmax (mean ± standard deviation) values of (68)Ga-DOTA-TOC were 29.8 ± 16.5 in 162 liver metastases, 19.8 ± 18.8 in 89 bone metastases and 34.6 ± 17.1 in 43 pancreatic NET (33.6 ± 14.3 in 30 tumours of the uncinate process and 36.3 ± 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUVmax (p TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUVmax can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUVmax, except in liver metastases of patients with NET.

  17. Biopsy proportion of tumour predicts pathological tumour response and benefit from chemotherapy in resectable oesophageal carcinoma: results from the UK MRC OE02 trial.

    Science.gov (United States)

    Hale, Matthew D; Nankivell, Matthew; Hutchins, Gordon G; Stenning, Sally P; Langley, Ruth E; Mueller, Wolfram; West, Nicholas P; Wright, Alexander I; Treanor, Darren; Hewitt, Lindsay C; Allum, William H; Cunningham, David; Hayden, Jeremy D; Grabsch, Heike I

    2016-11-22

    Neoadjuvant chemotherapy followed by surgery is the standard of care for UK patients with locally advanced resectable oesophageal carcinoma (OeC). However, not all patients benefit from multimodal treatment and there is a clinical need for biomarkers which can identify chemotherapy responders. This study investigated whether the proportion of tumour cells per tumour area (PoT) measured in the pre-treatment biopsy predicts chemotherapy benefit for OeC patients. PoT was quantified using digitized haematoxylin/eosin stained pre-treatment biopsy slides from 281 OeC patients from the UK MRC OE02 trial (141 treated by surgery alone (S); 140 treated by 5-fluorouracil/cisplatin followed by surgery (CS)). The relationship between PoT and clinicopathological data including tumour regression grade (TRG), overall survival and treatment interaction was investigated. PoT was associated with chemotherapy benefit in a non-linear fashion (test for interaction, P=0.006). Only patients with a biopsy PoT between 40% and 70% received a significant survival benefit from neoadjuvant chemotherapy (N=129; HR (95%CI):1.94 (1.39-2.71), unlike those with lower or higher PoT (PoT70% (N=28, HR:0.65 (0.36-1.18)). High pre-treatment PoT was related to lack of primary tumour regression (TRG 4 or 5), P=0.0402. This is the first study to identify in a representative subgroup of OeC patients from a large randomized phase III trial that the proportion of tumour in the pre-chemotherapy biopsy predicts benefit from chemotherapy and may be a clinically useful biomarker for patient treatment stratification.Proportion of tumour is a novel biomarker which can be measured in the pre-treatment diagnostic biopsy and which may enable the identification of chemotherapy responders and non-responders among patients with oesophageal carcinoma. Proportion of tumour could easily become part of the routine reporting of oesophageal cancer biopsies and may aid in managing patients with borderline resectable cancer.

  18. A Simple Model to Study Tau Pathology

    Directory of Open Access Journals (Sweden)

    Alexander L. Houck

    2016-01-01

    Full Text Available Tau proteins play a role in the stabilization of microtubules, but in pathological conditions, tauopathies, tau is modified by phosphorylation and can aggregate into aberrant aggregates. These aggregates could be toxic to cells, and different cell models have been used to test for compounds that might prevent these tau modifications. Here, we have used a cell model involving the overexpression of human tau in human embryonic kidney 293 cells. In human embryonic kidney 293 cells expressing tau in a stable manner, we have been able to replicate the phosphorylation of intracellular tau. This intracellular tau increases its own level of phosphorylation and aggregates, likely due to the regulatory effect of some growth factors on specific tau kinases such as GSK3. In these conditions, a change in secreted tau was observed. Reversal of phosphorylation and aggregation of tau was found by the use of lithium, a GSK3 inhibitor. Thus, we propose this as a simple cell model to study tau pathology in nonneuronal cells due to their viability and ease to work with.

  19. {sup 68}Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Kroiss, A.; Putzer, D.; Decristoforo, C.; Uprimny, C.; Warwitz, B.; Nilica, B.; Gabriel, M.; Kendler, D.; Waitz, D.; Virgolini, I.J. [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Widmann, G. [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria)

    2013-04-15

    We wanted to establish the range of {sup 68}Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). In 249 patients, 390 {sup 68}Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). SUV{sub max} (mean {+-} standard deviation) values of {sup 68}Ga-DOTA-TOC were 29.8 {+-} 16.5 in 162 liver metastases, 19.8 {+-} 18.8 in 89 bone metastases and 34.6 {+-} 17.1 in 43 pancreatic NET (33.6 {+-} 14.3 in 30 tumours of the uncinate process and 36.3 {+-} 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUV{sub max} (p < 0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUV{sub max} between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p < 0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUV{sub max} for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p < 0.0001). {sup 68}Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUV{sub max} can offer important clinical

  20. A Stochastic and State Space Model for Tumour Growth and Applications

    Directory of Open Access Journals (Sweden)

    Wai-Yuan Tan

    2009-01-01

    Full Text Available We develop a state space model documenting Gompertz behaviour of tumour growth. The state space model consists of two sub-models: a stochastic system model that is an extension of the deterministic model proposed by Gyllenberg and Webb (1991, and an observation model that is a statistical model based on data for the total number of tumour cells over time. In the stochastic system model we derive through stochastic equations the probability distributions of the numbers of different types of tumour cells. Combining with the statistic model, we use these distribution results to develop a generalized Bayesian method and a Gibbs sampling procedure to estimate the unknown parameters and to predict the state variables (number of tumour cells. We apply these models and methods to real data and to computer simulated data to illustrate the usefulness of the models, the methods, and the procedures.

  1. Modelling of Anti-Tumour Immune Response: Immunocorrective Effect of Weak Centimetre Electromagnetic Waves

    Directory of Open Access Journals (Sweden)

    O. G. Isaeva

    2009-01-01

    Full Text Available We formulate the dynamical model for the anti-tumour immune response based on intercellular cytokine-mediated interactions with the interleukin-2 (IL-2 taken into account. The analysis shows that the expression level of tumour antigens on antigen presenting cells has a distinct influence on the tumour dynamics. At low antigen presentation, a progressive tumour growth takes place to the highest possible value. At high antigen presentation, there is a decrease in tumour size to some value when the dynamical equilibrium between the tumour and the immune system is reached. In the case of the medium antigen presentation, both these regimes can be realized depending on the initial tumour size and the condition of the immune system. A pronounced immunomodulating effect (the suppression of tumour growth and the normalization of IL-2 concentration is established by considering the influence of low-intensity electromagnetic microwaves as a parametric perturbation of the dynamical system. This finding is in qualitative agreement with the recent experimental results on immunocorrective effects of centimetre electromagnetic waves in tumour-bearing mice.

  2. Oscillatory dynamics in a model of vascular tumour growth - implications for chemotherapy

    Directory of Open Access Journals (Sweden)

    Maini PK

    2010-04-01

    Full Text Available Abstract Background Investigations of solid tumours suggest that vessel occlusion may occur when increased pressure from the tumour mass is exerted on the vessel walls. Since immature vessels are frequently found in tumours and may be particularly sensitive, such occlusion may impair tumour blood flow and have a negative impact on therapeutic outcome. In order to study the effects that occlusion may have on tumour growth patterns and therapeutic response, in this paper we develop and investigate a continuum model of vascular tumour growth. Results By analysing a spatially uniform submodel, we identify regions of parameter space in which the combination of tumour cell proliferation and vessel occlusion give rise to sustained temporal oscillations in the tumour cell population and in the vessel density. Alternatively, if the vessels are assumed to be less prone to collapse, stable steady state solutions are observed. When spatial effects are considered, the pattern of tumour invasion depends on the dynamics of the spatially uniform submodel. If the submodel predicts a stable steady state, then steady travelling waves are observed in the full model, and the system evolves to the same stable steady state behind the invading front. When the submodel yields oscillatory behaviour, the full model produces periodic travelling waves. The stability of the waves (which can be predicted by approximating the system as one of λ-ω type dictates whether the waves develop into regular or irregular spatio-temporal oscillations. Simulations of chemotherapy reveal that treatment outcome depends crucially on the underlying tumour growth dynamics. In particular, if the dynamics are oscillatory, then therapeutic efficacy is difficult to assess since the fluctuations in the size of the tumour cell population are enhanced, compared to untreated controls. Conclusions We have developed a mathematical model of vascular tumour growth formulated as a system of partial

  3. Differential equations related to the Williams±Bjerknes tumour model

    Indian Academy of Sciences (India)

    Y n. A computer simulation shows that the solution of the preceding problem provides a good approximation to the Williams±Bjerknes tumour model. We prove that this problem has a unique solution, it is defined on ‰0Y ‡I‰, and, for some specially relevant situations, limt3‡Ipi…t† ˆ 1 Vi P I. 2. The tumour growth model.

  4. Referent 3D solid tumour model and absorbed dose calculations at cellular level in radionuclide therapy

    International Nuclear Information System (INIS)

    Spaic, R.; Ilic, R.; Petrovic, B.; Dragovic, M.; Toskovic, F.

    2007-01-01

    An average absorbed dose of the tumour calculated by the MIRD formalism has not always a good correlation with the clinical response. The basic assumption of the MIRD schema is that a uniform spatial dose distribution is opposite to heterogeneity of intratumoral distribution of the administered radionuclide which can lead to a spatial nonuniformity of the absorbed dose. Therefore, in clinical practice, an absorbed dose of the tumour at the cellular level has to be calculated. The aim of this study is to define a referent 3D solid tumour model and using the direct Monte Carlo radiation transport method to calculate: a) absorbed fraction, b) spatial 3D absorbed dose distribution, c) absorbed dose and relative absorbed dose of cells or clusters of cells, and d) differential and accumulated dose volume histograms. A referent 3D solid tumour model is defined as a sphere which is randomly filled with cells and necrosis with defined radii and volumetric density. Radiolabelling of the tumour is defined by intracellular to extracellular radionuclide concentration and radio-labelled cell density. All these parameters are input data for software which generates a referent 3D solid tumour model. The modified FOTELP Monte Carlo code was used on this model for simulation study with beta emitters which were applied on the tumour. The absorbed fractions of Cu-67, I- 131, Re-188 and Y-90 were calculated for different tumour sphere masses and radii. Absorbed doses of cells and spatial distributions of the absorbed doses in the referent 3D solid tumour were calculated for radionuclides I-131 and Y-90. Dose scintigram or voxel presentation of absorbed dose distributions showed higher homogeneity for Y-90 than for I-131. A differential dose volume histogram, or spectrum, of the relative absorbed dose of cells, was much closer to the average absorbed dose of the tumour for Y-90 than I-131. An accumulated dose volume histogram showed that most tumour cells received a lower dose than

  5. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    LENUS (Irish Health Repository)

    Zagozdzon, Agnieszka M

    2012-05-30

    AbstractBackgroundNumerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study.ResultsA new mouse strain (MMTV-Luc2 mice) expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal.ConclusionsWe have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and\\/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

  6. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    Directory of Open Access Journals (Sweden)

    Zagozdzon Agnieszka M

    2012-05-01

    Full Text Available Abstract Background Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study. Results A new mouse strain (MMTV-Luc2 mice expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal. Conclusions We have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques.

  7. Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice

    International Nuclear Information System (INIS)

    Zagozdzon, Agnieszka M; O’Leary, Patrick; Callanan, John J; Crown, John; Gallagher, William M; Zagozdzon, Radoslaw

    2012-01-01

    Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study. A new mouse strain (MMTV-Luc2 mice) expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based in vivo imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled ex vivo at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal. We have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques

  8. MicroRNA-184-mediated inhibition of tumour growth in an orthotopic murine model of neuroblastoma.

    Science.gov (United States)

    Tivnan, Amanda; Foley, Niamh H; Tracey, Lorraine; Davidoff, Andrew M; Stallings, Raymond L

    2010-11-01

    Neuroblastoma is a paediatric cancer which originates from precursor cells of the sympathetic nervous system. Previous studies have shown that miR-184 expression has anti-proliferative effects in neuroblastoma cells grown in culture. Therefore, it was of interest to evaluate this effect in vivo. Neuroblastoma cells overexpressing miR-184 were injected retroperitoneally into CB17-SCID mice and tumour burden was assessed by measuring bioluminescence. Overall survival was also evaluated. Ectopic overexpression of miR-184 in neuroblastoma cell lines is anti-proliferative. In addition, overexpression of miR-184 led to a significant reduction in tumour growth relative to negative control-treated cohorts in a xenograft model of neuroblastoma. This study demonstrated for the first time that miR-184 significantly reduces tumour growth and increases overall survival in an orthotopic murine model of neuroblastoma through assessment of tumour growth and moribundity relative to control miRNA-treated cohorts.

  9. Pathology

    Directory of Open Access Journals (Sweden)

    Huihong Xu MD

    2016-08-01

    Full Text Available Medical students are often unsure about the viability of a career as a physician in pathology. In particular, they are concerned that pathologists may not have a gratifying lifestyle or be well compensated. These worries may cause angst among medical students considering pathology and among junior pathology residents wondering if they made the correct career choice. A 2016 survey of nearly 20 000 physicians including nearly 400 pathologists provides reassuring data about compensation and career choice. This survey showed that 52% of pathologists are satisfied with their career choice and 63% are satisfied with their compensation. Among the 26 specialties that were surveyed, pathologists ranked 2 in believing that they were fairly compensated. Moreover, 66% of pathologists find that making diagnostic decisions, a core aspect of our discipline, is the most rewarding aspect of their career. Pathologists also ranked among the highest groups of physicians in reporting happiness at work and among the lowest groups reporting burnout. Overall, these 2016 surveys show that the majority of pathologists find deep satisfaction in their careers as pathologists.

  10. Separation of type and grade in cervical tumours using non-mono-exponential models of diffusion-weighted MRI

    International Nuclear Information System (INIS)

    Winfield, Jessica M.; Collins, David J.; Morgan, Veronica A.; DeSouza, Nandita M.; Orton, Matthew R.; Ind, Thomas E.J.; Attygalle, Ayoma; Hazell, Steve

    2017-01-01

    Assessment of empirical diffusion-weighted MRI (DW-MRI) models in cervical tumours to investigate whether fitted parameters distinguish between types and grades of tumours. Forty-two patients (24 squamous cell carcinomas, 14 well/moderately differentiated, 10 poorly differentiated; 15 adenocarcinomas, 13 well/moderately differentiated, two poorly differentiated; three rare types) were imaged at 3 T using nine b-values (0 to 800 s mm -2 ). Mono-exponential, stretched exponential, kurtosis, statistical, and bi-exponential models were fitted. Model preference was assessed using Bayesian Information Criterion analysis. Differences in fitted parameters between tumour types/grades and correlation between fitted parameters were assessed using two-way analysis of variance and Pearson's linear correlation coefficient, respectively. Non-mono-exponential models were preferred by 83 % of tumours with bi-exponential and stretched exponential models preferred by the largest numbers of tumours. Apparent diffusion coefficient (ADC) and diffusion coefficients from non-mono-exponential models were significantly lower in poorly differentiated tumours than well/moderately differentiated tumours. α (stretched exponential), K (kurtosis), f and D* (bi-exponential) were significantly different between tumour types. Strong correlation was observed between ADC and diffusion coefficients from other models. Non-mono-exponential models were preferred to the mono-exponential model in DW-MRI data from cervical tumours. Parameters of non-mono-exponential models showed significant differences between types and grades of tumours. (orig.)

  11. Separation of type and grade in cervical tumours using non-mono-exponential models of diffusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Winfield, Jessica M.; Collins, David J.; Morgan, Veronica A.; DeSouza, Nandita M. [The Royal Marsden NHS Foundation Trust, MRI Unit, Sutton, Surrey (United Kingdom); The Institute of Cancer Research, Cancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, London (United Kingdom); Orton, Matthew R. [The Institute of Cancer Research, Cancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, London (United Kingdom); Ind, Thomas E.J. [The Royal Marsden NHS Foundation Trust, Gynaecology Unit, London (United Kingdom); Attygalle, Ayoma; Hazell, Steve [The Royal Marsden NHS Foundation Trust, Department of Histopathology, London (United Kingdom)

    2017-02-15

    Assessment of empirical diffusion-weighted MRI (DW-MRI) models in cervical tumours to investigate whether fitted parameters distinguish between types and grades of tumours. Forty-two patients (24 squamous cell carcinomas, 14 well/moderately differentiated, 10 poorly differentiated; 15 adenocarcinomas, 13 well/moderately differentiated, two poorly differentiated; three rare types) were imaged at 3 T using nine b-values (0 to 800 s mm{sup -2}). Mono-exponential, stretched exponential, kurtosis, statistical, and bi-exponential models were fitted. Model preference was assessed using Bayesian Information Criterion analysis. Differences in fitted parameters between tumour types/grades and correlation between fitted parameters were assessed using two-way analysis of variance and Pearson's linear correlation coefficient, respectively. Non-mono-exponential models were preferred by 83 % of tumours with bi-exponential and stretched exponential models preferred by the largest numbers of tumours. Apparent diffusion coefficient (ADC) and diffusion coefficients from non-mono-exponential models were significantly lower in poorly differentiated tumours than well/moderately differentiated tumours. α (stretched exponential), K (kurtosis), f and D* (bi-exponential) were significantly different between tumour types. Strong correlation was observed between ADC and diffusion coefficients from other models. Non-mono-exponential models were preferred to the mono-exponential model in DW-MRI data from cervical tumours. Parameters of non-mono-exponential models showed significant differences between types and grades of tumours. (orig.)

  12. Mice deleted for cell division cycle 73 gene develop parathyroid and uterine tumours: model for the hyperparathyroidism-jaw tumour syndrome.

    Science.gov (United States)

    Walls, G V; Stevenson, M; Lines, K E; Newey, P J; Reed, A A C; Bowl, M R; Jeyabalan, J; Harding, B; Bradley, K J; Manek, S; Chen, J; Wang, P; Williams, B O; Teh, B T; Thakker, R V

    2017-07-13

    The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by occurrence of parathyroid tumours, often atypical adenomas and carcinomas, ossifying jaw fibromas, renal tumours and uterine benign and malignant neoplasms. HPT-JT is caused by mutations of the cell division cycle 73 (CDC73) gene, located on chromosome 1q31.2 and encodes a 531 amino acid protein, parafibromin. To facilitate in vivo studies of Cdc73 in tumourigenesis we generated conventional (Cdc73 +/- ) and conditional parathyroid-specific (Cdc73 +/L /PTH-Cre and Cdc73 L/L /PTH-Cre) mouse models. Mice were aged to 18-21 months and studied for survival, tumour development and proliferation, and serum biochemistry, and compared to age-matched wild-type (Cdc73 +/+ and Cdc73 +/+ /PTH-Cre) littermates. Survival of Cdc73 +/- mice, when compared to Cdc73 +/+ mice was reduced (Cdc73 +/- =80%; Cdc73 +/+ =90% at 18 months of age, Pfourfold higher than that in parathyroid glands of wild-type littermates (P<0.0001). Cdc73 +/- , Cdc73 +/L /PTH-Cre and Cdc73 L/L /PTH-Cre mice had higher mean serum calcium concentrations than wild-type littermates, and Cdc73 +/- mice also had increased mean serum parathyroid hormone (PTH) concentrations. Parathyroid tumour development, and elevations in serum calcium and PTH, were similar in males and females. Cdc73 +/- mice did not develop bone or renal tumours but female Cdc73 +/- mice, at 18 months of age, had uterine neoplasms comprising squamous metaplasia, adenofibroma and adenomyoma. Uterine neoplasms, myometria and jaw bones of Cdc73 +/- mice had increased proliferation rates that were 2-fold higher than in Cdc73 +/+ mice (P<0.05). Thus, our studies, which have established mouse models for parathyroid tumours and uterine neoplasms that develop in the HPT-JT syndrome, provide in vivo models for future studies of these tumours.

  13. Tumour budding and other prognostic pathological features at invasive margins in serrated colorectal adenocarcinoma: a comparative study with conventional carcinoma.

    Science.gov (United States)

    García-Solano, José; Conesa-Zamora, Pablo; Trujillo-Santos, Javier; Mäkinen, Markus J; Pérez-Guillermo, Miguel

    2011-12-01

    To assess the incidence of tumour budding (TB), cytoplasmic pseudo-fragments (CyPs), tumour growth pattern (TGP) and peritumoural lymphocytic infiltration (PLI) in a series of serrated adenocarcinoma (SAC) and conventional carcinomas (CCs) of the colorectum in order to ascertain whether such features could explain the worse prognosis of SAC and whether they have prognostic value in SACs. Tumour budding, CyPs, TGP and PLI were evaluated in 81 SACs and 81 matched CCs. Kaplan-Meier survival curves and Cox logistic regression analysis were obtained for histological parameters. SACs had more high-grade (HG) TB (HG-TB) (69.1%), HG-CyPs (47%), infiltrative TGP (42%) and weak PLI (W-PLI) (65.4%) than CCs (40.7%, P = 0.0003; 19.7%, P = 0.0002; 29.7%, P = 0.07; 45.7%, P = 0.0087). SACs with HG-TB (P = 0.017), HG-CyPs (P = 0.045), infiltrating TGP (P TGP (P = 0.047) and W-PLI (P = 0.04) compared with CCs. For SACs, infiltrative TGP and W-PLI were independent prognostic parameters on multivariate analysis, as was location and regional node status. Compared to CC, SAC displayed more HG-TB, HG-CyPs and fewer PLI at the invasive margins and this may account for its poorer clinical outcome. TB, CyPs, TGP and PLI are useful histological prognostic aids in SAC. © 2011 Blackwell Publishing Limited.

  14. Oregano demonstrates distinct tumour-suppressive effects in the breast carcinoma model.

    Science.gov (United States)

    Kubatka, Peter; Kello, Martin; Kajo, Karol; Kruzliak, Peter; Výbohová, Desanka; Mojžiš, Ján; Adamkov, Marián; Fialová, Silvia; Veizerová, Lucia; Zulli, Anthony; Péč, Martin; Statelová, Dagmar; Grančai, Daniel; Büsselberg, Dietrich

    2017-04-01

    There has been a considerable interest in the identification of natural plant foods for developing effective agents against cancer. Thus, the anti-tumour effects of oregano in the in vivo and in vitro breast cancer model were evaluated. Lyophilized oregano (ORE) was administered at two concentrations of 0.3 and 3 % through diet. The experiment was terminated 14 weeks after carcinogen administration. At autopsy, mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. Moreover, in vitro evaluation in MCF-7 cells was carried out. Low-dose ORE suppressed tumour frequency by 55.5 %, tumour incidence by 44 %, and tumour volume by 44.5 % compared to control animals. Analysis of rat tumour cells showed Ki67, VEGFR-2, CD24, and EpCAM expression decrease and caspase-3 expression increase after low-dose ORE treatment. High-dose ORE lengthened tumour latency by 12.5 days; moreover, Bcl-2, VEGFR-2, CD24, and EpCAM expression decrease and caspase-3 expression increase in carcinoma cells were observed. Histopathological analysis revealed a decrease in the ratio of high-/low-grade carcinomas in both treated groups. In vitro studies showed that ORE decreased survival and proliferation of MCF-7 cells. In ORE-treated MCF-7 cells, an increase in cells expressing sub-G 0 /G 1 DNA content and an increase in the percentage of annexin V/PI positive MCF-7 cells were observed. In vitro, both caspase-dependent and possible non-caspase-dependent apoptotic pathways were found. The deactivation of anti-apoptotic activity of Bcl-2, a decrease in mitochondrial membrane potential, and the activation of mitochondrial apoptosis pathway were observed in the ORE-treated MCF-7 cells. Our results demonstrate, for the first time, a distinct tumour-suppressive effect of oregano in the breast cancer model.

  15. Radiologic-pathologic analysis of quantitative 3D tumour enhancement on contrast-enhanced MR imaging: a study of ROI placement

    Energy Technology Data Exchange (ETDEWEB)

    Chockalingam, Arun; Duran, Rafael; Sohn, Jae Ho; Schernthaner, Ruediger; Chapiro, Julius; Lee, Howard; Sahu, Sonia; Nguyen, Sonny; Geschwind, Jean-Francois [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Lin, MingDe [Philips Research North America, U/S Imaging and Interventions (UII), Briarcliff Manor, NY (United States)

    2016-01-15

    To investigate the influence of region-of-interest (ROI) placement on 3D tumour enhancement [Quantitative European Association for the Study of the Liver (qEASL)] in hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE). Phase 1: 40 HCC patients had nine ROIs placed by one reader using systematic techniques (3 ipsilateral to the lesion, 3 contralateral to the lesion, and 3 dispersed throughout the liver) and qEASL variance was measured. Intra-class correlations were computed. Phase 2: 15 HCC patients with histosegmentation were selected. Six ROIs were systematically placed by AC (3 ROIs ipsilateral and 3 ROIs contralateral to the lesion). Three ROIs were placed by 2 radiologists. qEASL values were compared to histopathology by Pearson's correlation, linear regression, and median difference. Phase 1: The dispersed method (abandoned in phase 2) had low consistency and high variance. Phase 2: qEASL correlated strongly with pathology in systematic methods [Pearson's correlation coefficient = 0.886 (ipsilateral) and 0.727 (contralateral)] and in clinical methods (0.625 and 0.879). However, ipsilateral placement matched best with pathology (median difference: 5.4 %; correlation: 0.89; regression CI: [0.904, 0.1409]). qEASL is a robust method with comparable values among tested placements. Ipsilateral placement showed high consistency and better pathological correlation. (orig.)

  16. Strain and tumour specific variations in the effect of hypoxia on one-step's levels in experimental models

    International Nuclear Information System (INIS)

    Lukacova, Slavka; Overgaard, Jens; Alsner, Jan; Horsman, Michael R.

    2006-01-01

    Purpose: To investigate the relationship between tumour hypoxia and serum and tumour osteopontin (OPN) levels. Materials and methods: Experiments were performed in CDF1 or C3H/Km mice implanted with a C3H mammary carcinoma (CDF1) or SCCVII squamous cell carcinoma (C3H/Km), respectively. Mice were either untreated or gassed with 10% oxygen for 1-72 h. Serum and tumour OPN levels were measured with an ELISA and tumour OPN mRNA levels using RT-PCR. Tumour oxygenation was estimated using the Eppendorf histograph with the percentage of pO 2 values ≤5 mm Hg (HF5) as the endpoint. Results: OPN levels were 50-fold higher in the serum of non-tumour bearing CDF1 mice compared to C3H/Km mice. A tumour related increase in serum OPN levels was observed in CDF1 but not in C3H/Km mice. Low oxygen breathing increased HF5 in both tumour models and in the C3H mammary carcinoma model both serum and tumour OPN decreased after prolonged hypoxia (24 h and more). When 12 h of hypoxia was followed by 24 h reoxygenation there was a twofold increase in serum OPN levels. No changes were observed in the SCCVII model. No changes in tumour OPN mRNA expression were observed during hypoxia and reoxygenation in these tumour models. Conclusion: Clear strain and tumour specific differences in the effect of hypoxia on OPN levels have been observed in two different mouse tumour models. These data emphasize the complexity in the relationship between poor oxygenation (and/or reoxygenation) of tumours and serum levels of OPN

  17. Increased FDG uptake on late-treatment PET in non-tumour-affected oesophagus is prognostic for pathological complete response and disease recurrence in patients undergoing neoadjuvant radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zschaeck, Sebastian [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Hofheinz, Frank [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany). PET Center, Inst. of Radiopharmaceutical Cancer Research; Zoephel, Klaus; Kotzerke, Joerg [German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; University Hospital Carl Gustav Carus, Dresden (Germany). Dept. of Nuclear Medicine; National Center for Tumor Diseases (NCT), Dresden (Germany); Buetof, Rebecca; Schmollack, Julia [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Jentsch, Christina [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; National Center for Tumor Diseases (NCT), Dresden (Germany); Loeck, Steffen; Baumann, Michael; Krause, Mechthild [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; National Center for Tumor Diseases (NCT), Dresden (Germany); Baretton, Gustavo [German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (DE); National Center for Tumor Diseases (NCT), Dresden (DE); University Hospital Carl Gustav Carus Technische Univ. Dresden (DE). Dept. of Pathology; Weitz, Juergen [German Cancer Consortium (DKTK), Dresden (DE); German Cancer Research Center (DKFZ), Heidelberg (DE); National Center for Tumor Diseases (NCT), Dresden (DE); University Hospital Carl Gustav Carus Technische Univ. Dresden (DE). Dept. of Visceral, Thoracic and Vascular Surgery

    2017-10-15

    Early side effects including oesophagitis are potential prognostic factors in patients undergoing radiochemotherapy (RCT) for locally advanced oesophageal cancer (LAEC). We assessed the prognostic value of {sup 18}F-fluorodeoxyglucose (FDG) uptake within irradiated non-tumour-affected oesophagus (NTO) during restaging positron emission tomography (PET) as a surrogate for inflammation/oesophagitis. This retrospective evaluation included 64 patients with LAEC who had completed neoadjuvant RCT and had successful oncological resection. All patients underwent FDG PET/CT before and after RCT. In the restaging PET scan maximum and mean standardized uptake values (SUV{sub max}, SUV{sub mean}) were determined in the tumour and NTO. Univariate Cox regression with respect to overall survival, local control, distant metastases and treatment failure was performed. Independence of clinically relevant parameters was tested in a multivariate Cox regression analysis. Increased FDG uptake, measured in terms of SUV{sub mean} in NTO during restaging was significantly associated with complete pathological remission (p = 0.002) and did not show a high correlation with FDG response of the tumour (rho < 0.3). In the univariate analysis, increased SUV{sub max} and SUV{sub mean} in NTO was associated with improved overall survival (p = 0.011, p = 0.004), better local control (p = 0.051, p = 0.044), a lower rate of treatment failure (p < 0.001 for both) and development of distant metastases (p = 0.012, p = 0.001). In the multivariate analysis, SUV{sub max} and SUV{sub mean} in NTO remained a significant prognostic factor for treatment failure (p < 0.001, p = 0.004) and distant metastases (p = 0.040, p = 0.011). FDG uptake in irradiated normal tissues measured on restaging PET has significant prognostic value in patients undergoing neoadjuvant RCT for LAEC. This effect may potentially be of use in treatment personalization. (orig.)

  18. Expression of Multidrug Resistance-Associated Markers, Their Relation to Quantitative Pathologic Tumour Characteristics and Prognosis in Advanced Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Mariël Brinkhuis

    2002-01-01

    Full Text Available Mean nuclear area has been consistently shown by different researchers to be a strong and independent prognostic factor in advanced ovarian carcinoma. However, the biological background of the prognostic value of nuclear area remains unclear. Others have found that the multidrug‐resistance (MDR related protein LRP has strong prognostic value. In the present study we have analysed whether the mean nuclear area and LRP are related in tumour tissue of the ovary obtained at the debulking operation before the administration of chemotherapy in 40 patients. The mitotic activity index, volume percentage epithelium, standard deviation of nuclear area and the other MDR‐related proteins P‐glycoprotein (JSB‐1, MRK‐16 and MRP have been investigated additionally for correlations and prognostic value. No correlations were found between the morphometrical features and MDR‐related proteins. Mean nuclear area tended to be larger in LRP positive tumours, but the correlation was not significant. In multivariate analysis LRP‐protein expression and mean nuclear area had independent prognostic value. Further studies are required to elucidate the biological background of the strong prognostic value of mean nuclear area in advanced ovarian cancer.

  19. Dynamics of pathologic clot formation: a mathematical model.

    Science.gov (United States)

    Shavlyugin, Evgeny A; Hanin, Leonid G; Khanin, Mikhail A

    2014-01-07

    Recent studies have provided evidence of a significant role of the Hageman factor in pathologic clot formation. Since auto-activation of the Hageman factor triggers the intrinsic coagulation pathway, we study the dynamics of pathologic clot formation considering the intrinsic pathway as the predominant mechanism of this process. Our methodological approach to studying the dynamics of clot formation is based on mathematical modelling. Activation of the blood coagulation cascade, particularly its intrinsic pathway, is known to involve platelets. Therefore, equations accounting for the effects of activated platelets on the intrinsic pathway activation are included in our model. This brings about a considerable increase in the values of kinetic constants involved in the model of the principal biochemical processes resulting in clot formation. The purpose of this study is to elucidate the mechanism of pathologic clot formation. Since the time window of thrombolysis is 3-6h, we hypothesize that in many cases the rate of pathologic clot formation is much lower than that of haemostatic clot. This assumption is used to simplify the mathematical model and to estimate kinetic constants of biochemical reactions that initiate pathologic clot formation. The insights we gained from our mathematical model may lead to new approaches to the prophylaxis of pathologic clot formation. We believe that one of the most efficient ways to prevent pathologic clot formation is simultaneous inhibition of activated factors ХII and ХI. © 2013 Elsevier Ltd. All rights reserved.

  20. Modelling and Bayesian adaptive prediction of individual patients’ tumour volume change during radiotherapy

    International Nuclear Information System (INIS)

    Tariq, Imran; Chen, Tao; Kirkby, Norman F; Jena, Rajesh

    2016-01-01

    The aim of this study is to develop a mathematical modelling method that can predict individual patients’ response to radiotherapy, in terms of tumour volume change during the treatment. The main concept is to start from a population-average model, which is subsequently updated from an individual’s tumour volume measurement. The model becomes increasingly personalised and so too does the prediction it produces. This idea of adaptive prediction was realised by using a Bayesian approach for updating the model parameters. The feasibility of the developed method was demonstrated on the data from 25 non-small cell lung cancer patients treated with helical tomotherapy, during which tumour volume was measured from daily imaging as part of the image-guided radiotherapy. The method could provide useful information for adaptive treatment planning and dose scheduling based on the patient’s personalised response. (paper)

  1. Pathology and biofilms in a porcine model of heamatogenous osteomyelitis

    DEFF Research Database (Denmark)

    Johansen, Louise Kruse

    Aim Discriminative animal models in which bacterial virulence factors and the impact on the host can be studied are desirable. Therefore, a porcine model of haematogenous osteomyelitis based on intraarterial inoculation of Staphylococcus aureus was developed. In the model, the pathology of osteom......Aim Discriminative animal models in which bacterial virulence factors and the impact on the host can be studied are desirable. Therefore, a porcine model of haematogenous osteomyelitis based on intraarterial inoculation of Staphylococcus aureus was developed. In the model, the pathology....... The formation of a biofilm by S. aureus affects the pathology, since the consistent release of planktonic bacteria induces an ongoing inflammatory reaction. The presented discriminative porcine model presents an attractive model for studying the nature and role of biofilm formation in vivo and how to diagnose...

  2. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

    Directory of Open Access Journals (Sweden)

    Sergey V. Tokalov

    2010-01-01

    Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

  3. Determination of tumour hypoxia with the PET tracer [{sup 18}F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model

    Energy Technology Data Exchange (ETDEWEB)

    Christian, Nicolas; Bol, Anne; Bast, Marc de; Labar, Daniel; Lee, John; Mahy, Pierre; Gregoire, Vincent [Universite Catholique de Louvain, Center for Molecular Imaging and Experimental Radiotherapy, Brussels (Belgium)

    2007-09-15

    The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [{sup 18}F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [{sup 18}F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital). C3H mice were injected i.v. with an average of 12.95 MBq of [{sup 18}F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue. Ornidazole decreased the urinary excretion and increased the liver uptake of [{sup 18}F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio. Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation. (orig.)

  4. A model of the effects of cancer cell motility and cellular adhesion properties on tumour-immune dynamics.

    Science.gov (United States)

    Frascoli, Federico; Flood, Emelie; Kim, Peter S

    2017-06-01

    We present a three-dimensional model simulating the dynamics of an anti-cancer T-cell response against a small, avascular, early-stage tumour. Interactions at the tumour site are accounted for using an agent-based model (ABM), while immune cell dynamics in the lymph node are modelled as a system of delay differential equations (DDEs). We combine these separate approaches into a two-compartment hybrid ABM-DDE system to capture the T-cell response against the tumour. In the ABM at the tumour site, movement of tumour cells is modelled using effective physical forces with a specific focus on cell-to-cell adhesion properties and varying levels of tumour cell motility, thus taking into account the ability of cancer cells to spread and form clusters. We consider the effectiveness of the immune response over a range of parameters pertaining to tumour cell motility, cell-to-cell adhesion strength and growth rate. We also investigate the dependence of outcomes on the distribution of tumour cells. Low tumour cell motility is generally a good indicator for successful tumour eradication before relapse, while high motility leads, almost invariably, to relapse and tumour escape. In general, the effect of cell-to-cell adhesion on prognosis is dependent on the level of tumour cell motility, with an often unpredictable cross influence between adhesion and motility, which can lead to counterintuitive effects. In terms of overall tumour shape and structure, the spatial distribution of cancer cells in clusters of various sizes has shown to be strongly related to the likelihood of extinction. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  5. Prognostic value of pathological lymph node status and primary tumour regression grading following neoadjuvant chemotherapy - results from the MRC OE02 oesophageal cancer trial.

    Science.gov (United States)

    Davarzani, Nasser; Hutchins, Gordon G A; West, Nicholas P; Hewitt, Lindsay C; Nankivell, Matthew; Cunningham, David; Allum, William H; Smyth, Elizabeth; Valeri, Nicola; Langley, Ruth E; Grabsch, Heike I

    2018-02-21

    Neoadjuvant chemotherapy (NAC) remains an important therapeutic option for advanced oesophageal cancer (OC). Pathological tumour regression grade (TRG) may offer additional information by directing adjuvant treatment and/or follow-up but its clinical value remains unclear. We analysed the prognostic value of TRG and associated pathological factors in OC patients enrolled in the Medical Research Council (MRC) OE02 trial. Histopathology was reviewed in 497 resections from OE02 trial participants randomised to surgery (S group; n = 244) or NAC followed by surgery [chemotherapy plus surgery (CS) group; n = 253]. The association between TRG groups [responders (TRG1-3) versus non-responders (TRG4-5)], pathological lymph node (LN) status and overall survival (OS) was analysed. One hundred and ninety-five of 253 (77%) CS patients were classified as 'non-responders', with a significantly higher mortality risk compared to responders [hazard ratio (HR) = 1.53, 95% confidence interval (CI) = 1.05-2.24, P = 0.026]. OS was significantly better in patients without LN metastases irrespective of TRG [non-responders HR = 1.87, 95% CI = 1.33-2.63, P < 0.001 versus responders HR = 2.21, 95% CI = 1.11-4.10, P = 0.024]. In multivariate analyses, LN status was the only independent factor predictive of OS in CS patients (HR = 1.93, 95% CI = 1.42-2.62, P < 0.001). Exploratory subgroup analyses excluding radiotherapy-exposed patients (n = 48) showed similar prognostic outcomes. Lymph node status post-NAC is the most important prognostic factor in patients with resectable oesophageal cancer, irrespective of TRG. Potential clinical implications, e.g. adjuvant treatment or intensified follow-up, reinforce the importance of LN dissection for staging and prognostication. © 2018 The Authors. Histopathology published by John Wiley & Sons Ltd.

  6. A TRACER 3D Co-Culture tumour model for head and neck cancer.

    Science.gov (United States)

    Young, Miki; Rodenhizer, Darren; Dean, Teresa; D'Arcangelo, Elisa; Xu, Bin; Ailles, Laurie; McGuigan, Alison P

    2018-05-01

    Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment and have been shown to play an important role in the progression of cancer. To probe these tumour-stroma interactions, we incorporated CAFs derived from head and neck cancer patients and squamous carcinoma cells of the hypopharynx (FaDu) into the Tissue Roll for the Analysis of Cellular Environment and Response (TRACER) platform to establish a co-culture platform that simulates the CAF-tumour microenvironmental interactions in head and neck tumours. TRACER culture involves infiltrating cells into a thin fibrous scaffold and then rolling the resulting biocomposite around a mandrel to generate a 3D and layered structure. Patterning the fibrous scaffold biocomposite during fabrication enables control over the specific location of different cell populations in the rolled configuration. Here, we optimized the seeding densities and configurations of the CAF and FaDu cell tissue sections to enable a robust 3D co-culture system under normoxic conditions. Co-culture of CAFs with FaDu cells produced negligible effects on radiation resistance, but did produce increases in proliferation rate and invasive cell migration at 24 and 48 h of culture. Our study provides the basis for use of our in vitro co-culture TRACER model to investigate the tumour-stroma interactions, and to bridge the translational gap between preclinical and clinical studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Modelling the helium plasma jet delivery of reactive species into a 3D cancer tumour

    Science.gov (United States)

    Szili, Endre J.; Oh, Jun-Seok; Fukuhara, Hideo; Bhatia, Rishabh; Gaur, Nishtha; Nguyen, Cuong K.; Hong, Sung-Ha; Ito, Satsuki; Ogawa, Kotaro; Kawada, Chiaki; Shuin, Taro; Tsuda, Masayuki; Furihata, Mutsuo; Kurabayashi, Atsushi; Furuta, Hiroshi; Ito, Masafumi; Inoue, Keiji; Hatta, Akimitsu; Short, Robert D.

    2018-01-01

    Cold atmospheric plasmas have attracted significant worldwide attention for their potential beneficial effects in cancer therapy. In order to further improve the effectiveness of plasma in cancer therapy, it is important to understand the generation and transport of plasma reactive species into tissue fluids, tissues and cells, and moreover the rates and depths of delivery, particularly across physical barriers such as skin. In this study, helium (He) plasma jet treatment of a 3D cancer tumour, grown on the back of a live mouse, induced apoptosis within the tumour to a depth of 2.8 mm. The He plasma jet was shown to deliver reactive oxygen species through the unbroken skin barrier before penetrating through the entire depth of the tumour. The depth and rate of transport of He plasma jet generated H2O2, NO3 ‑ and NO2 ‑, as well as aqueous oxygen [O2(aq)], was then tracked in an agarose tissue model. This provided an approximation of the H2O2, NO3 ‑, NO2 ‑ and O2(aq) concentrations that might have been generated during the He plasma jet treatment of the 3D tumour. It is proposed that the He plasma jet can induce apoptosis within a tumour by the ‘deep’ delivery of H2O2, NO3 ‑ and NO2 ‑ coupled with O2(aq); the latter raising oxygen tension in hypoxic tissue.

  8. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L.; Youssef, S. A.; de Bruin, A.

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of geroscience,

  9. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L; Youssef, S A; de Bruin, A

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience,"

  10. Multiple model predictive control for optimal drug administration of mixed immunotherapy and chemotherapy of tumours.

    Science.gov (United States)

    Sharifi, N; Ozgoli, S; Ramezani, A

    2017-06-01

    Mixed immunotherapy and chemotherapy of tumours is one of the most efficient ways to improve cancer treatment strategies. However, it is important to 'design' an effective treatment programme which can optimize the ways of combining immunotherapy and chemotherapy to diminish their imminent side effects. Control engineering techniques could be used for this. The method of multiple model predictive controller (MMPC) is applied to the modified Stepanova model to induce the best combination of drugs scheduling under a better health criteria profile. The proposed MMPC is a feedback scheme that can perform global optimization for both tumour volume and immune competent cell density by performing multiple constraints. Although current studies usually assume that immunotherapy has no side effect, this paper presents a new method of mixed drug administration by employing MMPC, which implements several constraints for chemotherapy and immunotherapy by considering both drug toxicity and autoimmune. With designed controller we need maximum 57% and 28% of full dosage of drugs for chemotherapy and immunotherapy in some instances, respectively. Therefore, through the proposed controller less dosage of drugs are needed, which contribute to suitable results with a perceptible reduction in medicine side effects. It is observed that in the presence of MMPC, the amount of required drugs is minimized, while the tumour volume is reduced. The efficiency of the presented method has been illustrated through simulations, as the system from an initial condition in the malignant region of the state space (macroscopic tumour volume) transfers into the benign region (microscopic tumour volume) in which the immune system can control tumour growth. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Impact of dose escalation and adaptive radiotherapy for cervical cancers on tumour shrinkage—a modelling study

    Science.gov (United States)

    Røthe Arnesen, Marius; Paulsen Hellebust, Taran; Malinen, Eirik

    2017-03-01

    Tumour shrinkage occurs during fractionated radiotherapy and is regulated by radiation induced cellular damage, repopulation of viable cells and clearance of dead cells. In some cases additional tumour shrinkage during external beam therapy may be beneficial, particularly for locally advanced cervical cancer where a small tumour volume may simplify and improve brachytherapy. In the current work, a mathematical tumour model is utilized to investigate how local dose escalation affects tumour shrinkage, focusing on implications for brachytherapy. The iterative two-compartment model is based upon linear-quadratic radiation response, a doubling time for viable cells and a half-time for clearance of dead cells. The model was individually fitted to clinical tumour volume data from fractionated radiotherapy of 25 cervical cancer patients. Three different fractionation patterns for dose escalation, all with an additional dose of 12.2 Gy, were simulated and compared to standard fractionation in terms of tumour shrinkage. An adaptive strategy where dose escalation was initiated after one week of treatment was also considered. For 22 out of 25 patients, a good model fit was achieved to the observed tumour shrinkage. A large degree of inter-patient variation was seen in predicted volume reduction following dose escalation. For the 10 best responding patients, a mean tumour volume reduction of 34  ±  3% (relative to standard treatment) was estimated at the time of brachytherapy. Timing of initiating dose escalation had a larger impact than the number of fractions applied. In conclusion, the model was found useful in evaluating the impact from dose escalation on tumour shrinkage. The results indicate that dose escalation could be conducted from the start of external beam radiotherapy in order to obtain additional tumour shrinkage before brachytherapy.

  12. A Heterogeneous In Vitro Three Dimensional Model of Tumour-Stroma Interactions Regulating Sprouting Angiogenesis

    Science.gov (United States)

    Correa de Sampaio, Pedro; Auslaender, David; Krubasik, Davia; Failla, Antonio Virgilio; Skepper, Jeremy N.; Murphy, Gillian; English, William R.

    2012-01-01

    Angiogenesis, the formation of new blood vessels, is an essential process for tumour progression and is an area of significant therapeutic interest. Different in vitro systems and more complex in vivo systems have been described for the study of tumour angiogenesis. However, there are few human 3D in vitro systems described to date which mimic the cellular heterogeneity and complexity of angiogenesis within the tumour microenvironment. In this study we describe the Minitumour model – a 3 dimensional human spheroid-based system consisting of endothelial cells and fibroblasts in co-culture with the breast cancer cell line MDA-MB-231, for the study of tumour angiogenesis in vitro. After implantation in collagen-I gels, Minitumour spheroids form quantifiable endothelial capillary-like structures. The endothelial cell pre-capillary sprouts are supported by the fibroblasts, which act as mural cells, and their growth is increased by the presence of cancer cells. Characterisation of the Minitumour model using small molecule inhibitors and inhibitory antibodies show that endothelial sprout formation is dependent on growth factors and cytokines known to be important for tumour angiogenesis. The model also shows a response to anti-angiogenic agents similar to previously described in vivo data. We demonstrate that independent manipulation of the different cell types is possible, using common molecular techniques, before incorporation into the model. This aspect of Minitumour spheroid analysis makes this model ideal for high content studies of gene function in individual cell types, allowing for the dissection of their roles in cell-cell interactions. Finally, using this technique, we were able to show the requirement of the metalloproteinase MT1-MMP in endothelial cells and fibroblasts, but not cancer cells, for sprouting angiogenesis. PMID:22363483

  13. Relative clinical effectiveness of carbon ion radiotherapy. Theoretical modelling for H and N tumours

    International Nuclear Information System (INIS)

    Antonovic, Laura; Toma-Dasu, Iuliana; Dasu, Alexandru; Furusawa, Yoshiya

    2015-01-01

    Comparison of the efficiency of photon and carbon ion radiotherapy (RT) administered with the same number of fractions might be of limited clinical interest, since a wide range of fractionation patterns are used clinically today. Due to advanced photon treatment techniques, hypofractionation is becoming increasingly accepted for prostate and lung tumours, whereas patients with head and neck tumours still benefit from hyperfractionated treatments. In general, the number of fractions is considerably lower in carbon ion RT. A clinically relevant comparison would be between fractionation schedules that are optimal within each treatment modality category. In this in silico study, the relative clinical effectiveness (RCE) of carbon ions was investigated for human salivary gland tumours, assuming various radiation sensitivities related to their oxygenation. The results indicate that, for hypoxic tumours in the absence of reoxygenation, the RCE (defined as the ratio of D 50 for photons to carbon ions) ranges from 3.5 to 5.7, corresponding to carbon ion treatments given in 36 and 3 fractions, respectively, and 30 fractions for photons. Assuming that interfraction local oxygenation changes take place, results for RCE are lower than that for an oxic tumour if only a few fractions of carbon ions are used. If the carbon ion treatment is given in more than 12 fractions, the RCE is larger for the hypoxic than for the well-oxygenated tumour. In conclusion, this study showed that in silico modelling enables the study of a wide range of factors in the clinical considerations and could be an important step towards individualisation of RT treatments. (author)

  14. Modelling the interplay between hypoxia and proliferation in radiotherapy tumour response

    International Nuclear Information System (INIS)

    Jeong, J; Deasy, J O; Shoghi, K I

    2013-01-01

    A tumour control probability computational model for fractionated radiotherapy was developed, with the goal of incorporating the fundamental interplay between hypoxia and proliferation, including reoxygenation over a course of radiotherapy. The fundamental idea is that the local delivery of oxygen and glucose limits the amount of proliferation and metabolically-supported cell survival a tumour sub-volume can support. The model has three compartments: a proliferating compartment of cells receiving oxygen and glucose; an intermediate, metabolically-active compartment receiving glucose; and a highly hypoxic compartment of starving cells. Following the post-mitotic cell death of proliferating cells, intermediate cells move into the proliferative compartment and hypoxic cells move into the intermediate compartment. A key advantage of the proposed model is that the initial compartmental cell distribution is uniquely determined from the assumed local growth fraction (GF) and volume doubling time (T D ) values. Varying initial cell state distributions, based on the local (voxel) GF and T D , were simulated. Tumour response was simulated for head and neck squamous cell carcinoma using relevant parameter values based on published sources. The tumour dose required to achieve a 50% local control rate (TCD 50 ) was found for various GFs and T D ’s, and the effect of fraction size on TCD 50 was also evaluated. Due to the advantage of reoxygenation over a course of radiotherapy, conventional fraction sizes (2–2.4 Gy fx −1 ) were predicted to result in smaller TCD 50 's than larger fraction sizes (4–5 Gy fx –1 ) for a 10 cc tumour with GFs of around 0.15. The time to eliminate hypoxic cells (the reoxygenation time) was estimated for a given GF and decreased as GF increased. The extra dose required to overcome accelerated stem cell accumulation in longer treatment schedules was estimated to be 0.68 Gy/day (in EQD2 6.6 ), similar to published values derived from clinical

  15. A novel technique of serial biopsy in mouse brain tumour models.

    Directory of Open Access Journals (Sweden)

    Sasha Rogers

    Full Text Available Biopsy is often used to investigate brain tumour-specific abnormalities so that treatments can be appropriately tailored. Dacomitinib (PF-00299804 is a tyrosine kinase inhibitor (TKI, which is predicted to only be effective in cancers where the targets of this drug (EGFR, ERBB2, ERBB4 are abnormally active. Here we describe a method by which serial biopsy can be used to validate response to dacomitinib treatment in vivo using a mouse glioblastoma model. In order to determine the feasibility of conducting serial brain biopsies in mouse models with minimal morbidity, and if successful, investigate whether this can facilitate evaluation of chemotherapeutic response, an orthotopic model of glioblastoma was used. Immunodeficient mice received cortical implants of the human glioblastoma cell line, U87MG, modified to express the constitutively-active EGFR mutant, EGFRvIII, GFP and luciferase. Tumour growth was monitored using bioluminescence imaging. Upon attainment of a moderate tumour size, free-hand biopsy was performed on a subgroup of animals. Animal monitoring using a neurological severity score (NSS showed that all mice survived the procedure with minimal perioperative morbidity and recovered to similar levels as controls over a period of five days. The technique was used to evaluate dacomitinib-mediated inhibition of EGFRvIII two hours after drug administration. We show that serial tissue samples can be obtained, that the samples retain histological features of the tumour, and are of sufficient quality to determine response to treatment. This approach represents a significant advance in murine brain surgery that may be applicable to other brain tumour models. Importantly, the methodology has the potential to accelerate the preclinical in vivo drug screening process.

  16. MULTISCALE SPARSE APPEARANCE MODELING AND SIMULATION OF PATHOLOGICAL DEFORMATIONS

    Directory of Open Access Journals (Sweden)

    Rami Zewail

    2017-08-01

    Full Text Available Machine learning and statistical modeling techniques has drawn much interest within the medical imaging research community. However, clinically-relevant modeling of anatomical structures continues to be a challenging task. This paper presents a novel method for multiscale sparse appearance modeling in medical images with application to simulation of pathological deformations in X-ray images of human spine. The proposed appearance model benefits from the non-linear approximation power of Contourlets and its ability to capture higher order singularities to achieve a sparse representation while preserving the accuracy of the statistical model. Independent Component Analysis is used to extract statistical independent modes of variations from the sparse Contourlet-based domain. The new model is then used to simulate clinically-relevant pathological deformations in radiographic images.

  17. Prediction of tumour response induced by chemotherapy using modelling of CA-125 kinetics in recurrent ovarian cancer patients.

    Science.gov (United States)

    Wilbaux, M; Hénin, E; Oza, A; Colomban, O; Pujade-Lauraine, E; Freyer, G; Tod, M; You, B

    2014-03-18

    The main objective of the present study was to establish the relationships between CA-125 kinetics and tumour size changes during treatment. The data from the CALYPSO-randomised phase III trial, comparing two platinum-based regimens in recurrent ovarian cancer (ROC) patients, was randomly split into a 'learning data set' to estimate model parameters and a 'validation data set' to validate model performances. A kinetic-pharmacodynamic semi-mechanistic model was built to describe tumour size and CA-125 kinetics during chemotherapy. The ability of the model to predict tumour response induced by chemotherapy, based on CA-125 values, was assessed. Data from 535 ROC patients were used to model CA-125 kinetics and tumour size changes during the first 513 days after treatment initiation. Using the validated model, we could predict with accuracy the tumour size changes induced by chemotherapy based on the baseline imaging assessment and longitudinal CA-125 values (mean prediction error: 0.3%, mean absolute prediction error: 10.6%). Using a semi-mechanistic model, the dynamic relationships between tumour size changes and CA-125 kinetics induced by chemotherapy were established in ROC patients. A modelling approach allowed CA-125 to be assessed as a biomarker for tumour size dynamics, to predict treatment efficacy for research and clinical purposes.

  18. Mathematical modelling of the spatio-temporal response of cytotoxic T-lymphocytes to a solid tumour.

    Science.gov (United States)

    Matzavinos, Anastasios; Chaplain, Mark A J; Kuznetsov, Vladimir A

    2004-03-01

    In this paper a mathematical model describing the growth of a solid tumour in the presence of an immune system response is presented. In particular, attention is focused upon the attack of tumour cells by so-called tumour-infiltrating cytotoxic lymphocytes (TICLs), in a small, multicellular tumour, without necrosis and at some stage prior to (tumour-induced) angiogenesis. At this stage the immune cells and the tumour cells are considered to be in a state of dynamic equilibrium--cancer dormancy--a phenomenon which has been observed in primary tumours, micrometastases and residual disease after ablation of the primary tumour. Nonetheless, the precise biochemical and cellular mechanisms by which TICLs control cancer dormancy are still poorly understood from a biological and immunological point of view. Therefore we focus on the analysis of the spatio-temporal dynamics of tumour cells, immune cells and chemokines in an immunogenic tumour. The lymphocytes are assumed to migrate into the growing solid tumour and interact with the tumour cells in such a way that lymphocyte-tumour cell complexes are formed. These complexes result in either the death of the tumour cells (the normal situation) or the inactivation (sometimes even the death) of the lymphocytes. The migration of the TICLs is determined by a combination of random motility and chemotaxis in response to the presence of chemokines. The resulting system of four nonlinear partial differential equations (TICLs, tumour cells, complexes and chemokines) is analysed and numerical simulations are presented. We consider two different tumour geometries--multi-layered cell growth and multi-cellular spheroid growth. The numerical simulations demonstrate the existence of cell distributions that are quasi-stationary in time and heterogeneous in space. A linear stability analysis of the underlying (spatially homogeneous) ordinary differential equation (ODE) kinetics coupled with a numerical investigation of the ODE system reveals

  19. Differential equations related to the Williams±Bjerknes tumour model

    Indian Academy of Sciences (India)

    Williams±Bjerknes tumour model for a cancer which spreads through an epithelial basal layer modeled on I & Z2. The solution of this problem is a family p ˆ … pi…t††, where each pi…t† could be considered as an approximation to the probability that the cell situated at i is cancerous at time t. We prove that this problem has ...

  20. Towards personalized computational oncology: from spatial models of tumour spheroids, to organoids, to tissues.

    Science.gov (United States)

    Karolak, Aleksandra; Markov, Dmitry A; McCawley, Lisa J; Rejniak, Katarzyna A

    2018-01-01

    A main goal of mathematical and computational oncology is to develop quantitative tools to determine the most effective therapies for each individual patient. This involves predicting the right drug to be administered at the right time and at the right dose. Such an approach is known as precision medicine. Mathematical modelling can play an invaluable role in the development of such therapeutic strategies, since it allows for relatively fast, efficient and inexpensive simulations of a large number of treatment schedules in order to find the most effective. This review is a survey of mathematical models that explicitly take into account the spatial architecture of three-dimensional tumours and address tumour development, progression and response to treatments. In particular, we discuss models of epithelial acini, multicellular spheroids, normal and tumour spheroids and organoids, and multi-component tissues. Our intent is to showcase how these in silico models can be applied to patient-specific data to assess which therapeutic strategies will be the most efficient. We also present the concept of virtual clinical trials that integrate standard-of-care patient data, medical imaging, organ-on-chip experiments and computational models to determine personalized medical treatment strategies. © 2018 The Author(s).

  1. Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer.

    Science.gov (United States)

    Kubatka, Peter; Kapinová, Andrea; Kello, Martin; Kruzliak, Peter; Kajo, Karol; Výbohová, Desanka; Mahmood, Silvia; Murin, Radovan; Viera, Tischlerová; Mojžiš, Ján; Zulli, Anthony; Péč, Martin; Adamkov, Marián; Kassayová, Monika; Bojková, Bianka; Stollárová, Nadežda; Dobrota, Dušan

    2016-04-01

    Fruit and vegetable intake is inversely correlated with cancer; thus, it is proposed that an extract of phytochemicals as present in whole fruits, vegetables, or grains may have anti-carcinogenic properties. Thus, the anti-tumour effects of fruit peel polyphenols (Flavin7) in the chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. Lyophilized substance of Flavin7 (F7) was administered at two concentrations of 0.3 and 3 % through diet. The experiment was terminated 14 weeks after carcinogen administration, and mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. In addition, using an in vitro cytotoxicity assay, apoptosis and proliferation after F7 treatment in human breast adenocarcinoma (MCF-7) cells were performed. High-dose F7 suppressed tumour frequency by 58 % (P 0.05) in comparison with the control rats, whereas lower dose of F7 was less effective. Histopathological analysis of tumours showed significant decrease in the ratio of high-/low-grade carcinomas after high-dose F7 treatment. Immunohistochemical analysis of rat carcinoma cells in vivo found a significant increase in caspase-3 expression and significant decrease in Bcl-2, Ki67, and VEGFR-2 expression in the high-dose group. Both doses demonstrated significant positive effects on plasma lipid metabolism in rats. F7 significantly decreased survival of MCF-7 cells in vitro in MTT assay by dose- and time-dependent manner compared to control. F7 prevented cell cycle progression by significant enrichment in G1 cell populations. Incubation with F7 showed significant increase in the percentage of annexin V-/PI-positive MCF-7 cells and DNA fragmentation. Our results reveal a substantial tumour-suppressive effect of F7 in the breast cancer model. We propose that the effects of phytochemicals present in this fruit extract are responsible for observed potent anti-cancer activities.

  2. Pharmacokinetics and pharmacodynamics of propofol : Changes in patients with frontal brain tumours

    NARCIS (Netherlands)

    Sahinovic, M. M.; Eleveld, D. J.; Miyabe-Nishiwaki, T.; Struys, M. M. R. F.; Absalom, A. R.

    2017-01-01

    Background: Models of propofol pharmacokinetics and pharmacodynamics developed in patients without brain pathology are widely used for target-controlled infusion (TCI) during brain tumour excision operations. The goal of this study was to determine if the presence of a frontal brain tumour

  3. Monte Carlo modelling of photodynamic therapy treatments comparing clustered three dimensional tumour structures with homogeneous tissue structures

    Science.gov (United States)

    Campbell, C. L.; Wood, K.; Brown, C. T. A.; Moseley, H.

    2016-07-01

    We explore the effects of three dimensional (3D) tumour structures on depth dependent fluence rates, photodynamic doses (PDD) and fluorescence images through Monte Carlo radiation transfer modelling of photodynamic therapy. The aim with this work was to compare the commonly used uniform tumour densities with non-uniform densities to determine the importance of including 3D models in theoretical investigations. It was found that fractal 3D models resulted in deeper penetration on average of therapeutic radiation and higher PDD. An increase in effective treatment depth of 1 mm was observed for one of the investigated fractal structures, when comparing to the equivalent smooth model. Wide field fluorescence images were simulated, revealing information about the relationship between tumour structure and the appearance of the fluorescence intensity. Our models indicate that the 3D tumour structure strongly affects the spatial distribution of therapeutic light, the PDD and the wide field appearance of surface fluorescence images.

  4. Targeting Tumour Vasculature as a Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Christopher A. Honstvet

    2007-01-01

    Full Text Available Modelling blood flow and capillary growth in tumours has been the focus of several research groups with the aim of generating theoretical models that can be used to predict biological behaviour within these systems. Since dysfunctional angiogenesis is seen in a wide range of pathological conditions ranging from cardiovascular, to arthritis, to diabetes, it is easy to see how these models may have a far-reaching influence on future therapeutic strategies.

  5. Radiobiological and Magnetic Resonance Studies of Combined Radiation and Cisplatin Therapy in the 9l Rat Brain Tumour Model.

    Science.gov (United States)

    Wilkins, David E.

    1993-01-01

    The prognosis for adult patients with primary malignant brain tumours is poor. Radiation therapy is a standard adjutant to surgery in the treatment of these patients, but is rarely curative. The extreme radio-resistance of primary malignant brain tumours is due in part to their enhanced capacity for repair of potentially lethal radiation damage. The chemotherapeutic agent cisplatin has been shown to inhibit repair of radiation damage. Therefore combined cisplatin and radiation therapy could be a key to enhanced therapeutic gain in the treatment of primary malignant brain tumours. In this project, the 9L rat brain tumour model was used to investigate combined radiation and cisplatin treatments. In vitro experiments showed the 9L cell line to be highly radioresistant and, like human malignant brain tumour cells, to have a high capacity for repair of potentially lethal radiation damage. These cells were found to be moderately resistant to the cytotoxic effects of cisplatin. In vitro exposure to cisplatin at clinically relevant concentrations caused inhibition of potentially lethal damage repair, with the amount of inhibition depending on cisplatin dose and treatment sequence. Magnetic resonance imaging (MRI) was used to monitor the effects of combined radiation and cisplatin treatments of implanted intracranial 9L tumours in rats. A new technique for implanting experimental tumours was developed which resulted in more uniform tumour growth, and methods for radiation and cisplatin treatment of experimental intracranial tumours were developed and evaluated. Non-invasive measurements of tumour size using MRI were found to correlate well with measurements made from histological sections. Intraperitoneal administration of gadolinium contrast agent immediately before T1-weighted MRI was shown to be the most accurate and reliable method for MRI measurement of intracranial tumour size. The capability of MRI to provide early indications of radiation injury to normal brain

  6. p-[123I]iodo-l-phenylalanine for detection of pancreatic cancer: basic investigations of the uptake characteristics in primary human pancreatic tumour cells and evaluation in in vivo models of human pancreatic adenocarcinoma

    International Nuclear Information System (INIS)

    Samnick, Samuel; Hellwig, Dirk; Kirsch, Carl-Martin; Romeike, Bernd F.M.; Feiden, Wolfgang; Kubuschok, Boris; Amon, Michaela; Menger, Michael D.

    2004-01-01

    Pancreatic cancer is associated with the worst 5-year survival rate of any human cancer. This high mortality is due, in part, to difficulties in establishing early and accurate diagnosis. Because most tumours share the ability to accumulate amino acids more effectively than normal tissues and any other pathology, assessment of amino acid transport in tumour cells using radiolabelled amino acids has become one of the most promising tools for tumour imaging. This study investigated the potential of p-[ 123 I]iodo-l-phenylalanine (IPA) for detection of pancreatic cancer by single-photon emission tomography. IPA affinity for pancreatic tumour was investigated in human pancreatic adenocarcinoma PaCa44 and PanC1 cells, followed by analysis of the underlying mechanisms of tracer accumulation in neoplastic cells. Thereafter, IPA was evaluated for targeting of pancreatic tumours using SCID mice engrafted with primary human pancreatic adenocarcinoma cells, as well as in acute inflammation models in immunocompetent mice and rats. IPA accumulated intensively in human pancreatic tumour cells. Radioactivity accumulation in tumour cells following a 30-min incubation at 37 C/pH 7.4 varied from 41% to 58% of the total loaded activity per 10 6 cells. The cellular uptake was temperature and pH dependent and predominantly mediated by specific carriers for neutral amino acids, namely the sodium-independent and l-leucine-preferring (L-system) transporter and the alanine-, serine- and cysteine-preferring (ASC-system) transporter. Protein incorporation was less than 8%. Biodistribution studies showed rapid localization of the tracer to tumours, reaching 10%±2.5% to 15%±3% of the injected dose per gram (I.D./g) in heterotopic tumours compared with 17%±3.5% to 22%±4.3% I.D./g in the orthotopic tumours, at 60 and 240 min post injection of IPA, respectively. In contrast, IPA uptake in the gastrointestinal tract and areas of inflammation remained moderate and decreased with time. Excellent

  7. Cancerous Tumour Model Analysis and Constructing schemes of Anti-angiogenesis Therapy at an Early Stage

    Directory of Open Access Journals (Sweden)

    O. Yu. Mukhomorova

    2015-01-01

    Full Text Available Anti-angiogenesis therapy is an alternative and successfully employed method for treatment of cancerous tumour. However, this therapy isn't widely used in medicine because of expensive drugs. It leads naturally to elaboration of such treatment regimens which use minimum amount of drugs.The aim of the paper is to investigate the model of development of illness and elaborate appropriate treatment regimens in the case of early diagnosis of the disease. The given model reflects the therapy at an intermediate stage of the disease treatment. Further treatment is aimed to destroy cancer cells and may be continued by other means, which are not reflected in the model.Analysis of the main properties of the model was carried out with consideration of two types of auxiliary systems. In the first case, the system is considered without control, as a model of tumour development in the absence of medical treatment. The study of the equilibrium point and determination of its type allowed us to describe disease dynamics and to determine tumour size resulting in death. In the second case a model with a constant control was investigated. The study of its equilibrium point showed that continuous control is not sufficient to support satisfactory patient's condition, and it is necessary to elaborate more complex treatment regimens. For this purpose, we used the method of terminal problems consisting in the search for such program control which forces system to a given final state. Selecting the initial and final states is due to medical grounds.As a result, we found two treatment regimens | one-stage treatment regimen and multi-stage one. The properties of each treatment regimen are analyzed and compared. The total amount of used drugs was a criterion for comparing these two treatment regimens. The theoretical conclusions obtained in this work are supported by computer modeling in MATLAB environment.

  8. Improvement in tumour control probability with active breathing control and dose escalation: A modelling study

    International Nuclear Information System (INIS)

    Partridge, Mike; Tree, Alison; Brock, Juliet; McNair, Helen; Fernandez, Elizabeth; Panakis, Niki; Brada, Michael

    2009-01-01

    Introduction: The prognosis from non-small cell lung cancer remains poor, even in those patients suitable for radical radiotherapy. The ability of radiotherapy to achieve local control is hampered by the sensitivity of normal structures to irradiation at the high tumour doses needed. This study aimed to look at the potential gain in tumour control probability from dose escalation facilitated by moderate deep inspiration breath-hold. Method: The data from 28 patients, recruited into two separate studies were used. These patients underwent planning with and without the use of moderate deep inspiration breath-hold with an active breathing control (ABC) device. Whilst maintaining the mean lung dose (MLD) at the level of the conventional plan, the ABC plan dose was theoretically escalated to a maximum of 84 Gy, constrained by usual normal tissue tolerances. Calculations were performed using data for both lungs and for the ipsilateral lung only. Resulting local progression-free survival at 30 months was calculated using a standard logistic model. Results: The prescription dose could be escalated from 64 Gy to a mean of 73.7 ± 6.5 Gy without margin reduction, which represents a statistically significant increase in tumour control probability from 0.15 ± 0.01 to 0.29 ± 0.11 (p < 0.0001). The results were not statistically different whether both lungs or just the ipsilateral lung was used for calculations. Conclusion: A near-doubling of tumour control probability is possible with modest dose escalation, which can be achieved with no extra increase in lung dose if deep inspiration breath-hold techniques are used.

  9. Recurrence of squamous cell carcinoma of the oesophagus after curative surgery: rates and patterns on imaging studies correlated with tumour location and pathological stage

    International Nuclear Information System (INIS)

    Lee, S.J.; Lee, K.S.; Yim, Y.J.; Kim, T.S.; Shim, Y.M.; Kim, K.

    2005-01-01

    Many factors have been related to recurrence after resection of squamous cell carcinoma of the oesophagus. These include age, gender, location and local stage of tumours, cell differentiation, lymph node metastasis and vascular involvement. The recurrence rates of squamous cell carcinoma after curative surgery are high (34-79%). Tumour recurrence is categorized as locoregional or distant. Lymph node recurrence and haematogenous metastasis to solid organs (commonly to the lung) are the usual patterns of recurrence. Awareness of recurrence patterns, particularly on imaging studies, is essential for the diagnosis of recurrent tumours on follow-up examinations

  10. A five-factor model of developmental personality pathology precursors.

    Science.gov (United States)

    Verbeke, Lize; De Caluwé, Elien; De Clercq, Barbara

    2017-04-01

    There is growing consensus that the dimensional structure of early personality pathology can be organized within a similar framework as in adults (De Clercq, De Fruyt, Van Leeuwen, & Mervielde, 2006; Tromp & Koot, 2008). From this perspective, the Dimensional Personality Symptom Itempool (DIPSI) was recently expanded from a 4- to a 5-dimensional trait structure (Verbeke & De Clercq, 2014), including Disagreeableness, Emotional Instability, Introversion, Compulsivity, and Oddity. This developmental maladaptive trait structure is in need of further research, however, before it can be accepted as a valid framework for describing early manifestations of personality dysfunction. By use of exploratory structural equation modeling (ESEM) analyses, the current study explored the fit of the 5-factor DIPSI framework across 4 different samples (N = 1456), and replicated 5 higher-order factors that demonstrated scalar invariance across age and metric invariance across informants and clinical status. These results underscore the robustness of 5 underlying dimensions of personality pathology at a young age and highlight adequate psychometric properties of the proposed DIPSI measure for describing childhood personality pathology precursors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. The administration of milk fermented by the probiotic Lactobacillus casei CRL 431 exerts an immunomodulatory effect against a breast tumour in a mouse model.

    Science.gov (United States)

    Aragón, Félix; Carino, Silvia; Perdigón, Gabriela; de Moreno de LeBlanc, Alejandra

    2014-06-01

    Antitumour activity is one of the health-promoting effects attributed to probiotics specially analysed from preclinical models, mostly murine. Here, the effect of milk fermented by the probiotic bacterium Lactobacillus casei CRL 431, on a murine breast cancer model was analysed. Mice were fed with milk fermented by Lactobacillus casei or unfermented milk before and after tumour injection. Rate of tumour development, cytokines in serum, IgA, CD4, CD8, F4/80 and cytokines positive cells in mammary glands were determined. Microvasculature in the tumour tissues was monitored. The effect of fermented milk administration after tumour injection was also evaluated. It was observed that probiotic administration delayed or blocked tumour development. This effect was associated to modulation of the immune response triggered by the tumour. The area occupied by blood vessels decreased in the tumours from mice given fermented milk which agrees with their small tumours, and fewer side effects. Finally, it was observed that probiotic administration after tumour detection was also beneficial to delay the tumour growth. In conclusion, we showed in this study the potential of milk fermented by the probiotic Lactobacillus casei CRL431 to stimulate the immune response against this breast tumour, avoiding or delaying its growth when it was preventively administrated and also when the administration started after tumour cells injection. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

    Science.gov (United States)

    McAneney, H.; O'Rourke, S. F. C.

    2007-02-01

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

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

    International Nuclear Information System (INIS)

    McAneney, H; O'Rourke, S F C

    2007-01-01

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

  14. A margin model to account for respiration-induced tumour motion and its variability

    International Nuclear Information System (INIS)

    Coolens, Catherine; Webb, Steve; Evans, Phil M; Shirato, H; Nishioka, K

    2008-01-01

    In order to reduce the sensitivity of radiotherapy treatments to organ motion, compensation methods are being investigated such as gating of treatment delivery, tracking of tumour position, 4D scanning and planning of the treatment, etc. An outstanding problem that would occur with all these methods is the assumption that breathing motion is reproducible throughout the planning and delivery process of treatment. This is obviously not a realistic assumption and is one that will introduce errors. A dynamic internal margin model (DIM) is presented that is designed to follow the tumour trajectory and account for the variability in respiratory motion. The model statistically describes the variation of the breathing cycle over time, i.e. the uncertainty in motion amplitude and phase reproducibility, in a polar coordinate system from which margins can be derived. This allows accounting for an additional gating window parameter for gated treatment delivery as well as minimizing the area of normal tissue irradiated. The model was illustrated with abdominal motion for a patient with liver cancer and tested with internal 3D lung tumour trajectories. The results confirm that the respiratory phases around exhale are most reproducible and have the smallest variation in motion amplitude and phase (approximately 2 mm). More importantly, the margin area covering normal tissue is significantly reduced by using trajectory-specific margins (as opposed to conventional margins) as the angular component is by far the largest contributor to the margin area. The statistical approach to margin calculation, in addition, offers the possibility for advanced online verification and updating of breathing variation as more data become available

  15. A systems-based mathematical modelling framework for investigating the effect of drugs on solid tumours

    Directory of Open Access Journals (Sweden)

    Liu Cong

    2011-12-01

    Full Text Available Abstract Background Elucidating the effects of drugs on solid tumours is a highly challenging multi-level problem, since this involves many complexities associated with transport and cellular response, which in turn is characterized by highly non-linear chemical signal transduction. Appropriate systems frameworks are needed to seriously address the sources of these complexities, especially from the cellular side. Results We develop a skeletal modelling framework incorporating interstitial drug transport, intracellular signal processing and cell population descriptions. The descriptions aim to appropriately capture the nature of information flow. The model is deliberately formulated to start with simple intracellular descriptions so that additional features can be incorporated in a modular fashion. Two kinds of intracellular signalling modules which describe the drug effect were considered, one a monostable switch and the other a bistable switch. Analysis of our model revealed how different drug stimuli can lead to cell killing in the tumour. Interestingly both modules considered exhibited similar trends. The effects of important parameters were also studied. Conclusions We have created a predictive systems platform integrating drug transport and cellular response which can be systematically augmented to include additional layers of cellular complexity. Our results indicate that intracellular signalling models which are qualitatively different can give rise to similar behaviour to simple (and typical stimuli, and that validating intracellular descriptions must be performed with care by considering a variety of drug stimuli.

  16. Multiscale modelling of vascular tumour growth in 3D: the roles of domain size and boundary conditions.

    Directory of Open Access Journals (Sweden)

    Holger Perfahl

    2011-04-01

    Full Text Available We investigate a three-dimensional multiscale model of vascular tumour growth, which couples blood flow, angiogenesis, vascular remodelling, nutrient/growth factor transport, movement of, and interactions between, normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. In particular, we determine how the domain size, aspect ratio and initial vascular network influence the tumour's growth dynamics and its long-time composition. We establish whether it is possible to extrapolate simulation results obtained for small domains to larger ones, by constructing a large simulation domain from a number of identical subdomains, each subsystem initially comprising two parallel parent vessels, with associated cells and diffusible substances. We find that the subsystem is not representative of the full domain and conclude that, for this initial vessel geometry, interactions between adjacent subsystems contribute to the overall growth dynamics. We then show that extrapolation of results from a small subdomain to a larger domain can only be made if the subdomain is sufficiently large and is initialised with a sufficiently complex vascular network. Motivated by these results, we perform simulations to investigate the tumour's response to therapy and show that the probability of tumour elimination in a larger domain can be extrapolated from simulation results on a smaller domain. Finally, we demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.

  17. Lung Cancer Pathological Image Analysis Using a Hidden Potts Model

    Directory of Open Access Journals (Sweden)

    Qianyun Li

    2017-06-01

    Full Text Available Nowadays, many biological data are acquired via images. In this article, we study the pathological images scanned from 205 patients with lung cancer with the goal to find out the relationship between the survival time and the spatial distribution of different types of cells, including lymphocyte, stroma, and tumor cells. Toward this goal, we model the spatial distribution of different types of cells using a modified Potts model for which the parameters represent interactions between different types of cells and estimate the parameters of the Potts model using the double Metropolis-Hastings algorithm. The double Metropolis-Hastings algorithm allows us to simulate samples approximately from a distribution with an intractable normalizing constant. Our numerical results indicate that the spatial interaction between the lymphocyte and tumor cells is significantly associated with the patient’s survival time, and it can be used together with the cell count information to predict the survival of the patients.

  18. Lung Cancer Pathological Image Analysis Using a Hidden Potts Model

    Science.gov (United States)

    Li, Qianyun; Yi, Faliu; Wang, Tao; Xiao, Guanghua; Liang, Faming

    2017-01-01

    Nowadays, many biological data are acquired via images. In this article, we study the pathological images scanned from 205 patients with lung cancer with the goal to find out the relationship between the survival time and the spatial distribution of different types of cells, including lymphocyte, stroma, and tumor cells. Toward this goal, we model the spatial distribution of different types of cells using a modified Potts model for which the parameters represent interactions between different types of cells and estimate the parameters of the Potts model using the double Metropolis-Hastings algorithm. The double Metropolis-Hastings algorithm allows us to simulate samples approximately from a distribution with an intractable normalizing constant. Our numerical results indicate that the spatial interaction between the lymphocyte and tumor cells is significantly associated with the patient’s survival time, and it can be used together with the cell count information to predict the survival of the patients. PMID:28615918

  19. Joint modelling of longitudinal CEA tumour marker progression and survival data on breast cancer

    Science.gov (United States)

    Borges, Ana; Sousa, Inês; Castro, Luis

    2017-06-01

    This work proposes the use of Biostatistics methods to study breast cancer in patients of Braga's Hospital Senology Unit, located in Portugal. The primary motivation is to contribute to the understanding of the progression of breast cancer, within the Portuguese population, using a more complex statistical model assumptions than the traditional analysis that take into account a possible existence of a serial correlation structure within a same subject observations. We aim to infer which risk factors aect the survival of Braga's Hospital patients, diagnosed with breast tumour. Whilst analysing risk factors that aect a tumour markers used on the surveillance of disease progression the Carcinoembryonic antigen (CEA). As survival and longitudinal processes may be associated, it is important to model these two processes together. Hence, a joint modelling of these two processes to infer on the association of these was conducted. A data set of 540 patients, along with 50 variables, was collected from medical records of the Hospital. A joint model approach was used to analyse these data. Two dierent joint models were applied to the same data set, with dierent parameterizations which give dierent interpretations to model parameters. These were used by convenience as the ones implemented in R software. Results from the two models were compared. Results from joint models, showed that the longitudinal CEA values were signicantly associated with the survival probability of these patients. A comparison between parameter estimates obtained in this analysis and previous independent survival[4] and longitudinal analysis[5][6], lead us to conclude that independent analysis brings up bias parameter estimates. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary. Results indicate that the longitudinal progression of CEA is signicantly associated with the probability of survival of these patients. Hence, an assumption of

  20. Correlation between the Histo-Pathological Grade and Tumour Uptake Analysis of Tc99m-MIBI in Breast Cancer Nodules

    International Nuclear Information System (INIS)

    Haider, Saima

    2006-01-01

    Full text: Breast Cancer is the most common malignancy among women in the world. X-Ray mammography is the best screening device, but radionuclide imaging such as Tc-99m MIBI Scintimammography promises to play an important role as an adjunctive functional imaging tool in breast malignancies. The aim of the study was to correlate the Histopathological grade and semi-quantitative analysis of tracer uptake in Tc-99m MIBI Scintimammography. Seven (7) female patients (mean age 47.5+10) with locally advanced breast cancer were imaged. Informed written consent was taken from each patient. Average of 950 MBq (0.3 mCi/kg) Tc-99m MIBI was injected intravenously in the contra lateral arm to the site of lesion. Static prone MIBI Scintimammoscans of the affected side was acquired 5-10 minutes post injection for 10 minutes. Similarly 10 minute static view of normal side was also done. The background subtracted lesions to normal ratios (LNR) were acquired. Histopathological grading of tumours was done according to Bloom Richardson grading system. All the tumours were infiltrating ductal carcinoma. The mean LNR value is higher in high-grade lesions while less in low-grade tumours. Higher un-differentiation of malignant tumour is related with aggressive nature of the disease. This would suggest that more aggressive tumours have higher uptake of Tc-99m MIBI and therefore greater invasiveness of malignancy. (author)

  1. [Gastric mesenchymal tumours (GIST)].

    Science.gov (United States)

    Spivach, Arrigo; Fezzi, Margherita; Sartori, Alberto; Belgrano, Manuel; Rimondini, Alessandra; Cuttin-Zernich, Roberto; Covab, Maria Assunta; Bonifacio, Daniela; Buri, Luigi; Pagani, Carlo; Zanconati, Fabrizio

    2008-01-01

    The incidence of gastrointestinal stromal tumours (GIST) has increased in recent years. A number of authors have attempted to define the actual nature of these tumours. Immunohistochemistry highlighting the positivity of tyrosine-kinase (CD117/c-Kit) has revealed the difference between gastrointestinal stromal tumours and other mesenchymal tumours and, therefore, the possibility of medical rather than surgical therapy. We retrospectively reviewed 19 patients affected by primary gastric GIST, who underwent surgery in recent years with subsequent follow-up. Gastroscopy and gastrointestinal tract radiography were used not only to obtain the diagnosis but also to establish the size, density, contours, ulceration, regional lymphadenopathy, mesenteric infiltration and the presence of metastases. The aim of this study was to evaluate the roles of endoscopy and radiology in this pathology and the advantages and limitations of each individual technique.

  2. Proliferation index: a continuous model to predict prognosis in patients with tumours of the Ewing's sarcoma family.

    Directory of Open Access Journals (Sweden)

    Samantha Brownhill

    Full Text Available The prognostic value of proliferation index (PI and apoptotic index (AI, caspase-8, -9 and -10 expression have been investigated in primary Ewing's sarcoma family of tumours (ESFT. Proliferating cells, detected by immunohistochemistry for Ki-67, were identified in 91% (91/100 of tumours with a median PI of 14 (range 0-87. Apoptotic cells, identified using the TUNEL assay, were detected in 96% (76/79 of ESFT; the median AI was 3 (range 0-33. Caspase-8 protein expression was negative (0 in 14% (11/79, low (1 in 33% (26/79, medium (2 in 38% (30/79 and high (3 in 15% (12/79 of tumours, caspase-9 expression was low (1 in 66% (39/59 and high (3 in 34% (20/59, and caspase-10 protein was low (1 in 37% (23/62 and negative (0 in 63% (39/62 of primary ESFT. There was no apparent relationship between caspase-8, -9 and -10 expression, PI and AI. PI was predictive of relapse-free survival (RFS; p = 0.011 and overall survival (OS; p = <0.001 in a continuous model, whereas AI did not predict outcome. Patients with tumours expressing low levels of caspase-9 protein had a trend towards a worse RFS than patients with tumours expressing higher levels of caspase-9 protein (p = 0.054, log rank test, although expression of caspases-8, -9 and/or -10 did not significantly predict RFS or OS. In a multivariate analysis model that included tumour site, tumour volume, the presence of metastatic disease at diagnosis, PI and AI, PI independently predicts OS (p = 0.003. Consistent with previous publications, patients with pelvic tumours had a significantly worse OS than patients with tumours at other sites (p = 0.028; patients with a pelvic tumour and a PI≥20 had a 6 fold-increased risk of death. These studies advocate the evaluation of PI in a risk model of outcome for patients with ESFT.

  3. Modeling physiological and pathological human neurogenesis in the dish

    Directory of Open Access Journals (Sweden)

    Vania eBroccoli

    2014-07-01

    Full Text Available New advances in directing the neuronal differentiation of human embryonic and induced pluripotent stem cells (hPSCs, abbreviation intended to convey both categories of pluripotent stem cells have promoted the development of culture systems capable of modeling early neurogenesis and neural specification at some of their critical milestones. The hPSC-derived neural rosette can be considered the in vitro counterpart of the developing neural tube, since both structures share a virtually equivalent architecture and related functional properties. Epigenetic stimulation methods can modulate the identity of the rosette neural progenitors in order to generate authentic neuronal subtypes, as well as a full spectrum of neural crest derivatives. The intrinsic capacity of induced pluripotent cell-derived neural tissue to self-organize has become fully apparent with the emergence of innovative in vitro systems that are able to shape the neuronal differentiation of hPSCs into organized tissues that develop in three dimensions. However, significant hurdles remain that must be completely solved in order to facilitate the use of hPSCs in modeling (e.g., late-onset disorders or in building therapeutic strategies for cell replacement. In this direction, new procedures have been established to promote the maturation and functionality of hPSC-derived neurons. Meanwhile, new methods to accelerate the aging of in vitro differentiating cells are still in development. hPSC-based technology has matured enough to offer a significant and reliable model system for early and late neurogenesis that could be extremely informative for the study of the physiological and pathological events that occur during this process. Thus, full exploitation of this cellular system can provide a better understanding of the physiological events that shape human brain structures, as well as a solid platform to investigate the pathological mechanisms at the root of human diseases.

  4. TUMOUR VACCINE

    NARCIS (Netherlands)

    Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert

    1999-01-01

    The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a

  5. An imaging-based platform for high-content, quantitative evaluation of therapeutic response in 3D tumour models

    Science.gov (United States)

    Celli, Jonathan P.; Rizvi, Imran; Blanden, Adam R.; Massodi, Iqbal; Glidden, Michael D.; Pogue, Brian W.; Hasan, Tayyaba

    2014-01-01

    While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls for reliable quantification of fluorescence signal. This streamlined methodology reads out the high density of information embedded in 3D culture systems, while maintaining a level of speed and efficiency traditionally achieved with global colorimetric reporters in order to facilitate broader implementation of 3D tumour models in therapeutic screening.

  6. Primary tumour growth in an orthotopic osteosarcoma mouse model is not influenced by analgesic treatment with buprenorphine and meloxicam.

    Science.gov (United States)

    Husmann, K; Arlt, M J E; Jirkof, P; Arras, M; Born, W; Fuchs, B

    2015-10-01

    Little is known about the treatment of bone pain in animal models of bone cancer. In the present study, the orthotopic 143-B human osteosarcoma xenotransplantation model was used to address the following questions: (1) Can repetitive analgesic treatment extend the experimental period by prolonging the time to reach humane endpoints and (2) Does repetitive analgesic treatment affect bone tumour development and metastasis? The analgesics, buprenorphine and meloxicam, were either applied individually or in combination at 12 h intervals as soon as the animals began to avoid using the tumour cell injected leg. While control mice treated with NaCl showed continuous body weight loss, the major criterion previously for terminating the experiments, animals treated with analgesic substances did not. The control mice had to be sacrificed 26 days after tumour cell injection, whereas the groups of animals with the different pain treatments were euthanized after an additional eight days. Importantly, primary intratibial tumour growth was not affected in any of the experimental groups by any of the pain treatment procedures. Between days 26 and 34 after tumour cell injection an increase of about 100% of the number of lung metastases was found for the groups treated with buprenorphine alone or together with meloxicam, but not for the group treated with meloxicam alone. In summary, the results indicated that both buprenorphine and meloxicam are suitable analgesics for prolonging the experimental periods in an experimental intratibial osteosarcoma mouse model. © The Author(s) 2015.

  7. Clinical and pathological associations with p53 tumour-suppressor gene mutations and expression of p21WAF1/Cip1 in colorectal carcinoma

    NARCIS (Netherlands)

    Slebos, R. J.; Baas, I. O.; Clement, M.; Polak, M.; Mulder, J. W.; van den Berg, F. M.; Hamilton, S. R.; Offerhaus, G. J.

    1996-01-01

    Inactivation of the p53 tumour-suppressor gene is common in a wide variety of human neoplasms. In the majority of cases, single point mutations in the protein-encoding sequence of p53 lead to positive immunohistochemistry (IHC) for the p53 protein, and are accompanied by loss of the wild-type

  8. Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL

    NARCIS (Netherlands)

    Deans, Z.C.; Costa, J.L.; Cree, I.; Dequeker, E.; Edsjo, A.; Henderson, S.; Hummel, M.; Ligtenberg, M.J.L.; Loddo, M.; Machado, J.C.; Marchetti, A.; Marquis, K.; Mason, J.; Normanno, N.; Rouleau, E.; Schuuring, E.; Snelson, K.M.; Thunnissen, E.; Tops, B.B.; Williams, G.; Krieken, H. van; Hall, J.A.

    2017-01-01

    The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ

  9. Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL

    NARCIS (Netherlands)

    Deans, Zandra C.; Costa, Jose Luis; Cree, Ian; Dequeker, Els; Edsjo, Anders; Henderson, Shirley; Hummel, Michael; Ligtenberg, Marjolijn J. L.; Loddo, Marco; Machado, Jose Carlos; Marchetti, Antonio; Marquis, Katherine; Mason, Joanne; Normanno, Nicola; Rouleau, Etienne; Schuuring, Ed; Snelson, Keeda-Marie; Thunnissen, Erik; Tops, Bastiaan; Williams, Gareth; van Krieken, Han; Hall, Jacqueline A.

    The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ

  10. Computed 88% TCP dose for SBRT of NSCLC from tumour hypoxia modelling

    International Nuclear Information System (INIS)

    Ruggieri, Ruggero; Naccarato, Stefania; Stavreva, Nadejda; Stavrev, Pavel

    2013-01-01

    In small NSCLC, 88% local control at three years from SBRT was reported both for schedule (20–22 Gy ×3) (Fakiris et al 2009 Int. J. Radiat. Oncol. Biol. Phys. 75 677–82), actually close to (18–20 Gy ×3) if density correction is properly applied, and for schedules (18 Gy ×3) and (11 Gy ×5) (Palma et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 82 1149–56). Here, we compare our computed iso-TCP = 88% dose per fraction (d 88 ) for three and five fractions (n) with such clinically adopted ones. Our TCP model accounts for tumour repopulation, at rate λ (d −1 ), reoxygenation of chronic hypoxia (ch-), at rate a (d −1 ) and fluctuating oxygenation of acute hypoxia (ah-), with hypoxic fraction (C) of the acutely hypoxic fractional volume (AHF). Out of the eight free parameters whose values we had fitted to in vivo animal data (Ruggieri et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 83 1603–8), we here maintained (a(d −1 ), C, OER ch , OER ah /OER ch , AHF, CHF) = (0.026, 0.17, 1.9, 2.2, 0.033, 0.145) while rescaling the initial total number of clonogens (N o ) according to the ratio of NSCLC on animal median tumour volumes. From the clinical literature, the usually assumed (α o /β o (Gy), λ(d −1 )) = (10, 0.217) for the well-oxygenated (o-)cells were taken. By normal (lognormal) random sampling of all parameter values over their 95% C.I., the uncertainty on present d 88 (n) computations was estimated. Finally, SBRT intra-tumour dose heterogeneity was simulated by a 1.3 dose boost ratio on 50% of tumour volume. Computed d 88 (±1σ) were 19.0 (16.3; 21.7) Gy, for n = 3; 10.4 (8.7; 12.1) Gy, for n = 5; 5.8 (5.2; 6.4) Gy, for n = 8; 4.0 (3.6; 4.3) Gy, for n = 12. Furthermore, the iso-TCP = 88% total dose, D 88 (n) = d 88 (n)*n, exhibited a relative minimum around n = 8. Computed d 88 (n = 3, 5) are strictly consistent with the clinically adopted ones, which confirms the validity of LQ-model-based TCP predictions at the doses used in SBRT if a highly

  11. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

    Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

  12. Cardiac tumours: clinical, echocardiographic and pathological features Tumores cardíacos: aspectos clínicos, ecocardiográficos e histopatológicos

    Directory of Open Access Journals (Sweden)

    Ricardo Pereira Silva

    2003-10-01

    Full Text Available OBJECTIVE: The purpose of our paper was clinical and echocardiographic characterisation of patients with cardiac tumours and the evaluation of the surgery and tumour recurrence. METHOD: The first part of research was a retrospective investigation to identify cardiac tumours identification and to collect data from patients' records of the Messejana Hospital and Walter Cantídio University Hospital, from 1981 to 2001. In this period, 19 cases of cardiac tumours were discovered. The patients were submitted to clinical, electrocardiographic and echocardiographic re-evaluation from March to July 2002. RESULTS: Congestive symptoms and thoracic pain were the most frequent symptoms. The location in which most of the tumours were identified was left atrium. Among patients submitted to surgery, all of them had the tumour extracted from atrium. The most common histopathologic type was myxoma (78%. Surgical mortality was 14%. Tumour recurrence occurred in one patient. CONCLUSION: Cardiac tumours were more frequent in left atrium, benign tumours were more frequent than malignant tumours, and the most frequent histopathologic type was myxoma.OBJETIVO: Caracterização clínica e ecocardiográfica dos pacientes com tumores cardíacos, avaliação da terapêutica cirúrgica e da recidiva dos tumores. MÉTODO: Na primeira parte da pesquisa, o delineamento metodológico foi do tipo retrospectivo, através da identificação de tumores cardíacos e coleta de dados dos prontuários do Hospital Universitário Walter Cantídio (UFCE e Hospital de Messejana, no período de 1981 a 2001, onde foram encontrados 19 casos de tumores cardíacos. Os pacientes foram submetidos a uma reavaliação clínica, eletro e ecocardiográfica durante o período de março a julho de 2002. RESULTADOS: Sintomas congestivos e dor torácica foram os sintomas mais freqüentes em nossa série. A localização preferencial dos tumores cardíacos em nossa série foi no átrio esquerdo. Entre os

  13. The Role of Metacognition in Pathological Gambling: A Mediation Model.

    Science.gov (United States)

    Mansueto, Giovanni; Pennelli, Michele; De Palo, Valeria; Monacis, Lucia; Sinatra, Maria; De Caro, Maria Fara

    2016-03-01

    Pathological gambling involves multitudinous costs related to financial, legal, and public health care aspects, as well as to specific psychological disorders. Despite the overall evidence suggesting that comorbid disorders represent a risk factor for pathological gambling, there is scant evidence on the appropriate treatments for gamblers with such disorders. In this context, metacognitive therapy is an interesting approach because it considers psychological disorders as a result of the activation of perseverative cognitive processes and attentional strategies in response to inner events. Several studies report that metacognition is associated with different psychological problems. This study investigated the relationship among comorbid disorders, metacognition, and pathological gambling. 69 pathological gamblers at the first hospital admission and 58 controls drawn from general population (matched for age, gender, education) completed a battery of self report instruments: Symptom Checklist-90-R, Metacognition Questionnaire 30, South Oaks Gambling Scale. Compared to controls, pathological gamblers showed higher level of comorbid symptomatology and metacognition. Correlation analyses showed that: comorbid symptomatology and metacognition were positively and significantly correlated with pathological gambling; metacognition was positively and significantly associated with comorbid symptomatology. Mediation analysis indicated that dysfunctional metacognitive strategies could have an indirect effect on pathological gambling mediated by concurrent psychological disorders. These findings provide some implications for gambling treatment programs: pathological gamblers should be screened for psychiatric disorders, and metacognitive therapy could be considered a correct treatment of pathological gamblers. Metacognitive therapy might lead to the reduction of the pathological gambling by the diminishing of the concurrent psychological disorders.

  14. Yessotoxin, a Marine Toxin, Exhibits Anti-Allergic and Anti-Tumoural Activities Inhibiting Melanoma Tumour Growth in a Preclinical Model.

    Directory of Open Access Journals (Sweden)

    Araceli Tobío

    Full Text Available Yessotoxins (YTXs are a group of marine toxins produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. They may have medical interest due to their potential role as anti-allergic but also anti-cancer compounds. However, their biological activities remain poorly characterized. Here, we show that the small molecular compound YTX causes a slight but significant reduction of the ability of mast cells to degranulate. Strikingly, further examination revealed that YTX had a marked and selective cytotoxicity for the RBL-2H3 mast cell line inducing apoptosis, while primary bone marrow derived mast cells were highly resistant. In addition, YTX exhibited strong cytotoxicity against the human B-chronic lymphocytic leukaemia cell line MEC1 and the murine melanoma cell line B16F10. To analyse the potential role of YTX as an anti-cancer drug in vivo we used the well-established B16F10 melanoma preclinical mouse model. Our results demonstrate that a few local application of YTX around established tumours dramatically diminished tumour growth in the absence of any significant toxicity as determined by the absence of weight loss and haematological alterations. Our data support that YTX may have a minor role as an anti-allergic drug, but reveals an important potential for its use as an anti-cancer drug.

  15. Cortisol-secreting adrenocortical tumours in dogs and their relevance for human medicine.

    Science.gov (United States)

    Galac, Sara

    2016-02-05

    Spontaneous cortisol-secreting adrenocortical tumours in pet dogs are an attractive animal model for their human counterparts. Adrenal morphology and function are similar in dogs and humans, and adrenocortical tumours have comparable clinical and pathological characteristics. Their relatively high incidence in pet dogs represents a potential source of adrenocortical tumour tissue to facilitate research. The molecular characteristics of canine cortisol-secreting adrenocortical tumours suggest that they will be useful for the study of angiogenesis, the cAMP/protein kinase A pathway, and the role of Steroidogenic Factor-1 in adrenal tumourigenesis. Pet dogs with spontaneous cortisol-secreting adrenocortical tumours may also be useful in clinical testing of new drugs and in investigating the molecular background of adrenocortical tumours. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. In vivo suppression of solid Ehrlich cancer via chlorophyllin derivative mediated PDT: an albino mouse tumour model

    Science.gov (United States)

    Gomaa, Iman; Saraya, Hend; Zekri, Maha; Abdel-Kader, Mahmoud

    2015-03-01

    In this study, copper chlorophyllin was used as a photosensitizer for photodynamic therapy (PDT) in Ehrlich tumour mouse model. Six groups of animals comprising 5 animals per group were subcutaneously transplanted with 1x106 Ehrlich tumour cells. A single dose of 200 μg/gm body weight chlorophylin derivative was administered by intravenous (IV) or intratumoral (IT) routes. Mice were exposed to monochromatic red laser of 630 nm for 1 h, and tumour regression was followed up for three consecutive months post treatment. Several Biochemical, histological and molecular tests were performed in order to evaluate the efficacy and safety of the applied treatment. An interest has been also directed towards investigating the molecular mechanisms underlying chlorophyllin derivative mediated PDT. PDT-treated animals via either the IV or IT routes showed significant decrease in tumour size 72 h post-treatment. Tumours at the IV-PDT group disappeared totally within a week with no recurrence over three months follow up. In the IT-PDT, the decrease in tumour size at the first week was interrupted by a slight increase; however never reached the original size. Histological examination of tumour tissues of the IV-PDT group at 24 h post treatment demonstrated restoring the normal muscle tissue architecture, and the biochemical assays indicated normal liver functions. The immunohistochemical analysis of caspase-3, and the quantitative PCR results of caspases-8 and 9 proved the presence of extrinsic apoptotic pathway after cholorphyllin derivative-mediated PDT. In conclusion IV-PDT strategy proved better cure rate than the IT-PDT, with no recurrence over three months of follow up.

  17. An observer model for quantifying panning artifacts in digital pathology

    Science.gov (United States)

    Avanaki, Ali R. N.; Espig, Kathryn S.; Xthona, Albert; Lanciault, Christian; Kimpe, Tom R. L.

    2017-03-01

    Typically, pathologists pan from one region of a slide to another, choosing areas of interest for closer inspection. Due to finite frame rate and imperfect zero-order hold reconstruction (i.e., the non-zero time to reach the target brightness after a change in pixel drive), panning in whole slide images (WSI) cause visual artifacts. It is important to study the impact of such artifacts since research suggests that 49% of navigation is conducted in low-power/overview with digital pathology (Molin et al., Histopathology 2015). In this paper, we explain what types of medical information may be harmed by panning artifacts, propose a method to simulate panning artifacts, and design an observer model to predict the impact of panning artifacts on typical human observers' performance in basic diagnostically relevant visual tasks. The proposed observer model is based on derivation of perceived object border maps from luminance and chrominance information and may be tuned to account for visual acuity of the human observer to be modeled. Our results suggest that increasing the contrast (e.g., using a wide gamut display) with a slow response panel may not mitigate the panning artifacts which mostly affect visual tasks involving spatial discrimination of objects (e.g., normal vs abnormal structure, cell type and spatial relationships between them, and low-power nuclear morphology), and that the panning artifacts worsen with increasing panning speed. The proposed methods may be used as building blocks in an automatic WSI quality assessment framework.

  18. Three-Dimensional Printing Model as a Tool to Assist in Surgery for Large Mandibular Tumour: a Case Report

    Directory of Open Access Journals (Sweden)

    Kazuyuki Yusa

    2017-06-01

    Full Text Available Objectives: Recently, three-dimensional printing models based on preoperative computed tomography and magnetic resonance imaging images have been widely used in medical fields. This study presents an effective use of the three-dimensional printing model in exploring complex spatial relationship between the tumour and surrounding tissue and in simulation surgery based planning of the operative procedure. Material and Methods: The patient was a 7-year-old boy with ameloblastic fibro-odontoma. Prior to surgery, a hybrid three-dimensional printing model consisting of the jaw bone, the tumour and the inferior alveolar nerve was fabricated. After the simulation surgery based on this model, enucleation of the tumour, leaving tooth 46 intact (Universal Numbering System by ADA safe, was planned. Results: Enucleation of the tumour was successfully carried out. One year later, healing was found to be satisfactory both clinically and radiographically. Conclusions: The study presented an effective application of a novel hybrid three-dimensional printing model composed of hard and soft tissues. Such innovations can bring significant benefits, especially to the field of oncological surgery.

  19. Tumour imaging with non specific substances

    International Nuclear Information System (INIS)

    Pompe, W.B. van der.

    1978-01-01

    A short introduction concerning tumour imaging in nuclear medicine is given as well as the formulation of the problem treated in this thesis. In a literature review the most important tumour imaging radiopharmaceuticals used until now are described together with their clinical significance in the diagnosis of malignancy. The mechanism of uptake and subcellular distribution of most of the radiopharmaceuticals reviewed are discussed in chapter three with special reference to gallium-citrate. An ionic model to explain the distribution patterns of a number of these tumour imaging radiopharmaceuticals in normal and pathological tissues has been proposed. Evidence for the validity of this model is presented with specific reference to the ionic state of the reagents concerned. EXperimental evidence to support the proposed model is presented, with reference to the biologic behaviour of the radiopharmaceuticals in normal and pathological tissues. A limited number of selected case reports demonstrate how the results of the earlier described investigations can be applied to explain phenomena observed in clinical studies with ionic substances. The results obtained are discussed and the validity of the data with respect to the proposed model has been investigated. (Auth.)

  20. A tumour control probability model for radiotherapy of prostate cancer using magnetic resonance imaging-based apparent diffusion coefficient maps

    DEFF Research Database (Denmark)

    Casares Magaz, Oscar; Van der Heide, Uulke A; Rørvik, Jarle

    2016-01-01

    Background and purpose: Standard tumour control probability (TCP) models assume uniform tumour cell density across the tumour. The aim of this study was to develop an individualised TCP model by including index-tumour regions extracted form multi-parametric magnetic resonance imaging (MRI...... density: a linear, a binary and a sigmoid relation. All TCP models were based on linear- quadratic cell survival curves assuming a/b = 1.93 Gy (consistent with a recent meta-analysis) and a set to obtain a 70% of TCP when 77 Gy was delivered to the entire prostate in 35 fractions (a = 0.18 Gy?1). Results......: Overall, TCP curves based on ADC maps showed larger differences between individuals than those assuming uniform cell densities. The range of the dose required to reach 50% TCP across the patient cohort was 20.1 Gy, 18.7 Gy and 13.2 Gy using an MRI-based voxel density (linear, binary and sigmoid approach...

  1. Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study

    Science.gov (United States)

    Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

    2012-01-01

    Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2. Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most

  2. Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study.

    Science.gov (United States)

    Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

    2012-03-27

    Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1-7.2. Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1-7.2 is most promising.

  3. Pathological Buying Online as a Specific Form of Internet Addiction: A Model-Based Experimental Investigation.

    Science.gov (United States)

    Trotzke, Patrick; Starcke, Katrin; Müller, Astrid; Brand, Matthias

    2015-01-01

    The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior, cue-induced craving should also constitute an important factor for online pathological buying. The theoretical model was tested in this study by investigating 240 female participants with a cue-reactivity paradigm, which was composed of online shopping pictures, to assess excitability from shopping. Craving (before and after the cue-reactivity paradigm) and online shopping expectancies were measured. The tendency for pathological buying and online pathological buying were screened with the Compulsive Buying Scale (CBS) and the Short Internet Addiction Test modified for shopping (s-IATshopping). The results demonstrated that the relationship between individual's excitability from shopping and online pathological buying tendency was partially mediated by specific Internet use expectancies for online shopping (model's R² = .742, p online pathological buying tendencies were correlated (r = .556, p online pathological buying (t(28) = 2.98, p online pathological buying and suggests potential parallels. The presence of craving in individuals with a propensity for online pathological buying emphasizes that this behavior merits potential consideration within the non-substance/behavioral addictions.

  4. Skull base tumours

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Instituto Portugues de Oncologia Francisco Gentil, Servico de Radiologia, Rua Professor Lima Basto, 1093 Lisboa Codex (Portugal)], E-mail: borgesalexandra@clix.pt

    2008-06-15

    With the advances of cross-sectional imaging radiologists gained an increasing responsibility in the management of patients with skull base pathology. As this anatomic area is hidden to clinical exam, surgeons and radiation oncologists have to rely on imaging studies to plan the most adequate treatment. To fulfil these endeavour radiologists need to be knowledgeable about skull base anatomy, about the main treatment options available, their indications and contra-indications and needs to be aware of the wide gamut of pathologies seen in this anatomic region. This article will provide a radiologists' friendly approach to the central skull base and will review the most common central skull base tumours and tumours intrinsic to the bony skull base.

  5. A comparative study between mixed-type tumours from human salivary and canine mammary glands

    International Nuclear Information System (INIS)

    Genelhu, Marisa CLS; Cardoso, Sérgio V; Gobbi, Helenice; Cassali, Geovanni D

    2007-01-01

    In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours. Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, β-catenin, and E-cadherin. After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions. There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations

  6. Pathological Buying Online as a Specific Form of Internet Addiction: A Model-Based Experimental Investigation

    Science.gov (United States)

    Trotzke, Patrick; Starcke, Katrin; Müller, Astrid; Brand, Matthias

    2015-01-01

    The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior, cue-induced craving should also constitute an important factor for online pathological buying. The theoretical model was tested in this study by investigating 240 female participants with a cue-reactivity paradigm, which was composed of online shopping pictures, to assess excitability from shopping. Craving (before and after the cue-reactivity paradigm) and online shopping expectancies were measured. The tendency for pathological buying and online pathological buying were screened with the Compulsive Buying Scale (CBS) and the Short Internet Addiction Test modified for shopping (s-IATshopping). The results demonstrated that the relationship between individual’s excitability from shopping and online pathological buying tendency was partially mediated by specific Internet use expectancies for online shopping (model’s R² = .742, p online pathological buying tendencies were correlated (r = .556, p online pathological buying (t(28) = 2.98, p online pathological buying and suggests potential parallels. The presence of craving in individuals with a propensity for online pathological buying emphasizes that this behavior merits potential consideration within the non-substance/behavioral addictions. PMID:26465593

  7. Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model

    NARCIS (Netherlands)

    Marques, I.J.; Weiss, F.U.; Vlecken, D.H.; Nitsche, C.; Bakkers, J.; Lagendijk, A.K.; Partecke, L.I.; Heidecke, C.D.; Lerch, M.M.; Bagowski, C.P.

    2009-01-01

    BACKGROUND: Aberrant regulation of cell migration drives progression of many diseases, including cancer cell invasion and metastasis formation. Analysis of tumour invasion and metastasis in living organisms to date is cumbersome and involves difficult and time consuming investigative techniques. For

  8. In vivo fluorescence kinetics and localisation of aluminium phthalocyanine disulphonate in an autologous tumour model

    NARCIS (Netherlands)

    Witjes, MJH; Speelman, OC; Nikkels, PGJ; Nooren, CAAM; Nauta, JM; vanderHolt, B; vanLeengoed, HLLM; Roodenburg, JLN

    Sulphonated phthalocyanines are studied as photosensitisers for photodynamic therapy of cancer. Their strong fluorescence and tumour-localising properties make them also potentially useful for detection of cancer by fluorescence. For this purpose, we have studied the fluorescence kinetics and

  9. Anti-tumour efficacy of etoposide alone and in combination with piroxicam against canine osteosarcoma in a xenograft model.

    Science.gov (United States)

    Ong, S M; Saeki, K; Kok, M K; Tanaka, Y; Choisunirachon, N; Yoshitake, R; Nishimura, R; Nakagawa, T

    2017-08-01

    Osteosarcoma (OSA) in dogs is locally invasive and highly malignant. Distant metastasis is the most common cause of death. To date, the survival rate in dogs with OSA remains poor. The cytotoxic effects of etoposide against canine OSA cell lines, either alone or in combination with piroxicam, have been previously demonstrated in vitro. The aim of this study was to evaluate the anti-tumour effect of etoposide alone and in combination with piroxicam on canine OSA using murine models. Etoposide single agent treatment significantly delayed tumour progression with a marked reduction in Ki-67 immunoreactivity in tumour tissue. Concomitant treatment with piroxicam did not enhance the anti-tumour efficacy of etoposide. Etoposide single agent treatment and combination treatment with piroxicam down-regulated survivin expression, but was not followed by increased apoptotic activity. These findings indicate that etoposide might be a promising novel therapeutic for canine OSA. Further investigations into its potential for clinical application in veterinary oncology are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Imaging of CA IX with fluorescent labelled sulfonamides distinguishes hypoxic and (re)-oxygenated cells in a xenograft tumour model

    International Nuclear Information System (INIS)

    Dubois, Ludwig; Lieuwes, Natasja G.; Maresca, Alfonso; Thiry, Anne; Supuran, Claudiu T.; Scozzafava, Andrea; Wouters, Bradly G.; Lambin, Philippe

    2009-01-01

    Background and purpose: Carbonic anhydrase (CA) IX is suggested to be an endogenous marker of hypoxia. Fluorescent sulfonamides with a high affinity for CA IX (CAI) have been developed and shown to bind to cells only when CA IX protein was expressed and while cells were hypoxic. The aim of this study was to investigate the in vivo CAI binding properties in a xenograft tumour model using fluorescent imaging. Materials and methods: NMRI-nu mice subcutaneously transplanted with HT-29 colorectal tumours were treated with 7% oxygen or with nicotinamide and carbogen and were compared with control animals. CAI accumulation was monitored by non-invasive fluorescent imaging. Results: Specific CAI accumulation could be observed in delineated tumour areas as compared with a non-sulfonamide analogue (P < 0.01). Administration of nicotinamide and carbogen, decreasing acute and chronic hypoxia, respectively, prevented CAI accumulation (P < 0.05). When treated with 7% oxygen breathing, a 3-fold higher CAI accumulation (P < 0.01) was observed. Furthermore, the bound CAI fraction was rapidly reduced upon tumour reoxygenation (P < 0.01). Conclusions: Our in vivo imaging results confirm previous in vitro data demonstrating that CAI binding and retention require exposure to hypoxia. Fluorescent labelled sulfonamides provide a powerful tool to visualize hypoxia response. An important step is made towards clinical applicability, indicating the potential of patient selection for CA IX-directed therapies.

  11. Towards an integrated systems-based modelling framework for drug transport and its effect on tumour cells

    Science.gov (United States)

    2014-01-01

    Background A systematic understanding of chemotherapeutic influence on solid tumours is highly challenging and complex as it encompasses the interplay of phenomena occurring at multiple scales. It is desirable to have a multiscale systems framework capable of disentangling the individual roles of multiple contributing factors, such as transport and extracellular factors, and purely intracellular factors, as well as the interactions among these factors. Based on a recently developed systems-based modelling framework, we have developed a coupled system in order to further elucidate the role of drug transport, and its interplay with cellular signalling by incorporating intra- and extra-vascular drug transport in tumour, dynamic descriptions of intracellular signalling and tumour cell density dynamics. Results Different aspects of the interaction between transport and cell signalling and the effects of transport parameters have been investigated in silico. Limited drug penetration is found to be a major constraint in inducing drug effect; many aspects of the interaction of transport with cell signalling are independent of the details of cell signalling. A sensitivity analysis indicates that the effect of drug diffusivity depends on the balance between interstitial drug transport and the specific requirement for triggering apoptosis (governed by highly nonlinear signalling networks), suggesting that the effect of drug diffusivity in such cases must be considered in conjunction with descriptions of cellular dynamics. Conclusions The modelling framework developed in this study provides qualitative and mechanistic insights into the effect of drug on tumour cells. It provides an in silico experimental platform to investigate the interplay between extracellular factors (e.g. transport) and intracellular factors. Such a platform is essential to understanding the individual and combined effects of transport and cellular factors in solid tumour. PMID:24764492

  12. A spatio-temporal simulation model of the response of solid tumours to radiotherapy in vivo: parametric validation concerning oxygen enhancement ratio and cell cycle duration

    International Nuclear Information System (INIS)

    Antipas, Vassilis P; Stamatakos, Georgios S; Uzunoglu, Nikolaos K; Dionysiou, Dimitra D; Dale, Roger G

    2004-01-01

    Advanced bio-simulation methods are expected to substantially improve radiotherapy treatment planning. To this end a novel spatio-temporal patient-specific simulation model of the in vivo response of malignant tumours to radiotherapy schemes has been recently developed by our group. This paper discusses recent improvements to the model: an optimized algorithm leading to conformal shrinkage of the tumour as a response to radiotherapy, the introduction of the oxygen enhancement ratio (OER), a realistic initial cell phase distribution and finally an advanced imaging-based algorithm simulating the neovascularization field. A parametric study of the influence of the cell cycle duration T c , OER, OER β for the beta LQ parameter on tumour growth, shrinkage and response to irradiation under two different fractionation schemes has been made. The model has been applied to two glioblastoma multiforme (GBM) cases, one with wild type (wt) and another one with mutated (mt) p53 gene. Furthermore, the model has been applied to a hypothetical GBM tumour with α and β values corresponding to those of generic radiosensitive tumours. According to the model predictions, a whole tumour with shorter T c tends to repopulate faster, as is to be expected. Furthermore, a higher OER value for the dormant cells leads to a more radioresistant whole tumour. A small variation of the OER β value does not seem to play a major role in the tumour response. Accelerated fractionation proved to be superior to the standard scheme for the whole range of the OER values considered. Finally, the tumour with mt p53 was shown to be more radioresistant compared to the tumour with wt p53. Although all simulation predictions agree at least qualitatively with the clinical experience and literature, a long-term clinical adaptation and quantitative validation procedure is in progress

  13. Electrochemotherapy of tumours

    International Nuclear Information System (INIS)

    Sersa, G.; Cemazar, M.; Rudolf, Z.; Miklavcic, D.

    2006-01-01

    Electrochemotherapy consists of chemotherapy followed by local application of electric pulses to the tumour to increase drug delivery into cells. Drug uptake can be increased by electroporation for only those drugs whose transport through the plasma membrane is impeded. Among many drugs that have been tested so far, only bleomycin and cisplatin found their way from preclinical testing to clinical trials. In vitro studies demonstrated several fold increase of their cytotoxicity after electroporation of cells. In vivo, electroporation of tumours after local or systemic administration of either of the drugs, i.e. electrochemotherapy, proved to be an effective antitumour treatment. In preclinical studies on several tumour models, electrochemotherapy either with bleomycin or cisplatin was elaborated and parameters for effective local tumour control were determined. In veterinary medicine, electrochemotherapy also proved to be effective in the treatment of primary tumours in cats, dogs and horses. In human clinical studies, electrochemotherapy was performed on the patients with progressive disease and accessible tumour nodules of different malignancies. All clinical studies demonstrated that electrochemotherapy is an effective treatment for local tumour control in cancer patients. (author)

  14. A five-factor model of developmental personality pathology precursors

    NARCIS (Netherlands)

    Verbeke, Lize; De Caluwe, E.A.L.; De Clercq, Barbara

    There is growing consensus that the dimensional structure of early personality pathology can be organized within a similar framework as in adults (De Clercq, De Fruyt, Van Leeuwen, & Mervielde, 2006; Tromp & Koot, 2008). From this perspective, the Dimensional Personality Symptom Itempool (DIPSI) was

  15. Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

    Science.gov (United States)

    This paper shows that rat models of cardiovascular diseases have differential degrees of underlying pathologies at a young age. Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. How...

  16. How our practice of histopathology, especially tumour pathology has changed in the last two decades: reflections from a major referral center in Pakistan.

    Science.gov (United States)

    Ahmad, Zubair; Idrees, Romana; Fatima, Saira; Arshad, Huma; Din, Nasir-ud; Memon, Aisha; Minhas, Khurram; Ahmed, Arsalan; Fatima, Syeda Samia; Arif, Muhammad; Ahmed, Rashida; Haroon, Saroona; Pervez, Shahid; Hassan, Sheema; Kayani, Naila

    2014-01-01

    Continued advances in the field of histo-pathology (and cyto-pathology) over the past two decades have resulted in dramatic changes in the manner in which these disciplines are now practiced. This is especially true in the setting of a large university hospital where the role of pathologists as clinicians (diagnosticians), undergraduate and postgraduate educators, and researchers has evolved considerably. The world around us has changed significantly during this period bringing about a considerable change in our lifestyles and the way we live. This is the world of the internet and the world-wide web, the world of Google and Wikipedia, of Youtube and Facebook where anyone can obtain any information one desires at the push of a button. The practice of histo (and cyto) pathology has also evolved in line with these changes. For those practicing this discipline in a poor, developing country these changes have been breathtaking. This is an attempt to document these changes as experienced by histo (and cyto) pathologists practicing in the biggest center for Histopathology in Pakistan, a developing country in South Asia with a large (180 million) and ever growing population. The Section of Histopathology, Department of Pathology and Microbiology at the Aga Khan University Hospital (AKUH) in Karachi, Pakistan's largest city has since its inception in the mid-1980s transformed the way histopathology is practiced in Pakistan by incorporating modern methods and rescuing histopathology in Pakistan from the primitive and outdated groove in which it was stuck for decades. It set histopathology in Pakistan firmly on the path of modernity and change which are essential for better patient management and care through accurate and complete diagnosis and more recently prognostic and predictive information as well.

  17. Bayesian Model Selection for Pathological Neuroimaging Data Applied to White Matter Lesion Segmentation

    NARCIS (Netherlands)

    Sudre, Carole H.; Cardoso, M. Jorge; Bouvy, Willem H.; Biessels, Geert Jan; Barnes, Josephine; Ourselin, Sebastien

    2015-01-01

    In neuroimaging studies, pathologies can present themselves as abnormal intensity patterns. Thus, solutions for detecting abnormal intensities are currently under investigation. As each patient is unique, an unbiased and biologically plausible model of pathological data would have to be able to

  18. Immunosenescence, suppression and tumour progression.

    Science.gov (United States)

    Pawelec, G; Koch, S; Griesemann, H; Rehbein, A; Hähnel, K; Gouttefangeas, C

    2006-08-01

    There are good arguments for suggesting that two seminal papers published 50 years ago can be taken as the beginning of modern tumour immunology. These papers by R. Baldwin, "Immunity to transplanted tumour: the effect of tumour extracts on the growth of homologous tumours in rats" and "Immunity to methylcholanthrene-induced tumours in inbred rats following atrophy and regression of the implanted tumours" (Br J Cancer 9:646-51 and 652-657, 1955) showed that once tumours are established, they and their products can be recognised by the adaptive immune system and rejected. However, the tumour normally co-evolves with immunity, like a parasite, rather than being suddenly introduced as in these, and many other, experimental models. Dynamics of this co-evolution are illustrated by findings that inflammation enhances tumorigenicity, yet is important to enable T cells to respond properly to tumour antigen and exert anti-tumour effects. The important thing is to maintain the balance between effective anti-tumour immunity and tumour escape and/or stimulatory mechanisms. Tumours almost always co-exist with immune defence systems over extended periods and interact chronically with T cells. The effect of this is potentially similar to other situations of chronic antigenic stress, particularly lifelong persistent virus infection, most strikingly, CMV infection. The questions briefly explored in this symposium paper are what happens when T lymphocyte clones are chronically stimulated by antigen which is not or cannot be eliminated? What are the similarities and differences between chronic antigenic stimulation by tumour antigen versus CMV antigen? What can we learn in one system which may illuminate the other?

  19. Pathological Buying Online as a Specific Form of Internet Addiction: A Model-Based Experimental Investigation.

    Directory of Open Access Journals (Sweden)

    Patrick Trotzke

    Full Text Available The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior, cue-induced craving should also constitute an important factor for online pathological buying. The theoretical model was tested in this study by investigating 240 female participants with a cue-reactivity paradigm, which was composed of online shopping pictures, to assess excitability from shopping. Craving (before and after the cue-reactivity paradigm and online shopping expectancies were measured. The tendency for pathological buying and online pathological buying were screened with the Compulsive Buying Scale (CBS and the Short Internet Addiction Test modified for shopping (s-IATshopping. The results demonstrated that the relationship between individual's excitability from shopping and online pathological buying tendency was partially mediated by specific Internet use expectancies for online shopping (model's R² = .742, p < .001. Furthermore, craving and online pathological buying tendencies were correlated (r = .556, p < .001, and an increase in craving after the cue presentation was observed solely in individuals scoring high for online pathological buying (t(28 = 2.98, p < .01, d = 0.44. Both screening instruments were correlated (r = .517, p < .001, and diagnostic concordances as well as divergences were indicated by applying the proposed cut-off criteria. In line with the model for specific Internet addiction, the study identified potential vulnerability factors for online pathological buying and suggests potential parallels. The presence of

  20. Residual tumour detection in post-treatment granulation tissue by using advanced diffusion models in head and neck squamous cell carcinoma patients.

    Science.gov (United States)

    Fujima, Noriyuki; Yoshida, Daisuke; Sakashita, Tomohiro; Homma, Akihiro; Kudo, Kohsuke; Shirato, Hiroki

    2017-05-01

    To evaluate the detectability of the residual tumour in post-treatment granulation tissue using parameters obtained with an advanced diffusion model in patients with head and neck squamous cell carcinoma (HNSCC) treated by chemoradiation therapy. We retrospectively evaluated 23 patients with HNSCC after the full course of chemoradiation therapy. The diffusion-weighted image (DWI) acquisition used single-shot spin-echo echo-planar imaging with 11 b-values (0-1000). We calculated 10 DWI parameters using a mono-exponential model, a bi-exponential model, a stretched exponential model (SEM), a diffusion kurtosis imaging (DKI) model and a statistical diffusion model (SDM) in the region of interest (ROI) placed on the post-treatment granulation tissue. The presence of residual tumour was determined by histological findings or clinical follow-up. Among the 23 patients, seven patients were revealed to have residual tumour. The univariate analysis revealed significant differences in six parameters between the patients with and without residual tumour. From the receiver operating characteristic curve analysis, the highest area under curve was detected in the center of the Gaussian distribution of diffusion coefficient (D s ) obtained by the SDM. The multivariate analysis revealed that the D s and diffusion heterogeneity (α) obtained by the SEM were predictors for the presence of residual tumour. DWI parameters obtained by advanced fitting models will be one of the diagnostic tools for the detection of residual tumour. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Perfusion imaging of parotid gland tumours: usefulness of arterial spin labeling for differentiating Warthin's tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Hiroki; Watanabe, Haruo [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Kanematsu, Masayuki [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Gifu University Hospital, High-level Imaging Diagnosis Center, Gifu (Japan); Kajita, Kimihiro [Gifu University Hospital, High-level Imaging Diagnosis Center, Gifu (Japan); Mizuta, Keisuke; Aoki, Mitsuhiro [Gifu University School of Medicine, Department of Otolaryngology, Gifu (Japan); Okuaki, Tomoyuki [Philips Healthcare, Tokyo (Japan)

    2015-11-15

    To assess prospectively the efficacy of arterial spin labelling (ASL) against conventional and diffusion-weighted (DW) MR imaging for differentiating parotid gland tumours. We included 10 pleomorphic adenomas, 12 Warthin's tumours, and nine malignant tumours of the parotid glands. Only tumours larger than 10 mm were included in this study. All parotid gland tumours underwent T1-weighted, T2-weighted, DW, and ASL imaging. Tumour-to-parotid gland signal intensity ratios (SIRs) and apparent diffusion coefficients (ADCs) of solid components were correlated with these pathologies. SIRs on T2-weighted images and ADCs were higher in pleomorphic adenomas than in Warthin's tumours (p <.01) and malignant tumours (p <.01). SIRs on ASL were higher in Warthin's tumours than in pleomorphic adenomas (p <.01) and malignant tumours (p <.05). Az value of SIRs on ASL for differentiating Warthin's tumours from the other pathologies was 0.982. The sensitivity, specificity, and accuracy of SIRs on ASL for the diagnosis of Warthin's tumours at an optimal SIR threshold of over 8.70 were 91.7 %, 94.7 %, and 93.5 %, respectively. ASL with SIR measurements could non-invasively evaluate tumour blood flow of parotid gland tumours and differentiate Warthin's tumours from pleomorphic adenomas and malignant tumours. (orig.)

  2. A metastructural model of mental disorders and pathological personality traits.

    Science.gov (United States)

    Wright, A G C; Simms, L J

    2015-08-01

    Psychiatric co-morbidity is extensive in both psychiatric settings and the general population. Such co-morbidity challenges whether DSM-based mental disorders serve to effectively carve nature at its joints. In response, a substantial literature has emerged showing that a small number of broad dimensions - internalizing, externalizing and psychoticism - can account for much of the observed covariation among common mental disorders. However, the location of personality disorders within this emerging metastructure has only recently been studied, and no studies have yet examined where pathological personality traits fit within such a broad metastructural framework. We conducted joint structural analyses of common mental disorders, personality disorders and pathological personality traits in a sample of 628 current or recent psychiatric out-patients. Bridging across the psychopathology and personality trait literatures, the results provide evidence for a robust five-factor metastructure of psychopathology, including broad domains of symptoms and features related to internalizing, disinhibition, psychoticism, antagonism and detachment. These results reveal evidence for a psychopathology metastructure that (a) parsimoniously accounts for much of the observed covariation among common mental disorders, personality disorders and related personality traits, and (b) provides an empirical basis for the organization and classification of mental disorder.

  3. Malignant Appendage Tumours in Zaria | Samaila | Sudanese ...

    African Journals Online (AJOL)

    They were diagnosed malignant adnexeal tumour of Eccrine sweat gland origin. Conclusion: Malignant appendage tumours showed a higher frequency in middle aged men in this review. A good knowledge and understanding of the pathology, high index of suspicion and immunohistochemical studies should help in ...

  4. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

    Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

  5. Contrast-enhanced MRI after neoadjuvant chemotherapy of breast cancer: lesion-to-background parenchymal signal enhancement ratio for discriminating pathological complete response from minimal residual tumour.

    Science.gov (United States)

    Kim, Soo-Yeon; Cho, Nariya; Shin, Sung Ui; Lee, Han-Byoel; Han, Wonshik; Park, In Ae; Kwon, Bo Ra; Kim, Soo Yeon; Lee, Su Hyun; Chang, Jung Min; Moon, Woo Kyung

    2018-01-29

    To retrospectively investigate whether the lesion-to-background parenchymal signal enhancement ratio (SER) on breast MRI can distinguish pathological complete response (pCR) from minimal residual cancer following neoadjuvant chemotherapy (NAT), and compare its performance with the conventional criterion. 216 breast cancer patients who had undergone NAT and MRI and achieved pCR or minimal residual cancer on surgical histopathology were included. Clinical-pathological features, SER and lesion size on MR images were analysed. Multivariate logistic regression, ROC curve and McNemar's test were performed. SER on early-phase MR images was independently associated with pCR (odds ratio [OR], 0.286 [95% CI: 0.113-0.725], p = .008 for Reader 1; OR, 0.306 [95% CI: 0.111-0.841], p = .022 for Reader 2). Compared with the conventional criterion, SER ≤1.6 increased AUC (0.585-0.599 vs. 0.709-0.771, p=.001-.033) and specificity (21.9-27.4% vs. 80.8-86.3%, p highest specificity of 90.4%. SER on early-phase MR images was independently associated with pCR, and showed improved AUC and specificity compared to the conventional criterion. The combined criterion of SER and size could be used to select candidates to avoid surgery in a future study. • Compared with conventional criterion, SER ≤ 1.6 criterion increased AUC and specificity. • Simple measurement of signal intensity could differentiate pCR from minimal residual cancer. • SER ≤1.6 and/or size≤0.2cm criterion showed the highest specificity of 90.4 %. • The combined criterion could be used for a study to avoid surgery.

  6. Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy.

    Science.gov (United States)

    Nash, Kevin R; Lee, Daniel C; Hunt, Jerry B; Morganti, Josh M; Selenica, Maj-Linda; Moran, Peter; Reid, Patrick; Brownlow, Milene; Guang-Yu Yang, Clement; Savalia, Miloni; Gemma, Carmelina; Bickford, Paula C; Gordon, Marcia N; Morgan, David

    2013-06-01

    Alzheimer's disease is characterized by amyloid plaques, neurofibrillary tangles, glial activation, and neurodegeneration. In mouse models, inflammatory activation of microglia accelerates tau pathology. The chemokine fractalkine serves as an endogenous neuronal modulator to quell microglial activation. Experiments with fractalkine receptor null mice suggest that fractalkine signaling diminishes tau pathology, but exacerbates amyloid pathology. Consistent with this outcome, we report here that soluble fractalkine overexpression using adeno-associated viral vectors significantly reduced tau pathology in the rTg4510 mouse model of tau deposition. Furthermore, this treatment reduced microglial activation and appeared to prevent neurodegeneration normally found in this model. However, in contrast to studies with fractalkine receptor null mice, parallel studies in an APP/PS1 model found no effect of increased fractalkine signaling on amyloid deposition. These data argue that agonism at fractalkine receptors might be an excellent target for therapeutic intervention in tauopathies, including those associated with amyloid deposition. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Pathological Buying Online as a Specific Form of Internet Addiction: A Model-Based Experimental Investigation

    OpenAIRE

    Trotzke, Patrick; Starcke, Katrin; M?ller, Astrid; Brand, Matthias

    2015-01-01

    The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior,...

  8. Experimental tumour treatment

    International Nuclear Information System (INIS)

    1985-08-01

    This report of 1984 is the seventh in a series and presents that year's results of continuous studies in the domain of experimental tumour radiotherapy. In the year under review, more personnel has been available for the studies, and the scientific programmes for the assessment of acute and chronic side effects of radiotherapies have been extended. New models have been developed, among them a first system based on animal experiments, for quantifying the mucositis of the oral and pharyngeal mucosa, a limiting condition in the radiotherapy of head and throat tumours. Another significant advancement is a model for quantification of chronical damage to the ureter, which still is a serious problem in the radiotherapy of gynaecological tumours. The 1984 experimental tumour studies have been mainly devoted to the repopulation and split-dose recovery in various tumours, concentrating on dose fractionation as one of the major problems studies. Particular interest has been attached to the processes involved in treatments over several weeks with a daily effective dose of 2 Gy. (orig./MG) [de

  9. Pathology of Rodent Models of Intestinal Cancer: Progress Report and Recommendations

    Science.gov (United States)

    Washington, Mary Kay; Powell, Anne E.; Sullivan, Ruth; Sundberg, John; Wright, Nicholas; Coffey, Robert J.; Dove, William F.

    2013-01-01

    In October 2010, a pathology review of rodent models of intestinal neoplasia was held at The Jackson Laboratory. This review complemented 2 other concurrent events: a workshop on methods of modeling colon cancer in rodents and a conference on current issues in murine and human colon cancer. We summarize the results of the pathology review and the committee’s recommendations for tumor nomenclature. A virtual high-resolution image slide box of these models has been developed. This report discusses significant recent developments in rodent modeling of intestinal neoplasia, including the role of stem cells in cancer and the creation of models of metastatic intestinal cancer. PMID:23415801

  10. Development of pathological anthropomorphic models using 3D modelling techniques for numerical dosimetry

    International Nuclear Information System (INIS)

    Costa, Kleber Souza Silva; Barbosa, Antonio Konrado de Santana; Vieira, Jose Wilson; Lima, Fernando Roberto de Andrade

    2011-01-01

    Computational exposure models can be used to estimate human body absorbed dose in a series of situations such as X-Ray exams for diagnosis, accidents and medical treatments. These models are fundamentally composed of an anthropomorphic simulator (phantom), an algorithm that simulates a radioactive source and a Monte Carlo Code. The accuracy of data obtained in the simulation is strongly connected to the adequacy of such simulation to the real situation. The phantoms are one of the key factors for the researcher manipulation. They are generally developed in supine position and its anatomy is patronized by compiled data from international institutions such as ICRP or ICRU. Several pathologies modify the structure of organs and body tissues. In order to measure how significant these alterations are, an anthropomorphic model was developed for this study: patient mastectomies. This model was developed using voxel phantom FASH and then coupled with EGSnrc Monte Carlo code

  11. The role of choline (Cho) in the diagnostics and differentiation of brain tumours with HMRS technique

    International Nuclear Information System (INIS)

    Sobiecka, B.; Urbanik, A.

    2009-01-01

    Background: The aim of the research was a comprehensive analysis of Cho concentration and Cho/Cr, NAA/Cho, NAA/Cho+Cr ratios for the purposes of the diagnostics and differentiation of brain tumours (the type of the pathological lesion in patients with brain tumours) with the use of HMRS technique. Material/Methods: The HMRS examinations were performed with the use of the MRI Signa Excite 1.5 T system, in PRESS technique (TR = 1500 ms, TE = 35 ms) and involved 100 patients with brain tumours (age range: 18 to 81 yrs, mean age 50.61). Spectra were taken from three different locations: tumour centre, the tumour edge and contralateral unchanged cerebral tissue. All patients underwent surgery followed by histopathological analysis, on the basis of which two groups were separated (benign tumours, malignant tumours - 50 cases each). Additionally, 30 healthy volunteers in the age of 20 to 79 years (mean age 40.8) were examined. Results: The comparison of the examined patients with the control group revealed significantly higher Cho concentrations in patients with brain tumours. The analysis of Cho concentration was also performed with consideration of the age factor (under and over 60 years of age). Significantly lower mean Cho concentrations were discovered in a group of patients under 60 years of age. The analysis of Cho concentrations and Cho/Cr ratios reveled statistical significance for two factors: voxel location factor and the type of the pathological lesion. The average of Cho concentration and Cho/Cr ratios were higher in the group of patients with malignant tumours. The highest Cho concentrations and Cho/Cr ratios were observed in the tumour centre. The relative NAA/Cho and NAA/Cho+Cr ratios were statistically significant when taking into consideration the voxel location factor only. The results received from contralateral normal cerebral tissue (the internal model) were compared with control group (the external model). Mean values of Cho concentration were

  12. [Historic malignant tumour: 27 observations].

    Science.gov (United States)

    Sparsa, A; Doffoel-Hantz, V; Durox, H; Gaston, J; Delage-Core, M; Bédane, C; Labrousse, F; Sannajust, J P; Bonnetblanc, J-M

    2012-03-01

    When used in the French medical literature to describe a pathological state, the word "historic" normally refers to tumours of startling appearance because of their size. It is difficult to understand how a patient can allow such tumours to continue to grow. We attempt to define this concept. Two dermatologists carried out a retrospective, independent and comparative selection of photographs taken between 1978 and 2008 of malignant cutaneous tumours of unusual size given the histological diagnosis. Socio-professional, demographic, clinical, histological psychological data, and details of treatment history and progress were collected. Twenty-seven patients (11 M, 16 F) of mean age 74 years (34-99 years) presented a "historic" tumour. Twelve patients lived in rural regions. Five patients were company executives. The average duration of development of the "historic" tumours was 4.5 years (6-420 months). The tumours were classed histologically as epidermoid carcinomas (nine) and melanomas (seven). The mean size was 13 cm (6-30 cm). Psychiatric problems, membership of sects or dementia were noted for 13 patients. Treatment consisted of chemotherapy, radiotherapy or, less frequently, surgery. Eighteen patients died on average 13 months after diagnosis. "Historic" malignant tumour (also described in the literature as "giant" tumour) is a real-life fact. No studies have been made of a series of such patients. Despite histological diagnosis, the size was associated with slow tumoral progress and/or late treatment, chiefly accounted for by psychiatric disorders. Socio-professional data indicate that "historic" tumours are equally common in urban and rural areas. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  13. Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology.

    Science.gov (United States)

    Belarbi, Karim; Burnouf, Sylvie; Fernandez-Gomez, Francisco-Jose; Laurent, Cyril; Lestavel, Sophie; Figeac, Martin; Sultan, Audrey; Troquier, Laetitia; Leboucher, Antoine; Caillierez, Raphaëlle; Grosjean, Marie-Eve; Demeyer, Dominique; Obriot, Hélène; Brion, Ingrid; Barbot, Bérangère; Galas, Marie-Christine; Staels, Bart; Humez, Sandrine; Sergeant, Nicolas; Schraen-Maschke, Susanna; Muhr-Tailleux, Anne; Hamdane, Malika; Buée, Luc; Blum, David

    2011-08-01

    Tau pathology is encountered in many neurodegenerative disorders known as tauopathies, including Alzheimer's disease. Physical activity is a lifestyle factor affecting processes crucial for memory and synaptic plasticity. Whether long-term voluntary exercise has an impact on Tau pathology and its pathophysiological consequences is currently unknown. To address this question, we investigated the effects of long-term voluntary exercise in the THY-Tau22 transgenic model of Alzheimer's disease-like Tau pathology, characterized by the progressive development of Tau pathology, cholinergic alterations and subsequent memory impairments. Three-month-old THY-Tau22 mice and wild-type littermates were assigned to standard housing or housing supplemented with a running wheel. After 9 months of exercise, mice were evaluated for memory performance and examined for hippocampal Tau pathology, cholinergic defects, inflammation and genes related to cholesterol metabolism. Exercise prevented memory alterations in THY-Tau22 mice. This was accompanied by a decrease in hippocampal Tau pathology and a prevention of the loss of expression of choline acetyltransferase within the medial septum. Whereas the expression of most cholesterol-related genes remained unchanged in the hippocampus of running THY-Tau22 mice, we observed a significant upregulation in mRNA levels of NPC1 and NPC2, genes involved in cholesterol trafficking from the lysosomes. Our data support the view that long-term voluntary physical exercise is an effective strategy capable of mitigating Tau pathology and its pathophysiological consequences. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Directory of Open Access Journals (Sweden)

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  15. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Science.gov (United States)

    Gobin, Bérengère; Moriceau, Gatien; Ory, Benjamin; Charrier, Céline; Brion, Régis; Blanchard, Frederic; Redini, Françoise; Heymann, Dominique

    2014-01-01

    Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma), a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1). Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma) and POS-1 (undifferentiated osteosarcoma). Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R), appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor status of patients.

  16. Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences

    Directory of Open Access Journals (Sweden)

    Gillian M. Lavelle

    2016-01-01

    Full Text Available Cystic fibrosis (CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF.

  17. Role of tumour associated macrophages in tumour angiogenesis and lymphangiogenesis

    Directory of Open Access Journals (Sweden)

    Julia eKzhyshkowska

    2014-03-01

    Full Text Available Tumour angiogenesis is an essential process for supplying rapidly growing malignant tissues with essential nutrients and oxygen. An angiogenic switch allows tumour cells to survive and grow, and provides them access to vasculature resulting in metastatic disease. Monocyte-derived macrophages recruited and reprogrammed by tumour cells serve as a major source of angiogenic factors boosting the angiogenic switch. Tumour endothelium releases angiopoietin-2 and further facilitates recruitment of TIE2 receptor expressing monocytes (TEM into tumor sites. Tumour-associated macrophages (TAM sense hypoxia in avascular areas of tumours, and react by production of angiogenic factors such as VEGFA. VEGFA stimulates chemotaxis of endothelial cells (EC and macrophages. In some tumours, TAM appeared to be a major source of MMP9. Elevated expression of MMP9 by TAM mediates extracellular matrix degradation and the release of bioactive VEGFA. Other angiogenic factors released by TAM include bFGF, thymidine phosphorylase (TP, urokinase-type plasminogen activator (uPA, and adrenomedullin. The same factors used by macrophages for the induction of angiogenesis (like VEGF-A and MMP9 support lymphangiogenesis. TAM can express LYVE-1, one of the established markers of lymphatic endothelium. TAM support tumour lymphangiogenesis not only by secretion of pro-lymphangiogenic factors but also by trans-differentiation into lymphatic EC. New pro-angiogenic factor YKL-40 belongs to a family of mammalian chitinase-like proteins (CLP that act as cytokines or growth factors. Human CLP family comprises YKL-40, YKL-39 and SI-CLP. Production of all three CLP in macrophages is antagonistically regulated by cytokines. It was recently established that YKL-40 induces angiogenesis in vitro and in animal tumour models. YKL-40-neutralizing monoclonal antibody blocks tumour angiogenesis and progression. The role of YKL-39 and SI-CLP in tumour angiogenesis and lymphangiogenesis remains to be

  18. Comparing Dimensional Models Assessing Personality Traits and Personality Pathology Among Adult ADHD and Borderline Personality Disorder.

    Science.gov (United States)

    Koerting, Johanna; Pukrop, Ralf; Klein, Philipp; Ritter, Kathrin; Knowles, Mark; Banzhaf, Anke; Gentschow, Laura; Vater, Aline; Heuser, Isabella; Colla, Michael; Roepke, Stefan

    2016-08-01

    This pilot study was a comparison of dimensional models assessing personality traits and personality pathology in a clinical sample of adults diagnosed with ADHD and adults diagnosed with borderline personality disorder (BPD), and a nonclinical control sample of healthy adults. Personality traits were assessed using the NEO-Personality Inventory-Revised (NEO-PI-R) and dimensional personality pathology with the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ). Adults with ADHD and BPD produced higher Emotional Dysregulation/Neuroticism and Dissocial Behavior scores than controls. For the Extraversion/Inhibitedness scale, adults with BPD produced significantly lower scores than adults with ADHD and controls. On the Conscientiousness/Compulsivity domains, Conscientiousness scores were lower for both disorders, whereas low Compulsivity values were specific to adult ADHD. Our results suggest that patients with adult ADHD and BPD have distinguishable profiles of personality traits and personality pathology. © The Author(s) 2012.

  19. Yeast models of Parkinson's disease-associated molecular pathologies.

    Science.gov (United States)

    Tenreiro, Sandra; Franssens, Vanessa; Winderickx, Joris; Outeiro, Tiago Fleming

    2017-06-01

    The aging of the human population is resulting in an increase in the number of people afflicted by neurodegenerative disorders such as Parkinson's disease (PD), creating tremendous socio-economic challenges. This requires the urgent for the development of effective therapies, and of tools for early diagnosis of the disease. However, our understanding of the molecular mechanisms underlying PD pathogenesis is still incomplete, hampering progress in those areas. In recent years, the progression made in genetics has considerably contributed to our knowledge, by identifying several novel PD genes. Furthermore, many cellular and animal models have proven their value to decipher pathways involved in PD development. In this review we highlight the value of the yeast Saccharomyces cerevisiae as a model for PD. This unicellular eukaryote has contributed to our understanding of the cellular mechanisms targeted by most important PD genes and offers an excellent tool for discovering novel players via powerful and informative high throughput screens that accelerate further validation in more complex models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models.

    Directory of Open Access Journals (Sweden)

    Mohamed A Alfaleh

    Full Text Available Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Therefore, increasing the selectivity of anti-cancer agents has the potential to dramatically enhance drug efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs which target the EDV and a cancer cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN. Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize within mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.

  1. The risk factors of laryngeal pathology in Korean adults using a decision tree model.

    Science.gov (United States)

    Byeon, Haewon

    2015-01-01

    The purpose of this study was to identify risk factors affecting laryngeal pathology in the Korean population and to evaluate the derived prediction model. Cross-sectional study. Data were drawn from the 2008 Korea National Health and Nutritional Examination Survey. The subjects were 3135 persons (1508 male and 2114 female) aged 19 years and older living in the community. The independent variables were age, sex, occupation, smoking, alcohol drinking, and self-reported voice problems. A decision tree analysis was done to identify risk factors for predicting a model of laryngeal pathology. The significant risk factors of laryngeal pathology were age, gender, occupation, smoking, and self-reported voice problem in decision tree model. Four significant paths were identified in the decision tree model for the prediction of laryngeal pathology. Those identified as high risk groups for laryngeal pathology included those who self-reported a voice problem, those who were males in their 50s who did not recognize a voice problem, those who were not economically active males in their 40s, and male workers aged 19 and over and under 50 or 60 and over who currently smoked. The results of this study suggest that individual risk factors, such as age, sex, occupation, health behavior, and self-reported voice problem, affect the onset of laryngeal pathology in a complex manner. Based on the results of this study, early management of the high-risk groups is needed for the prevention of laryngeal pathology. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  2. Hendra and Nipah Infection: Pathology, Models and Potential Therapies

    Science.gov (United States)

    Vigant, Frederic; Lee, Benhur

    2011-01-01

    The Paramyxoviridae family comprises of several genera that contain emerging or re-emerging threats for human and animal health with no real specific effective treatment available. Hendra and Nipah virus are members of a newly identified genus of emerging paramyxoviruses, Henipavirus. Since their discovery in the 1990s, henipaviruses outbreaks have been associated with high economic and public health threat potential. When compared to other paramyxoviruses, henipaviruses appear to have unique characteristics. Henipaviruses are zoonotic paramyxoviruses with a broader tropism than most other paramyxoviruses, and can cause severe acute encephalitis with unique features among viral encephalitides. There are currently no approved effective prophylactic or therapeutic treatments for henipavirus infections. Although ribavirin was empirically used and seemed beneficial during the biggest outbreak caused by one of these viruses, the Nipah virus, its efficacy is disputed in light of its lack of efficacy in several animal models of henipavirus infection. Nevertheless, because of its highly pathogenic nature, much effort has been spent in developing anti-henipavirus therapeutics. In this review we describe the unique features of henipavirus infections and the different strategies and animal models that have been developed so far in order to identify and test potential drugs to prevent or treat henipavirus infections. Some of these components have the potential to be broad-spectrum antivirals as they target effectors of viral pathogenecity common to other viruses. We will focus on small molecules or biologics, rather than vaccine strategies, that have been developed as anti-henipaviral therapeutics. PMID:21488828

  3. Oxygen Distributions-Evaluation of Computational Methods, Using a Stochastic Model for Large Tumour Vasculature, to Elucidate the Importance of Considering a Complete Vascular Network.

    Directory of Open Access Journals (Sweden)

    Jakob H Lagerlöf

    Full Text Available To develop a general model that utilises a stochastic method to generate a vessel tree based on experimental data, and an associated irregular, macroscopic tumour. These will be used to evaluate two different methods for computing oxygen distribution.A vessel tree structure, and an associated tumour of 127 cm3, were generated, using a stochastic method and Bresenham's line algorithm to develop trees on two different scales and fusing them together. The vessel dimensions were adjusted through convolution and thresholding and each vessel voxel was assigned an oxygen value. Diffusion and consumption were modelled using a Green's function approach together with Michaelis-Menten kinetics. The computations were performed using a combined tree method (CTM and an individual tree method (ITM. Five tumour sub-sections were compared, to evaluate the methods.The oxygen distributions of the same tissue samples, using different methods of computation, were considerably less similar (root mean square deviation, RMSD≈0.02 than the distributions of different samples using CTM (0.001< RMSD<0.01. The deviations of ITM from CTM increase with lower oxygen values, resulting in ITM severely underestimating the level of hypoxia in the tumour. Kolmogorov Smirnov (KS tests showed that millimetre-scale samples may not represent the whole.The stochastic model managed to capture the heterogeneous nature of hypoxic fractions and, even though the simplified computation did not considerably alter the oxygen distribution, it leads to an evident underestimation of tumour hypoxia, and thereby radioresistance. For a trustworthy computation of tumour oxygenation, the interaction between adjacent microvessel trees must not be neglected, why evaluation should be made using high resolution and the CTM, applied to the entire tumour.

  4. Distinctive serum miRNA profile in mouse models of striated muscular pathologies.

    Directory of Open Access Journals (Sweden)

    Nicolas Vignier

    Full Text Available Biomarkers are critically important for disease diagnosis and monitoring. In particular, close monitoring of disease evolution is eminently required for the evaluation of therapeutic treatments. Classical monitoring methods in muscular dystrophies are largely based on histological and molecular analyses of muscle biopsies. Such biopsies are invasive and therefore difficult to obtain. The serum protein creatine kinase is a useful biomarker, which is however not specific for a given pathology and correlates poorly with the severity or course of the muscular pathology. The aim of the present study was the systematic evaluation of serum microRNAs (miRNAs as biomarkers in striated muscle pathologies. Mouse models for five striated muscle pathologies were investigated: Duchenne muscular dystrophy (DMD, limb-girdle muscular dystrophy type 2D (LGMD2D, limb-girdle muscular dystrophy type 2C (LGMD2C, Emery-Dreifuss muscular dystrophy (EDMD and hypertrophic cardiomyopathy (HCM. Two-step RT-qPCR methodology was elaborated, using two different RT-qPCR miRNA quantification technologies. We identified miRNA modulation in the serum of all the five mouse models. The most highly dysregulated serum miRNAs were found to be commonly upregulated in DMD, LGMD2D and LGMD2C mouse models, which all exhibit massive destruction of striated muscle tissues. Some of these miRNAs were down rather than upregulated in the EDMD mice, a model without massive myofiber destruction. The dysregulated miRNAs identified in the HCM model were different, with the exception of one dysregulated miRNA common to all pathologies. Importantly, a specific and distinctive circulating miRNA profile was identified for each studied pathological mouse model. The differential expression of a few dysregulated miRNAs in the DMD mice was further evaluated in DMD patients, providing new candidates of circulating miRNA biomarkers for DMD.

  5. A novel animal model of thymic tumour: Development of epithelial thymoma in transgenic rats carrying human T lymphocyte virus type I pX gene

    Science.gov (United States)

    Kikuchi, Kazunori; Ikeda, Hitoshi; Tsuchikawa, Takahiro; Tsuji, Takahiro; Tanaka, Satoshi; Fugo, Kazunori; Sugaya, Toshiaki; Tanaka, Yuetsu; Tateno, Masatoshi; Maruyama, Naoki; Yoshiki, Takashi

    2002-01-01

    The pX region encodes a major product of human T lymphocyte virus type I (HTLV-I) that has been implicated previously in tumour formation. To investigate the pathogenesis of pX gene in lymphoid tissues, we established a series of novel transgenic rats carrying the pX gene under the control of a rat lymphocyte-specific protein tyrosine kinase (p56lck) proximal promoter. The transgene was constructed with the −269 to +26 region of a rat p56lck proximal promoter and the pX cDNA, and was microinjected into fertilized ova of Fischer 344/jcl female rats. Six transgenic lines from 114 pups were established. Integration and expression of the transgene were detected by polymerase chain reaction (PCR) and Southern hybridization or by reverse transcriptase-PCR, northern hybridization, and immunostaining.  Thymic tumours with lethal expansion occurred in 4 of 6 transgenic lines. The tumour consisted of spindle shaped cells. Immunohistochemical and ultra-structural analysis characterized the tumour cells to as epithelial cell type, and in the tumour arose in the medulla. Therefore, the tumour is classified into predominantly epithelial and spindle cell of medullary thymoma (type A of the new World Health Organization classification), as based on the human classification. Tumor occurrence increased in proportion to levels of the pX transcription in the thymus, for each line, and sex distinction was evident regarding rates related to tumour expansion. The transgenic rat model described here is suitable as a model for analysing tumorigenesis in epithelial thymoma occurring in humans. PMID:12641821

  6. Integrated Case-Based Applied Pathology (ICAP): a diagnostic-approach model for the learning and teaching of veterinary pathology.

    Science.gov (United States)

    Krockenberger, Mark B; Bosward, Katrina L; Canfield, Paul J

    2007-01-01

    Integrative Case-Based Applied Pathology (ICAP) cases form one component of learning and understanding the role of pathology in the veterinary diagnostic process at the Faculty of Veterinary Science, University of Sydney. It is a strategy that focuses on student-centered learning in a problem-solving context in the year 3 curriculum. Learning exercises use real case material and are primarily delivered online, providing flexibility for students with differing learning needs, who are supported by online, peer, and tutor support. The strategy relies heavily on the integration of pre-clinical and para-clinical information with the introduction of clinical material for the purposes of a logical three-level, problem-oriented approach to the diagnosis of disease. The focus is on logical diagnostic problem solving, primarily using gross pathology and histopathological material, with the inclusion of microbiological, parasitological, and clinical pathological data. The ICAP approach is linked to and congruent with the problem-oriented approach adopted in veterinary medicine and the case-based format used by one of the authors (PJC) for the teaching and learning of veterinary clinical pathology in year 4. Additionally, final-year students have the opportunity, during a diagnostic pathology rotation, to assist in the development and refinement of further ICAPs, which reinforces the importance of pathology in the veterinary diagnostic process. Evidence of the impact of the ICAP approach, based primarily on student surveys and staff peer feedback collected over five years, shows that discipline-specific learning, vertical and horizontal integration, alignment of learning outcomes and assessment, and both veterinary and generic graduate attributes were enhanced. Areas for improvement were identified in the approach, most specifically related to assistance in the development of generic teamwork skills.

  7. Gastric Calcifying Fibrous Tumour

    Directory of Open Access Journals (Sweden)

    Tan Attila

    2006-01-01

    Full Text Available Intramucosal gastric tumours are most commonly found to be gastrointestinal stromal tumours or leiomyomas (smooth muscle tumours; however, a variety of other uncommon mesenchymal tumours can occur in the stomach wall. A rare benign calcifying fibrous tumour is reported and the endoscopic appearance, ultrasound findings and morphology are documented. A review of the literature found only two similar cases.

  8. Toluidine blue O modifies hippocampal amyloid pathology in a transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Yuksel, Melike; Biberoglu, Kevser; Onder, Seda; Akbulut, K Gonca; Tacal, Ozden

    2018-03-01

    Recently, we have demonstrated that toluidine blue O (TBO), a phenothiazine dye, shows inhibitory effects on both cholinesterases and amyloid pathology in Alzheimer's disease (AD) cellular model. In the present study, we aimed to determine the effects of TBO (in a purity of 85%) on amyloid and tau pathologies in a triple transgenic mouse model of AD (3xTg-AD). Beginning at 7.5 (mild pathology) or 13 (severe pathology) months of age, 3xTg-AD mice were treated intraperitoneally with 4 mg/kg TBO or vehicle daily for 30 days. TBO treatment significantly reduced the levels of insoluble Aβ40 and Aβ42 in the hippocampi of mild and severe pathology groups compared to vehicle-treated counterparts. When the levels of full-length amyloid precursor protein (APP) and β-site APP-cleaving enzyme 1 (BACE1) were assessed in 3xTg-AD mice at late pathological stage, no significant changes were observed after TBO treatment. Similarly, TBO did not recover hyperphosphorylation of tau at residues Thr181 and Ser202/Thr205 significantly in soluble and insoluble hippocampal fractions of 3xTg-AD mice. Taken together, the current study is the first in vivo report, to our knowledge, demonstrating that TBO mitigates amyloid pathology in 3xTg-AD mice with no apparent change on tau phosphorylation. Overall, the preliminary data presented here support the possible use of TBO as a disease-modifying drug for AD treatment. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  9. Diabetes Mellitus Induces Alzheimer’s Disease Pathology: Histopathological Evidence from Animal Models

    Directory of Open Access Journals (Sweden)

    Nobuyuki Kimura

    2016-04-01

    Full Text Available Alzheimer’s disease (AD is the major causative disease of dementia and is characterized pathologically by the accumulation of senile plaques (SPs and neurofibrillary tangles (NFTs in the brain. Although genetic studies show that β-amyloid protein (Aβ, the major component of SPs, is the key factor underlying AD pathogenesis, it remains unclear why advanced age often leads to AD. Interestingly, several epidemiological and clinical studies show that type II diabetes mellitus (DM patients are more likely to exhibit increased susceptibility to AD. Moreover, growing evidence suggests that there are several connections between the neuropathology that underlies AD and DM, and there is evidence that the experimental induction of DM can cause cognitive dysfunction, even in rodent animal models. This mini-review summarizes histopathological evidence that DM induces AD pathology in animal models and discusses the possibility that aberrant insulin signaling is a key factor in the induction of AD pathology.

  10. Functional and molecular characterisation of EO771.LMB tumours, a new C57BL/6-mouse-derived model of spontaneously metastatic mammary cancer

    Directory of Open Access Journals (Sweden)

    Cameron N. Johnstone

    2015-03-01

    Full Text Available The translation of basic research into improved therapies for breast cancer patients requires relevant preclinical models that incorporate spontaneous metastasis. We have completed a functional and molecular characterisation of a new isogenic C57BL/6 mouse model of breast cancer metastasis, comparing and contrasting it with the established BALB/c 4T1 model. Metastatic EO771.LMB tumours were derived from poorly metastatic parental EO771 mammary tumours. Functional differences were evaluated using both in vitro assays and spontaneous metastasis assays in mice. Results were compared to non-metastatic 67NR and metastatic 4T1.2 tumours of the 4T1 model. Protein and transcript levels of markers of human breast cancer molecular subtypes were measured in the four tumour lines, as well as p53 (Tp53 tumour-suppressor gene status and responses to tamoxifen in vivo and in vitro. Array-based expression profiling of whole tumours identified genes and pathways that were deregulated in metastatic tumours. EO771.LMB cells metastasised spontaneously to lung in C57BL/6 mice and displayed increased invasive capacity compared with parental EO771. By immunohistochemical assessment, EO771 and EO771.LMB were basal-like, as was the 4T1.2 tumour, whereas 67NR had a luminal phenotype. Primary tumours from all lines were negative for progesterone receptor, Erb-b2/Neu and cytokeratin 5/6, but positive for epidermal growth factor receptor (EGFR. Only 67NR displayed nuclear estrogen receptor alpha (ERα positivity. EO771 and EO771.LMB expressed mutant p53, whereas 67NR and 4T1.2 were p53-null. Integrated molecular analysis of both the EO771/EO771.LMB and 67NR/4T1.2 pairs indicated that upregulation of matrix metalloproteinase-3 (MMP-3, parathyroid hormone-like hormone (Pthlh and S100 calcium binding protein A8 (S100a8 and downregulation of the thrombospondin receptor (Cd36 might be causally involved in metastatic dissemination of breast cancer.

  11. Targeted radionuclide therapy with RAFT-RGD radiolabelled with {sup 90}Y or {sup 177}Lu in a mouse model of αvβ3-expressing tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bozon-Petitprin, A.; Bacot, S.; Ahmadi, M.; Marti-Batlle, D.; Perret, P.; Broisat, A.; Riou, L.M. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); Gauchez, A.S.; Bourre, J.C.; Fagret, D.; Vuillez, J.P. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); CHRU Grenoble, Hopital Michallon, Service de Medecine Nucleaire, Grenoble (France); Claron, M.; Boturyn, D. [CNRS, UMR 5250, Departement de Chimie Moleculaire, Grenoble (France); Ghezzi, Catherine [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); INSERM U1039, Radiopharmaceutiques biocliniques, Batiment Jean Roget, Domaine de la Merci, Faculte de Medecine, La Tronche (France)

    2014-08-28

    The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK]){sub 4} (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β{sup -} emitters in a nude mouse model of αvβ3 integrin-expressing tumours. Biodistribution and SPECT/CT imaging studies were performed after injection of {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD and {sup 90}Y-RAFT-RAD or {sup 177}Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. Injection of 37 MBq of {sup 90}Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of {sup 177}Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of {sup 90}Y-RAFT-RAD or 37 MBq of {sup 177}Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of {sup 90}Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours. {sup 90}Y-RAFT-RGD and {sup 177}Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy. (orig.)

  12. Accelerated microglial pathology is associated with Aβ plaques in mouse models of Alzheimer's disease

    DEFF Research Database (Denmark)

    Baron, Rona; Babcock, Alicia A; Nemirovsky, Anna

    2014-01-01

    with a chronic proinflammatory reaction in the brain, aging causes a significant reduction in the capacity of microglia to scan their environment. This type of pathology is markedly accelerated in mouse models of AD, resulting in a severe microglial process deficiency, and possibly contributing to enhanced...... cognitive decline....

  13. Identification of imaging biomarkers for the assessment of tumour response to different treatments in a preclinical glioma model

    Energy Technology Data Exchange (ETDEWEB)

    Lo Dico, A.; Martelli, C. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); University of Milan, Centre of Molecular and Cellular Imaging-IMAGO, Milan (Italy); Valtorta, S.; Belloli, S. [National Researches Council (CNR), Institute of Molecular Bioimaging and Physiology (IBFM), Segrate, MI (Italy); IRCCS San Raffaele Scientific Institute, Experimental Imaging Center, Milan (Italy); Raccagni, I.; Moresco, R.M. [IRCCS San Raffaele Scientific Institute, Experimental Imaging Center, Milan (Italy); University of Milano-Bicocca, Department of Health Sciences, Monza (Italy); Diceglie, C. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); University of Milan, Doctorate School of Molecular Medicine, Milan (Italy); Gianelli, U.; Bosari, S. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Division of Pathology, Milan (Italy); Vaira, V. [Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Division of Pathology, Milan (Italy); Istituto Nazionale Genetica Molecolare ' ' Romeo ed Enrica Invernizzi' ' (INGM), Milan (Italy); Politi, L.S. [IRCCS San Raffaele Scientific Institute, Neuroradiology Department and Neuroradiology Research Group, Milan (Italy); Lucignani, G. [University of Milan, Centre of Molecular and Cellular Imaging-IMAGO, Milan (Italy); University of Milan, Department of Health Sciences, Milan (Italy); San Paolo Hospital, Department of Diagnostic Services, Unit of Nuclear Medicine, Milan (Italy); Ottobrini, L. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); University of Milan, Centre of Molecular and Cellular Imaging-IMAGO, Milan (Italy); National Researches Council (CNR), Institute of Molecular Bioimaging and Physiology (IBFM), Segrate, MI (Italy)

    2015-03-27

    Hypoxia-inducible factor 1α (HIF-1α) activity is one of the major players in hypoxia-mediated glioma progression and resistance to therapies, and therefore the focus of this study was the evaluation of HIF-1α modulation in relation to tumour response with the purpose of identifying imaging biomarkers able to document tumour response to treatment in a murine glioma model. U251-HRE-mCherry cells expressing Luciferase under the control of a hypoxia responsive element (HRE) and mCherry under the control of a constitutive promoter were used to assess HIF-1α activity and cell survival after treatment, both in vitro and in vivo, by optical, MRI and positron emission tomography imaging. This cell model can be used to monitor HIF-1α activity after treatment with different drugs modulating transduction pathways involved in its regulation. After temozolomide (TMZ) treatment, HIF-1α activity is early reduced, preceding cell cytotoxicity. Optical imaging allowed monitoring of this process in vivo, and carbonic anhydrase IX (CAIX) expression was identified as a translatable non-invasive biomarker with potential clinical significance. A preliminary in vitro evaluation showed that reduction of HIF-1α activity after TMZ treatment was comparable to the effect of an Hsp90 inhibitor, opening the way for further elucidation of its mechanism of action. The results of this study suggest that the U251-HRE-mCherry cell model can be used for the monitoring of HIF-1α activity through luciferase and CAIX expression. These cells can become a useful tool for the assessment and improvement of new targeted tracers for potential theranostic procedures. (orig.)

  14. Impulsivity, self-regulation,and pathological video gaming among youth: testing a mediation model.

    Science.gov (United States)

    Liau, Albert K; Neo, Eng Chuan; Gentile, Douglas A; Choo, Hyekyung; Sim, Timothy; Li, Dongdong; Khoo, Angeline

    2015-03-01

    Given the potential negative mental health consequences of pathological video gaming, understanding its etiology may lead to useful treatment developments. The purpose of the study was to examine the influence of impulsive and regulatory processes on pathological video gaming. Study 1 involved 2154 students from 6 primary and 4 secondary schools in Singapore. Study 2 involved 191 students from 2 secondary schools. The results of study 1 and study 2 supported the hypothesis that self-regulation is a mediator between impulsivity and pathological video gaming. Specifically, higher levels of impulsivity was related to lower levels of self-regulation, which in turn was related to higher levels of pathological video gaming. The use of impulsivity and self-regulation in predicting pathological video gaming supports the dual-system model of incorporating both impulsive and reflective systems in the prediction of self-control outcomes. The study highlights the development of self-regulatory resources as a possible avenue for future prevention and treatment research. © 2011 APJPH.

  15. Coarse-graining and hybrid methods for efficient simulation of stochastic multi-scale models of tumour growth

    Science.gov (United States)

    de la Cruz, Roberto; Guerrero, Pilar; Calvo, Juan; Alarcón, Tomás

    2017-12-01

    The development of hybrid methodologies is of current interest in both multi-scale modelling and stochastic reaction-diffusion systems regarding their applications to biology. We formulate a hybrid method for stochastic multi-scale models of cells populations that extends the remit of existing hybrid methods for reaction-diffusion systems. Such method is developed for a stochastic multi-scale model of tumour growth, i.e. population-dynamical models which account for the effects of intrinsic noise affecting both the number of cells and the intracellular dynamics. In order to formulate this method, we develop a coarse-grained approximation for both the full stochastic model and its mean-field limit. Such approximation involves averaging out the age-structure (which accounts for the multi-scale nature of the model) by assuming that the age distribution of the population settles onto equilibrium very fast. We then couple the coarse-grained mean-field model to the full stochastic multi-scale model. By doing so, within the mean-field region, we are neglecting noise in both cell numbers (population) and their birth rates (structure). This implies that, in addition to the issues that arise in stochastic-reaction diffusion systems, we need to account for the age-structure of the population when attempting to couple both descriptions. We exploit our coarse-graining model so that, within the mean-field region, the age-distribution is in equilibrium and we know its explicit form. This allows us to couple both domains consistently, as upon transference of cells from the mean-field to the stochastic region, we sample the equilibrium age distribution. Furthermore, our method allows us to investigate the effects of intracellular noise, i.e. fluctuations of the birth rate, on collective properties such as travelling wave velocity. We show that the combination of population and birth-rate noise gives rise to large fluctuations of the birth rate in the region at the leading edge of

  16. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    Science.gov (United States)

    Williams, Jonathan M.

    2017-01-01

    ABSTRACT Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. PMID:28151409

  17. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

    Directory of Open Access Journals (Sweden)

    Michael D. Burkitt

    2017-02-01

    Full Text Available Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems.

  18. Pairwise mixture model for unmixing partial volume effect in multi-voxel MR spectroscopy of brain tumour patients

    Science.gov (United States)

    Olliverre, Nathan; Asad, Muhammad; Yang, Guang; Howe, Franklyn; Slabaugh, Gregory

    2017-03-01

    Multi-Voxel Magnetic Resonance Spectroscopy (MV-MRS) provides an important and insightful technique for the examination of the chemical composition of brain tissue, making it an attractive medical imaging modality for the examination of brain tumours. MRS, however, is affected by the issue of the Partial Volume Effect (PVE), where the signals of multiple tissue types can be found within a single voxel and provides an obstacle to the interpretation of the data. The PVE results from the low resolution achieved in MV-MRS images relating to the signal to noise ratio (SNR). To counteract PVE, this paper proposes a novel Pairwise Mixture Model (PMM), that extends a recently reported Signal Mixture Model (SMM) for representing the MV-MRS signal as normal, low or high grade tissue types. Inspired by Conditional Random Field (CRF) and its continuous variant the PMM incorporates the surrounding voxel neighbourhood into an optimisation problem, the solution of which provides an estimation to a set of coefficients. The values of the estimated coefficients represents the amount of each tissue type (normal, low or high) found within a voxel. These coefficients can then be visualised as a nosological rendering using a coloured grid representing the MV-MRS image overlaid on top of a structural image, such as a Magnetic Resonance Image (MRI). Experimental results show an accuracy of 92.69% in classifying patient tumours as either low or high grade compared against the histopathology for each patient. Compared to 91.96% achieved by the SMM, the proposed PMM method demonstrates the importance of incorporating spatial coherence into the estimation as well as its potential clinical usage.

  19. [Mediastinal pathology: pathological treatment of frozen section].

    Science.gov (United States)

    Saint-Blancard, P; Jancovici, R

    2010-10-01

    Tumoral pathology of the mediastinum is extremely varied, with different prognoses and treatments. The pathological examination is essential, both etiologically and prognostically. Mediastinoscopy is generally used to check for lymph node metastases, bronchopulmonary carcinoma, but also, to a lesser degree, for the exploration of isolated mediastinal adenopathy. Finally, this technique enables a diagnostic approach to mediastinal tumours. The frozen section has its place, at the first indication, making it possible to prescribe neoadjuvant chemotherapy, and in the other situations to make sure that the quantity of material removed is sufficient or even to carry out complementary techniques. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  20. Comparison and analysis of the animal models used to study the effect of morphine on tumour growth and metastasis

    NARCIS (Netherlands)

    Afsharimani, B.; Doornebal, C. W.; Cabot, P. J.; Hollmann, M. W.; Parat, M.-O.

    2015-01-01

    The effect of opioids on tumour growth and metastasis has been debated for many years, with recent emphasis on the possibility that they might influence the rate of disease-free survival after tumour resection when used in the perioperative pain management of cancer surgery patients. The literature

  1. Evolution of Coronary Flow in an Experimental Slow Flow Model in Swines: Angiographic and Pathological Insights

    Directory of Open Access Journals (Sweden)

    Yupeng Bai

    2015-01-01

    Full Text Available Objective. Pathomechanism of coronary slow flow phenomenon remains largely unclear now. Present study observed the pathological and angiographic evolution in a pig model of coronary slow flow. Methods. Coronary slow flow was induced by repeat coronary injection of small doses of 40 µm microspheres in 18 male domestic pigs and angiographic and pathological changes were determined at 3 hours, 7 days, and 28 days after microspheres injection. Results. Compared to control group treated with coronary saline injection n=6 and baseline level, coronary flow was significantly reduced at 3 hours and 7 days but completely recovered at 28 days after coronary microsphere injection in slow flow group. Despite normal coronary flow at 28 days after microsphere injection, enhanced myocardial cytokine expression, left ventricular dysfunction, adverse remodelling, and ischemia/microembolism related pathological changes still persisted or even progressed from 3 hours to 28 days after coronary microsphere injection. Conclusions. Our results show that this large animal slow flow model could partly reflect the chronic angiographic, hemodynamic, and pathological changes of coronary slow flow and could be used to test new therapy strategies against the slow flow phenomenon.

  2. Self-pathology, the five-factor model, and bloated specific factors: A cautionary tale.

    Science.gov (United States)

    Oltmanns, Joshua R; Widiger, Thomas A

    2016-04-01

    The five-factor model (FFM) is widely regarded as a useful model for the structure of both normal and maladaptive personality traits. However, recent factor analytic studies have suggested that deficits in the sense of self fall outside the FFM. The current study replicates and extends these findings, illustrating that factors can be situated outside a higher-order domain by including a relatively large number of closely related scales, forming what is known as a bloated specific factor. A total of 1,553 participants (M age = 37.8 years, SD = 13.1) were recruited across 3 studies. One measure of self-pathology (including 15 scales) and 2 measures of the FFM were administered, along with 17 measures of anxiousness and 12 measures of social withdrawal/sociability. Across 2 independent samples and 2 different measures of the FFM, deficits in the sense of self separated from neuroticism when all 15 scales of self-pathology were included. However, self-pathology loaded with FFM neuroticism when only a subset of the self-pathology scales was included. This finding was replicated with measures of social withdrawal/sociability, although only partially replicated with measures of anxiousness. Implications of these findings for past and future factor analytic studies of the structure of psychopathology are discussed. (c) 2016 APA, all rights reserved).

  3. Lack of miRNA misregulation at early pathological stages in Drosophila neurodegenerative disease models

    Directory of Open Access Journals (Sweden)

    Anita eReinhardt

    2012-10-01

    Full Text Available Late onset neurodegenerative diseases represent a major public health concern as the population in many countries ages. Both frequent diseases such as Alzheimer disease (AD, 14% incidence for 80-84 year old Europeans or Parkinson disease (PD, 1.4% prevalence for > 55 years old share, with other low-incidence neurodegenerative pathologies such as spinocerebellar ataxias (SCAs, 0.01% prevalence and frontotemporal lobar degeneration (FTLD, 0.02% prevalence, a lack of efficient treatment in spite of important research efforts. Besides significant progress, studies with animal models have revealed unexpected complexities in the degenerative process, emphasizing a need to better understand the underlying pathological mechanisms. Recently, microRNAs, a class of small regulatory non-coding RNAs, have been implicated in some neurodegenerative diseases. The current data supporting a role of miRNAs in PD, tauopathies, dominant ataxias and FTLD will first be discussed to emphasize the different levels of the pathological processes which may be affected by miRNAs. To investigate a potential involvement of miRNA dysregulation in the early stages of these neurodegenerative diseases we have used Drosophila models for 7 diseases (PD, 3 FTLD, 3 dominant ataxias that recapitulate many features of the human diseases. We performed deep sequencing of head small RNAs after 3 days of pathological protein expression in the fly head neurons. We found no evidence for a statistically significant difference in miRNA expression in this early stage of the pathological process. In addition, we could not identify small non coding CAG repeat RNAs (sCAG in polyQ disease models. Thus our data suggest that transcriptional deregulation of miRNAs or sCAG is unlikely to play a significant role in the initial stages of neurodegenerative diseases.

  4. Benchmarking in pathology: development of an activity-based costing model.

    Science.gov (United States)

    Burnett, Leslie; Wilson, Roger; Pfeffer, Sally; Lowry, John

    2012-12-01

    Benchmarking in Pathology (BiP) allows pathology laboratories to determine the unit cost of all laboratory tests and procedures, and also provides organisational productivity indices allowing comparisons of performance with other BiP participants. We describe 14 years of progressive enhancement to a BiP program, including the implementation of 'avoidable costs' as the accounting basis for allocation of costs rather than previous approaches using 'total costs'. A hierarchical tree-structured activity-based costing model distributes 'avoidable costs' attributable to the pathology activities component of a pathology laboratory operation. The hierarchical tree model permits costs to be allocated across multiple laboratory sites and organisational structures. This has enabled benchmarking on a number of levels, including test profiles and non-testing related workload activities. The development of methods for dealing with variable cost inputs, allocation of indirect costs using imputation techniques, panels of tests, and blood-bank record keeping, have been successfully integrated into the costing model. A variety of laboratory management reports are produced, including the 'cost per test' of each pathology 'test' output. Benchmarking comparisons may be undertaken at any and all of the 'cost per test' and 'cost per Benchmarking Complexity Unit' level, 'discipline/department' (sub-specialty) level, or overall laboratory/site and organisational levels. We have completed development of a national BiP program. An activity-based costing methodology based on avoidable costs overcomes many problems of previous benchmarking studies based on total costs. The use of benchmarking complexity adjustment permits correction for varying test-mix and diagnostic complexity between laboratories. Use of iterative communication strategies with program participants can overcome many obstacles and lead to innovations.

  5. MRI of pineal region tumours: relationship between tumours and adjacent structures

    International Nuclear Information System (INIS)

    Satoh, H.; Kurisu, K.

    1995-01-01

    A variety of tumours may arise in the pineal region; accurate diagnosis is important in the selection of treatment and prognosis. A retrospective analysis of the MRI studies of 25 patients with pathologically proven pineal region tumours was performed, focused on the relationship between the tumour and neighbouring structures. Compression of the tectal plate was classified as expansive or invasive, and compression of the corpus callosum as inferior, anterior or posterior. In 10 of the 14 patients (71 %) with germ cell tumours tectal compression was of the invasive type; 8 patients (57 %) had multiple tumours and in 13 (93 %) the tumour margins were irregular. Teratomas were readily diagnosed because of characteristic heterogeneous signal intensity. Pineal cell tumours were differentiated from germ cell tumours by their rounded shape, solid nature, sharp margins, and expansive type of tectal compression. Meningiomas were characterised by their falcotentorial attachments, posterior callosal compression, and a low-intensity rim on T2-weighted images. Gd-DTPA injection enabled clear demonstration of the site and extent of tumour spread and was useful in differentiating cystic and solid components. The appearances described, while not pathognomonic, are helpful in the differential diagnosis of pineal region tumours, and valuable in planning appropriate treatment. (orig.). With 4 figs., 6 tabs

  6. Predicting problematic alcohol use with the DSM-5 alternative model of personality pathology.

    Science.gov (United States)

    Creswell, Kasey G; Bachrach, Rachel L; Wright, Aidan G C; Pinto, Anthony; Ansell, Emily

    2016-01-01

    High comorbidity between personality disorders and alcohol use disorders appears related to individual differences in underlying personality dimensions of behavioral undercontrol and affective dysregulation. However, very little is known about how the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5) Section III trait model of personality pathology relates to alcohol problems or how the strength of the relationship between personality pathology and alcohol problems changes with age and across gender. The current study examined these questions in a sample of 877 participants using the General Assessment of Personality Disorder to assess general personality dysfunction, the Personality Inventory for DSM-5 to measure specific traits, and the Alcohol Use Disorder Identification Test (AUDIT) to assess problematic alcohol use. Results demonstrated that general personality pathology (Criterion A) was significantly related to problematic alcohol use after controlling for age and gender effects. Furthermore, 2 of the 5 higher-order personality trait domains (Criterion B), Antagonism and Disinhibition, remained significant predictors of problematic alcohol use after accounting for the influence of general personality pathology; however, general personality pathology no longer predicted hazardous alcohol use once Antagonism and Disinhibition were added into the model. Finally, these 2 specific traits interacted with age, such that Antagonism was a stronger predictor of AUDIT scores among older individuals and Disinhibition was a stronger predictor of alcohol problems among younger individuals. Findings support the general validity of this new personality disorder diagnostic system and suggest important age effects in the relationship between traits and problematic alcohol use. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  7. Pharmacokinetics and pharmacodynamics of propofol: changes in patients with frontal brain tumours.

    Science.gov (United States)

    Sahinovic, M M; Eleveld, D J; Miyabe-Nishiwaki, T; Struys, M M R F; Absalom, A R

    2017-06-01

    Models of propofol pharmacokinetics and pharmacodynamics developed in patients without brain pathology are widely used for target-controlled infusion (TCI) during brain tumour excision operations. The goal of this study was to determine if the presence of a frontal brain tumour influences propofol pharmacokinetics and pharmacodynamics and existing PK-PD model performance. Twenty patients with a frontal brain tumour and 20 control patients received a propofol infusion to achieve an induction-emergence-induction anaesthetic sequence. Propofol plasma concentration was measured every 4 min and at each transition of the conscious state. Bispectral index (BIS) values were continuously recorded. We used non-linear mixed-effects modelling to analyse the effects of the presence of a brain tumour on the pharmacokinetics and pharmacodynamics of propofol. Subsequently we calculated the predictive performance of Marsh, Schnider, and Eleveld models in terms of median prediction error (MdPE) and median absolute prediction error (MdAPE). Patients with brain tumours showed 40% higher propofol clearance than control patients. Performance of the Schnider model (MdPEpk -20.0%, MdAPEpk 23.4%) and Eleveld volunteer model (MdPEpk -8.58%, MdAPEpk 21.6%) were good. The Marsh model performed less well (MdPEpk -14.3%, MdAPEpk 41.4%), as did the Eleveld patient model (MdPEpk -30.8%, MdAPEpk 32.1%). Brain tumours might alter the pharmacokinetics of propofol. Caution should be exerted when using propofol TCI in patients with frontal brain tumours due to higher clearance. NCT01060631. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. Integrating oddity traits in a dimensional model for personality pathology precursors.

    Science.gov (United States)

    Verbeke, Lize; De Clercq, Barbara

    2014-08-01

    Current dimensional measures of early personality pathology (e.g., the Dimensional Personality Symptom Item Pool, DIPSI; De Clercq, De Fruyt, Van Leeuwen, & Mervielde, 2006) describe personality difficulties within a 4-dimensional framework. The present study corroborates recent evidence on the relevance of including a 5th Oddity-related domain for a more comprehensive description of personality pathology, and presents the construction of an empirically based taxonomy of early Oddity features. Psychometric and factor analytic procedures were conducted on self- and maternal ratings of adolescents (N = 434), resulting in 4 internally consistent facets that empirically collapse in 1 higher-order "Oddity" factor. From a structural perspective, this Oddity factor emerged as a clear 5th factor beyond the earlier proposed 4-dimensional structure of child and adolescent personality pathology. Significant associations of Oddity with both general and maladaptive trait equivalents support the construct validity of this 5th factor, and challenge current hypotheses on the applicability of the continuity hypothesis on general and maladaptive trait variance within the openness field. The results further suggest that Oddity traits are meaningfully associated with general psychopathology at a young age. These findings are discussed in terms of the importance of including a 5th Oddity-related factor in dimensional models of developmental personality pathology in order to acquire a more comprehensive description of the building blocks that underlie early personality difficulties. (c) 2014 APA, all rights reserved.

  9. Processing system of jaws tomograms for pathology identification and surgical guide modeling

    International Nuclear Information System (INIS)

    Putrik, M. B.; Ivanov, V. Yu.; Lavrentyeva, Yu. E.

    2015-01-01

    The aim of the study is to create an image processing system, which allows dentists to find pathological resorption and to build surgical guide surface automatically. X-rays images of jaws from cone beam tomography or spiral computed tomography are the initial data for processing. One patient’s examination always includes up to 600 images (or tomograms), that’s why the development of processing system for fast automation search of pathologies is necessary. X-rays images can be useful not for only illness diagnostic but for treatment planning too. We have studied the case of dental implantation – for successful surgical manipulations surgical guides are used. We have created a processing system that automatically builds jaw and teeth boundaries on the x-ray image. After this step, obtained teeth boundaries used for surgical guide surface modeling and jaw boundaries limit the area for further pathologies search. Criterion for the presence of pathological resorption zones inside the limited area is based on statistical investigation. After described actions, it is possible to manufacture surgical guide using 3D printer and apply it in surgical operation

  10. Neurofibromatosis type 1: brain stem tumours

    International Nuclear Information System (INIS)

    Bilaniuk, L.T.; Molloy, P.T.; Zimmerman, R.A.; Phillips, P.C.; Vaughan, S.N.; Liu, G.T.; Sutton, L.N.; Needle, M.

    1997-01-01

    We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. (orig.). With 7 figs., 3 tabs

  11. 3D Printed Models of Cleft Palate Pathology for Surgical Education

    OpenAIRE

    Lioufas, Peter A.; Quayle, Michelle R.; Leong, James C.; McMenamin, Paul G.

    2016-01-01

    Objective: To explore the potential viability and limitations of 3D printed models of children with cleft palate deformity. Background: The advantages of 3D printed replicas of normal anatomical specimens have previously been described. The creation of 3D prints displaying patient-specific anatomical pathology for surgical planning and interventions is an emerging field. Here we explored the possibility of taking rare pediatric radiographic data sets to create 3D prints for surgical education...

  12. Liposomal Nanoparticles Carrying anti-IL6R Antibody to the Tumour Microenvironment Inhibit Metastasis in Two Molecular Subtypes of Breast Cancer Mouse Models.

    Science.gov (United States)

    Guo, Chunlei; Chen, Yanan; Gao, Wenjuan; Chang, Antao; Ye, Yujie; Shen, Wenzhi; Luo, Yunping; Yang, Shengyong; Sun, Peiqing; Xiang, Rong; Li, Na

    2017-01-01

    Tumour microenvironment (TME) contributes significantly towards potentiating the stemness and metastasis properties of cancer cells. IL6-Stat3 is one of the important cell signaling pathways in mediating the communication between tumour and immune cells. Here, we have systematically developed a novel anti-CD44 antibody-mediated liposomal nanoparticle delivery system loaded with anti-IL6R antibody, which could specifically target the TME of CD44 + breast cancer cells in different mouse models for triple negative and luminal breast cancer. This nanoparticle had an enhanced and specific tumour targeting efficacy with dramatic anti-tumour metastasis effects in syngeneic BALB/c mice bearing 4T1 cells as was in the syngeneic MMTV-PyMT mice. It inhibited IL6R-Stat3 signaling and moderated the TME, characterized by the reduced expression of genes encoding Stat3, Sox2, VEGFA, MMP-9 and CD206 in the breast tissues. Furthermore, this nanoparticle reduced the subgroups of Sox2 + and CD206 + cells in the lung metastatic foci, demonstrating its inhibitory effect on the lung metastatic niche for breast cancer stem cells. Taken together, the CD44 targeted liposomal nanoparticles encapsulating anti-IL6R antibody achieved a significant effect to inhibit the metastasis of breast cancer in different molecular subtypes of breast cancer mouse models. Our results shed light on the application of nanoparticle mediated cancer immune-therapy through targeting TME.

  13. Tumours of the foot

    International Nuclear Information System (INIS)

    Bohndorf, K.

    1983-01-01

    The radiological diagnosis of tumours of the foot is difficult, especially, since these tumours are rare and the bones of the foot are small. The latter leads to a more uniform radiographic manifestation of the tumours. We differentiate tumours of the foot arising in the foot primarily and soft tissue tumours, affecting the bones secondarily. Cystic lesions of the calcaneus are discussed in further detail. (orig.) [de

  14. Adnexal Tumours Of Skin

    Directory of Open Access Journals (Sweden)

    Parate Sanjay N

    1998-01-01

    Full Text Available A total 120 cases of epidermal appendage tumours of skin were analysed and classified according to the classification provided by WHO’. Epidermal appendage tumours accounted for 12.87% of all skin tumours, of which 29.17% were benign and 70.83% were malignant. Most of the tumours (75.83% were in the head and face region. The most common tumour was basal cell epithelioma (55%.

  15. Tumour targeting with systemically administered bacteria.

    LENUS (Irish Health Repository)

    Morrissey, David

    2012-01-31

    Challenges for oncology practitioners and researchers include specific treatment and detection of tumours. The ideal anti-cancer therapy would selectively eradicate tumour cells, whilst minimising side effects to normal tissue. Bacteria have emerged as biological gene vectors with natural tumour specificity, capable of homing to tumours and replicating locally to high levels when systemically administered. This property enables targeting of both the primary tumour and secondary metastases. In the case of invasive pathogenic species, this targeting strategy can be used to deliver genes intracellularly for tumour cell expression, while non-invasive species transformed with plasmids suitable for bacterial expression of heterologous genes can secrete therapeutic proteins locally within the tumour environment (cell therapy approach). Many bacterial genera have been demonstrated to localise to and replicate to high levels within tumour tissue when intravenously (IV) administered in rodent models and reporter gene tagging of bacteria has permitted real-time visualisation of this phenomenon. Live imaging of tumour colonising bacteria also presents diagnostic potential for this approach. The nature of tumour selective bacterial colonisation appears to be tumour origin- and bacterial species- independent. While originally a correlation was drawn between anaerobic bacterial colonisation and the hypoxic nature of solid tumours, it is recently becoming apparent that other elements of the unique microenvironment within solid tumours, including aberrant neovasculature and local immune suppression, may be responsible. Here, we consider the pre-clinical data supporting the use of bacteria as a tumour-targeting tool, recent advances in the area, and future work required to develop it into a beneficial clinical tool.

  16. Imaging of Cerebrovascular Pathology in Animal Models of Alzheimer`s Disease

    Directory of Open Access Journals (Sweden)

    Jan eKlohs

    2014-03-01

    Full Text Available In Alzheimer’s disease (AD, vascular pathology may interact with neurodegeneration and thus aggravate cognitive decline. As the relationship between these two processes is poorly understood, research has been increasingly focused on understanding the link between cerebrovascular alterations and AD. This has at last been spurred by the engineering of transgenic animals, which display pathological features of AD and develop cerebral amyloid angiopathy to various degrees. Transgenic models are versatile for investigating the role of amyloid deposition and vascular dysfunction, and for evaluating novel therapeutic concepts. In addition, research has benefited from the development of novel imaging techniques, which are capable of characterizing vascular pathology in vivo. They provide vascular structural read-outs and have the ability to assess the functional consequences of vascular dysfunction as well as to visualize and monitor the molecular processes underlying these pathological alterations. This article focusses on recent in vivo small animal imaging studies addressing vascular aspects related to AD. With the technical advances of imaging modalities such as magnetic resonance, nuclear and microscopic imaging, molecular, functional and structural information related to vascular pathology can now be visualized in vivo in small rodents. Imaging vascular and parenchymal amyloid-β (Aβ deposition as well as Aβ transport pathways have been shown to be useful to characterize their dynamics and to elucidate their role in the development of cerebral amyloid angiopathy and AD. Structural and functional imaging read-outs have been employed to describe the deleterious affects of Aβ on vessel morphology, hemodynamics and vascular integrity. More recent imaging studies have also addressed how inflammatory processes partake in the pathogenesis of the disease. Moreover, imaging can be pivotal in the search for novel therapies targeting the vasculature.

  17. Refractive index of carcinogen-induced rat mammary tumours

    International Nuclear Information System (INIS)

    Zysk, Adam M; Chaney, Eric J; Boppart, Stephen A

    2006-01-01

    Near-infrared optical techniques for clinical breast cancer screening in humans are rapidly advancing. Based on the computational inversion of the photon diffusion process through the breast, these techniques rely on optical tissue models for accurate image reconstruction. Recent interest has surfaced regarding the effect of refractive index variations on these reconstructions. Although many data exist regarding the scattering and absorption properties of normal and diseased tissue, no measurements of refractive index appear in the literature. In this paper, we present near-infrared refractive index data acquired from N-methyl-N-nitrosourea-induced rat mammary tumours, which are similar in pathology and disease progression to human ductal carcinoma. Eight animals, including one control, were employed in this study, yielding data from 32 tumours as well as adjacent adipose and connective tissues

  18. Refractive index of carcinogen-induced rat mammary tumours

    Science.gov (United States)

    Zysk, Adam M.; Chaney, Eric J.; Boppart, Stephen A.

    2006-05-01

    Near-infrared optical techniques for clinical breast cancer screening in humans are rapidly advancing. Based on the computational inversion of the photon diffusion process through the breast, these techniques rely on optical tissue models for accurate image reconstruction. Recent interest has surfaced regarding the effect of refractive index variations on these reconstructions. Although many data exist regarding the scattering and absorption properties of normal and diseased tissue, no measurements of refractive index appear in the literature. In this paper, we present near-infrared refractive index data acquired from N-methyl-N-nitrosourea-induced rat mammary tumours, which are similar in pathology and disease progression to human ductal carcinoma. Eight animals, including one control, were employed in this study, yielding data from 32 tumours as well as adjacent adipose and connective tissues.

  19. Gastrointestinal stromal tumour: From the clinic to the molecules

    Directory of Open Access Journals (Sweden)

    Hapkova I

    2014-03-01

    Full Text Available GastroIntestional stromal tumours (GISTs, the most frequent sarcoma in the gastro-intestinal (GI tract, are highly resistant to conventional chemotherapy and radiotherapy. These tumours have activating mutations in two closely related genes, KIT (75-80% or/and PDGFRA (5-10%. Targeting these mutated activated proteins with imatinib mesylate has proven efficient in the treatment of GISTs. The median survival after diagnosis of GIST increased from 1.5 to 4.8 years with imatinib treatment. However, resistance to imatinib eventually develops and new-targeted therapies are needed. This paper reviews the medical, clinical and pathological aspects of GISTs based on latest research in human cell lines and animal models.

  20. MRI EVALUATION OF SPINAL CORD TUMOURS WITH HISTOPATHOLOGICAL CORRELATION

    Directory of Open Access Journals (Sweden)

    Ashok Srikar Chowdhary

    2017-12-01

    Full Text Available BACKGROUND Spinal cord tumours are relatively rare tumours and can present with a wide variety of symptoms. If they are not diagnosed early and treated immediately, they can lead to neurological deficits and disability. Therefore, accurate diagnosis is necessary, which will help in directing the therapy. Nowadays, MRI is the most commonly used modality for spinal cord tumour diagnosis unless there is a contraindication. The aim of this study was to study the demographic profile of patients with spinal cord tumours to assess the distribution, features, localisation and extent of spinal cord tumours by MRI and correlate the tissue characterisation by MRI with that of histopathological examination. MATERIALS AND METHODS A prospective study was conducted in the Departments of Radiodiagnosis, Neurosurgery and Pathology at SCBMCH, Cuttack, from October 2010 to October 2012. 52 patients diagnosed as having spinal cord tumours by clinical examination and MRI were followed till post-surgery discharge. RESULTS Out of the 52 patients with spinal cord tumours, 28 patients (54% were males and females made up around 46% (24 patients. Around 6% of the patients were in the paediatric age group. Our study showed that intradural extramedullary tumours 36/52 (69% were the commonest followed by intramedullary tumours 10/52 (19% and extradural tumours 6/52 (12%. Overall, schwannoma was the commonest spinal cord tumour accounting for 46.1% of the tumours. Out of 52 cases, MRI diagnosed 46 cases (88.46% correctly and misdiagnosed 6 cases. MRI was able to correctly diagnose 91.67% of the intradural extramedullary tumours, 90% of the intramedullary tumours and 66.67% of the extradural tumours. CONCLUSION MRI is the preoperative investigation of choice in the evaluation of spinal cord tumours. MRI can accurately diagnose spinal tumours and guide surgical resection.

  1. Rat models of spinal cord injury: from pathology to potential therapies

    Directory of Open Access Journals (Sweden)

    Jacob Kjell

    2016-10-01

    Full Text Available A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials.

  2. Rat models of spinal cord injury: from pathology to potential therapies

    Science.gov (United States)

    2016-01-01

    ABSTRACT A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials. PMID:27736748

  3. High grade glioma: Imaging combined with pathological grade defines management and predicts prognosis

    International Nuclear Information System (INIS)

    Burnet, Neil G.; Lynch, Andrew G.; Jefferies, Sarah J.; Price, Stephen J.; Jones, Phil H.; Antoun, Nagui M.; Xuereb, John H.; Pohl, Ute

    2007-01-01

    Introduction: There is ambiguity in pathological grading of high grade gliomas within the WHO 2000 classification, especially those with predominant oligodendroglial differentiation. Patients and methods: All adult high grade gliomas treated radically, 1996-2005, were assessed. Cases in which pathology was grade III but radiology suggested glioblastoma (GBM) were classified as 'grade III/IV'; their pathology was reviewed. Results: Data from 245 patients (52 grade III, 18 grade III/IV, 175 GBM) were analysed using a Cox Proportional Hazards model. On pathology review, features suggestive of more aggressive behaviour were found in all 18 grade III/IV tumours. Oligodendroglial components with both necrosis and microvascular proliferation were present in 7. MIB-1 counts for the last 8 were all above 14%, mean 27%. Median survivals were: grade III 34 months, grade III/IV 10 months, GBM 11 months. Survival was not significantly different between grade III/IV and GBM. Patients with grade III/IV tumours had significantly worse outcome than grade III, with a hazard of death 3.7 times higher. Conclusions: The results highlight the current inconsistency in pathological grading of high grade tumours, especially those with oligodendroglial elements. Patients with histological grade III tumours but radiological appearances suggestive of GBM should be managed as glioblastoma

  4. The big seven model of personality and its relevance to personality pathology.

    Science.gov (United States)

    Simms, Leonard J

    2007-02-01

    Proponents of the Big Seven model of personality have suggested that Positive Valence (PV) and Negative Valence (NV) are independent of the Big Five personality dimensions and may be particularly relevant to personality disorder. These hypotheses were tested with 403 undergraduates who completed a Big Seven measure and markers of the Big Five and personality pathology. Results revealed that PV and NV incrementally predicted personality pathology dimensions beyond those predicted by multiple markers of the Big Five. However, factor analyses suggested that PV and NV might be best understood as specific, maladaptive aspects of positive emotionality and low agreeableness, respectively, as opposed to independent factors of personality. Implications for the description of normal and abnormal personality are discussed.

  5. Mapping pathological phenotypes in a mouse model of CDKL5 disorder.

    Directory of Open Access Journals (Sweden)

    Elena Amendola

    Full Text Available Mutations in cyclin-dependent kinase-like 5 (CDKL5 cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG responses to convulsant treatment, decreased visual evoked responses (VEPs, and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.

  6. Neuropathological diagnosis of brain tumours.

    Science.gov (United States)

    Pollo, Bianca

    2011-11-01

    With recent progress in radiological, pathological, immunohistochemical, molecular and genetic diagnoses, the characterisation of brain tumours has improved. The last World Health Organization (WHO) Classification of Tumours of the Central Nervous System was done in 2007, based on morphological features, growth pattern and molecular profile of neoplastic cells, defined malignancy grade. The neuropathological diagnosis and the grading of each histotype are based on identification of histopathological criteria and immunohistochemical data. Molecular and genetic profiles may identify different tumour subtypes varying in biological and clinical behaviour, indicating prognostic and predictive factors. In order to investigate new therapeutic approaches, it is important to study the molecular pathways responsible for proliferation, invasion, angiogenesis, and anaplastic transformation. Different prognostic and predictive factors for glioma patients were identified by genetic studies, such as the loss of heterozygosis on chromosome 1p and 19q for oligodendrogliomas, proangiogenic factors such as Vascular Endothelial Growth Factor for glioblastomas and the methylation status of gene promoter of MethylGuanine-MethylTransferase. In conclusion, the prognostic evaluation and the therapeutic strategies for patients depend on the synthesis of histological diagnosis, malignancy grade, gene-molecular profile, radiological images, surgical resection and clinical findings (age, tumour location, and "performance status").

  7. Three-Dimensional Blood-Brain Barrier Model for in vitro Studies of Neurovascular Pathology

    Science.gov (United States)

    Cho, Hansang; Seo, Ji Hae; Wong, Keith H. K.; Terasaki, Yasukazu; Park, Joseph; Bong, Kiwan; Arai, Ken; Lo, Eng H.; Irimia, Daniel

    2015-10-01

    Blood-brain barrier (BBB) pathology leads to neurovascular disorders and is an important target for therapies. However, the study of BBB pathology is difficult in the absence of models that are simple and relevant. In vivo animal models are highly relevant, however they are hampered by complex, multi-cellular interactions that are difficult to decouple. In vitro models of BBB are simpler, however they have limited functionality and relevance to disease processes. To address these limitations, we developed a 3-dimensional (3D) model of BBB on a microfluidic platform. We verified the tightness of the BBB by showing its ability to reduce the leakage of dyes and to block the transmigration of immune cells towards chemoattractants. Moreover, we verified the localization at endothelial cell boundaries of ZO-1 and VE-Cadherin, two components of tight and adherens junctions. To validate the functionality of the BBB model, we probed its disruption by neuro-inflammation mediators and ischemic conditions and measured the protective function of antioxidant and ROCK-inhibitor treatments. Overall, our 3D BBB model provides a robust platform, adequate for detailed functional studies of BBB and for the screening of BBB-targeting drugs in neurological diseases.

  8. Accelerated aging exacerbates a pre-existing pathology in a tau transgenic mouse model.

    Science.gov (United States)

    Bodea, Liviu-Gabriel; Evans, Harrison Tudor; Van der Jeugd, Ann; Ittner, Lars M; Delerue, Fabien; Kril, Jillian; Halliday, Glenda; Hodges, John; Kiernan, Mathew C; Götz, Jürgen

    2017-04-01

    Age is a critical factor in the prevalence of tauopathies, including Alzheimer's disease. To observe how an aging phenotype interacts with and affects the pathological intracellular accumulation of hyperphosphorylated tau, the tauopathy mouse model pR5 (expressing P301L mutant human tau) was back-crossed more than ten times onto a senescence-accelerated SAMP8 background to establish the new strain, SApT. Unlike SAMP8 mice, pR5 mice are characterized by a robust tau pathology particularly in the amygdala and hippocampus. Analysis of age-matched SApT mice revealed that pathological tau phosphorylation was increased in these brain regions compared to those in the parental pR5 strain. Moreover, as revealed by immunohistochemistry, phosphorylation of critical tau phospho-epitopes (P-Ser202/P-Ser205 and P-Ser235) was significantly increased in the amygdala of SApT mice in an age-dependent manner, suggesting an age-associated effect of tau phosphorylation. Anxiety tests revealed that the older cohort of SApT mice (10 months vs. 8 months) exhibited a behavioural pattern similar to that observed for age-matched tau transgenic pR5 mice and not the SAMP8 parental mice. Learning and memory, however, appeared to be governed by the accelerated aging background of the SAMP8 strain, as at both ages investigated, SAMP8 and SApT mice showed a decreased learning capacity compared to pR5 mice. We therefore conclude that accelerated aging exacerbates pathological tau phosphorylation, leading to changes in normal behaviour. These findings further suggest that SApT mice may be a useful novel model in which to study the role of a complex geriatric phenotype in tauopathy. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  9. Oral Tumours In Zaria | Rafindadi | Nigerian Journal of Surgical ...

    African Journals Online (AJOL)

    Oral tumours are common worldwide and are attributed to factors like tobacco smoke, ill-fitting dentures, alcohol, and syphilis. Viruses like HPV and HIV play an important role in some premalignant conditions like leukoplakia. This is a retrospective analysis of 210 oral tumours see at the Pathology department of the ABUTH, ...

  10. Clinicopathological features of liver tumours: a ten-year study

    International Nuclear Information System (INIS)

    Zahir, S.T.; Aalipour, E.

    2015-01-01

    Various diseases affect the liver, among them, malignant and benign tumours with hepatic nodules are the most important. We aimed to evaluate the clinicopathological findings related to hepatic tumours and nodules. Methods: This retrospective study was carried out during November 2014 to August 2015 by reviewing the hospital medical records of 164 registered patients with liver biopsies referred to Shahid Sadoughi educational General Hospital, Yazd, Iran, between 2004 and 2014. The samples were selected through the census method. Age, gender, clinical symptoms, initial clinical diagnosis, pathology reports and ultrasound results were considered as variables. Data were analysed by using SPSS-17. Results: There were 87 (53%) men and 77 (47%) women. The mean ages of presentation for malignant and benign tumours were 57.9 ±17.2 and 44.9±19.4 years, respectively. Seventy benign tumours and 147 malignant tumours were recorded. The most frequent chief complaint was abdominal pain (54.9%) in both malignant (56.50%) and benign tumours (41.20%). Hepatocellular carcinoma (HCC) and hemangioma were the most prevalent malignant and benign hepatic tumours, respectively. In our study, correlation between pathology reports and primary diagnoses was 40.9%, and a significant relationship was found between sonography and pathological findings (p=0.038). Conclusions: We found that only when primary clinical diagnosis and sonography were in favour of malignancy, they were correlated with pathology results. Clinicopathological assessments can help physicians in their diagnosis in order to facilitate the management of hepatic tumours. (author)

  11. Breast tumours of adolescents in an African population | Umanah ...

    African Journals Online (AJOL)

    Materials and Methods: Eighty-four breast tumour materials from patients aged 10–19 years were analyzed over a 10-year period at the. Department of Pathology, University of Benin Teaching Hospital (UBTH), Benin City, Edo State, Benin City, Nigeria. Results: A majority of the breast tumours were benign. Fibroadenoma ...

  12. Tumour control in ion beam radiotherapy with different ions in the presence of hypoxia: an oxygen enhancement ratio model based on the microdosimetric kinetic model

    Science.gov (United States)

    Strigari, L.; Torriani, F.; Manganaro, L.; Inaniwa, T.; Dalmasso, F.; Cirio, R.; Attili, A.

    2018-03-01

    Few attempts have been made to include the oxygen enhancement ratio (OER) in treatment planning for ion beam therapy, and systematic studies to evaluate the impact of hypoxia in treatment with the beam of different ion species are sorely needed. The radiobiological models used to quantify the OER in such studies are mainly based on the dose-averaged LET estimates, and do not explicitly distinguish between the ion species and fractionation schemes. In this study, a new type of OER modelling, based on the microdosimetric kinetic model, taking into account the specificity of the different ions, LET spectra, tissues and fractionation schemes, has been developed. The model has been benchmarked with published in vitro data, HSG, V79 and CHO cells in aerobic and hypoxic conditions, for different ion irradiation. The model has been included in the simulation of treatments for a clinical case (brain tumour) using proton, lithium, helium, carbon and oxygen ion beams. A study of the tumour control probability (TCP) as a function of oxygen partial pressure, dose per fraction and primary ion type has been performed. The modelled OER depends on both the LET and ion type, also showing a decrease for an increased dose per fraction with a slope that depends on the LET and ion type, in good agreement with the experimental data. In the investigated clinical case, a significant increase in TCP has been found upon increasing the ion charge. Higher OER variations as a function of dose per fraction have also been found for low-LET ions (up to 15% varying from 2 to 8 Gy(RBE) for protons). This model could be exploited in the identification of treatment condition optimality in the presence of hypoxia, including fractionation and primary particle selection.

  13. Occurrence studies of intracranial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Larjavaara, S.

    2011-07-01

    Intracranial tumours are a histopathologically heterogeneous group of tumours. This thesis focused on three types of intracranial tumours; gliomas, meningiomas and vestibular schwannomas (VS). The main objectives of the dissertation were to estimate the occurrence of intracranial tumours by different subtypes, and to assess the validity and completeness of the cancer registry data. The specific aims of the publications were to evaluate the validity of reported incidence rates of meningioma cases, to describe the trends of VS incidence in four Nordic countries, and to define the anatomic distribution of gliomas and to investigate their location in relation to mobile phone use. Completeness of meningioma registration was examined by comparing five separate sources of information, and by defining the frequencies of cases reported to the Finnish Cancer Registry (FCR). Incidence trends of VS were assessed in the four Nordic countries over a twenty-one-year period (1987 - 2007) using cancer registry data. The anatomic site of gliomas was evaluated using both crude locations in the cerebral lobes and, in more detail, a three-dimensional (3D) distribution in the brain. In addition, a study on specific locations of gliomas in relation to the typical position of mobile phones was conducted using two separate approaches: a case-case and a case-specular analysis. The thesis was based on four sets of materials. Data from the international Interphone study were used for the studies on gliomas, while the two other studies were register-based. The dataset for meningiomas included meningioma cases from the FCR and four clinical data sources in Tampere University Hospital (neurosurgical clinic, pathology database, hospital discharge register and autopsy register). The data on VS were obtained from the national cancer registries of Denmark, Finland, Norway and Sweden. The coverage of meningiomas was not comprehensive in any of the data sources. The completeness of FCR was

  14. Automatically extracting cancer disease characteristics from pathology reports into a Disease Knowledge Representation Model.

    Science.gov (United States)

    Coden, Anni; Savova, Guergana; Sominsky, Igor; Tanenblatt, Michael; Masanz, James; Schuler, Karin; Cooper, James; Guan, Wei; de Groen, Piet C

    2009-10-01

    We introduce an extensible and modifiable knowledge representation model to represent cancer disease characteristics in a comparable and consistent fashion. We describe a system, MedTAS/P which automatically instantiates the knowledge representation model from free-text pathology reports. MedTAS/P is based on an open-source framework and its components use natural language processing principles, machine learning and rules to discover and populate elements of the model. To validate the model and measure the accuracy of MedTAS/P, we developed a gold-standard corpus of manually annotated colon cancer pathology reports. MedTAS/P achieves F1-scores of 0.97-1.0 for instantiating classes in the knowledge representation model such as histologies or anatomical sites, and F1-scores of 0.82-0.93 for primary tumors or lymph nodes, which require the extractions of relations. An F1-score of 0.65 is reported for metastatic tumors, a lower score predominantly due to a very small number of instances in the training and test sets.

  15. Red blood cells inhibit tumour cell adhesion to the peritoneum.

    Science.gov (United States)

    van Rossen, M E; Stoop, M P; Hofland, L J; van Koetsveld, P M; Bonthuis, F; Jeekel, J; Marquet, R L; van Eijck, C H

    1999-04-01

    Perioperative blood transfusion has been associated with increased tumour recurrence and poor prognosis in colorectal cancer. Blood loss in the peritoneal cavity might be a tumour-promoting factor for local recurrence. The aim of this study was to investigate whether blood in the peritoneal cavity affects local tumour recurrence. In an established in vivo rat model the effect of 1.5 ml syngeneic whole blood on tumour cell adhesion and tumour growth was investigated. In the same model the effect of 1.5 ml pure red blood cell (RBC) concentrate and 1.5 ml RBC-derived substances on tumour cell adhesion was studied. In an established in vitro model the effect of increasing numbers of RBCs (0-250 bx 10(6)) on tumour cell adhesion and tumour growth was assessed. Both the presence of blood and RBC concentrate in the peritoneal cavity prevented tumour cell adhesion in vivo (overall P effect on tumour cell adhesion. In in vitro studies RBCs inhibited tumour cell adhesion but not tumour growth. RBC-derived factors prevent tumour cell adhesion to the peritoneum, and consequently tumour recurrence.

  16. Pathological Deformations of Brain Vascular System Modelling Using Analogous Eletromagnetic Systems

    Directory of Open Access Journals (Sweden)

    Klara Capova

    2004-01-01

    Full Text Available The contribution deals with the modelling and simulation of human brain haemodynamics using analogous electromagnetic systems characteristic especially propagation properties of distributed parameters circuits. The cascade connection of analogical transmission line elements represents the vascular tree both from the point of the parameters and the topology as well. In the paper there are presented simulation examples of the healthy cerebral system mainly in the big arteries in comparing with the pathologically changed ones. The various degrees of stenosis are considered for the simulations of blood pressure and blood flow velocity and the results are compared with the healthy arteries. According to the last investigations the pathological deformations of brain arteries are th most frequently reasons of deaths in the world. The stenoses or aneurysms change the physical properties of arteries and they follow insufficient vascularisation of the brain. These computer-aided non-invasive methods together with the non-invasive experimental techniques represent a helpful tool both for the diagnostics and the treatment of vascular pathological deformations.

  17. Amyloid Accumulation Drives Proteome-wide Alterations in Mouse Models of Alzheimer's Disease-like Pathology.

    Science.gov (United States)

    Savas, Jeffrey N; Wang, Yi-Zhi; DeNardo, Laura A; Martinez-Bartolome, Salvador; McClatchy, Daniel B; Hark, Timothy J; Shanks, Natalie F; Cozzolino, Kira A; Lavallée-Adam, Mathieu; Smukowski, Samuel N; Park, Sung Kyu; Kelly, Jeffery W; Koo, Edward H; Nakagawa, Terunaga; Masliah, Eliezer; Ghosh, Anirvan; Yates, John R

    2017-11-28

    Amyloid beta (Aβ) peptides impair multiple cellular pathways and play a causative role in Alzheimer's disease (AD) pathology, but how the brain proteome is remodeled by this process is unknown. To identify protein networks associated with AD-like pathology, we performed global quantitative proteomic analysis in three mouse models at young and old ages. Our analysis revealed a robust increase in Apolipoprotein E (ApoE) levels in nearly all brain regions with increased Aβ levels. Taken together with prior findings on ApoE driving Aβ accumulation, this analysis points to a pathological dysregulation of the ApoE-Aβ axis. We also found dysregulation of protein networks involved in excitatory synaptic transmission. Analysis of the AMPA receptor (AMPAR) complex revealed specific loss of TARPγ-2, a key AMPAR-trafficking protein. Expression of TARPγ-2 in hAPP transgenic mice restored AMPA currents. This proteomic database represents a resource for the identification of protein alterations responsible for AD. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Study of non-linear models for the evaluation of cancerous tumours

    International Nuclear Information System (INIS)

    Gonzalez, J.A.; Quintanar M, L.; Ortiz H, E.

    1994-01-01

    A complete investigation of some models of interaction between population of lymphocytes and cancer cells was carried out. Bifurcations of this dynamical systems are described. Some recommendations are given for the medical treatment. (Author)

  19. Mammalian Models of Duchenne Muscular Dystrophy: Pathological Characteristics and Therapeutic Applications

    Directory of Open Access Journals (Sweden)

    Akinori Nakamura

    2011-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is a devastating X-linked muscle disorder characterized by muscle wasting which is caused by mutations in the DMD gene. The DMD gene encodes the sarcolemmal protein dystrophin, and loss of dystrophin causes muscle degeneration and necrosis. Thus far, therapies for this disorder are unavailable. However, various therapeutic trials based on gene therapy, exon skipping, cell therapy, read through therapy, or pharmaceutical agents have been conducted extensively. In the development of therapy as well as elucidation of pathogenesis in DMD, appropriate animal models are needed. Various animal models of DMD have been identified, and mammalian (murine, canine, and feline models are indispensable for the examination of the mechanisms of pathogenesis and the development of therapies. Here, we review the pathological features of DMD and therapeutic applications, especially of exon skipping using antisense oligonucleotides and gene therapies using viral vectors in murine and canine models of DMD.

  20. Diagnosis and treatment of bronchopulmonary neuroendocrine tumours

    DEFF Research Database (Denmark)

    Tabaksblat, Elizaveta Mitkina; Langer, Seppo W; Knigge, Ulrich

    2016-01-01

    Bronchopulmonary neuroendocrine tumours (BP-NET) are a heterogeneous population of neoplasms with different pathology, clinical behaviour and prognosis compared to the more common lung cancers. The management of BP-NET patients is largely based on studies with a low level of evidence...

  1. The origin of Pasteurella multocida impacts pathology and inflammation when assessed in a mouse model

    DEFF Research Database (Denmark)

    Pors, Susanne E.; Chadfield, Mark S.; Sorensen, Dorte B.

    2016-01-01

    Host-pathogen interactions of Pasteurella multocida isolates of different origin were studied in a mouse model, focusing on pathology, bacterial load and expression of the metalloproteinase MMP9 and its inhibitor TIMP1. Intranasal inoculation with one of three doses (10(6), 10(4), 10(2) CFU...... dose dependent and consisted of exudative bronchopneumonia, abscess formation in liver and a lower bacterial load in lung and liver. Both isolates caused increased expression of MMP9 and TIMP1. In conclusion, evaluation and comparison of pathogenicity and host-pathogen interaction of P. multocida...

  2. Wilms' tumour (nephroblastoma)

    African Journals Online (AJOL)

    Wilms' tumour or nephroblastoma is a cancer of the kidney that typically occurs in children and very rarely in adults. The common name is an eponym, referring to Dr Max Wilms, the German surgeon who first described this type of tumour in 1899. Wilms' tumour is the most common form of kidney cancer in children.

  3. Incidence and prevalence of salivary gland tumours in Valparaiso, Chile

    Science.gov (United States)

    Araya, Juan; Martinez, René; Niklander, Sven; Marshall, Maureen

    2015-01-01

    Background To determine the incidence and prevalence of salivary gland tumours in the province of Valparaíso, Chile. Material and Methods Retrospective review of salivary gland tumours diagnosed between the years 2000 and 2011 from four local pathology services. Information on demographics and histopathology were retrieved from the medical records. Results The study sample consisted of 279 salivary gland tumours. Prevalence and incidence rates per 100.000 persons were 15.4 and 2.51, respectively. Most of the neoplasms corresponded to benign tumours (70.3%). The most affected gland was the parotid gland. Pleomorphic adenoma was the most common benign tumour (53.8%) and mucoepidermoid carcinoma was the most common malignant tumour (7.2%). Conclusions Salivary gland tumours are uncommon neoplasms that usually arise in the parotid gland. Pleomorphic adenoma and mucoepidermoid carcinoma were the most common benign and malignant tumours reported in this series. Key words:Salivary gland tumours, benign tumours, malignant tumours, salivary glands neoplasms, cancer, neoplasia. PMID:26034925

  4. Maintaining Tumour Heterogeneity in Patient-Derived Tumour Xenografts

    Science.gov (United States)

    Cassidy, John W; Caldas, Carlos; Bruna, Alejandra

    2015-01-01

    Pre-clinical models often fail to capture the diverse heterogeneity of human malignancies and as such lack clinical predictive power. Patient-derived tumour xenografts (PDXs) have emerged as a powerful technology: capable of retaining the molecular heterogeneity of their originating sample. However, heterogeneity within a tumour is governed by both cell-autonomous (e.g. genetic and epigenetic heterogeneity) and non-cell-autonomous (e.g. stromal heterogeneity) drivers. Whilst PDXs can largely recapitulate the polygenomic architecture of human tumours, they do not fully account for heterogeneity in the tumour microenvironment. Hence, these models have substantial utility in basic and translational research in cancer biology; but study of stromal or immune drivers of malignant progression may be limited. Similarly, PDX models offer the ability to conduct patient specific in vivo and ex vivo drug screens, but stromal contributions to treatment responses may be under-represented. This review discusses the sources and consequences of intratumour heterogeneity and how these are recapitulated in the PDX model. Limitations of the current generation of PDXs are discussed and strategies to improve several aspects of the model with respect to preserving heterogeneity are proposed. PMID:26180079

  5. A database survey of equine tumours in the United Kingdom.

    Science.gov (United States)

    Knowles, E J; Tremaine, W H; Pearson, G R; Mair, T S

    2016-05-01

    Survey data on equine tumours are sparse compared with other species and may have changed over time. To describe the most frequently diagnosed equine tumours recorded by a diagnostic pathology laboratory over 29 years, to identify background factors associated with tumour type, and to identify any changes in the tumours diagnosed or the background of cases submitted during the study period. Observational; cross-sectional analysis of records of a diagnostic pathology laboratory. The records of all neoplastic equine histology submissions to the University of Bristol (January 1982-December 2010) were accessed from a database, and a list of diagnoses compiled. The 6 most commonly diagnosed tumour types were analysed using logistic regression to identify background factors associated with tumour type. The overall population of equine tumour submissions and the relative frequency of diagnosis of the most common tumour types were compared between decades. There were 964 cases included. The most frequently diagnosed tumours were: sarcoid (24% cases), squamous cell carcinoma (SCC) (19%), lymphoma (14%), melanoma (6%), gonadal stromal tumour (6%) and mast cell tumour (MCT) (4%). With sarcoid, Thoroughbred/Thoroughbred cross and gelding as reference categories: increasing age was significantly associated with the odds of each of the other tumour types, mares were at reduced risk of SCC, Arab/Arab cross had a higher risk of MCT, Cob/Cob cross had an increased risk of SCC and MCT, and ponies had an increased risk of melanoma. The mean age of submissions increased in each successive decade and the breed composition became broader. Sarcoids and lymphoma formed a smaller proportion of diagnoses in later decades. The types of tumours submitted to this laboratory have changed over the last 3 decades. Current data inform clinicians and researchers and further studies are warranted to follow trends. © 2015 EVJ Ltd.

  6. An inverse model for locating skin tumours in 3D using the genetic algorithm with the Dual Reciprocity Boundary Element Method

    Directory of Open Access Journals (Sweden)

    Fabrício Ribeiro Bueno

    Full Text Available Here, the Dual Reciprocity Boundary Element Method is used to solve the 3D Pennes Bioheat Equation, which together with a Genetic Algorithm, produces an inverse model capable of obtaining the location and the size of a tumour, having as data input the temperature distribution measured on the skin surface. Given that the objective function, which is solved inversely, involves the DRBEM (Dual Reciprocity Boundary Element Method the Genetic Algorithm in its usual form becomes slower, in such a way that it was necessary to develop functions based the solution history in order that the process becomes quicker and more accurate. Results for 8 examples are presented including cases with convection and radiation boundary conditions. Cases involving noise in the readings of the equipment are also considered. This technique is intended to assist health workers in the diagnosis of tumours.

  7. A neural mass model of basal ganglia nuclei simulates pathological beta rhythm in Parkinson's disease

    Science.gov (United States)

    Liu, Fei; Wang, Jiang; Liu, Chen; Li, Huiyan; Deng, Bin; Fietkiewicz, Chris; Loparo, Kenneth A.

    2016-12-01

    An increase in beta oscillations within the basal ganglia nuclei has been shown to be associated with movement disorder, such as Parkinson's disease. The motor cortex and an excitatory-inhibitory neuronal network composed of the subthalamic nucleus (STN) and the external globus pallidus (GPe) are thought to play an important role in the generation of these oscillations. In this paper, we propose a neuron mass model of the basal ganglia on the population level that reproduces the Parkinsonian oscillations in a reciprocal excitatory-inhibitory network. Moreover, it is shown that the generation and frequency of these pathological beta oscillations are varied by the coupling strength and the intrinsic characteristics of the basal ganglia. Simulation results reveal that increase of the coupling strength induces the generation of the beta oscillation, as well as enhances the oscillation frequency. However, for the intrinsic properties of each nucleus in the excitatory-inhibitory network, the STN primarily influences the generation of the beta oscillation while the GPe mainly determines its frequency. Interestingly, describing function analysis applied on this model theoretically explains the mechanism of pathological beta oscillations.

  8. The origin of Pasteurella multocida impacts pathology and inflammation when assessed in a mouse model.

    Science.gov (United States)

    Pors, Susanne E; Chadfield, Mark S; Sørensen, Dorte B; Offenberg, Hanne; Bisgaard, Magne; Jensen, Henrik E

    2016-04-01

    Host-pathogen interactions of Pasteurella multocida isolates of different origin were studied in a mouse model, focusing on pathology, bacterial load and expression of the metalloproteinase MMP9 and its inhibitor TIMP1. Intranasal inoculation with one of three doses (10(6), 10(4), 10(2)CFU) of an isolate from porcine pneumonia or fowl cholera showed marked differences between the two isolates. The avian isolate was highly pathogenic with severe signs of necrotizing pneumonia, liver necrosis and high bacterial load in lung and liver. Clinical signs and pathology related to the porcine isolate were dose dependent and consisted of exudative bronchopneumonia, abscess formation in liver and a lower bacterial load in lung and liver. Both isolates caused increased expression of MMP9 and TIMP1. In conclusion, evaluation and comparison of pathogenicity and host-pathogen interaction of P. multocida isolates from different hosts is possible in the intranasal murine model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Pathologic evaluation of hemostatic agents in percutaneous nephrolithotomy tracts in a porcine model.

    Science.gov (United States)

    Lipkin, Michael E; Mancini, John G; Simmons, W Neal; Raymundo, Maria E; Yong, Daniel Z; Wang, Agnes J; Ferrandino, Michael N; Albala, David M; Preminger, Glenn M

    2011-08-01

    Hemostatic agents have been suggested as an adjunct for tubeless percutaneous nephrolithotomy (PCNL). We pathologically evaluated the percutaneous tracts injected with the fibrin sealant (FS) Evicel and hemostatic gelatin matrix (HGM) Surgiflo at various time intervals to determine their absorption and tract closure rates. We also evaluated whether these agents reduced urine leak rates in a porcine model. Percutaneous access was obtained in 19 kidneys in 10 domestic swine. The tracts were dilated to 30F using a balloon dilating catheter. Ten kidneys served as controls. Surgiflo was injected into the tract of four kidneys, and Evicel was injected into the tract of five kidneys. Intravenous urography (IVU) was performed on postoperative days (POD) 1 and 10 to 14. IVU was performed on two pigs at POD 30. The pigs were sacrificed and kidneys were harvested for pathologic evaluation. Two (20%) control kidneys had a urine leak on IVU on POD 1. None of the kidneys treated with HGM or FS had a urine leak on POD 1. None of the kidneys had a leak on POD 10 to 14 or POD 30. On pathologic inspection, the tracts of all the control kidneys and HGM kidneys had closed completely at POD 14. Two kidneys treated with FS had fistula at POD 6 and POD 14. At POD 30, the tracts in the control kidneys and kidney treated with HGM had completely healed. Fibrin sealant remained in the tract at POD 30. Fibrin sealant should be used with caution because it can persist in the tract for up to 30 days and may inhibit wound healing. Hemostatic gelatin matrix is the preferable agent because the tract closed by POD 10 to 14, similar to the findings in the control animals. The use of hemostatic agents in a nephroscopy tract may reduce the risk of early urine leak after tubeless PCNL.

  10. Modeling the Circle of Willis Using Electrical Analogy Method under both Normal and Pathological Circumstances

    Science.gov (United States)

    Abdi, Mohsen; Karimi, Alireza; Navidbakhsh, Mahdi; Rahmati, Mohammadali; Hassani, Kamran; Razmkon, Ali

    2013-01-01

    Background and objective: The circle of Willis (COW) supports adequate blood supply to the brain. The cardiovascular system, in the current study, is modeled using an equivalent electronic system focusing on the COW. Methods: In our previous study we used 42 compartments to model whole cardiovascular system. In the current study, nevertheless, we extended our model by using 63 compartments to model whole CS. Each cardiovascular artery is modeled using electrical elements, including resistor, capacitor, and inductor. The MATLAB Simulink software is used to obtain the left and right ventricles pressure as well as pressure distribution at efferent arteries of the circle of Willis. Firstly, the normal operation of the system is shown and then the stenosis of cerebral arteries is induced in the circuit and, consequently, the effects are studied. Results: In the normal condition, the difference between pressure distribution of right and left efferent arteries (left and right ACA–A2, left and right MCA, left and right PCA–P2) is calculated to indicate the effect of anatomical difference between left and right sides of supplying arteries of the COW. In stenosis cases, the effect of internal carotid artery occlusion on efferent arteries pressure is investigated. The modeling results are verified by comparing to the clinical observation reported in the literature. Conclusion: We believe the presented model is a useful tool for representing the normal operation of the cardiovascular system and study of the pathologies. PMID:25505747

  11. Magnetic resonance-imaging of the effect of targeted antiangiogenic gene delivery in a melanoma tumour model

    Energy Technology Data Exchange (ETDEWEB)

    Hundt, Walter [Stanford School of Medicine, Department of Radiology, Lucas MRS Research Center, Stanford, CA (United States); Philipps University Marburg, Department of Radiology, Marburg (Germany); Steinbach, Silke [Philipps University Marburg, Department of Otolaryngology Head and Neck Surgery, Marburg (Germany); Mayer, Dirk; Guccione, Samira [Stanford School of Medicine, Department of Radiology, Lucas MRS Research Center, Stanford, CA (United States); Burbelko, Mykhaylo; Kiessling, Andreas; Figiel, Jens [Philipps University Marburg, Department of Radiology, Marburg (Germany)

    2015-04-01

    We investigated the effect of targeted gene therapy to melanoma tumours (M21) by MR-imaging. M21 and M21-L tumours were grown to a size of 850 mm{sup 3}. M21 and M21-L tumours were intravenously treated with an αvβ3-integrin-ligand-coupled nanoparticle (RGDNP)/RAF(-) complex five times every 72 hours. MRI was performed at set time intervals 24h and 72h after the i.v. injection of the complex. The MRI protocol was T1-wt-SE±CM, T2-wt-FSE, DCE-MRI, Diffusion-wt-STEAM-sequence, T2-time obtained on a 1.5-T-GE-MRI device. The size of the treated M21 tumours kept nearly constant during the treatment phase (847.8±31.4 mm{sup 3} versus 904.8±44.4 mm{sup 3}). The SNR value (T2-weighted images) of the tumours was 36.7±0.6 and dropped down to 30.6±1.9 (p=0.004). At the beginning the SNR value (T1-weighted images) of the tumours after contrast medium application was 42.3±1.9 and dropped down to 28.5±3.0 (p<0.001). In the treatment group the diffusion coefficient increased significantly under therapy (0.54±0.01x10{sup -3} mm{sup 2}/s versus 0.67±0.04x10{sup -3} mm{sup 2}/s). The DCE-MRI showed a reduction of the slope and of the Akep of 67.8±4.3 % respectively 64.8±3.3 % compared to baseline. Targeted gene delivery therapy induces significant changes in MR-imaging. MRI showed a significant reduction of contrast medium uptake parameters and increase of the diffusion coefficient of the tumours. (orig.)

  12. Preparation of 125IUdR and its evaluation in animal tumour model as a potential therapeutic agent

    International Nuclear Information System (INIS)

    Korde, A.; Venkatesh, M.; Banerjee, S.; Pillai, M.R.A.; Sarma, H.D.

    1998-01-01

    5-Iodo-2'-deoxyuridine or iodoxyuridine (IUdR), an analogue of thymidine, is taken up by the proliferating cells during DNA synthesis. Radioiodinated IUdR is a potential therapeutic agent since radiohalogenated thymidine analogues are used for in-vivo tumour targeting and Auger electrons from radionuclides such as 123 I and 125 I are very effective in cell destruction when internalised. 125 IUdR was prepared and studied for its suitability as an in-vivo tumour therapy agent. 125 IUdR was prepared both by direct iodination of 2'-deoxyuridine and iododemercuration of 5-chloromercury-2'-deoxyuridine. Radioiodination yields were between 60-80% at pH 7. Iododemercuration was preferred since with direct iodination poor yields were observed when high specific activity product was desired and also the purification procedure was lengthier. The identity of 125 IUdR was established by comparison of TLC and HPLC patterns with those of authentic IUdR. The purified 125 IUdR had radiochemical purity >95% and was stable for 20 days at 4 deg. C and for a week at 23 deg. C and 37 deg. C. Bio-uptake of 125 IUdR was studied by injecting the tracer in tumour bearing mice (Sarcoma S-180). The uptake in tumour cells was 4.28 +- 2.7% per gram at 3 h and 1.48 +- 0.19% at 24 h post injection. In-vivo deiodination of the product was observed as seen by the uptake of the activity in the thyroid. About 40% the activity from all other organs was excreted in 70 h. The optimum time for injection of the tracer for therapy was studied by observing the delay in tumour growth and survival rate in mice injected at 0,3,9 and 12 days after tumour induction. Injection of the tracer on the third day was found to be the most beneficial for retardation of tumour growth, while injection of the activity on the zeroth and ninth day had no effect. (author)

  13. Edema-induced increase in tumour cell survival for 125I and 103Pd prostate permanent seed implants - a bio-mathematical model

    International Nuclear Information System (INIS)

    Yue Ning; Chen Zhe; Nath, Ravinder

    2002-01-01

    Edema caused by the surgical procedure of prostate seed implantation expands the source-to-point distances within the prostate and hence decreases the dose coverage. The decrease of dose coverage results in an increase in tumour cell survival. To investigate the effects of edema on tumour cell survival, a bio-mathematical model of edema and the corresponding cell killing by continuous low dose rate irradiation (CLDRI) was developed so that tumour cell surviving fractions can be estimated in an edematous prostate for both 125 I and 103 Pd seed implants. The dynamic nature of edema and its resolution were modelled with an exponential function V(T)=V p (1+M exp(-0.693T/T e )) where V p is the prostate volume before implantation, M is the edema magnitude and T e is edema half-life (EHL). The dose rate of a radioactive seed was calculated according to AAPM TG43, i.e. D radical S k Δg(r) φ-bar an /r 2 , where r is the distance between a seed and a given point. The distance r is now a function of time because of edema. The g(r) was approximated as 1/r 0.4 and 1/r 0.8 for 125 I and 103 Pd, respectively. By expanding the mathematical expression of the resultant dose rate in a Taylor series of exponential functions of time, the dose rate was made equivalent to that produced from multiple fictitious radionuclides of different decay constants and strengths. The biologically effective dose (BED) for an edematous prostate implant was then calculated using a generalized Dale equation. The cell surviving fraction was computed as exp(-αBED), where α is the linear coefficient of the survival curve. The tumour cell survival was calculated for both 125 I and 103 Pd seed implants and for different tumour potential doubling time (TPDT) (from 5 days to 30 days) and for edemas of different magnitudes (from 0% to 95%) and edema half-lives (from 4 days to 30 days). Tumour cell survival increased with the increase of edema magnitude and EHL. For a typical edema of a half-life of 10 days

  14. Edema-induced increase in tumour cell survival for {sup 125}I and {sup 103}Pd prostate permanent seed implants - a bio-mathematical model

    Energy Technology Data Exchange (ETDEWEB)

    Yue Ning; Chen Zhe; Nath, Ravinder [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT (United States)

    2002-04-01

    Edema caused by the surgical procedure of prostate seed implantation expands the source-to-point distances within the prostate and hence decreases the dose coverage. The decrease of dose coverage results in an increase in tumour cell survival. To investigate the effects of edema on tumour cell survival, a bio-mathematical model of edema and the corresponding cell killing by continuous low dose rate irradiation (CLDRI) was developed so that tumour cell surviving fractions can be estimated in an edematous prostate for both {sup 125}I and {sup 103}Pd seed implants. The dynamic nature of edema and its resolution were modelled with an exponential function V(T)=V{sub p} (1+M exp(-0.693T/T{sub e})) where V{sub p} is the prostate volume before implantation, M is the edema magnitude and T{sub e} is edema half-life (EHL). The dose rate of a radioactive seed was calculated according to AAPM TG43, i.e. D radical S{sub k}{delta}g(r) {phi}-bar{sub an}/r{sup 2}, where r is the distance between a seed and a given point. The distance r is now a function of time because of edema. The g(r) was approximated as 1/r{sup 0.4} and 1/r{sup 0.8} for {sup 125}I and {sup 103}Pd, respectively. By expanding the mathematical expression of the resultant dose rate in a Taylor series of exponential functions of time, the dose rate was made equivalent to that produced from multiple fictitious radionuclides of different decay constants and strengths. The biologically effective dose (BED) for an edematous prostate implant was then calculated using a generalized Dale equation. The cell surviving fraction was computed as exp(-{alpha}BED), where {alpha} is the linear coefficient of the survival curve. The tumour cell survival was calculated for both {sup 125}I and {sup 103}Pd seed implants and for different tumour potential doubling time (TPDT) (from 5 days to 30 days) and for edemas of different magnitudes (from 0% to 95%) and edema half-lives (from 4 days to 30 days). Tumour cell survival increased

  15. A data model and database for high-resolution pathology analytical image informatics

    Directory of Open Access Journals (Sweden)

    Fusheng Wang

    2011-01-01

    Full Text Available Background: The systematic analysis of imaged pathology specimens often results in a vast amount of morphological information at both the cellular and sub-cellular scales. While microscopy scanners and computerized analysis are capable of capturing and analyzing data rapidly, microscopy image data remain underutilized in research and clinical settings. One major obstacle which tends to reduce wider adoption of these new technologies throughout the clinical and scientific communities is the challenge of managing, querying, and integrating the vast amounts of data resulting from the analysis of large digital pathology datasets. This paper presents a data model, which addresses these challenges, and demonstrates its implementation in a relational database system. Context: This paper describes a data model, referred to as Pathology Analytic Imaging Standards (PAIS, and a database implementation, which are designed to support the data management and query requirements of detailed characterization of micro-anatomic morphology through many interrelated analysis pipelines on whole-slide images and tissue microarrays (TMAs. Aims: (1 Development of a data model capable of efficiently representing and storing virtual slide related image, annotation, markup, and feature information. (2 Development of a database, based on the data model, capable of supporting queries for data retrieval based on analysis and image metadata, queries for comparison of results from different analyses, and spatial queries on segmented regions, features, and classified objects. Settings and Design: The work described in this paper is motivated by the challenges associated with characterization of micro-scale features for comparative and correlative analyses involving whole-slides tissue images and TMAs. Technologies for digitizing tissues have advanced significantly in the past decade. Slide scanners are capable of producing high-magnification, high-resolution images from whole

  16. Personality correlates of pathological gambling derived from Big Three and Big Five personality models.

    Science.gov (United States)

    Miller, Joshua D; Mackillop, James; Fortune, Erica E; Maples, Jessica; Lance, Charles E; Keith Campbell, W; Goodie, Adam S

    2013-03-30

    Personality traits have proved to be consistent and important factors in a variety of externalizing behaviors including addiction, aggression, and antisocial behavior. Given the comorbidity of these behaviors with pathological gambling (PG), it is important to test the degree to which PG shares these trait correlates. In a large community sample of regular gamblers (N=354; 111 with diagnoses of pathological gambling), the relations between measures of two major models of personality - Big Three and Big Five - were examined in relation to PG symptoms derived from a semi-structured diagnostic interview. Across measures, traits related to the experience of strong negative emotions were the most consistent correlates of PG, regardless of whether they were analyzed using bivariate or multivariate analyses. In several instances, however, the relations between personality and PG were moderated by demographic variable such as gender, race, and age. It will be important for future empirical work of this nature to pay closer attention to potentially important moderators of these relations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Altered protein glycosylation predicts Alzheimer's disease and modulates its pathology in disease model Drosophila.

    Science.gov (United States)

    Frenkel-Pinter, Moran; Stempler, Shiri; Tal-Mazaki, Sharon; Losev, Yelena; Singh-Anand, Avnika; Escobar-Álvarez, Daniela; Lezmy, Jonathan; Gazit, Ehud; Ruppin, Eytan; Segal, Daniel

    2017-08-01

    The pathological hallmarks of Alzheimer's disease (AD) are pathogenic oligomers and fibrils of misfolded amyloidogenic proteins (e.g., β-amyloid and hyper-phosphorylated tau in AD), which cause progressive loss of neurons in the brain and nervous system. Although deviations from normal protein glycosylation have been documented in AD, their role in disease pathology has been barely explored. Here our analysis of available expression data sets indicates that many glycosylation-related genes are differentially expressed in brains of AD patients compared with healthy controls. The robust differences found enabled us to predict the occurrence of AD with remarkable accuracy in a test cohort and identify a set of key genes whose expression determines this classification. We then studied in vivo the effect of reducing expression of homologs of 6 of these genes in transgenic Drosophila overexpressing human tau, a well-established invertebrate AD model. These experiments have led to the identification of glycosylation genes that may augment or ameliorate tauopathy phenotypes. Our results indicate that OstDelta, l(2)not and beta4GalT7 are tauopathy suppressors, whereas pgnat5 and CG33303 are enhancers, of tauopathy. These results suggest that specific alterations in protein glycosylation may play a causal role in AD etiology. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Klotho gene silencing promotes pathology in the mdx mouse model of Duchenne muscular dystrophy

    Science.gov (United States)

    Wehling-Henricks, Michelle; Li, Zhenzhi; Lindsey, Catherine; Wang, Ying; Welc, Steven S.; Ramos, Julian N.; Khanlou, Négar; Kuro-o, Makoto; Tidball, James G.

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a lethal muscle disease involving progressive loss of muscle regenerative capacity and increased fibrosis. We tested whether epigenetic silencing of the klotho gene occurs in the mdx mouse model of DMD and whether klotho silencing is an important feature of the disease. Our findings show that klotho undergoes muscle-specific silencing at the acute onset of mdx pathology. Klotho experiences increased methylation of CpG sites in its promoter region, which is associated with gene silencing, and increases in a repressive histone mark, H3K9me2. Expression of a klotho transgene in mdx mice restored their longevity, reduced muscle wasting, improved function and greatly increased the pool of muscle-resident stem cells required for regeneration. Reductions of fibrosis in late, progressive stages of the mdx pathology achieved by transgene expression were paralleled by reduced expression of Wnt target genes (axin-2), transforming growth factor-beta (TGF-β1) and collagens types 1 and 3, indicating that Klotho inhibition of the profibrotic Wnt/TGFβ axis underlies its anti-fibrotic effect in aging, dystrophic muscle. Thus, epigenetic silencing of klotho during muscular dystrophy contributes substantially to lost regenerative capacity and increased fibrosis of dystrophic muscle during late progressive stages of the disease. PMID:27154199

  19. Allograft in bone tumour surgery

    International Nuclear Information System (INIS)

    Sengupta, S.

    1999-01-01

    In the last twenty years, there has been a vast improvement in the prognosis of primary malignant tumours of bone. This is due to many factors including early detection, staging and classification of tumours as a result of better staining and imaging techniques, better surgical technology, e.g. endoprosthesis and most importantly adjuvant treatment with cytotoxic drugs. As a result of long term survival, amputation of limb has more or less been replaced by limb salvage surgery. This procedure consists of two parts. Primary objective is of course complete removal of the tumour by adequate soft tissue cover and secondarily by reconstruction of the locomotor system, If possible with retention of the function of the limb. These procedures include endo-prosthetic replacement or arthroplasty and arthrodesis using autologus grafts, allograft or combination. With the development of bone banks and assured safety of preserved bones, reconstructive limb salvage surgery using massive allograft is gradually replacing prosthetic implants. The advantages include replacement of articular surfaces, incorporation of the graft to the host bone, attachment of bone tissue and increased probably permanent survival. Allograft can be used for intercalary replacement, osteo-articular arthroplasty arthrodesis or filling large cavities. Inherent complication of massive allograft are disease transmission, infection, delayed and non-union, pathological fractures, mechanical failure and joint destruction. Several limb salvage procedures using allografts have been carried out in our institution with one failure due to infection. Paucity of available allograft has restricted more such procedures to be carried out

  20. The joint structure of normal and pathological personality: further evidence for a dimensional model.

    Science.gov (United States)

    Hengartner, Michael P; Ajdacic-Gross, Vladeta; Rodgers, Stephanie; Müller, Mario; Rössler, Wulf

    2014-04-01

    The literature proposes a joint structure of normal and pathological personality with higher-order factors mainly based on the five-factor model of personality (FFM). The purpose of the present study was to examine the joint structure of the FFM and the DSM-IV personality disorders (PDs) and to discuss this structure with regard to higher-order domains commonly reported in the literature. We applied a canonical correlation analysis, a series of principal component analyses with oblique Promax rotation and a bi-factor analysis with Geomin rotation on 511 subjects of the general population of Zurich, Switzerland, using data from the ZInEP Epidemiology Survey. The 5 FFM traits and the 10 DSM-IV PD dimensions shared 77% of total variance. Component extraction tests pointed towards a two- and three-component solution. The two-component solution comprised a first component with strong positive loadings on neuroticism and all 10 PD dimensions and a second component with strong negative loadings on extraversion and openness and positive loadings on schizoid and avoidant PDs. The three-component solution added a third component with strong positive loadings on conscientiousness and agreeableness and a negative loading on antisocial PD. The bi-factor model provided evidence for 1 general personality dysfunction factor related to neuroticism and 5 group factors, although the interpretability of the latter was limited. Normal and pathological personality domains are not isomorphic or superposable, although they share a substantial proportion of variance. The two and three higher-order domains extracted in the present study correspond well to equivalent factor-solutions reported in the literature. Moreover, these superordinate factors can consistently be integrated within a hierarchical structure of alternative four- and five-factor models. The top of the hierarchy presumably constitutes a general personality dysfunction factor which is closely related to neuroticism. © 2014.

  1. Anorexia-cachexia syndrome in hepatoma tumour-bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC-1/GDF15.

    Science.gov (United States)

    Borner, Tito; Arnold, Myrtha; Ruud, Johan; Breit, Samuel N; Langhans, Wolfgang; Lutz, Thomas A; Blomqvist, Anders; Riediger, Thomas

    2017-06-01

    The cancer-anorexia-cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour-derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour-derived macrophage inhibitory cytokine-1 (MIC-1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC-1 in mice. Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC-1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response. In tumour-bearing sham-operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer-induced anorexia or body weight loss. Tumour-bearing rats had substantially increased MIC-1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake. These findings demonstrate the importance of the AP in the mediation of cancer-dependent anorexia and body weight loss and support a pathological role of MIC-1 as a tumour-derived factor mediating CACS, possibly via an AP-dependent action. © 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle

  2. Why are epididymal tumours so rare?

    Science.gov (United States)

    Yeung, Ching-Hei; Wang, Kai; Cooper, Trevor G

    2012-01-01

    Epididymal tumour incidence is at most 0.03% of all male cancers. It is an enigma why the human epididymis does not often succumb to cancer, when it expresses markers of stem and cancer cells, and constitutively expresses oncogenes, pro-proliferative and pro-angiogenic factors that allow tumour cells to escape immunosurveillance in cancer-prone tissues. The privileged position of the human epididymis in evading tumourigenicity is reflected in transgenic mouse models in which induction of tumours in other organs is not accompanied by epididymal neoplasia. The epididymis appears to: (i) prevent tumour initiation (it probably lacks stem cells and has strong anti-oxidative mechanisms, active tumour suppressors and inactive oncogene products); (ii) foster tumour monitoring and destruction (by strong immuno-surveillance and -eradication, and cellular senescence); (iii) avert proliferation and angiogenesis (with persistent tight junctions, the presence of anti-angiogenic factors and misplaced pro-angiogenic factors), which together (iv) promote dormancy and restrict dividing cells to hyperplasia. Epididymal cells may be rendered non-responsive to oncogenic stimuli by the constitutive expression of factors generally inducible in tumours, and resistant to the normal epididymal environment, which mimics that of a tumour niche promoting tumour growth. The threshold for tumour initiation may thus be higher in the epididymis than in other organs. Several anti-tumour mechanisms are those that maintain spermatozoa quiescent and immunologically silent, so the low incidence of cancer in the epididymis may be a consequence of its role in sperm maturation and storage. Understanding these mechanisms may throw light on cancer prevention and therapy in general. PMID:22522502

  3. Diffusion-weighted MR imaging of metastatic abdominal and pelvic tumours is sensitive to early changes induced by a VEGF inhibitor using alternative diffusion attenuation models

    Energy Technology Data Exchange (ETDEWEB)

    Orton, Matthew R. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Institute of Cancer Research, Sutton, Surrey (United Kingdom); Messiou, Christina; DeSouza, Nandita [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Royal Marsden NHS Foundation Trust, Department of Radiology, Sutton, Surrey (United Kingdom); Collins, David; Leach, Martin O. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Morgan, Veronica A. [Royal Marsden NHS Foundation Trust, Department of Radiology, Sutton, Surrey (United Kingdom); Tessier, Jean; Young, Helen [Early Clinical Development, AstraZeneca, Macclesfield (United Kingdom)

    2016-05-15

    To assess the utility of diffusion weighted imaging for monitoring early treatment effects associated with a VEGF inhibitor. Twenty-nine patients with metastatic abdominal and pelvic tumours were recruited and imaged with DW-MRI: twice at baseline, and after 7 and 28 days of treatment with cediranib. Tumour measures were derived using mono-exponential, bi-exponential and stretched-exponential models, and parameter repeatability and treatment effects seen after 7 and 28 days were assessed. Correlations with volume changes and DCE-MRI metrics were also assessed. Diffusion coefficient repeatabilities from all models were < 6 %; f and D* (bi-exponential) were 22 % and 44 %; α (stretched-exponential) was 4.2 %. Significant increases in the diffusion coefficients from all models were observed at day 28 but not day 7. Significant decreases in D* and f.D* were observed at day 7 and in f at day 28; significant increases in α were observed at both time-points. Weak correlations between DW-MRI changes and volume changes and DCE-MRI changes were observed. DW-MRI is sensitive to early and late treatment changes caused by a VEGF inhibitor using non-mono-exponential models. Evidence of over-fitting using the bi-exponential model suggests that the stretched-exponential model is best suited to monitor such changes. (orig.)

  4. Histology types of chest wall tumours: Fifteen year single center ...

    African Journals Online (AJOL)

    Materials and Methods: We performed a retrospective study of chest wall tumours at our institution(NCTCE, UNTH, Enugu, Nigeria), for a period of 15 years, spanning October, 2001 to September, 2015.The pathologic reports were retrieved from the hospital pathology archives and correlated with patients' copies in the ...

  5. The dimensional nature of eating pathology: Evidence from a direct comparison of categorical, dimensional, and hybrid models.

    Science.gov (United States)

    Luo, Xiaochen; Donnellan, M Brent; Burt, S Alexandra; Klump, Kelly L

    2016-07-01

    Eating disorders are conceptualized as categorical rather than dimensional in the current major diagnostic system (Diagnostic and Statistical Manual of Mental Disorders; 5th ed.; American Psychiatric Association, 2013) and in many previous studies. However, previous research has not critically evaluated this assumption or tested hybrid models (e.g., modeling latent variables with both dimensional and categorical features). Accordingly, the current study directly compared categorical, dimensional, and hybrid models for eating pathology in a large, population-based sample. Participants included 3,032 female and male twins (ages 9-30 years) from the Michigan State University Twin Registry. The Minnesota Eating Behaviors Survey was used to assess disordered eating symptoms including body dissatisfaction, weight preoccupation, binge eating, and compensatory behaviors. Results showed that dimensional models best fit the data in the overall sample as well as across subgroups divided by sex and pubertal status (e.g., prepubertal vs. postpubertal). It is interesting to note that the results favored more categorical models when using a case-control subset of our sample with participants who either endorsed substantial eating pathology or no/little eating pathology. Overall, findings provide support for a dimensional conceptualization of eating pathology and underscore the importance of using community samples to capture the full range of severity of eating pathology when investigating questions about taxonomy. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  6. Dynamic pathology for circulating free DNA in a dextran sodium sulfate colitis mouse model.

    Science.gov (United States)

    Koike, Yuhki; Uchida, Keiichi; Tanaka, Koji; Ide, Shozo; Otake, Kohei; Okita, Yoshiki; Inoue, Mikihiro; Araki, Toshimitsu; Mizoguchi, Akira; Kusunoki, Masato

    2014-12-01

    In sepsis, circulating free DNA (cf-DNA) is increased, and is a marker of severity and prognosis of septic patients. This study aimed to evaluate cf-DNA in a dextran sodium sulfate-induced colitis mouse model, and its clinical implications. Dynamic pathology of the cecum wall in the DSS-induced colitis mouse model was analyzed using multiphoton microscopy (MPM). Plasma cf-DNA concentrations in colitis mouse were quantified using PicoGreen dsDNA Assay Kit. Plasma cf-DNA was also measured in 123 human ulcerative colitis (UC) patients [mean age: 35.9 years (3-75 years) with 20 pediatric patients] to assess its relationships with clinical severity and Matt's grade. Real-time images of cf-DNA were detected in the colitis model. The amount of labeled cf-DNA in the circulation of the colitis mice group was significantly higher compared with that in the control group (P UC blood samples, plasma cf-DNA concentrations in UC patients were significantly positively correlated with the clinical severity of UC and Matt's grade (P colitis mouse model. Plasma cf-DNA is a potential non-invasive blood marker for reflecting clinical severity and mucosal damage in UC patients.

  7. Knockdown of aberrantly expressed nuclear localized decorin attenuates tumour angiogenesis related mediators in oral cancer progression model in vitro.

    Science.gov (United States)

    Dil, Nyla; Banerjee, Abhijit G

    2012-06-08

    Oral cancer accounts for roughly 3% of cancer cases in the world with about 350,000 newly reported cases annually and a 5-year survival rate of only 50%. Majority of oral cancers are squamous cell carcinomas that originate in the oral mucosal epithelial linings. We have previously shown that in human malignant squamous cells carcinoma (SCC-25) as well as in dysplastic oral keratinocytes (DOK), a small leucine-rich multifunctional proteoglycan decorin is aberrantly expressed and localized in the nucleus where it interacts with nuclear epidermal growth factor receptor (EGFR). Post-transcriptional silencing of nuclear decorin significantly reduced IL-8 and IL8-dependent migration and invasion in these dysplastic and malignant oral epithelia. The objective of this study was to further examine the effects of nuclear decorin silencing on angiogenesis and angiogenesis related mediators in this oral cancer progression cell line model. We have used multiplex PCR, western blotting, and in vitro endothelial tube formation assay to study angiogenesis and related pathways in nuclear decorin silenced (stable knockdown) DOK and SCC-25 cells. Nuclear decorin knockdown resulted in significant down regulation of IL-8 expression, however IL-10, and TGF-β expression was not affected in either DOK or SCC25 cells as measured by multiplex RT PCR. IL-8 receptor CXCR 1 and 2 expression was slightly lower in nuclear decorin silenced cells indicating a contributing mechanism in previously shown reduced IL-8 mediated migration and invasion phenotype in these cells. IL-8 is known to induce Matrix metalloproteinase 9 (MMP9) which not only plays a role in tumour migration and invasion but also induces angiogenic switch. We found MMP9 to be significantly reduced in nuclear decorin silenced dysplastic and malignant oral epithelia. Other potent angiogenic mediators, VEGF189 and ANG-1 were either significantly reduced or completely abrogated in these cells. Angiogenesis as measured by endothelial

  8. Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology.

    Directory of Open Access Journals (Sweden)

    Wen Liang

    Full Text Available The recently developed histological scoring system for non-alcoholic fatty liver disease (NAFLD by the NASH Clinical Research Network (NASH-CRN has been widely used in clinical settings, but is increasingly employed in preclinical research as well. However, it has not been systematically analyzed whether the human scoring system can directly be converted to preclinical rodent models. To analyze this, we systematically compared human NAFLD liver pathology, using human liver biopsies, with liver pathology of several NAFLD mouse models. Based upon the features pertaining to mouse NAFLD, we aimed at establishing a modified generic scoring system that is applicable to broad spectrum of rodent models.The histopathology of NAFLD was analyzed in several different mouse models of NAFLD to define generic criteria for histological assessment (preclinical scoring system. For validation of this scoring system, 36 slides of mouse livers, covering the whole spectrum of NAFLD, were blindly analyzed by ten observers. Additionally, the livers were blindly scored by one observer during two separate assessments longer than 3 months apart.The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient between the ten observers was high for the analysis of macrovesicular steatosis and microvesicular steatosis (ICC = 0.784 and 0.776, all p<0.001, respectively and moderate for the analysis of hypertrophy and inflammation (ICC = 0.685 and 0.650, all p<0.001, respectively. The intra-observer reproducibility between the different observations of one observer was high for the analysis of macrovesicular steatosis, microvesicular steatosis and hypertrophy (ICC = 0.871, 0.871 and 0.896, all p<0.001, respectively and very high for the analysis of inflammation (ICC = 0.931, p

  9. Passive immunization with phospho-tau antibodies reduces tau pathology and functional deficits in two distinct mouse tauopathy models.

    Directory of Open Access Journals (Sweden)

    Sethu Sankaranarayanan

    Full Text Available In Alzheimer's disease (AD, an extensive accumulation of extracellular amyloid plaques and intraneuronal tau tangles, along with neuronal loss, is evident in distinct brain regions. Staging of tau pathology by postmortem analysis of AD subjects suggests a sequence of initiation and subsequent spread of neurofibrillary tau tangles along defined brain anatomical pathways. Further, the severity of cognitive deficits correlates with the degree and extent of tau pathology. In this study, we demonstrate that phospho-tau (p-tau antibodies, PHF6 and PHF13, can prevent the induction of tau pathology in primary neuron cultures. The impact of passive immunotherapy on the formation and spread of tau pathology, as well as functional deficits, was subsequently evaluated with these antibodies in two distinct transgenic mouse tauopathy models. The rTg4510 transgenic mouse is characterized by inducible over-expression of P301L mutant tau, and exhibits robust age-dependent brain tau pathology. Systemic treatment with PHF6 and PHF13 from 3 to 6 months of age led to a significant decline in brain and CSF p-tau levels. In a second model, injection of preformed tau fibrils (PFFs comprised of recombinant tau protein encompassing the microtubule-repeat domains into the cortex and hippocampus of young P301S mutant tau over-expressing mice (PS19 led to robust tau pathology on the ipsilateral side with evidence of spread to distant sites, including the contralateral hippocampus and bilateral entorhinal cortex 4 weeks post-injection. Systemic treatment with PHF13 led to a significant decline in the spread of tau pathology in this model. The reduction in tau species after p-tau antibody treatment was associated with an improvement in novel-object recognition memory test in both models. These studies provide evidence supporting the use of tau immunotherapy as a potential treatment option for AD and other tauopathies.

  10. Diffusion kurtosis imaging of a human nasopharyngeal carcinoma xenograft model: Initial experience with pathological correlation.

    Science.gov (United States)

    Zhong, Jing; Shi, Peng; Chen, Yunbin; Huang, Rongfang; Xiao, Youping; Zheng, Xiang; Zheng, Dechun; Peng, Li

    2018-04-01

    The aim of this study was to investigate the relationship between diffusion kurtosis imaging (DKI)-related parameters and pathological measures using human nasopharyngeal carcinoma (NPC) xenografts in a nude mouse model. Twenty-six BALB/c-nu nude mice were divided into two groups that were injected with two different nasopharyngeal squamous cell carcinoma cell lines (CNE1 and CNE2). DK magnetic resonance (MR) imaging was performed on a 3.0 Tesla MR scanner. DWI and DKI-related parameters, including apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis (MK) were measured. Mice were euthanatized when the maximum diameter of the primary tumor reached 1.5cm after MR scanning. Tumor tissues were then processed for hematoxylin and eosin staining. The pathological images were analyzed using a computer-aided pixel-wise clustering method to evaluate tumor cellular density, nuclei portion, cytoplasm portion, extracellular space portion, the ratio of nuclei to cytoplasm and the ratio of nuclei to extracellular space. The relationships between DWI and DKI-related parameters and pathological features were analyzed statistically. The ADC and MD values of the CNE1 group (1.16±0.24×10 -3 mm 2 /s, 2.28±0.29×10 -3 mm 2 /s) was higher than that of the CNE2 group (0.82±0.14×10 -3 mm 2 /s, 1.53±0.24×10 -3 mm 2 /s, P0.05). A Pearson test showed that the ADC and MD values were significantly correlated with cellular density, nuclei portion, extracellular space portion and the ratio of nuclei to extracellular space (r=-0.861; -0.909, P<0.001; r=-0.487; 0.591, P<0.05; r=0.567; 0.625, P<0.05; r=-0.645; -0.745, P<0.001, respectively). The MK values were significantly correlated with nuclei portion, cytoplasm portion and the ratio of nuclei to cytoplasm (r=-0.475, P<0.05; r=0.665, P<0.001; r=-0.494, P<0.05, respectively). The preliminary animal results suggest that DKI findings can provide valuable bio-information for NPC tissue characterization. DKI imaging

  11. Specificity of paediatric jawbone lesions: tumours and pseudotumours.

    Science.gov (United States)

    Kadlub, Natacha; Kreindel, Tamara; Belle Mbou, Valère; Coudert, Amélie; Ansari, Edward; Descroix, Vianney; Ruhin-Poncet, Blandine; Coulomb L'hermine, Aurore; Berdal, Ariane; Vazquez, Marie-Paule; Ducou Lepointe, Hubert; Picard, Arnaud

    2014-03-01

    Characteristics and epidemiology of jaw tumours have been described mostly in adults. Compared with their adult counterparts, childhood jaw tumours show considerable differences. The aim of this study was to describe the different jaw tumours in children, define diagnostic tools to determine their specificity and describe optimal treatment. All children patients with jaw lesions, excluding cysts, apical granuloma and osteitis were included in our study between 1999 and 2009. The medical records were analyzed for clinical, radiological, and pathological findings, treatments and recurrences. Mean patient age was 10.9 years old, ranging from 2 months to 18 years old. Of the 63 lesions, 18 were odontogenic and 45 non-odontogenic lesions. 6% of all cases were malignant tumours; the mean age of presentation was 7.25 years old, [ranging from 0.2 to 18 years old]. Approximately 80% of the tumours developed after 6 years of age. Odontogenic tumours occurred more often after the age of 6. Compared with their adult counterpart, childhood jaw tumours show considerable differences in their clinical behaviour and radiological and pathological characteristics. Clinical features of some tumours can be specific to children. Tumourigenesis is related to dental development and facial growth. Conservative treatment should be considered. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  12. Recapitulating physiological and pathological shear stress and oxygen to model vasculature in health and disease

    Science.gov (United States)

    Abaci, Hasan Erbil; Shen, Yu-I.; Tan, Scott; Gerecht, Sharon

    2014-05-01

    Studying human vascular disease in conventional cell cultures and in animal models does not effectively mimic the complex vascular microenvironment and may not accurately predict vascular responses in humans. We utilized a microfluidic device to recapitulate both shear stress and O2 levels in health and disease, establishing a microfluidic vascular model (μVM). Maintaining human endothelial cells (ECs) in healthy-mimicking conditions resulted in conversion to a physiological phenotype namely cell elongation, reduced proliferation, lowered angiogenic gene expression and formation of actin cortical rim and continuous barrier. We next examined the responses of the healthy μVM to a vasotoxic cancer drug, 5-Fluorouracil (5-FU), in comparison with an in vivo mouse model. We found that 5-FU does not induce apoptosis rather vascular hyperpermeability, which can be alleviated by Resveratrol treatment. This effect was confirmed by in vivo findings identifying a vasoprotecting strategy by the adjunct therapy of 5-FU with Resveratrol. The μVM of ischemic disease demonstrated the transition of ECs from a quiescent to an activated state, with higher proliferation rate, upregulation of angiogenic genes, and impaired barrier integrity. The μVM offers opportunities to study and predict human ECs with physiologically relevant phenotypes in healthy, pathological and drug-treated environments.

  13. Individualizing Management of Complex Esophageal Pathology Using Three-Dimensional Printed Models.

    Science.gov (United States)

    Dickinson, Karen J; Matsumoto, Jane; Cassivi, Stephen D; Reinersman, J Matthew; Fletcher, Joel G; Morris, Jonathan; Wong Kee Song, Louis M; Blackmon, Shanda H

    2015-08-01

    In complex esophageal cases, conventional two-dimensional imaging is limited in demonstrating anatomic relationships. We describe the utility of three-dimensional (3D) printed models for complex patients to individualize care. Oral effervescent agents, with positive enteric contrast, distended the esophagus during computed tomography (CT) scanning to facilitate segmentation during post-processing. The CT data were segmented, converted into a stereolithography file, and printed using photopolymer materials. In 1 patient with a left pneumonectomy, aortic bypass, and esophageal diversion, 3D printing enabled visualization of the native esophagus and facilitated endoscopic mucosal resection, followed by hiatal dissection and division of the gastroesophageal junction as treatment. In a second patient, 3D printing allowed enhanced visualization of multiple esophageal diverticula, allowing for optimization of the surgical approach. Printing of 3D anatomic models in patients with complex esophageal pathology facilitates planning the optimal surgical approach and anticipating potential difficulties for the multidisciplinary team. These models are invaluable for patient education. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  14. 3D Printed Models of Cleft Palate Pathology for Surgical Education.

    Science.gov (United States)

    Lioufas, Peter A; Quayle, Michelle R; Leong, James C; McMenamin, Paul G

    2016-09-01

    To explore the potential viability and limitations of 3D printed models of children with cleft palate deformity. The advantages of 3D printed replicas of normal anatomical specimens have previously been described. The creation of 3D prints displaying patient-specific anatomical pathology for surgical planning and interventions is an emerging field. Here we explored the possibility of taking rare pediatric radiographic data sets to create 3D prints for surgical education. Magnetic resonance imaging data of 2 children (8 and 14 months) were segmented, colored, and anonymized, and stereolothographic files were prepared for 3D printing on either multicolor plastic or powder 3D printers and multimaterial 3D printers. Two models were deemed of sufficient quality and anatomical accuracy to print unamended. One data set was further manipulated digitally to artificially extend the length of the cleft. Thus, 3 models were printed: 1 incomplete soft-palate deformity, 1 incomplete anterior palate deformity, and 1 complete cleft palate. All had cleft lip deformity. The single-material 3D prints are of sufficient quality to accurately identify the nature and extent of the deformities. Multimaterial prints were subsequently created, which could be valuable in surgical training. Improvements in the quality and resolution of radiographic imaging combined with the advent of multicolor multiproperty printer technology will make it feasible in the near future to print 3D replicas in materials that mimic the mechanical properties and color of live human tissue making them potentially suitable for surgical training.

  15. The evaluation of in vitro effect of daunorubicin and tamoxifen in ehrlich ascites tumour (EAT) cells

    International Nuclear Information System (INIS)

    Topcul, M.; Topcul, F.; Oezalpan, A.

    2001-01-01

    In the most countries, breast cancer is still the most important cancer among women. It is known that Ehrlich Ascites Tumour is experimental breast cancer model in animal. The cells used in the study are hyper diploid line of Ehrlich Ascites Tumour (EAT) cells, initially provided to us from Institute of Pathology, Koln University. In the present study, an hyper diploid line which is estrogen receptor positive was used. An anthracycline-derived antibiotic, Daunorubicin (DNR, Cerubidine) is one of the clinically used anticancer drugs. DNR has been used alone or in combination with other cytotoxic agents against a variety of animal and human tumours. In vitro cell culture studies show that DNR enters the cell nuclei, inhibits nucleic acid synthesis, and arrest cell division. Tamoxifen (TAM, Nolvadex) is a semi-synthetical estrogen antagonist, used in the management of pre and post menopausal breast cancer. This drug bind to intracellular estrogen receptors, and prevents endogenous estrogens from binding to their own receptors. It is known that Ehrlich Ascites Tumour is experimental breast cancer model in animal. The cells used in the study are hyper diploid line of EAT cells initially provided to us from Institute of Pathology, Koln University. In the present study, an hyper diploid line which is Estrogen Receptor (+) was used. Estrogen Receptor levels were studied by the methods of Lippman and Huff and Raynaud et al. with minor modifications. Estrogen Receptor activity as demonstrated by dextran-coated charcoal technique is closely correlated with the clinical ability of Tamoxifen to inhibit tumour growth

  16. Relationships: empirical contribution. Understanding personality pathology in adolescents: the five factor model of personality and social information processing.

    Science.gov (United States)

    Hessels, Christel; van den Hanenberg, Danique; de Castro, Bram Orobio; van Aken, Marcel A G

    2014-02-01

    This study seeks to integrate two research traditions that lie at the base of the understanding of personality pathology in adolescents. The first research tradition refers to normal personality according to the Five Factor Model (FFM). The second tradition specifies the key feature of personality disorder as the capacity to mentalize, which can be reflected in Social Information Processing (SIP). In a clinical sample of 96 adolescents, the authors investigated response generation, coping strategy, and memories of past frustrating experiences as part of SIP, as mediator in the relationship between personality and personality pathology, and a possible moderating role of personality on the relationship between SIP and personality pathology. The hypothesized mediation, by which the effects of personality dimensions on personality pathology was expected to be mediated by SIP variables, was found only for the effect of Neuroticism, most specifically on BPD, which appeared to be mediated by memories the patients had about past frustrating conflict situations with peers. Some moderating effects of personality on the relationship between SIP variables and personality pathology were found, suggesting that high Agreeableness and sometimes low Neuroticism can buffer this relationship. These results suggest that personality dimensions and social cognitions both independently and together play a role in adolescents' personality pathology.

  17. Radiation-induced brain tumours: potential late complications of radiation therapy for brain tumours

    International Nuclear Information System (INIS)

    Nishio, S.; Morioka, T.; Inamura, T.; Takeshita, I.; Fukui, M.; Sasaki, M.; Nakamura, K.; Wakisaka, S.

    1998-01-01

    The development of neoplasms subsequent to therapeutic cranial irradiation is a rare but serious and potentially fatal complication. In this study, we retrospectively reviewed the clinical and pathological aspects of 11 patients who underwent cranial irradiation (range, 24-110 cGy) to treat their primary disease and thereafter developed secondary tumours within a span of 13 years. All tumours arose within the previous radiation fields, and satisfied the widely used criteria for the definition of radiation-induced neoplasms. There was no sex predominance (M: 5, F: 6) and the patients tended to be young at irradiation (1.3 - 42 years; median age: 22 years). The median latency period before the detection of the secondary tumour was 14.5 years (range: 6.5 - 24 years). Meningiomas developed in 5 patients, sarcomas in 4, and malignant gliomas in 2. A pre-operative diagnosis of a secondary tumour was correctly obtained in 10 patients based on the neuro-imaging as well as nuclear medicine findings. All patients underwent a surgical removal of the secondary tumour, 3 underwent additional chemotherapy, and one received stereotactic secondary irradiation therapy. During a median of 2 years of follow-up review after the diagnosis of a secondary tumour, 3 patients died related to the secondary tumours (2 sarcomas, 1 glioblastoma), one died of a recurrent primary glioma, while the remaining 7 have been alive for from 10 months to 12 years after being treated for the secondary tumours (median: 3 years). Based on these data, the clinicopathological characteristics and possible role of treatment for secondary tumours are briefly discussed. (author)

  18. Magnetic resonance imaging of reconstructed ferritin as an iron-induced pathological model system

    Energy Technology Data Exchange (ETDEWEB)

    Balejcikova, Lucia [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia); Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Strbak, Oliver [Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin (Slovakia); Baciak, Ladislav [Faculty of Chemical and Food Technology STU, Radlinskeho 9, 812 37 Bratislava (Slovakia); Kovac, Jozef [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia); Masarova, Marta; Krafcik, Andrej; Frollo, Ivan [Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Dobrota, Dusan [Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin (Slovakia); Kopcansky, Peter [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia)

    2017-04-01

    Iron, an essential element of the human body, is a significant risk factor, particularly in the case of its concentration increasing above the specific limit. Therefore, iron is stored in the non-toxic form of the globular protein, ferritin, consisting of an apoferritin shell and iron core. Numerous studies confirmed the disruption of homeostasis and accumulation of iron in patients with various diseases (e.g. cancer, cardiovascular or neurological conditions), which is closely related to ferritin metabolism. Such iron imbalance enables the use of magnetic resonance imaging (MRI) as a sensitive technique for the detection of iron-based aggregates through changes in the relaxation times, followed by the change in the inherent image contrast. For our in vitrostudy, modified ferritins with different iron loadings were prepared by chemical reconstruction of the iron core in an apoferritin shell as pathological model systems. The magnetic properties of samples were studied using SQUID magnetometry, while the size distribution was detected via dynamic light scattering. We have shown that MRI could represent the most advantageous method for distinguishing native ferritin from reconstructed ferritin which, after future standardisation, could then be suitable for the diagnostics of diseases associated with iron accumulation. - Highlights: • MRI is the sensitive technique for detecting iron-based aggregates. • Reconstructed Ferritin is suitable model system of iron-related disorders. • MRI allow distinguish of native ferritin from reconstructed ferritin. • MRI could be useful for diagnostics of diseases associated with iron accumulation.

  19. Finding regions of interest in pathological images: an attentional model approach

    Science.gov (United States)

    Gómez, Francisco; Villalón, Julio; Gutierrez, Ricardo; Romero, Eduardo

    2009-02-01

    This paper introduces an automated method for finding diagnostic regions-of-interest (RoIs) in histopathological images. This method is based on the cognitive process of visual selective attention that arises during a pathologist's image examination. Specifically, it emulates the first examination phase, which consists in a coarse search for tissue structures at a "low zoom" to separate the image into relevant regions.1 The pathologist's cognitive performance depends on inherent image visual cues - bottom-up information - and on acquired clinical medicine knowledge - top-down mechanisms -. Our pathologist's visual attention model integrates the latter two components. The selected bottom-up information includes local low level features such as intensity, color, orientation and texture information. Top-down information is related to the anatomical and pathological structures known by the expert. A coarse approximation to these structures is achieved by an oversegmentation algorithm, inspired by psychological grouping theories. The algorithm parameters are learned from an expert pathologist's segmentation. Top-down and bottom-up integration is achieved by calculating a unique index for each of the low level characteristics inside the region. Relevancy is estimated as a simple average of these indexes. Finally, a binary decision rule defines whether or not a region is interesting. The method was evaluated on a set of 49 images using a perceptually-weighted evaluation criterion, finding a quality gain of 3dB when comparing to a classical bottom-up model of attention.

  20. Explaining pathological changes in axonal excitability through dynamical analysis of conductance-based models

    Science.gov (United States)

    Coggan, Jay S.; Ocker, Gabriel K.; Sejnowski, Terrence J.; Prescott, Steven A.

    2011-10-01

    Neurons rely on action potentials, or spikes, to relay information. Pathological changes in spike generation likely contribute to certain enigmatic features of neurological disease, like paroxysmal attacks of pain and muscle spasm. Paroxysmal symptoms are characterized by abrupt onset and short duration, and are associated with abnormal spiking although the exact pathophysiology remains unclear. To help decipher the biophysical basis for 'paroxysmal' spiking, we replicated afterdischarge (i.e. continued spiking after a brief stimulus) in a minimal conductance-based axon model. We then applied nonlinear dynamical analysis to explain the dynamical basis for initiation and termination of afterdischarge. A perturbation could abruptly switch the system between two (quasi-)stable attractor states: rest and repetitive spiking. This bistability was a consequence of slow positive feedback mediated by persistent inward current. Initiation of afterdischarge was explained by activation of the persistent inward current forcing the system to cross a saddle point that separates the basins of attraction associated with each attractor. Termination of afterdischarge was explained by the attractor associated with repetitive spiking being destroyed. This occurred when ultra-slow negative feedback, such as intracellular sodium accumulation, caused the saddle point and stable limit cycle to collide; in that regard, the active attractor is not truly stable when the slowest dynamics are taken into account. The model also explains other features of paroxysmal symptoms, including temporal summation and refractoriness.

  1. ERP-based detection of brain pathology in rat models for preclinical Alzheimer's disease

    Science.gov (United States)

    Nouriziabari, Seyed Berdia

    Early pathological features of Alzheimer's disease (AD) include the accumulation of hyperphosphorylated tau protein (HP-tau) in the entorhinal cortex and progressive loss of basal forebrain (BF) cholinergic neurons. These pathologies are known to remain asymptomatic for many years before AD is clinically diagnosed; however, they may induce aberrant brain processing which can be captured as an abnormality in event-related potentials (ERPs). Here, we examined cortical ERPs while a differential associative learning paradigm was applied to adult male rats with entorhinal HP-tau, pharmacological blockade of muscarinic acetylcholine receptors, or both conditions. Despite no impairment in differential associative and reversal learning, each pathological feature induced distinct abnormality in cortical ERPs to an extent that was sufficient for machine classifiers to accurately detect a specific type of pathology based on these ERP features. These results highlight a potential use of ERPs during differential associative learning as a biomarker for asymptomatic AD pathology.

  2. Radiosensitivity of malignant tumours

    International Nuclear Information System (INIS)

    Partskhaladze, N.N.

    1980-01-01

    Tumour tissue has been transplanted to 5 groups of rats to study the effect of general pre-transplantation X-ray irradiation of the recipient on the effect of transplantation of the irradiated tumour tissue. In the first group - the suspension of native timour tissue has been transplanted to intact rats; in the second group - the suspension of native tumour tissue has been transplanted to rats that have formerly been subjected to a single immunization with subcutaneously irradiated timour material; in the third group - the suspension of native tumour tissue has been transplanted to totally irradiated animals; in the fourth group - the syspension of irradiated tumour tissue has been transplanted to intact rats; in the fifts group - the suspension of irradiated timour tissue has been transplanted to totally irradiated rats. The reseach has shown that there exists a weak antitumoral immunity that manifests itself only at the time of gratting tumour tissue in a small amount. In this case one can observe the decrease in the tumour development in rats formerly subjected to the effect of lethally irradiated tumour cells and the increase of cell transplantation in totally irradiated mice. Transplanted irradiated 0.77 Coul/kg timour tissue in the irradiated organism develops better than in the organism of intact animals

  3. Computational modelling of traumatic brain injury predicts the location of chronic traumatic encephalopathy pathology.

    Science.gov (United States)

    Ghajari, Mazdak; Hellyer, Peter J; Sharp, David J

    2017-02-01

    Traumatic brain injury can lead to the neurodegenerative disease chronic traumatic encephalopathy. This condition has a clear neuropathological definition but the relationship between the initial head impact and the pattern of progressive brain pathology is poorly understood. We test the hypothesis that mechanical strain and strain rate are greatest in sulci, where neuropathology is prominently seen in chronic traumatic encephalopathy, and whether human neuroimaging observations converge with computational predictions. Three distinct types of injury were simulated. Chronic traumatic encephalopathy can occur after sporting injuries, so we studied a helmet-to-helmet impact in an American football game. In addition, we investigated an occipital head impact due to a fall from ground level and a helmeted head impact in a road traffic accident involving a motorcycle and a car. A high fidelity 3D computational model of brain injury biomechanics was developed and the contours of strain and strain rate at the grey matter-white matter boundary were mapped. Diffusion tensor imaging abnormalities in a cohort of 97 traumatic brain injury patients were also mapped at the grey matter-white matter boundary. Fifty-one healthy subjects served as controls. The computational models predicted large strain most prominent at the depths of sulci. The volume fraction of sulcal regions exceeding brain injury thresholds were significantly larger than that of gyral regions. Strain and strain rates were highest for the road traffic accident and sporting injury. Strain was greater in the sulci for all injury types, but strain rate was greater only in the road traffic and sporting injuries. Diffusion tensor imaging showed converging imaging abnormalities within sulcal regions with a significant decrease in fractional anisotropy in the patient group compared to controls within the sulci. Our results show that brain tissue deformation induced by head impact loading is greatest in sulcal locations

  4. Salivary gland tumours in a Mexican sample. A retrospective study.

    Science.gov (United States)

    Ledesma-Montes, C; Garces-Ortiz, M

    2002-01-01

    Salivary gland tumours are an important part of the Oral and Maxillofacial Pathology, unfortunately, only few studies on these tumours have been done in Latin-American population. The aim of this study was to compare demographic data on salivary gland tumours in a Mexican sample with those previously published from Latin American and non-Latin American countries. All cases of salivary gland tumours or lesions diagnosed in our service were reviewed. Of the reviewed cases,67 were confirmed as salivary gland tumours. Out of these 64.2% were benign neoplasms, 35.8% were malignant and a slight female predominance (56.7%) was found. The most common location was palate followed by lips and floor of the mouth. Mean age for benign tumours was 40.6 years with female predominance (60.5%). Mean age for malignant tumours was 41 years and female predominance was found again. Palate followed by retromolar area were the usual locations. Pleomorphic adenoma (58.2%), mucoepidermoid carcinoma (17.9%) and adenoid cystic carcinoma (11.9%) were the more frequent neoplasms. All retromolar cases were malignant and all submandibular gland tumours were benign. We found a high proportion of salivary gland neoplasms in children. Our results showed that differences of the studied tumours among our sample and previously reported series exist. These differences can be related to race and geographical location.

  5. Tumour control probability derived from dose distribution in homogeneous and heterogeneous models: assuming similar pharmacokinetics, 125Sn–177Lu is superior to 90Y–177Lu in peptide receptor radiotherapy

    International Nuclear Information System (INIS)

    Walrand, Stephan; Hanin, François-Xavier; Pauwels, Stanislas; Jamar, François

    2012-01-01

    Clinical trials on 177 Lu– 90 Y therapy used empirical activity ratios. Radionuclides (RN) with larger beta maximal range could favourably replace 90 Y. Our aim is to provide RN dose-deposition kernels and to compare the tumour control probability (TCP) of RN combinations. Dose kernels were derived by integration of the mono-energetic beta-ray dose distributions (computed using Monte Carlo) weighted by their respective beta spectrum. Nine homogeneous spherical tumours (1–25 mm in diameter) and four spherical tumours including a lattice of cold, but alive, spheres (1, 3, 5, 7 mm in diameter) were modelled. The TCP for 93 Y, 90 Y and 125 Sn in combination with 177 Lu in variable proportions (that kept constant the renal cortex biological effective dose) were derived by 3D dose kernel convolution. For a mean tumour-absorbed dose of 180 Gy, 2 mm homogeneous tumours and tumours including 3 mm diameter cold alive spheres were both well controlled (TCP > 0.9) using a 75–25% combination of 177 Lu and 90 Y activity. However, 125 Sn– 177 Lu achieved a significantly better result by controlling 1 mm-homogeneous tumour simultaneously with tumours including 5 mm diameter cold alive spheres. Clinical trials using RN combinations should use RN proportions tuned to the patient dosimetry. 125 Sn production and its coupling to somatostatin analogue appear feasible. Assuming similar pharmacokinetics 125 Sn is the best RN for combination with 177 Lu in peptide receptor radiotherapy justifying pharmacokinetics studies in rodent of 125 Sn-labelled somatostatin analogues. (paper)

  6. Human breast cancer bone metastasis in vitro and in vivo: a novel 3D model system for studies of tumour cell-bone cell interactions.

    Science.gov (United States)

    Holen, I; Nutter, F; Wilkinson, J M; Evans, C A; Avgoustou, P; Ottewell, Penelope D

    2015-10-01

    Bone is established as the preferred site of breast cancer metastasis. However, the precise mechanisms responsible for this preference remain unidentified. In order to improve outcome for patients with advanced breast cancer and skeletal involvement, we need to better understand how this process is initiated and regulated. As bone metastasis cannot be easily studied in patients, researchers have to date mainly relied on in vivo xenograft models. A major limitation of these is that they do not contain a human bone microenvironment, increasingly considered to be an important component of metastases. In order to address this shortcoming, we have developed a novel humanised bone model, where 1 × 10(5) luciferase-expressing MDA-MB-231 or T47D human breast tumour cells are seeded on viable human subchaodral bone discs in vitro. These discs contain functional osteoclasts 2-weeks after in vitro culture and positive staining for calcine 1-week after culture demonstrating active bone resorption/formation. In vitro inoculation of MDA-MB-231 or T47D cells colonised human bone cores and remained viable for <4 weeks, however, use of matrigel to enhance adhesion or a moving platform to increase diffusion of nutrients provided no additional advantage. Following colonisation by the tumour cells, bone discs pre-seeded with MDA-MB-231 cells were implanted subcutaneously into NOD SCID mice, and tumour growth monitored using in vivo imaging for up to 6 weeks. Tumour growth progressed in human bone discs in 80 % of the animals mimicking the later stages of human bone metastasis. Immunohistochemical and PCR analysis revealed that growing MDA-MB-231 cells in human bone resulted in these cells acquiring a molecular phenotype previously associated with breast cancer bone metastases. MDA-MB-231 cells grown in human bone discs showed increased expression of IL-1B, HRAS and MMP9 and decreased expression of S100A4, whereas, DKK2 and FN1 were unaltered compared with the same cells grown in

  7. Radiological and Pathological Predictors of Response to Neoadjuvant Chemotherapy in Breast Cancer: A Brief Literature Review.

    Science.gov (United States)

    Parekh, Tejal; Dodwell, David; Sharma, Nisha; Shaaban, Abeer M

    2015-09-01

    Early clinical response to neoadjuvant chemotherapy (NACT) in breast cancer correlates with pathological response at surgery. A tailored approach using biomarkers to predict response to NACT has become a research priority. Predictors of response can be divided into pathological and radiological biomarkers. Advances in gene expression profiling and diffusion-weighted MRI techniques are used to predict tumour response, and combinations thereof are the future of predicting response to NACT in early-stage breast cancer. We searched Medline, CINAHL and Embase databases for studies on NACT. Key words used were NACT, breast cancer, pathological* complete response, primary chemotherapy, radiological*, predictor*, gene expression and biomarkers limited to the English language. Pathological markers such as tumour subtypes, topoisomerase IIα expression, Ki67, apoptosis-related markers and gene expression profiling were included. From 119 articles, 42 studies were reviewed; the majority of studies identified used pathological clinical response as an end point to NACT, whilst others used complete clinical response. Despite extensive studies, results regarding long-term survival following NACT and potential predictors are inconclusive. Future development of a predictive model combining key pathological and radiological biomarkers could provide personalised treatment regimens that improve pathological complete response rates and longer-term outcomes. © 2015 S. Karger AG, Basel.

  8. Hepatic tumours in childhood: an experience at the Children Hospital and Institute of Child Health, Lahore.

    Science.gov (United States)

    Zaman, Samina; Hanif, Ghazala; Hussain, Mahvish; Basit, Zunaira; Khan, Saadia; Rathore, Zonaira; Naeem, Awais; Nasir, Mehreen

    2011-11-01

    In this report, we share our experience about the common types of childhood hepatic tumours during 10 years (2001-2010) and compare them with other studies. During 10 years (2001-2010), all the hepatic tumours of childhood received at Pathology Department of the Children Hospital and Institute of Child Health, Lahore Pakistan are recorded. This includes both resected specimens and biopsies. All the slides were reviewed and the pathologic diagnosis was confirmed. We diagnosed 48 liver tumour cases in children (below 18 years of age). Among these tumours, 39 (81.25%) were malignant. Male to female ratio was 2:1. Hepatoblastoma was the most common liver tumour in this age group accounting for 69.23% of all malignant tumours (27 cases). The second most common primary tumour was hepatocellular carcinoma diagnosed in six patients (15.38%). Other malignant tumours were undifferentiated embryonal sarcoma and biliary rhabdomyosarcoma. Benign tumours included mesenchymal hamartoma, infantile haemangioendotheloima, hemangioma and benign cyst. There were also three metastatic tumours during these 10 years. In one case there was tumour necrosis only and as such no definitive diagnosis was rendered. The spectrum of hepatic tumours in children is different from that found in the older age group and most of them are malignant.

  9. Mouse model of GM2 activator deficiency manifests cerebellar pathology and motor impairment.

    Science.gov (United States)

    Liu, Y; Hoffmann, A; Grinberg, A; Westphal, H; McDonald, M P; Miller, K M; Crawley, J N; Sandhoff, K; Suzuki, K; Proia, R L

    1997-07-22

    The GM2 activator deficiency (also known as the AB variant), Tay-Sachs disease, and Sandhoff disease are the major forms of the GM2 gangliosidoses, disorders caused by defective degradation of GM2 ganglioside. Tay-Sachs and Sandhoff diseases are caused by mutations in the genes (HEXA and HEXB) encoding the subunits of beta-hexosaminidase A. The GM2 activator deficiency is caused by mutations in the GM2A gene encoding the GM2 activator protein. For degradation of GM2 ganglioside by beta-hexosamindase A, the GM2 activator protein must participate by forming a soluble complex with the ganglioside. In each of the disorders, GM2 ganglioside and related lipids accumulate to pathologic levels in neuronal lysosomes, resulting in clinically similar disorders with an onset in the first year of life, progressive neurodegeneration, and death by early childhood. We previously have described mouse models of Tay-Sachs (Hexa -/-) and Sandhoff (Hexb -/-) diseases with vastly different clinical phenotypes. The Hexa -/- mice were asymptomatic whereas the Hexb -/- mice were severely affected. Through gene disruption in embryonic stem cells we now have established a mouse model of the GM2 activator deficiency that manifests an intermediate phenotype. The Gm2a -/- mice demonstrated neuronal storage but only in restricted regions of the brain (piriform, entorhinal cortex, amygdala, and hypothalamic nuclei) reminiscent of the asymptomatic Tay-Sachs model mice. However, unlike the Tay-Sachs mice, the Gm2a -/- mice displayed significant storage in the cerebellum and defects in balance and coordination. The abnormal ganglioside storage in the Gm2a -/- mice consisted of GM2 with a low amount of GA2. The results demonstrate that the activator protein is required for GM2 degradation and also may indicate a role for the GM2 activator in GA2 degradation.

  10. Mouse model of GM2 activator deficiency manifests cerebellar pathology and motor impairment

    Science.gov (United States)

    Liu, Yujing; Hoffmann, Alexander; Grinberg, Alexander; Westphal, Heiner; McDonald, Michael P.; Miller, Katherine M.; Crawley, Jacqueline N.; Sandhoff, Konrad; Suzuki, Kinuko; Proia, Richard L.

    1997-01-01

    The GM2 activator deficiency (also known as the AB variant), Tay–Sachs disease, and Sandhoff disease are the major forms of the GM2 gangliosidoses, disorders caused by defective degradation of GM2 ganglioside. Tay–Sachs and Sandhoff diseases are caused by mutations in the genes (HEXA and HEXB) encoding the subunits of β-hexosaminidase A. The GM2 activator deficiency is caused by mutations in the GM2A gene encoding the GM2 activator protein. For degradation of GM2 ganglioside by β-hexosamindase A, the GM2 activator protein must participate by forming a soluble complex with the ganglioside. In each of the disorders, GM2 ganglioside and related lipids accumulate to pathologic levels in neuronal lysosomes, resulting in clinically similar disorders with an onset in the first year of life, progressive neurodegeneration, and death by early childhood. We previously have described mouse models of Tay–Sachs (Hexa −/−) and Sandhoff (Hexb −/−) diseases with vastly different clinical phenotypes. The Hexa −/− mice were asymptomatic whereas the Hexb −/− mice were severely affected. Through gene disruption in embryonic stem cells we now have established a mouse model of the GM2 activator deficiency that manifests an intermediate phenotype. The Gm2a −/− mice demonstrated neuronal storage but only in restricted regions of the brain (piriform, entorhinal cortex, amygdala, and hypothalamic nuclei) reminiscent of the asymptomatic Tay–Sachs model mice. However, unlike the Tay–Sachs mice, the Gm2a −/− mice displayed significant storage in the cerebellum and defects in balance and coordination. The abnormal ganglioside storage in the Gm2a −/− mice consisted of GM2 with a low amount of GA2. The results demonstrate that the activator protein is required for GM2 degradation and also may indicate a role for the GM2 activator in GA2 degradation. PMID:9223328

  11. Magnetic resonance imaging of reconstructed ferritin as an iron-induced pathological model system

    Science.gov (United States)

    Balejcikova, Lucia; Strbak, Oliver; Baciak, Ladislav; Kovac, Jozef; Masarova, Marta; Krafcik, Andrej; Frollo, Ivan; Dobrota, Dusan; Kopcansky, Peter

    2017-04-01

    Iron, an essential element of the human body, is a significant risk factor, particularly in the case of its concentration increasing above the specific limit. Therefore, iron is stored in the non-toxic form of the globular protein, ferritin, consisting of an apoferritin shell and iron core. Numerous studies confirmed the disruption of homeostasis and accumulation of iron in patients with various diseases (e.g. cancer, cardiovascular or neurological conditions), which is closely related to ferritin metabolism. Such iron imbalance enables the use of magnetic resonance imaging (MRI) as a sensitive technique for the detection of iron-based aggregates through changes in the relaxation times, followed by the change in the inherent image contrast. For our in vitrostudy, modified ferritins with different iron loadings were prepared by chemical reconstruction of the iron core in an apoferritin shell as pathological model systems. The magnetic properties of samples were studied using SQUID magnetometry, while the size distribution was detected via dynamic light scattering. We have shown that MRI could represent the most advantageous method for distinguishing native ferritin from reconstructed ferritin which, after future standardisation, could then be suitable for the diagnostics of diseases associated with iron accumulation.

  12. Novel insights into SLC25A46-related pathologies in a genetic mouse model.

    Directory of Open Access Journals (Sweden)

    Maria Eirini Terzenidou

    2017-04-01

    Full Text Available The mitochondrial protein SLC25A46 has been recently identified as a novel pathogenic cause in a wide spectrum of neurological diseases, including inherited optic atrophy, Charcot-Marie-Tooth type 2, Leigh syndrome, progressive myoclonic ataxia and lethal congenital pontocerebellar hypoplasia. SLC25A46 is an outer membrane protein, member of the Solute Carrier 25 (SLC25 family of nuclear genes encoding mitochondrial carriers, with a role in mitochondrial dynamics and cristae maintenance. Here we identified a loss-of-function mutation in the Slc25a46 gene that causes lethal neuropathology in mice. Mutant mice manifest the main clinical features identified in patients, including ataxia, optic atrophy and cerebellar hypoplasia, which were completely rescued by expression of the human ortholog. Histopathological analysis revealed previously unseen lesions, most notably disrupted cytoarchitecture in the cerebellum and retina and prominent abnormalities in the neuromuscular junction. A distinct lymphoid phenotype was also evident. Our mutant mice provide a valid model for understanding the mechanistic basis of the complex SLC25A46-mediated pathologies, as well as for screening potential therapeutic interventions.

  13. Computational Pathology

    Science.gov (United States)

    Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.

    2016-01-01

    Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131

  14. A pictorial review of imaging of abdominal tumours in adolescence

    International Nuclear Information System (INIS)

    Rasalkar, Darshana D.; Chu, Winnie C.W.; Cheng, Frankie W.T.; Li, Chi Kong; Hui, Sze Ki; Ling, Siu Cheung

    2010-01-01

    Neoplastic abdominal tumours, particularly those originating from embryonal tissue (such as hepatoblastoma and nephroblastoma) and neural crest cells (such as neuroblastoma), are well-documented in young children. Neoplasms of adulthood, most commonly carcinoma of different visceral organs, are also well-documented. Abdominal tumours in adolescence constitute a distinct pathological group. The radiological features of some of these tumours have been described only in isolated reports. The purpose of this pictorial essay was to review the imaging findings of various kinds of abdominal tumours in adolescent patients (with an age range of 10-16 years) who presented to the Children Cancer Center of our institution in the past 15 years. Some tumours, though rare, have characteristic imaging appearances (especially in CT) that enable an accurate diagnosis before definite histological confirmation. (orig.)

  15. A pictorial review of imaging of abdominal tumours in adolescence

    Energy Technology Data Exchange (ETDEWEB)

    Rasalkar, Darshana D.; Chu, Winnie C.W. [Chinese University of Hong Kong, Prince of Wales Hospital, Department of Diagnostic Radiology and Organ Imaging, Shatin, New Territories, Hong Kong (China); Cheng, Frankie W.T.; Li, Chi Kong [Chinese University of Hong Kong, Prince of Wales Hospital, Department of Paediatrics, Shatin, Hong Kong (China); Hui, Sze Ki [Princess Margaret Hospital, Department of Obstetrics and Gynaecology, Hong Kong (China); Ling, Siu Cheung [Princess Margaret Hospital, Department of Paediatric and Adolescent Medicine, Hong Kong (China)

    2010-09-15

    Neoplastic abdominal tumours, particularly those originating from embryonal tissue (such as hepatoblastoma and nephroblastoma) and neural crest cells (such as neuroblastoma), are well-documented in young children. Neoplasms of adulthood, most commonly carcinoma of different visceral organs, are also well-documented. Abdominal tumours in adolescence constitute a distinct pathological group. The radiological features of some of these tumours have been described only in isolated reports. The purpose of this pictorial essay was to review the imaging findings of various kinds of abdominal tumours in adolescent patients (with an age range of 10-16 years) who presented to the Children Cancer Center of our institution in the past 15 years. Some tumours, though rare, have characteristic imaging appearances (especially in CT) that enable an accurate diagnosis before definite histological confirmation. (orig.)

  16. Leptin Reduces Pathology and Improves Memory in a Transgenic Mouse Model of Alzheimer’s Disease

    Science.gov (United States)

    Greco, Steven J.; Bryan, Kathryn J.; Sarkar, Sraboni; Zhu, Xiongwei; Smith, Mark A.; Ashford, J. Wesson; Johnston, Jane M.; Tezapsidis, Nikolaos; Casadesus, Gemma

    2010-01-01

    We have previously reported anti-amyloidogenic effects of leptin using in vitro and in vivo models and, more recently, demonstrated the ability of leptin to reduce tau phosphorylation in neuronal cells. The present study examined the efficacy of leptin in ameliorating the Alzheimer’s disease (AD)-like pathology in 6-month old CRND8 transgenic mice (TgCRND8) following 8 weeks of treatment. Leptin-treated transgenic mice showed significantly reduced levels of amyloid-β (Aβ)1-40 in both brain extracts (52% reduction, p=0.047) and serum (55% reduction, p=0.049), as detected by ELISA, and significant reduction in amyloid burden (47% reduction, p=0.041) in the hippocampus, as detected by immunocytochemistry. The decrease in the levels of Aβ in the brain correlated with a decrease in the levels of C99 C-terminal fragments of the amyloid-β protein precursor, consistent with a role for β-secretase in mediating the effect of leptin. In addition, leptin-treated TgCRND8 mice had significantly lower levels of phosphorylated tau, as detected by AT8 and anti-tau-Ser396 antibodies. Importantly, after 4 or 8 weeks of treatment, there was no significant increase in the levels of C-reactive protein, tumor necrosis factor-α, and cortisol in the plasma of leptin-treated TgCRND8 animals compared to saline-treated controls, indicating no inflammatory reaction. These biochemical and pathological changes were correlated with behavioral improvements, as early as after 4 weeks of treatment, as recorded by a novel object recognition test and particularly the contextual and cued fear conditioning test after 8 weeks of treatment. Leptin-treated TgCRND8 animals significantly outperformed saline-treated littermates in these behavioral tests. These findings solidly demonstrate the potential for leptin as a disease modifying therapeutic in transgenic animals of AD, driving optimism for its safety and efficacy in humans. PMID:20308782

  17. Comparison of tumour age response to radiation for cells derived from tissue culture or solid tumours

    International Nuclear Information System (INIS)

    Keng, P.C.; Siemann, D.W.; Rochester Univ., NY; Rochester Univ., NY; Wheeler, K.T.

    1984-01-01

    Direct comparison of the cell age response of 9L and KHT tumour cells derived either from tissue culture or solid tumours was achieved. Cells from dissociated KHT and 9L tumours (the latter implanted either subcutaneously or intracerebrally) and cells from tissue culture were separated into homogenous sized populations by centrifugal elutriation. In both tumour models these homogeneous sized populations correspond to populations enriched at different stages of the cell cycle. The survival of these elutriated cell populations was measured after a single dose of Cs-137 gamma rays. For cells isolated from 9L solid tumours, there was little variation in radiosensitivity throughout the cell cycle; however, a very small but significant increase in resistance was found in late G 1 cells. This lack of a large variation in radiosensitivity through the cell cycle for 9L cells from solid tumours also was seen in 9L cells growing in monolayer tissue culture. When similar experiments were performed using the KHT sarcoma tumour model, the results showed that KHT cells in vitro exhibited a fairly conventional increase in radioresistance in both mid G 1 and late S. However, the cell age response of KHT cells from solid tumours was different; particularly in the late S and G 2 + M phases. (author)

  18. Introduction of Hypermatrix and Operator Notation into a Discrete Mathematics Simulation Model of Malignant Tumour Response to Therapeutic Schemes In Vivo. Some Operator Properties

    Directory of Open Access Journals (Sweden)

    Georgios S. Stamatakos

    2009-10-01

    Full Text Available The tremendous rate of accumulation of experimental and clinical knowledge pertaining to cancer dictates the development of a theoretical framework for the meaningful integration of such knowledge at all levels of biocomplexity. In this context our research group has developed and partly validated a number of spatiotemporal simulation models of in vivo tumour growth and in particular tumour response to several therapeutic schemes. Most of the modeling modules have been based on discrete mathematics and therefore have been formulated in terms of rather complex algorithms (e.g. in pseudocode and actual computer code. However, such lengthy algorithmic descriptions, although sufficient from the mathematical point of view, may render it difficult for an interested reader to readily identify the sequence of the very basic simulation operations that lie at the heart of the entire model. In order to both alleviate this problem and at the same time provide a bridge to symbolic mathematics, we propose the introduction of the notion of hypermatrix in conjunction with that of a discrete operator into the already developed models. Using a radiotherapy response simulation example we demonstrate how the entire model can be considered as the sequential application of a number of discrete operators to a hypermatrix corresponding to the dynamics of the anatomic area of interest. Subsequently, we investigate the operators’ commutativity and outline the “summarize and jump” strategy aiming at efficiently and realistically address multilevel biological problems such as cancer. In order to clarify the actual effect of the composite discrete operator we present further simulation results which are in agreement with the outcome of the clinical study RTOG 83–02, thus strengthening the reliability of the model developed.

  19. Introduction of hypermatrix and operator notation into a discrete mathematics simulation model of malignant tumour response to therapeutic schemes in vivo. Some operator properties.

    Science.gov (United States)

    Stamatakos, Georgios S; Dionysiou, Dimitra D

    2009-10-21

    The tremendous rate of accumulation of experimental and clinical knowledge pertaining to cancer dictates the development of a theoretical framework for the meaningful integration of such knowledge at all levels of biocomplexity. In this context our research group has developed and partly validated a number of spatiotemporal simulation models of in vivo tumour growth and in particular tumour response to several therapeutic schemes. Most of the modeling modules have been based on discrete mathematics and therefore have been formulated in terms of rather complex algorithms (e.g. in pseudocode and actual computer code). However, such lengthy algorithmic descriptions, although sufficient from the mathematical point of view, may render it difficult for an interested reader to readily identify the sequence of the very basic simulation operations that lie at the heart of the entire model. In order to both alleviate this problem and at the same time provide a bridge to symbolic mathematics, we propose the introduction of the notion of hypermatrix in conjunction with that of a discrete operator into the already developed models. Using a radiotherapy response simulation example we demonstrate how the entire model can be considered as the sequential application of a number of discrete operators to a hypermatrix corresponding to the dynamics of the anatomic area of interest. Subsequently, we investigate the operators' commutativity and outline the "summarize and jump" strategy aiming at efficiently and realistically address multilevel biological problems such as cancer. In order to clarify the actual effect of the composite discrete operator we present further simulation results which are in agreement with the outcome of the clinical study RTOG 83-02, thus strengthening the reliability of the model developed.

  20. Methylene blue does not reverse existing neurofibrillary tangle pathology in the rTg4510 mouse model of tauopathy.

    Science.gov (United States)

    Spires-Jones, Tara L; Friedman, Taylor; Pitstick, Rose; Polydoro, Manuela; Roe, Allyson; Carlson, George A; Hyman, Bradley T

    2014-03-06

    Alzheimer's disease is characterized pathologically by aggregation of amyloid beta into senile plaques and aggregation of pathologically modified tau into neurofibrillary tangles. While changes in amyloid processing are strongly implicated in disease initiation, the recent failure of amyloid-based therapies has highlighted the importance of tau as a therapeutic target. "Tangle busting" compounds including methylene blue and analogous molecules are currently being evaluated as therapeutics in Alzheimer's disease. Previous studies indicated that methylene blue can reverse tau aggregation in vitro after 10 min, and subsequent studies suggested that high levels of drug reduce tau protein levels (assessed biochemically) in vivo. Here, we tested whether methylene blue could remove established neurofibrillary tangles in the rTg4510 model of tauopathy, which develops robust tangle pathology. We find that 6 weeks of methylene blue dosing in the water from 16 months to 17.5 months of age decreases soluble tau but does not remove sarkosyl insoluble tau, or histologically defined PHF1 or Gallyas positive tangle pathology. These data indicate that methylene blue treatment will likely not rapidly reverse existing tangle pathology. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. p53-independent DUX4 pathology in cell and animal models of facioscapulohumeral muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Darko Bosnakovski

    2017-10-01

    Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is a genetically dominant myopathy caused by mutations that disrupt repression of the normally silent DUX4 gene, which encodes a transcription factor that has been shown to interfere with myogenesis when misexpressed at very low levels in myoblasts and to cause cell death when overexpressed at high levels. A previous report using adeno-associated virus to deliver high levels of DUX4 to mouse skeletal muscle demonstrated severe pathology that was suppressed on a p53-knockout background, implying that DUX4 acted through the p53 pathway. Here, we investigate the p53 dependence of DUX4 using various in vitro and in vivo models. We find that inhibiting p53 has no effect on the cytoxicity of DUX4 on C2C12 myoblasts, and that expression of DUX4 does not lead to activation of the p53 pathway. DUX4 does lead to expression of the classic p53 target gene Cdkn1a (p21 but in a p53-independent manner. Meta-analysis of 5 publicly available data sets of DUX4 transcriptional profiles in both human and mouse cells shows no evidence of p53 activation, and further reveals that Cdkn1a is a mouse-specific target of DUX4. When the inducible DUX4 mouse model is crossed onto the p53-null background, we find no suppression of the male-specific lethality or skin phenotypes that are characteristic of the DUX4 transgene, and find that primary myoblasts from this mouse are still killed by DUX4 expression. These data challenge the notion that the p53 pathway is central to the pathogenicity of DUX4.

  2. DNA methylation-based classification of central nervous system tumours

    DEFF Research Database (Denmark)

    Capper, David; Jones, David T.W.; Sill, Martin

    2018-01-01

    Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging - with substantial inter......-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show...

  3. Reorganization of pathological control functions of memory-A neural model for tissue healing by shock waves

    Science.gov (United States)

    Wess, Othmar

    2005-04-01

    Since 1980 shock waves have proven effective in the field of extracorporeal lithotripsy. More than 10 years ago shock waves were successfully applied for various indications such as chronic pain, non-unions and, recently, for angina pectoris. These fields do not profit from the disintegration power but from stimulating and healing effects of shock waves. Increased metabolism and neo-vascularization are reported after shock wave application. According to C. J. Wang, a biological cascade is initiated, starting with a stimulating effect of physical energy resulting in increased circulation and metabolism. Pathological memory of neural control patterns is considered the reason for different pathologies characterized by insufficient metabolism. This paper presents a neural model for reorganization of pathological reflex patterns. The model acts on associative memory functions of the brain based on modification of synaptic junctions. Accordingly, pathological memory effects of the autonomous nervous system are reorganized by repeated application of shock waves followed by development of normal reflex patterns. Physiologic control of muscle and vascular tone is followed by increased metabolism and tissue repair. The memory model may explain hyper-stimulation effects in pain therapy.

  4. Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model.

    Science.gov (United States)

    Choisunirachon, N; Jaroensong, T; Yoshida, K; Saeki, K; Mochizuki, M; Nishimura, R; Sasaki, N; Nakagawa, T

    2015-12-01

    Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma. © 2013 John Wiley & Sons Ltd.

  5. Expression pattern of clinically relevant markers in paediatric germ cell- and sex-cord stromal tumours is similar to adult testicular tumours

    DEFF Research Database (Denmark)

    Mosbech, Christiane Hammershaimb; Svingen, Terje; Nielsen, John Erik

    2014-01-01

    , elaborate on clinical-pathological associations and better understand their developmental divergence. The tumours were screened for expression of stemness-related factors (OCT4, AP-2γ, SOX2), classical yolk sac tumours (YSTs; AFP, SALL4), GCTs (HCG, PLAP, PDPN/D2-40), as well as markers for sex-cord stromal...

  6. Study of inhaled radio-active pollutants: 1. Current data; II. Pathology; III. Validity of animal model. Dose-effect relations

    International Nuclear Information System (INIS)

    Lafuma, J.; Masse, R.; Metivier, H.; Nolibe, D.; Fritsch, P.; Nenot, J.C.; Morin, M.

    1974-01-01

    An attempt has been made to develop an animal for human industrial exposure to airradiation. That will give results applicable to man both qualitatively and quantitavely. Using over 2000 animals. The following studies were made. Radon, rat and occupationally exposed man; 239 plutonium oxide, rat and monkey; 12 different α and emitters, rat with different exposure media (aerosols particles) and exposure shcedules (acute chronic). Scrupulous pathological, microscopic, autoradiographic and ultrastructural analysis of animals followed their deaths. Acute changes are characterized by alveolaroedema, capillary and arteriolar thrombisus, and desquamation of type 1 pneumatocytes. There is interstitial pneumonia, hyaline membrane formation, and extensive bronchiolar and alveolar metaplasia. In a study of long-term effects a wide variety of both benign and malignant tumours was discovered. There are variations in species lateney and radiation sensitivity. The pathological changes, found in these studies are qualitatively very similar to changes found in man [fr

  7. Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model.

    Science.gov (United States)

    Li, Jian; Niu, Jian-Zhao; Wang, Ji-Feng; Li, Yu; Tao, Xiao-Hua

    2005-11-07

    To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. Fifty SD rats were divided into control group (n=20) and model group (n=30). Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole (1 000:250:3). Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid (HA), type IV collagen (CoIV) and laminin (LN) were determined by radioimmunoassay. Liver tissue was fixed in formalin (10%) and 6-mum thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polyclonal antibody against LN and ColIV. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. The diameter (2.207+/-0.096 vs 1.528+/-0.054 mm, Pportal vein were significantly higher in model group than those in the control group. Plasma HA (129.97+/-16.10 vs 73.09+/-2.38 ng/mL, Pmodel group. Abundant collagen deposited around the central vein of lobules, hepatic sinusoids and hepatocytes in model group. ColI and ColIII increased remarkably and perisinusoids were almost surrounded by ColIII. Immunohistochemical staining showed that ColIV protein level (0.130+/-0.007 vs 0.032+/-0.004, Pprotein level (0.152+/-0.005 vs 0.029+/-0.005, Pmodel group. MMP-2 protein expression (2.306+/-1.089 vs 0.612+/-0.081, Pprotein expression (3.015+/-1.364 vs 0.446+/-0.009, Pmodel group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression (2.669+/-0.170 vs 1.695+/-0.008, Pportal hypertension in rats.

  8. Deuterium MR spectroscopy at 4.7 T. Quantification of tumour and subcutaneous tissue blood flow in animal models

    DEFF Research Database (Denmark)

    Wirestam, R; Larsen, V.A.; Stubgaard, M

    1995-01-01

    Deuterium MR spectroscopy was used for the determination of tissue blood flow (TBF). The tracer D2O was injected into the tissue of interest, and tracer washout was followed using a 4.7 T spectroscopy/imaging unit. Normal subcutaneous tissue in rats was studied, as well as tissue influenced...... by vasoactive agents (papaverine and adrenaline). The vasoactive agents introduced changes of 40% in TBF, compared with normal tissue. Normal tissue measurements were repeated using various D2O injection volumes (5-400 microliters). The injection volume 5 microliters gave TBF 11.7 +/- 2.0 ml/100 g.min (mean...... observed in dead rats. Blood flow measurements in human colon tumours implanted in nude mice showed a rather poor reproducibility, not improved by the use of a multiple site injection technique...

  9. Dose-volume and biological-model based comparison between helical tomotherapy and (inverse-planned) IMAT for prostate tumours

    International Nuclear Information System (INIS)

    Iori, Mauro; Cattaneo, Giovanni Mauro; Cagni, Elisabetta; Fiorino, Claudio; Borasi, Gianni; Riccardo, Calandrino; Iotti, Cinzia; Fazio, Ferruccio; Nahum, Alan E.

    2008-01-01

    Background and purpose: Helical tomotherapy (HT) and intensity-modulated arc therapy (IMAT) are two arc-based approaches to the delivery of intensity-modulated radiotherapy (IMRT). Through plan comparisons we have investigated the potential of IMAT, both with constant (conventional or IMAT-C) and variable (non-conventional or IMAT-NC, a theoretical exercise) dose-rate, to serve as an alternative to helical tomotherapy. Materials and methods: Six patients with prostate tumours treated by HT with a moderately hypo-fractionated protocol, involving a simultaneous integrated boost, were re-planned as IMAT treatments. A method for IMAT inverse-planning using a commercial module for static IMRT combined with a multi-leaf collimator (MLC) arc-sequencing was developed. IMAT plans were compared to HT plans in terms of dose statistics and radiobiological indices. Results: Concerning the planning target volume (PTV), the mean doses for all PTVs were similar for HT and IMAT-C plans with minimum dose, target coverage, equivalent uniform dose (EUD) and tumour control probability (TCP) values being generally higher for HT; maximum dose and degree of heterogeneity were instead higher for IMAT-C. In relation to organs at risk, mean doses and normal tissue complication probability (NTCP) values were similar between the two modalities, except for the penile bulb where IMAT was significantly better. Re-normalizing all plans to the same rectal toxicity (NTCP = 5%), the HT modality yielded higher TCP than IMAT-C but there was no significant difference between HT and IMAT-NC. The integral dose with HT was higher than that for IMAT. Conclusions: with regards to the plan analysis, the HT is superior to IMAT-C in terms of target coverage and dose homogeneity within the PTV. Introducing dose-rate variation during arc-rotation, not deliverable with current linac technology, the simulations result in comparable plan indices between (IMAT-NC) and HT

  10. Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model.

    Directory of Open Access Journals (Sweden)

    Georgina Cosma

    Full Text Available The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA level, the biopsy most common tumor pattern (Primary Gleason pattern and the second most common tumor pattern (Secondary Gleason pattern in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD or Extra-Prostatic Disease (ED using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC, with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812. The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR

  11. Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model

    Science.gov (United States)

    Acampora, Giovanni; Brown, David; Rees, Robert C.

    2016-01-01

    The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA) level, the biopsy most common tumor pattern (Primary Gleason pattern) and the second most common tumor pattern (Secondary Gleason pattern) in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD) or Extra-Prostatic Disease (ED) using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA) Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC) points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC), with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812). The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR = 0.032, TPR

  12. Targeting radiation to tumours

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Greater Glasgow Health Board, Glasgow

    1994-01-01

    Biologically targeted radiotherapy entails the preferential delivery of radiation to solid tumours or individual tumour cells by means of tumour-seeking delivery vehicles to which radionuclides can be conjugated. Monoclonal antibodies have attracted attention for some years as potentially selective targeting agents, but advances in tumour and molecular biology are now providing a much wider choice of molecular species. General radiobiological principles may be derived which are applicable to most forms of targeted radiotherapy. These principles provide guidelines for the appropriate choice of radionuclide in specific treatment situations and its optimal combination with other treatment modalities. In future, the availability of gene targeting agents will focus attention on the use of Auger electron emitters whose high potency and short range selectivity makes them attractive choices for specific killing of cancer cells whose genetic peculiarities are known. (author)

  13. Targeting ALCAM in the cryo-treated tumour microenvironment successfully induces systemic anti-tumour immunity.

    Science.gov (United States)

    Kudo-Saito, Chie; Fuwa, Takafumi; Kawakami, Yutaka

    2016-07-01

    Cryoablative treatment has been widely used for treating cancer. However, the therapeutic efficacies are still controversial. The molecular mechanisms of the cryo-induced immune responses, particularly underlying the ineffectiveness, remain to be fully elucidated. In this study, we identified a new molecular mechanism involved in the cryo failure. We used cryo-ineffective metastatic tumour models that murine melanoma B16-F10 cells were subcutaneously and intravenously implanted into C57BL/6 mice. When the subcutaneous tumours were treated cryoablation on day 7 after tumour implantation, cells expressing activated leucocyte cell adhesion molecule (ALCAM/CD166) were significantly expanded not only locally in the treated tumours but also systemically in spleen and bone marrow of the mice. The cryo-induced ALCAM(+) cells including CD45(-) mesenchymal stem/stromal cells, CD11b(+)Gr1(+) myeloid-derived suppressor cells, and CD4(+)Foxp3(+) regulatory T cells significantly suppressed interferon γ production and cytotoxicity of tumour-specific CD8(+) T cells via ALCAM expressed in these cells. This suggests that systemic expansion of the ALCAM(+) cells negatively switches host-immune directivity to the tumour-supportive mode. Intratumoural injection with anti-ALCAM blocking monoclonal antibody (mAb) following the cryo treatment systemically induced tumour-specific CD8(+) T cells with higher cytotoxic activities, resulting in suppression of tumour growth and metastasis in the cryo-resistant tumour models. These suggest that expansion of ALCAM(+) cells is a determinant of limiting the cryo efficacy. Further combination with an immune checkpoint inhibitor anti-CTLA4 mAb optimized the anti-tumour efficacy of the dual-combination therapy. Targeting ALCAM may be a promising strategy for overcoming the cryo ineffectiveness leading to the better practical use of cryoablation in clinical treatment of cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Parapharyngeal Tumours - Surgical Expertise

    OpenAIRE

    Kinjal Shankar Majumdar

    2014-01-01

    Introduction We present our experience in the management of parapharyngeal tumours. A conservative trans-cervical approach was found to be feasible and effective in majority of the cases over radical ones, which may be required in malignancies and skull-base involvement.   Methods Fifteen patients with parapharyngeal tumours treated surgically in the Department of ENT, Nilratan Sircar Medical College in last 3 years were included in the study. 80% of the cases were benign, mos...

  15. The UK Pathology Harmony initiative; The foundation of a global model.

    Science.gov (United States)

    Berg, Jonathan

    2014-05-15

    The United Kingdom Pathology Harmony project commenced in 2007 and has been widely mirrored around the world. This initiative evolved through three separate phases of work. Fundamental to the project has been the ability to question variation in the work of the pathology laboratory that has been in place sometimes for a very long time, and yet appears to have little scientific foundation. Work has been undertaken on a methodological approach to studying variation in reference intervals and then moving forward with consensus values. On a wider level there is much else in pathology that can be harmonised from test names and units, through to the clinical guidance we offer for using our tests and work has been undertaken in several of these areas. © 2013.

  16. Fractionated Radiotherapy with 3 x 8 Gy Induces Systemic Anti-Tumour Responses and Abscopal Tumour Inhibition without Modulating the Humoral Anti-Tumour Response.

    Directory of Open Access Journals (Sweden)

    Thomas H P M Habets

    Full Text Available Accumulating evidence indicates that fractionated radiotherapy (RT can result in distant non-irradiated (abscopal tumour regression. Although preclinical studies indicate the importance of T cells in this infrequent phenomenon, these studies do not preclude that other immune mechanisms exhibit an addition role in the abscopal effect. We therefore addressed the question whether in addition to T cell mediated responses also humoral anti-tumour responses are modulated after fractionated RT and whether systemic dendritic cell (DC stimulation can enhance tumour-specific antibody production. We selected the 67NR mammary carcinoma model since this tumour showed spontaneous antibody production in all tumour-bearing mice. Fractionated RT to the primary tumour was associated with a survival benefit and a delayed growth of a non-irradiated (contralateral secondary tumour. Notably, fractionated RT did not affect anti-tumour antibody titers and the composition of the immunoglobulin (Ig isotypes. Likewise, we demonstrated that treatment of tumour-bearing Balb/C mice with DC stimulating growth factor Flt3-L did neither modulate the magnitude nor the composition of the humoral immune response. Finally, we evaluated the immune infiltrate and Ig isotype content of the tumour tissue using flow cytometry and found no differences between treatment groups that were indicative for local antibody production. In conclusion, we demonstrate that the 67NR mammary carcinoma in Balb/C mice is associated with a pre-existing antibody response. And, we show that in tumour-bearing Balb/C mice with abscopal tumour regression such pre-existing antibody responses are not altered upon fractionated RT and/or DC stimulation with Flt3-L. Our research indicates that evaluating the humoral immune response in the setting of abscopal tumour regression is not invariably associated with therapeutic effects.

  17. Androgen secreting adrenocortical tumours.

    Science.gov (United States)

    Wolthers, O D; Cameron, F J; Scheimberg, I; Honour, J W; Hindmarsh, P C; Savage, M O; Stanhope, R G; Brook, C G

    1999-01-01

    Androgen secreting adrenocortical tumours are rare in children and the determination of their malignant potential can be difficult. To assess the presentation, histology, and clinical behaviour of these tumours. Two tertiary referral centres. Retrospective analysis of children diagnosed with an androgen secreting adrenocortical tumour between 1976 and 1996. Twenty three girls and seven boys aged 0-14 years. Pubic hair was observed in all children, clitoromegaly or growth of the phallus in 23 children, acceleration of linear growth in 22 children, and advanced bone age (> 1.5 years) in 18 children. Hypersecretion of androgens was detected by assessment of serum androgen concentrations alone in four patients and by 24 hour urine steroid excretion profiles in 22 patients. All 16 tumours measuring 10 cm were malignant. Histological slides were available for reassessment in 25 children. Although mitoses and necrosis were more characteristic of tumours with malignant behaviour, no exclusive histological features of malignancy were seen. Histological criteria for malignancy are not reliable, whereas tumour size is important in assessing malignant potential.

  18. Utility of multimaterial 3D printers in creating models with pathological entities to enhance the training experience of neurosurgeons.

    Science.gov (United States)

    Waran, Vicknes; Narayanan, Vairavan; Karuppiah, Ravindran; Owen, Sarah L F; Aziz, Tipu

    2014-02-01

    The advent of multimaterial 3D printers allows the creation of neurosurgical models of a more realistic nature, mimicking real tissues. The authors used the latest generation of 3D printer to create a model, with an inbuilt pathological entity, of varying consistency and density. Using this model the authors were able to take trainees through the basic steps, from navigation and planning of skin flap to performing initial steps in a craniotomy and simple tumor excision. As the technology advances, models of this nature may be able to supplement the training of neurosurgeons in a simulated operating theater environment, thus improving the training experience.

  19. Reduction of β-amyloid pathology by celastrol in a transgenic mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Bachmeier Corbin

    2010-03-01

    Full Text Available Abstract Background Aβ deposits represent a neuropathological hallmark of Alzheimer's disease (AD. Both soluble and insoluble Aβ species are considered to be responsible for initiating the pathological cascade that eventually leads to AD. Therefore, the identification of therapeutic approaches that can lower Aβ production or accumulation remains a priority. NFκB has been shown to regulate BACE-1 expression level, the rate limiting enzyme responsible for the production of Aβ. We therefore explored whether the known NFκB inhibitor celastrol could represent a suitable compound for decreasing Aβ production and accumulation in vivo. Methods The effect of celastrol on amyloid precursor protein (APP processing, Aβ production and NFκB activation was investigated by western blotting and ELISAs using a cell line overexpressing APP. The impact of celastrol on brain Aβ accumulation was tested in a transgenic mouse model of AD overexpressing the human APP695sw mutation and the presenilin-1 mutation M146L (Tg PS1/APPsw by immunostaining and ELISAs. An acute treatment with celastrol was investigated by administering celastrol intraperitoneally at a dosage of 1 mg/Kg in 35 week-old Tg PS1/APPsw for 4 consecutive days. In addition, a chronic treatment (32 days with celastrol was tested using a matrix-driven delivery pellet system implanted subcutaneously in 5 month-old Tg PS1/APPsw to ensure a continuous daily release of 2.5 mg/Kg of celastrol. Results In vitro, celastrol dose dependently prevented NFκB activation and inhibited BACE-1 expression. Celastrol potently inhibited Aβ1-40 and Aβ1-42 production by reducing the β-cleavage of APP, leading to decreased levels of APP-CTFβ and APPsβ. In vivo, celastrol appeared to reduce the levels of both soluble and insoluble Aβ1-38, Aβ1-40 and Aβ1-42. In addition, a reduction in Aβ plaque burden and microglial activation was observed in the brains of Tg PS1/APPsw following a chronic administration of

  20. Tumour bed irradiation of human tumour xenografts in a nude rat ...

    Indian Academy of Sciences (India)

    small cell lung cancer xenograft tumours transplanted to and growing subcutaneously on the right lower limb in a nude rat model were investigated. Procedures and results described herein prove the feasibility of use of the device, which is ...

  1. Monte Carlo dose calculations and radiobiological modelling: analysis of the effect of the statistical noise of the dose distribution on the probability of tumour control

    International Nuclear Information System (INIS)

    Buffa, Francesca M.

    2000-01-01

    The aim of this work is to investigate the influence of the statistical fluctuations of Monte Carlo (MC) dose distributions on the dose volume histograms (DVHs) and radiobiological models, in particular the Poisson model for tumour control probability (tcp). The MC matrix is characterized by a mean dose in each scoring voxel, d, and a statistical error on the mean dose, σ d ; whilst the quantities d and σ d depend on many statistical and physical parameters, here we consider only their dependence on the phantom voxel size and the number of histories from the radiation source. Dose distributions from high-energy photon beams have been analysed. It has been found that the DVH broadens when increasing the statistical noise of the dose distribution, and the tcp calculation systematically underestimates the real tumour control value, defined here as the value of tumour control when the statistical error of the dose distribution tends to zero. When increasing the number of energy deposition events, either by increasing the voxel dimensions or increasing the number of histories from the source, the DVH broadening decreases and tcp converges to the 'correct' value. It is shown that the underestimation of the tcp due to the noise in the dose distribution depends on the degree of heterogeneity of the radiobiological parameters over the population; in particular this error decreases with increasing the biological heterogeneity, whereas it becomes significant in the hypothesis of a radiosensitivity assay for single patients, or for subgroups of patients. It has been found, for example, that when the voxel dimension is changed from a cube with sides of 0.5 cm to a cube with sides of 0.25 cm (with a fixed number of histories of 10 8 from the source), the systematic error in the tcp calculation is about 75% in the homogeneous hypothesis, and it decreases to a minimum value of about 15% in a case of high radiobiological heterogeneity. The possibility of using the error on the

  2. Synthesis of L-2,4-diamino[4-11C]butyric acid and its use in some in vitro and in vivo tumour models

    International Nuclear Information System (INIS)

    Antoni, G.; Omura, H.; Bergstroem, M.; Furuya, Y.; Moulder, R.; Roberto, A.; Sundin, A.; Watanabe, Y.; Laangstroem, B.

    1997-01-01

    L-2,4-Diamino[4- 11 C]butyric acid (DAB) was synthesized by an enzyme catalysed carrier added (0.1 μmol KCN) reaction of hydrogen [ 11 C]cyanide with O-acetyl-L-serine followed by reduction. L-[ 11 C]DAB was obtained with a radiochemical purity higher than 96% and with a decay corrected radiochemical yield of 30-40% within a 32 min reaction time. The enantiomeric excess was 98%. The uptake of L-[ 11 C]DAB was investigated in multicellular aggregates of six different cell lines and animal tumour models. L-[ 11 C]DAB is potentially useful for the assessment of pharmacokinetics of L-DAB in vivo for part of its evaluation as an antitumoural agent, although its use for diagnostic purposes seems limited

  3. Statistical clustering of parametric maps from dynamic contrast enhanced MRI and an associated decision tree model for non-invasive tumour grading of T1b solid clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Xi, Yin; Yuan, Qing; Zhang, Yue; Fulkerson, Michael; Madhuranthakam, Ananth J.; Margulis, Vitaly; Cadeddu, Jeffrey A.; Brugarolas, James; Kapur, Payal; Pedrosa, Ivan

    2018-01-01

    To apply a statistical clustering algorithm to combine information from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) into a single tumour map to distinguish high-grade from low-grade T1b clear cell renal cell carcinoma (ccRCC). This prospective, Institutional Review Board -approved, Health Insurance Portability and Accountability Act -compliant study included 18 patients with solid T1b ccRCC who underwent pre-surgical DCE MRI. After statistical clustering of the parametric maps of the transfer constant between the intravascular and extravascular space (K trans ), rate constant (K ep ) and initial area under the concentration curve (iAUC) with a fuzzy c-means (FCM) algorithm, each tumour was segmented into three regions (low/medium/high active areas). Percentages of each region and tumour size were compared to tumour grade at histopathology. A decision-tree model was constructed to select the best parameter(s) to predict high-grade ccRCC. Seven high-grade and 11 low-grade T1b ccRCCs were included. High-grade histology was associated with higher percent high active areas (p = 0.0154) and this was the only feature selected by the decision tree model, which had a diagnostic performance of 78% accuracy, 86% sensitivity, 73% specificity, 67% positive predictive value and 89% negative predictive value. The FCM integrates multiple DCE-derived parameter maps and identifies tumour regions with unique pharmacokinetic characteristics. Using this approach, a decision tree model using criteria beyond size to predict tumour grade in T1b ccRCCs is proposed. (orig.)

  4. Statistical clustering of parametric maps from dynamic contrast enhanced MRI and an associated decision tree model for non-invasive tumour grading of T1b solid clear cell renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Yin; Yuan, Qing; Zhang, Yue; Fulkerson, Michael [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); Madhuranthakam, Ananth J. [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); UT Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); Margulis, Vitaly; Cadeddu, Jeffrey A. [UT Southwestern Medical Center, Department of Urology, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); Brugarolas, James [UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); UT Southwestern Medical Center, Department of Internal Medicine, Dallas, TX (United States); Kapur, Payal [UT Southwestern Medical Center, Department of Urology, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); UT Southwestern Medical Center, Department of Pathology, Dallas, Texas (United States); Pedrosa, Ivan [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); UT Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States)

    2018-01-15

    To apply a statistical clustering algorithm to combine information from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) into a single tumour map to distinguish high-grade from low-grade T1b clear cell renal cell carcinoma (ccRCC). This prospective, Institutional Review Board -approved, Health Insurance Portability and Accountability Act -compliant study included 18 patients with solid T1b ccRCC who underwent pre-surgical DCE MRI. After statistical clustering of the parametric maps of the transfer constant between the intravascular and extravascular space (K{sup trans}), rate constant (K{sub ep}) and initial area under the concentration curve (iAUC) with a fuzzy c-means (FCM) algorithm, each tumour was segmented into three regions (low/medium/high active areas). Percentages of each region and tumour size were compared to tumour grade at histopathology. A decision-tree model was constructed to select the best parameter(s) to predict high-grade ccRCC. Seven high-grade and 11 low-grade T1b ccRCCs were included. High-grade histology was associated with higher percent high active areas (p = 0.0154) and this was the only feature selected by the decision tree model, which had a diagnostic performance of 78% accuracy, 86% sensitivity, 73% specificity, 67% positive predictive value and 89% negative predictive value. The FCM integrates multiple DCE-derived parameter maps and identifies tumour regions with unique pharmacokinetic characteristics. Using this approach, a decision tree model using criteria beyond size to predict tumour grade in T1b ccRCCs is proposed. (orig.)

  5. Multifunctional Effect of Human Serum Albumin Reduces Alzheimer's Disease Related Pathologies in the 3xTg Mouse Model.

    Science.gov (United States)

    Ezra, Assaf; Rabinovich-Nikitin, Inna; Rabinovich-Toidman, Polina; Solomon, Beka

    2016-01-01

    Alzheimer's disease (AD), the prevalent dementia in the elderly, involves many related and interdependent pathologies that manifests simultaneously, eventually leading to cognitive impairment and death. No treatment is currently available; however, an agent addressing several key pathologies simultaneously has a better therapeutic potential. Human serum albumin (HSA) is a highly versatile protein, harboring multifunctional properties that are relevant to key pathologies underlying AD. This study provides insight into the mechanism for HSA's therapeutic effect. In vivo, a myriad of beneficial effects were observed by pumps infusing HSA intracerebroventricularly, for the first time in an AD 3xTg mice model. A significant effect on amyloid-β (Aβ) pathology was observed. Aβ1-42, soluble oligomers, and total plaque area were reduced. Neuroblastoma SHSY5Y cell line confirmed that the reduction in Aβ1-42 toxicity was due to direct binding rather than other properties of HSA. Total and hyperphosphorylated tau were reduced along with an increase in tubulin, suggesting increased microtubule stability. HSA treatment also reduced brain inflammation, affecting both astrocytes and microglia markers. Finally, evidence for blood-brain barrier and myelin integrity repair was observed. These multidimensional beneficial effects of intracranial administrated HSA, together or individually, contributed to an improvement in cognitive tests, suggesting a non-immune or Aβ efflux dependent means for treating AD.

  6. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    International Nuclear Information System (INIS)

    Shumilov, V. N.; Syryamkin, V. I.; Syryamkin, M. V.

    2015-01-01

    formation of connections between neurons in simplest biological objects. Based on the correspondence of function of the created models to function of biological nervous systems we suggest the use of computational and electronic models of the brain for the study of its function under normal and pathological conditions, because operating principles of the models are built on principles imitating the function of biological nervous systems and the brain

  7. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    Energy Technology Data Exchange (ETDEWEB)

    Shumilov, V. N., E-mail: vnshumilov@rambler.ru; Syryamkin, V. I., E-mail: maximus70sir@gmail.com; Syryamkin, M. V., E-mail: maximus70sir@gmail.com [National Research Tomsk State University, 634050, Tomsk, Lenin Avenue, 36 (Russian Federation)

    2015-11-17

    formation of connections between neurons in simplest biological objects. Based on the correspondence of function of the created models to function of biological nervous systems we suggest the use of computational and electronic models of the brain for the study of its function under normal and pathological conditions, because operating principles of the models are built on principles imitating the function of biological nervous systems and the brain.

  8. Experimental tumour therapy. 1985 report

    International Nuclear Information System (INIS)

    1986-08-01

    The 1985 annual report documents - once again - the collaboration between the members of the University's Radiobiological Institute and the Radiobiological Department of GSF in the field of experimental radiotherapy. As in the previous years, key areas were concerned with the examination of clinically relevant radiation-induced injuries in normal tissue, the clarification of their pathogenesis and their fractionation behaviour but also possible methods of their prevention. New areas of interest included the experiments performed on rat stomach which allowed to establish a promising animal model for the radiobiological examination of this organ. Experimental tumours were continued to be studied for factors important for tumour resistance in fractionated irradiation; in this context, the high repopulation capacity of a differentiated squamous-cell carcinoma under quasi-clinical fractionation revealed to be particularly remarkable. A further key area was concerned with investigations into the combined action of cytostatics and irradiation or else hyperthermia which were mostly performed in vitro on cell cultures but also on experimental tumours and some normal tissues. (orig./MG) [de

  9. Pathology of Isfahan University of Medical Sciences based on Weisbord six box model and its relation with mental health

    OpenAIRE

    Karimian, Jahangir; Taheri, Behjat; Sadeghpour, Masoumeh; Sadeghpour, Akram

    2015-01-01

    Background: The aim of this research was to study the pathology of Isfahan University of Medical Sciences based on Weisbord six box model and to find its relation with mental health. Materials and Methods: The research method followed was a descriptive survey. The statistical society consisted of all staffs of the Isfahan University of Medical Sciences consisting of professors in the year 2012 (personnel of deputy of treatment, deputy of training, cultural-student deputy, supporting deputy, d...

  10. Mouse Model of Devil Facial Tumour Disease establishes that an effective immune response can be generated against the cancer cells

    Directory of Open Access Journals (Sweden)

    Terry L Pinfold

    2014-05-01

    Full Text Available The largest carnivorous marsupial in Australia, the Tasmanian devil (Sarcophilus harrisii is facing extinction in the wild due to a transmissible cancer known as Devil Facial Tumour Disease (DFTD. DFTD is a clonal cell line transmitted from host to host with 100% mortality and no known immunity. While it was first considered that low genetic diversity of the population of devils enabled the allograft transmission of DFTD recent evidence reveals that genetically diverse animals succumb to the disease. The lack of an immune response against the DFTD tumor cells may be due to a lack of immunogenicity of the tumor cells. This could facilitate transmission between devils. To test immunogenicity, mice were injected with viable DFTD cells and anti-DFTD immune responses analyzed. A range of antibody isotypes against DFTD cells was detected, indicating that as DFTD cells can induce an immune response they are immunogenic. This was supported by cytokine production, when splenocytes from mice injected with DFTD cells were cultured in vitro with DFTD cells and the supernatant analyzed. There was a significant production of IFN-γ and TNF-α following the first injection with DFTD cells and a significant production of IL-6 and IL-10 following the second injection. Splenocytes from naïve or immunized mice killed DFTD cells in in vitro cytotoxicity assays. Thus they are also targets for immunological destruction. We conclude that as an immune response can be generated against DFTD cells they would be suitable targets for a vaccine.

  11. Lethal giant larvae 1 tumour suppressor activity is not conserved in models of mammalian T and B cell leukaemia.

    Directory of Open Access Journals (Sweden)

    Edwin D Hawkins

    Full Text Available In epithelial and stem cells, lethal giant larvae (Lgl is a potent tumour suppressor, a regulator of Notch signalling, and a mediator of cell fate via asymmetric cell division. Recent evidence suggests that the function of Lgl is conserved in mammalian haematopoietic stem cells and implies a contribution to haematological malignancies. To date, direct measurement of the effect of Lgl expression on malignancies of the haematopoietic lineage has not been tested. In Lgl1⁻/⁻ mice, we analysed the development of haematopoietic malignancies either alone, or in the presence of common oncogenic lesions. We show that in the absence of Lgl1, production of mature white blood cell lineages and long-term survival of mice are not affected. Additionally, loss of Lgl1 does not alter leukaemia driven by constitutive Notch, c-Myc or Jak2 signalling. These results suggest that the role of Lgl1 in the haematopoietic lineage might be restricted to specific co-operating mutations and a limited number of cellular contexts.

  12. Subthalamic deep brain stimulation reduces pathological information transmission to the thalamus in a rat model of parkinsonism

    Directory of Open Access Journals (Sweden)

    Collin James Anderson

    2015-07-01

    Full Text Available The degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to parkinsonian motor symptoms via changes in electrophysiological activity throughout the basal ganglia. High-frequency deep brain stimulation (DBS partially treats these symptoms, but the mechanisms are unclear. We hypothesize that motor symptoms of Parkinson's disease are associated with increased information transmission from basal ganglia output neurons to motor thalamus input neurons, and that therapeutic DBS of the subthalamic nucleus (STN treats these symptoms by reducing this extraneous information transmission. We tested these hypotheses in a unilateral, 6-hydroxydopamine-lesioned rodent model of hemiparkinsonism. Information transfer between basal ganglia output neurons and motor thalamus input neurons increased in both the orthodromic and antidromic directions with hemiparkinsonian onset, and these changes were reversed by behaviorally therapeutic STN-DBS. Omnidirectional information increases in the parkinsonian state underscore the detrimental nature of that pathological information, and suggest a loss of information channel independence. Therapeutic STN-DBS reduced that pathological information, suggesting an effective increase in the number of independent information channels. We interpret these data with a model in which pathological information and fewer information channels diminishes the scope of possible motor activities, driving parkinsonian symptoms. In this model, STN-DBS restores information-channel independence by eliminating or masking the parkinsonism-associated information, and thus enlarges the scope of possible motor activities, alleviating parkinsonian symptoms.

  13. Tumour macrophages as potential targets of bisphosphonates

    Science.gov (United States)

    2011-01-01

    Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use. Bisphosphonates (BPs), such as zoledronic acid, are anti-resorptive agents approved for treatment of skeletal complication associated with metastatic breast cancer and prostate cancer. These agents act on osteoclasts, key cells in the bone microenvironment, to inhibit bone resorption. Over the past 30 years this has led to a great reduction in skeletal-related events (SRE's) in patients with advanced cancer and improved the morbidity associated with cancer-induced bone disease. However, there is now a growing body of evidence, both from in vitro and in vivo models, showing that zoledronic acid can also target tumour cells to increase apoptotic cell death and decrease proliferation, migration and invasion, and that this effect is significantly enhanced in combination with chemotherapy agents. Whether macrophages in the peripheral tumour microenvironment are exposed to sufficient levels of bisphosphonate to be affected is currently unknown. Macrophages belong to the same cell lineage as osteoclasts, the major target of BPs, and are highly phagocytic cells shown to be sensitive to

  14. Site-specific volumetric analysis of lung tumour motion

    International Nuclear Information System (INIS)

    Pepin, Eric W; Wu Huanmei; Sandison, George A; Langer, Mark; Shirato, Hiroki

    2010-01-01

    The treatment of lung cancer with radiation therapy is hindered by respiratory motion. Real-time adjustments to compensate for this motion are hampered by mechanical system latencies and imaging-rate restrictions. To better understand tumour motion behaviour for adaptive image-guided radiation therapy of lung cancer, the volume of a tumour's motion space was investigated. Motion data were collected by tracking an implanted fiducial using fluoroscopy at 30 Hz during treatment sessions. A total of 637 treatment fractions from 31 tumours were used in this study. For each fraction, data points collected from three consecutive breathing cycles were used to identify instantaneous tumour location. A convex hull was created over these data points, defining the tumour motion envelope. The study sought a correlation between the tumour location in the lung and the convex hull's volume and shape. It was found that tumours located in the upper apex had smaller motion envelopes ( 3 ), whereas tumours located near the chest wall or diaphragm had larger envelopes (>70 mm 3 ). Tumours attached to fixed anatomical structures had small motion spaces. Three general shapes described the tumour motion envelopes: 50% of motion envelopes enclosed largely 1D oscillation, 38% enclosed an ellipsoid path, 6% enclosed an arced path and 6% were of hybrid shape. This location-space correlation suggests it may be useful in developing a predictive model, but more work needs to be done to verify it.

  15. Differential effects of delayed aging on phenotype and striatal pathology in a murine model of Huntington disease.

    Science.gov (United States)

    Tallaksen-Greene, Sara J; Sadagurski, Marianna; Zeng, Li; Mauch, Roseanne; Perkins, Matthew; Banduseela, Varuna C; Lieberman, Andrew P; Miller, Richard A; Paulson, Henry L; Albin, Roger L

    2014-11-19

    The common neurodegenerative syndromes exhibit age-related incidence, and many Mendelian neurodegenerative diseases exhibit age-related penetrance. Mutations slowing aging retard age related pathologies. To assess whether delayed aging retards the effects of a mutant allele causing a Huntington's disease (HD)-like syndrome, we generated compound mutant mice, placing a dominant HD knock-in polyglutamine allele onto the slow-aging Snell dwarf genotype. The Snell genotype did not affect mutant huntingtin protein expression. Bigenic and control mice were evaluated prospectively from 10 to 100 weeks of age. Adult HD knock-in allele mice lost weight progressively with weight loss blunted significantly in male bigenic HD knock-in/Snell dwarf mice. Impaired balance beam performance developed significantly more slowly in bigenic HD knock-in/Snell dwarf mice. Striatal dopamine receptor expression was diminished significantly and similarly in all HD-like mice, regardless of the Snell genotype. Striatal neuronal intranuclear inclusion burden was similar between HD knock-in mice with and without the Snell genotype, whereas nigral neuropil aggregates were diminished in bigenic HD knock-in/Snell dwarf mice. Compared with control mice, Snell dwarf mice exhibited differences in regional benzodiazepine and cannabinoid receptor binding site expression. These results indicate that delaying aging delayed behavioral decline with little effect on the development of striatal pathology in this model of HD but may have altered synaptic pathology. These results indicate that mutations prolonging lifespan in mice delay onset of significant phenotypic features of this model and also demonstrate dissociation between striatal pathology and a commonly used behavioral measure of disease burden in HD models. Copyright © 2014 the authors 0270-6474/14/3415658-11$15.00/0.

  16. Impacts of allergic airway inflammation on lung pathology in a mouse model of influenza A virus infection.

    Science.gov (United States)

    Kawaguchi, Akira; Suzuki, Tadaki; Ohara, Yuki; Takahashi, Kenta; Sato, Yuko; Ainai, Akira; Nagata, Noriyo; Tashiro, Masato; Hasegawa, Hideki

    2017-01-01

    Influenza A virus is the respiratory pathogen responsible for influenza. Infection by the 2009 pandemic influenza A (H1N1) virus caused severe lower airway inflammation and pneumonia. Asthma is a chronic inflammatory disorder of the airways that affects the entire brachial tree, and was one of the commonest underlying medical conditions among patients hospitalized with the 2009 pandemic influenza virus infection. Although respiratory virus infections are the major causes of asthma exacerbation, the mechanism by which influenza exacerbates asthma is poorly understood. Animal models of disease comorbidity are crucial to understanding host-pathogen interactions and elucidating complex pathologies. Existing murine models of influenza virus infection in asthmatics show that asthmatic mice are highly resistant to influenza virus infection, which contradicts clinical observations in humans. Here, we developed a murine model of influenza virus/asthma comorbidity using NC/Nga mice, which are highly sensitive to allergic reactions such as atopic dermatitis and allergic airway inflammation. This model was then used to examine the impact of allergic airway inflammation on lung pathology in the 2009 pandemic influenza virus infected mice. The results showed that induction of acute allergic airway inflammation in pre-existing influenza virus infection had additive effects on exacerbation of lung pathology, which mirrors findings in human epidemiological studies. In contrast, pre-existing allergic airway inflammation protected from subsequent influenza virus infection, which was compatible with those of previous murine models of influenza virus infection in asthmatic mice. These variable outcomes of this murine model indicate that the temporal relation between allergic airway inflammation and influenza virus infection might play a critical role in asthma and influenza comorbidity. Thus, this murine model will further our understanding of how influenza virus infection affects an

  17. Serial MR Imaging of Intramuscular Hematoma: Experimental Study in a Rat Model with the Pathologic Correlation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yeon Soo; Kim, Jong Ok; Choi, Eun Seok [Daejeon St. Mary' s Hospital, The Catholic University of Korea, Daejeon (Korea, Republic of); Kwon, Soon Tae [Chungnam National University, School of Medicine, Daejeon (Korea, Republic of)

    2011-02-15

    We wanted to demonstrate the temporal changes of the magnetic resonance imaging (MRI) findings in experimentally-induced intramuscular hematomas in rats and to correlate these data with the concurrent pathologic observations. Intramuscular hematoma was induced in 30 rats. The MR images were obtained at 1, 4, 7 and 10 days and at 2, 3, 4, 6 and 8 weeks after muscle injury. The characteristic serial MRI findings were evaluated and the relative signal intensities were calculated. Pathologic specimens were obtained at each time point. On the T1-weighted imaging (T1WI), the intramuscular hematomas exhibited isointensity compared to that of muscle or the development of a high signal intensity (SI) rim on day one after injury. The high SI persisted until eight weeks after injury. On the T2-weighted imaging (T2WI), the hematomas showed high SI or centrally low SI on day one after injury, and mainly high SI after four days. A dark signal rim was apparent after seven days, which was indicative of hemosiderin on the pathology. The gradient echo (GRE) imaging yielded dark signal intensities at all stages. Unlike brain hematomas, experimentally-induced intramuscular hematomas show increased SI on both the T1WI and T2WI from the acute stage onward, and this is pathologically correlated with a rich blood supply and rapid healing response to injury in the muscle. On the T2WI and GRE imaging, high SI with a peripheral dark signal rim is apparent from seven days to the chronic stage

  18. Serial MR Imaging of Intramuscular Hematoma: Experimental Study in a Rat Model with the Pathologic Correlation

    International Nuclear Information System (INIS)

    Lee, Yeon Soo; Kim, Jong Ok; Choi, Eun Seok; Kwon, Soon Tae

    2011-01-01

    We wanted to demonstrate the temporal changes of the magnetic resonance imaging (MRI) findings in experimentally-induced intramuscular hematomas in rats and to correlate these data with the concurrent pathologic observations. Intramuscular hematoma was induced in 30 rats. The MR images were obtained at 1, 4, 7 and 10 days and at 2, 3, 4, 6 and 8 weeks after muscle injury. The characteristic serial MRI findings were evaluated and the relative signal intensities were calculated. Pathologic specimens were obtained at each time point. On the T1-weighted imaging (T1WI), the intramuscular hematomas exhibited isointensity compared to that of muscle or the development of a high signal intensity (SI) rim on day one after injury. The high SI persisted until eight weeks after injury. On the T2-weighted imaging (T2WI), the hematomas showed high SI or centrally low SI on day one after injury, and mainly high SI after four days. A dark signal rim was apparent after seven days, which was indicative of hemosiderin on the pathology. The gradient echo (GRE) imaging yielded dark signal intensities at all stages. Unlike brain hematomas, experimentally-induced intramuscular hematomas show increased SI on both the T1WI and T2WI from the acute stage onward, and this is pathologically correlated with a rich blood supply and rapid healing response to injury in the muscle. On the T2WI and GRE imaging, high SI with a peripheral dark signal rim is apparent from seven days to the chronic stage

  19. Pathological, Disabled, Transgender: The Ethics, History, Laws, and Contradictions in Models that Best Serve Transgender Rights.

    Science.gov (United States)

    Wahlert, Lance; Gill, Sabrina

    This article addresses the precarious place of transgender and gender non-cis persons in relation to their discrimination-protections in recent legal, medical, and ethical policies in the United States. At present, there exists a contradiction such that trans persons are considered "pathological" enough that they are included in the latest iteration of the American Psychiatric Association's Diagnostic and Statistical Manual (DSM-V) as "gender dysphoric," but they are not included in the category of "disabled" under the Americans with Disabilities Act (ADA). As such, trans persons in America are subject to the stigma of pathology (albeit with medical treatment) without the full protections of the ADA. By contrast, transgender and non-cis-gender Americans find their queer cohorts who are HIV-positive to be fully protected by the ADA. We ask whether transgender and non-cis-gender persons should embrace their (already pathologized) personhood as a disability. Sometimes "choosing disability" affords more rights than it deploys stigma.

  20. Improved classification and visualization of healthy and pathological hard dental tissues by modeling specular reflections in NIR hyperspectral images

    Science.gov (United States)

    Usenik, Peter; Bürmen, Miran; Fidler, Aleš; Pernuš, Franjo; Likar, Boštjan

    2012-03-01

    Despite major improvements in dental healthcare and technology, dental caries remains one of the most prevalent chronic diseases of modern society. The initial stages of dental caries are characterized by demineralization of enamel crystals, commonly known as white spots, which are difficult to diagnose. Near-infrared (NIR) hyperspectral imaging is a new promising technique for early detection of demineralization which can classify healthy and pathological dental tissues. However, due to non-ideal illumination of the tooth surface the hyperspectral images can exhibit specular reflections, in particular around the edges and the ridges of the teeth. These reflections significantly affect the performance of automated classification and visualization methods. Cross polarized imaging setup can effectively remove the specular reflections, however is due to the complexity and other imaging setup limitations not always possible. In this paper, we propose an alternative approach based on modeling the specular reflections of hard dental tissues, which significantly improves the classification accuracy in the presence of specular reflections. The method was evaluated on five extracted human teeth with corresponding gold standard for 6 different healthy and pathological hard dental tissues including enamel, dentin, calculus, dentin caries, enamel caries and demineralized regions. Principal component analysis (PCA) was used for multivariate local modeling of healthy and pathological dental tissues. The classification was performed by employing multiple discriminant analysis. Based on the obtained results we believe the proposed method can be considered as an effective alternative to the complex cross polarized imaging setups.

  1. Integrated biology approach reveals molecular and pathological interactions among Alzheimer's Aβ42, Tau, TREM2, and TYROBP in Drosophila models.

    Science.gov (United States)

    Sekiya, Michiko; Wang, Minghui; Fujisaki, Naoki; Sakakibara, Yasufumi; Quan, Xiuming; Ehrlich, Michelle E; De Jager, Philip L; Bennett, David A; Schadt, Eric E; Gandy, Sam; Ando, Kanae; Zhang, Bin; Iijima, Koichi M

    2018-03-29

    Cerebral amyloidosis, neuroinflammation, and tauopathy are key features of Alzheimer's disease (AD), but interactions among these features remain poorly understood. Our previous multiscale molecular network models of AD revealed TYROBP as a key driver of an immune- and microglia-specific network that was robustly associated with AD pathophysiology. Recent genetic studies of AD further identified pathogenic mutations in both TREM2 and TYROBP. In this study, we systematically examined molecular and pathological interactions among Aβ, tau, TREM2, and TYROBP by integrating signatures from transgenic Drosophila models of AD and transcriptome-wide gene co-expression networks from two human AD cohorts. Glial expression of TREM2/TYROBP exacerbated tau-mediated neurodegeneration and synergistically affected pathways underlying late-onset AD pathology, while neuronal Aβ42 and glial TREM2/TYROBP synergistically altered expression of the genes in synaptic function and immune modules in AD. The comprehensive pathological and molecular data generated through this study strongly validate the causal role of TREM2/TYROBP in driving molecular networks in AD and AD-related phenotypes in flies.

  2. Tumours associated with medical X-ray therapy exposure in childhood

    International Nuclear Information System (INIS)

    Colman, M.; Kirsch, M.; Creditor, M.

    1978-01-01

    A total of 5166 persons who were exposed to limited field (80-100 cm 2 ) X-ray irradiation to the head, neck and upper chest region during childhood and adolescence have provided an outstanding opportunity for the study of tumour incidence following medical X-ray therapy. More than 3254 subjects have been traced, 3108 have completed questionnaires eliciting information on tumour incidence, and 1539 of these were subjected to a thorough clinical screening procedure that included a thyroid scintigram. The prevalence of thyroid tumours in the 1539 clinically screened subjects and the prevalence of all other tumours in the 3254 subjects traced can therefore be assumed to reflect the risks in the group of irradiated subjects as a whole. Median age at irradiation was 3.5 years, and median radiation dose 790 rads (7.9 Gy). Thyroid tumour was diagnosed in 413 subjects. Of those undergoing surgery (273) 30.3% were found to have thyroid cancer. A total of 366 surgical pathology specimens of the thyroid, including 93 from subjects who were diagnosed at other hospitals, were examined revealing 73 papillary carcinomas, 12 follicular carcinomas and 26 microscopic papillary carcinomas. One hundred and eighty-seven other (non-thyroid) neoplasmas identified included 27 benign and 10 malignant salivary gland tumours, 16 benign and seven malignant tumours of neural origin (brain, spinal cord, cranial and peripheral nerves), 37 skin tumours, 9 lymphomas, 8 gonadal tumours, 45 breast tumours and 28 tumours of miscellaneous sites. The incidence of thyroid tumours, salivary gland tumours and primary brain tumours was considerably in excess of the expected incidence (p values<0.0001), and a radiation dose-effect correlation was observed for thyroid and brain tumours. Gonadal tumours and lymphomas did not occur in excess of the expected incidence

  3. Parapharyngeal Tumours - Surgical Expertise

    Directory of Open Access Journals (Sweden)

    Kinjal Shankar Majumdar

    2014-12-01

    Full Text Available Introduction We present our experience in the management of parapharyngeal tumours. A conservative trans-cervical approach was found to be feasible and effective in majority of the cases over radical ones, which may be required in malignancies and skull-base involvement.   Methods Fifteen patients with parapharyngeal tumours treated surgically in the Department of ENT, Nilratan Sircar Medical College in last 3 years were included in the study. 80% of the cases were benign, most common being Schwannoma. Most important investigation was found to be MRI.   Conclusion The study gives an overview regarding the surgical approach, based upon the extent and histology of the tumour. Trans-cervical approachwas found to be the most effective.

  4. Bone marrow oedema associated with benign and malignant bone tumours

    Energy Technology Data Exchange (ETDEWEB)

    James, S.L.J. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)], E-mail: steven.james@roh.nhs.uk; Panicek, D.M. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Davies, A.M. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)

    2008-07-15

    Bone marrow oedema is associated with a wide variety of pathological processes including both benign and malignant bone tumours. This imaging finding in relation to intraosseous tumours can aid in providing a more focused differential diagnosis. In this review, we will discuss the MR imaging of bone marrow oedema surrounding intraosseous neoplasms. The different pulse sequences used in differentiating underlying tumour from surrounding oedema are discussed along with the role of dynamic contrast enhanced MRI. Benign lesions commonly associated with bone marrow oedema include osteoid osteoma, osteoblastoma, chondroblastoma and Langerhan's cell histiocytosis. Metastases and malignant primary bone tumours such as osteosarcoma, Ewing's sarcoma and chondrosarcoma may also be surrounded by bone marrow oedema. The imaging findings of these conditions are reviewed and illustrated. Finally, the importance of bone marrow oedema in assessment of post chemotherapeutic response is addressed.

  5. Bone marrow oedema associated with benign and malignant bone tumours

    International Nuclear Information System (INIS)

    James, S.L.J.; Panicek, D.M.; Davies, A.M.

    2008-01-01

    Bone marrow oedema is associated with a wide variety of pathological processes including both benign and malignant bone tumours. This imaging finding in relation to intraosseous tumours can aid in providing a more focused differential diagnosis. In this review, we will discuss the MR imaging of bone marrow oedema surrounding intraosseous neoplasms. The different pulse sequences used in differentiating underlying tumour from surrounding oedema are discussed along with the role of dynamic contrast enhanced MRI. Benign lesions commonly associated with bone marrow oedema include osteoid osteoma, osteoblastoma, chondroblastoma and Langerhan's cell histiocytosis. Metastases and malignant primary bone tumours such as osteosarcoma, Ewing's sarcoma and chondrosarcoma may also be surrounded by bone marrow oedema. The imaging findings of these conditions are reviewed and illustrated. Finally, the importance of bone marrow oedema in assessment of post chemotherapeutic response is addressed

  6. Tumour heterogeneity promotes collective invasion and cancer metastatic dissemination.

    Science.gov (United States)

    Hallou, Adrien; Jennings, Joel; Kabla, Alexandre J

    2017-08-01

    Heterogeneity within tumour cell populations is commonly observed in most cancers. However, its impact on metastatic dissemination, one of the primary determinants of the disease prognosis, remains poorly understood. Working with a simplified numerical model of tumour spheroids, we investigated the impact of mechanical heterogeneity on the onset of tumour invasion into surrounding tissues. Our work establishes a positive link between tumour heterogeneity and metastatic dissemination, and recapitulates a number of invasion patterns identified in vivo , such as multicellular finger-like protrusions. Two complementary mechanisms are at play in heterogeneous tumours. A small proportion of stronger cells are able to initiate and lead the escape of cells, while collective effects in the bulk of the tumour provide the coordination required to sustain the invasive process through multicellular streaming. This suggests that the multicellular dynamics observed during metastasis is a generic feature of mechanically heterogeneous cell populations and might rely on a limited and generic set of attributes.

  7. CpG oligodeoxynucleotides are effective in therapy of minimal residual tumour disease after chemotherapy or surgery in a murine model of MHC class I-deficient, HPV16-associated tumours

    Czech Academy of Sciences Publication Activity Database

    Reiniš, Milan; Šímová, Jana; Indrová, Marie; Bieblová, Jana; Bubeník, Jan

    2007-01-01

    Roč. 30, č. 5 (2007), s. 1247-1251 ISSN 1019-6439 R&D Projects: GA ČR GA301/04/0492; GA ČR GA301/06/0774 EU Projects: European Commission(XE) 18933 - CLINIGENE Grant - others:Liga proti rakovině, Praha(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV16 * minimal residual tumour disease * CpG oligonucleotides Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.295, year: 2007

  8. Double gastrointestinal stromal tumour (GIST) of the stomach.

    Science.gov (United States)

    Gołąbek-Dropiewska, Katarzyna; Kardel-Reszkewicz, Ewelina; Hać, Stanisław; Pawłowska, Anna; Sledziński, Zbigniew

    2009-01-01

    Gastrointestinal stromal tumour (GIST), within its definition, is a gastrointestinal (GI) mesenchymal tumour containing spindle cells and showing CD 117 immunopositivity. The incidence of GISTs is estimated at 10-20/million. GISTs occur typically in people over 50 years of age. Over 95% of primary GISTs are solitary. Rarely, GISTs are multifocal and occur in young adults and children. A case of a 60-year-old women with double GIST of the stomach is reported here. The patient approached her general practitioner because of stomach ache, chronic diarrhoea and weight loss. Ultrasonography showed an abdominal tumour. During gastroscopy a submucosal tumour in the antral part of the stomach was found. Computed tomography revealed a pathological lesion between the stomach and the liver and an intramural tumour of the stomach. Two stomach tumours were found, and a Bilroth I gastrectomy was performed. Histopathological examination showed GIST in both tumours. This case shows that multifocal GISTs of the stomach can arise in older patients.

  9. A Multiple-Plasticity Spiking Neural Network Embedded in a Closed-Loop Control System to Model Cerebellar Pathologies.

    Science.gov (United States)

    Geminiani, Alice; Casellato, Claudia; Antonietti, Alberto; D'Angelo, Egidio; Pedrocchi, Alessandra

    2018-06-01

    The cerebellum plays a crucial role in sensorimotor control and cerebellar disorders compromise adaptation and learning of motor responses. However, the link between alterations at network level and cerebellar dysfunction is still unclear. In principle, this understanding would benefit of the development of an artificial system embedding the salient neuronal and plastic properties of the cerebellum and operating in closed-loop. To this aim, we have exploited a realistic spiking computational model of the cerebellum to analyze the network correlates of cerebellar impairment. The model was modified to reproduce three different damages of the cerebellar cortex: (i) a loss of the main output neurons (Purkinje Cells), (ii) a lesion to the main cerebellar afferents (Mossy Fibers), and (iii) a damage to a major mechanism of synaptic plasticity (Long Term Depression). The modified network models were challenged with an Eye-Blink Classical Conditioning test, a standard learning paradigm used to evaluate cerebellar impairment, in which the outcome was compared to reference results obtained in human or animal experiments. In all cases, the model reproduced the partial and delayed conditioning typical of the pathologies, indicating that an intact cerebellar cortex functionality is required to accelerate learning by transferring acquired information to the cerebellar nuclei. Interestingly, depending on the type of lesion, the redistribution of synaptic plasticity and response timing varied greatly generating specific adaptation patterns. Thus, not only the present work extends the generalization capabilities of the cerebellar spiking model to pathological cases, but also predicts how changes at the neuronal level are distributed across the network, making it usable to infer cerebellar circuit alterations occurring in cerebellar pathologies.

  10. Relationship between tumour size and response to neoadjuvant ...

    African Journals Online (AJOL)

    2018-03-16

    Mar 16, 2018 ... independent predictor of complete response to neoadjuvant chemotherapy4. Contrary to intuition, a report by Baron et al on data from 62 institutions in the United States of America did not find significant relationship between tumour size and pathologic complete response to neoadjuvant chemotherapy1.

  11. melanotic neuroectodermal tumour of infancy (progonoma) treated ...

    African Journals Online (AJOL)

    2009-06-01

    Jun 1, 2009 ... tumour recurrence. Key words: Melanotic neuroectodermal tumour of infancy, melanotic progonoma, radical maxillary sur- gery. INTRODUCTION. Melanotic neuroectodermal tumour of infancy (MNTI), also known as melanotic progonoma, melano- ameloblastoma or retinal anlage tumour is a rare lo-.

  12. Amyloid Accumulation Drives Proteome-wide Alterations in Mouse Models of Alzheimer’s Disease-like Pathology

    Directory of Open Access Journals (Sweden)

    Jeffrey N. Savas

    2017-11-01

    Full Text Available Amyloid beta (Aβ peptides impair multiple cellular pathways and play a causative role in Alzheimer’s disease (AD pathology, but how the brain proteome is remodeled by this process is unknown. To identify protein networks associated with AD-like pathology, we performed global quantitative proteomic analysis in three mouse models at young and old ages. Our analysis revealed a robust increase in Apolipoprotein E (ApoE levels in nearly all brain regions with increased Aβ levels. Taken together with prior findings on ApoE driving Aβ accumulation, this analysis points to a pathological dysregulation of the ApoE-Aβ axis. We also found dysregulation of protein networks involved in excitatory synaptic transmission. Analysis of the AMPA receptor (AMPAR complex revealed specific loss of TARPγ-2, a key AMPAR-trafficking protein. Expression of TARPγ-2 in hAPP transgenic mice restored AMPA currents. This proteomic database represents a resource for the identification of protein alterations responsible for AD.

  13. Mice lacking caspase-2 are protected from behavioral changes, but not pathology, in the YAC128 model of Huntington disease

    Directory of Open Access Journals (Sweden)

    Bissada Nagat

    2011-08-01

    Full Text Available Abstract Background Huntington Disease (HD is a neurodegenerative disorder in which caspase activation and cleavage of substrates, including the huntingtin protein, has been invoked as a pathological mechanism. Specific changes in caspase-2 (casp2 activity have been suggested to contribute to the pathogenesis of HD, however unique casp2 cleavage substrates have remained elusive. We thus utilized mice completely lacking casp2 (casp2-/- to examine the role played by casp2 in the progression of HD. This 'substrate agnostic' approach allows us to query the effect of casp2 on HD progression without pre-defining proteolytic substrates of interest. Results YAC128 HD model mice lacking casp2 show protection from well-validated motor and cognitive features of HD, including performance on rotarod, swimming T-maze, pre-pulse inhibition, spontaneous alternation and locomotor tasks. However, the specific pathological features of the YAC128 mice including striatal volume loss and testicular degeneration are unaltered in mice lacking casp2. The application of high-resolution magnetic resonance imaging (MRI techniques validates specific neuropathology in the YAC128 mice that is not altered by ablation of casp2. Conclusions The rescue of behavioral phenotypes in the absence of pathological improvement suggests that different pathways may be operative in the dysfunction of neural circuitry in HD leading to behavioral changes compared to the processes leading to cell death and volume loss. Inhibition of caspase-2 activity may be associated with symptomatic improvement in HD.

  14. Genetically modified tumour vaccines

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2005-01-01

    Roč. 3, Suppl. 1 (2005), S7 ISSN 1214-021X. [Cells VI - Biological Days /18./. 24.10.2005-26.10.2005, České Budějovice] Institutional research plan: CEZ:AV0Z50520514 Keywords : tumour vaccines * HPV16 Subject RIV: EC - Immunology

  15. of brain tumours

    African Journals Online (AJOL)

    hallucinations other than the typical auditory hallucinations that we so often see in patients with schizophrenia and may include visual ... memory, may show reduced ability for new learning and may also have problems with visuo-spatial memory, particularly if the tumour is in the non-dominant hemisphere.11. The parietal ...

  16. Comparative assessment of students' performance and perceptions on objective structured practical models in undergraduate pathology teaching.

    Science.gov (United States)

    Htwe, Than Than; Ismail, Sabaridah Binti; Low, Gary Kim Kuan

    2014-09-01

    Assessment is an important factor that drives student learning, as students tend to mainly focus on the material to be assessed. The current practice in teaching pathology extensively applies objective-structured practical examination for the assessment of students. As students will have to deal with real patients during clinical years, it is preferred that students learn and practise via potted specimens and slides instead of picture plates. This study aimed to assess the preferred assesment method of pathology practical exercises. This was a cross-sectional survey carried out in two consecutive batches of Phase 2 medical students. Student competency was assessed using both the traditional (TD) (i.e. use of potted specimens and slides) and picture plate (PP) methods. To compare the two assessment methods, we compared the mean scores obtained by the students and examined student perception of the two methods. The mean scores obtained via the PP method were significantly higher than those obtained via the TD method for almost all the components tested. We found that students performed significantly better (p visuals, thus aiding understanding, than the TD method. The findings of this study are valuable in identifying and improving our current teaching and assessment methods of medical students, in line with advancements in information technology.

  17. Comparative assessment of students’ performance and perceptions on objective structured practical models in undergraduate pathology teaching

    Science.gov (United States)

    Htwe, Than Than; Ismail, Sabaridah Binti; Low, Gary Kim Kuan

    2014-01-01

    INTRODUCTION Assessment is an important factor that drives student learning, as students tend to mainly focus on the material to be assessed. The current practice in teaching pathology extensively applies objective-structured practical examination for the assessment of students. As students will have to deal with real patients during clinical years, it is preferred that students learn and practise via potted specimens and slides instead of picture plates. This study aimed to assess the preferred assesment method of pathology practical exercises. METHODS This was a cross-sectional survey carried out in two consecutive batches of Phase 2 medical students. Student competency was assessed using both the traditional (TD) (i.e. use of potted specimens and slides) and picture plate (PP) methods. To compare the two assessment methods, we compared the mean scores obtained by the students and examined student perception of the two methods. RESULTS The mean scores obtained via the PP method were significantly higher than those obtained via the TD method for almost all the components tested. CONCLUSION We found that students performed significantly better (p visuals, thus aiding understanding, than the TD method. The findings of this study are valuable in identifying and improving our current teaching and assessment methods of medical students, in line with advancements in information technology. PMID:25273936

  18. Diversity of Mitochondrial Pathology in a Mouse Model of Axonal Degeneration in Synucleinopathies

    Directory of Open Access Journals (Sweden)

    Akio Sekigawa

    2013-01-01

    Full Text Available There is mounting evidence for a role of mitochondrial dysfunction in the pathogenesis of α-synucleinopathies such as Parkinson's disease (PD and dementia with Lewy bodies (DLB. In particular, recent studies have demonstrated that failure of mitochondrial quality control caused by loss of function of the PTEN-induced kinase 1 (PINK1, PARK6 Parkin (PARK2 pathway may be causative in some familial PD. In sporadic PD, α-synuclein aggregation may interfere with mitochondrial function, and this might be further exacerbated by leucine-rich repeat kinase 2 (LRRK2. The majority of these findings have been obtained in Drosophila and cell cultures, whereas the objective of this paper is to discuss our recent results on the axonal pathology of brains derived from transgenic mice expressing α-synuclein or DLB-linked P123H β-synuclein. In line with the current view of the pathogenesis of sporadic PD, mitochondria abnormally accumulated in α-synuclein/LRRK2-immunopositive axonal swellings in mice expressing α-synuclein. Curiously, neither mitochondria nor LRRK2 was present in the swellings of mice expressing P123H β-synuclein, suggesting that α- and β-synuclein might play differential roles in the mitochondrial pathology of α-synucleinopathies.

  19. Change in the Pathologic Supraspinatus: A Three-Dimensional Model of Fiber Bundle Architecture within Anterior and Posterior Regions

    Directory of Open Access Journals (Sweden)

    Soo Y. Kim

    2015-01-01

    Full Text Available Supraspinatus tendon tears are common and lead to changes in the muscle architecture. To date, these changes have not been investigated for the distinct regions and parts of the pathologic supraspinatus. The purpose of this study was to create a novel three-dimensional (3D model of the muscle architecture throughout the supraspinatus and to compare the architecture between muscle regions and parts in relation to tear severity. Twelve cadaveric specimens with varying degrees of tendon tears were used. Three-dimensional coordinates of fiber bundles were collected in situ using serial dissection and digitization. Data were reconstructed and modeled in 3D using Maya. Fiber bundle length (FBL and pennation angle (PA were computed and analyzed. FBL was significantly shorter in specimens with large retracted tears compared to smaller tears, with the deeper fibers being significantly shorter than other parts in the anterior region. PA was significantly greater in specimens with large retracted tears, with the superficial fibers often demonstrating the largest PA. The posterior region was absent in two specimens with extensive tears. Architectural changes associated with tendon tears affect the regions and varying depths of supraspinatus differently. The results provide important insights on residual function of the pathologic muscle, and the 3D model includes detailed data that can be used in future modeling studies.

  20. Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer's disease.

    LENUS (Irish Health Repository)

    Colgan, N

    2015-10-23

    Increased hyperphosphorylated tau and the formation of intracellular neurofibrillary tangles are associated with the loss of neurons and cognitive decline in Alzheimer\\'s disease, and related neurodegenerative conditions. We applied two diffusion models, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to in vivo diffusion magnetic resonance images (dMRI) of a mouse model of human tauopathy (rTg4510) at 8.5months of age. In grey matter regions with the highest degree of tau burden, microstructural indices provided by both NODDI and DTI discriminated the rTg4510 (TG) animals from wild type (WT) controls; however only the neurite density index (NDI) (the volume fraction that comprises axons or dendrites) from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein. Reductions in diffusion directionality were observed when implementing both models in the white matter region of the corpus callosum, with lower fractional anisotropy (DTI) and higher orientation dispersion (NODDI) observed in the TG animals. In comparison to DTI, histological measures of tau pathology were more closely correlated with NODDI parameters in this region. This in vivo dMRI study demonstrates that NODDI identifies potential tissue sources contributing to DTI indices and NODDI may provide greater specificity to pathology in Alzheimer\\'s disease.

  1. Predictive value and modeling analysis of MSCT signs in gastrointestinal stromal tumors (GISTs) to pathological risk degree.

    Science.gov (United States)

    Wang, J-K

    2017-03-01

    By analyzing MSCT (multi-slice computed tomography) signs with different risks in gastrointestinal stromal tumors, this paper aimed to discuss the predictive value and modeling analysis of MSCT signs in GISTs (gastrointestinal stromal tumor) to pathological risk degree. 100 cases of primary GISTs with abdominal and pelvic MSCT scan were involved in this study. All MSCT scan findings and enhanced findings were analyzed and compared among cases with different risk degree of pathology. Then GISTs diagnostic model was established by using support vector machine (SVM) algorithm, and its diagnostic value was evaluated as well. All lesions were solitary, among which there were 46 low-risk cases, 24 medium-risk cases and 30 high-risk cases. For all high-risk, medium-risk and low-risk GISTs, there were statistical differences in tumor growth pattern, size, shape, fat space, with or without calcification, ulcer, enhancement method and peritumoral and intratumoral vessels (pvalue at each period (plain scan, arterial phase, venous phase) (p>0.05). The apparent difference lied in plain scan, arterial phase and venous phase for each risk degree. The diagnostic accuracy of SVM diagnostic model established with 10 imaging features as indexes was 70.0%, and it was especially reliable when diagnosing GISTs of high or low risk. Preoperative analysis of MSCT features is clinically significant for its diagnosis of risk degree and prognosis; GISTs diagnostic model established on the basis of SVM possesses high diagnostic value.

  2. Pathological gambling

    Science.gov (United States)

    ... diagnose pathological gambling. Screening tools such as the Gamblers Anonymous 20 Questions www.gamblersanonymous.org/ga/content/20- ... therapy (CBT). Self-help support groups , such as Gamblers Anonymous. Gamblers Anonymous www.gamblersanonymous.org/ga is a ...

  3. Urothelial Tumours of the Urinary Bladder: A Histopathological Study of Cystoscopic Biopsies

    Directory of Open Access Journals (Sweden)

    Sujan Vaidya

    2013-09-01

    Full Text Available ABSTRACT Introduction: Bladder tumours constitute one of the most common urological conditions. Urothelial (transitional cell carcinoma accounts for 90% of all primary tumours of the bladder. These tumours are an important cause of morbidity and mortality. The objective of this study was to present the histopathological patterns of urothelial tumours and to determine the grade and stage of these tumours. Methods: This is a 3 year retrospective study of urothelial tumours carried out in the Department of Pathology, Patan Academy of Health Sciences (PAHS, Lalitpur, Nepal. Data of all cystoscopic biopsies collected during this period were analyzed. Results: Urothelial (transitional cell tumours accounted for 97.59% (81 cases of all bladder tumours. Transitional cell carcinoma (TCC was the most common tumour which was present in 67 cases (80.72%. Of these, 32 (47.76% were low grade TCC while 35 (52.24% were high grade TCC. Maximum number of tumours (70.37% were superficial (pTa and pT1 while (29.63% were muscle invasive (pT2. Sixteen percent of low grade and 76.92% of high grade tumours showed muscle invasion. Detrusor muscle was absent in 23.88% cases (16/67. Conclusion: Transitional cell carcinoma was the most common bladder cancer. Most of these tumours were high grade. A large percentage of high grade carcinomas presented with muscle invasion. Pathological grade and muscle invasion are the most valuable prognostic predictors of survival. The importance of including smooth muscle in the biopsy specimens needs to be emphasized Key words: cancer, high grade, low grade, transitional, tumour, urinary bladder.

  4. A generalised age- and phase-structured model of human tumour cell populations both unperturbed and exposed to a range of cancer therapies.

    Science.gov (United States)

    Basse, Britta; Ubezio, Paolo

    2007-07-01

    We develop a general mathematical model for a population of cells differentiated by their position within the cell division cycle. A system of partial differential equations governs the kinetics of cell densities in certain phases of the cell division cycle dependent on time t (hours) and an age-like variable tau (hours) describing the time since arrival in a particular phase of the cell division cycle. Transition rate functions control the transfer of cells between phases. We first obtain a theoretical solution on the infinite domain -infinity course, these age distributions are unknown. All is not lost, however, because a cell line before treatment usually lies in a state of asynchronous balanced growth where the proportion of cells in each phase of the cell cycle remain constant. We assume that an unperturbed cell line has four distinct phases and that the rate of transition between phases is constant within a short period of observation ('short' relative to the whole history of the tumour growth) and we show that under certain conditions, this is equivalent to exponential growth or decline. We can then gain expressions for the age distributions. So, in short, our approach is to assume that we have an unperturbed cell line on t model.

  5. [Gender differences in the use of tumour markers].

    Science.gov (United States)

    Moreno-Campoy, E E; Mérida-De la Torre, F J; Martos-Crespo, F; Plebani, M

    2015-01-01

    Gender is one of the factors that can influence the use of health resources. The use of tumour markers is widespread, due to the importance of these in monitoring cancer development. The aim of this study is to analyse the influence of gender on the use of tumour markers, and to investigate whether there are differences in their use. A longitudinal, retrospective and descriptive study, with a 2-year follow-up, was conducted in the catchment area of the University Hospital of Padua. An analysis was performed on 23,059 analytical requests for tumour markers. A descriptive and frequency analysis was performed on all variables. The statistical analysis was performed using Chi squared, Student t and Mann-Whitney U to test for significance. The number of requests for women (1.5) was lower than men (1.6). In patients with tumour pathology, the number of requests was higher than in patients without tumour disease. In the analysis by disease and gender, the difference remained significant. As regards the number of tumour markers per request, the difference between genders was also significant: 2.13 in males versus 2.85 in women. Similar results were obtained when requests for tumour markers linked to gender-related diseases were eliminated. There are differences in the use of tumour markers by gender with the number of requests for male patients being higher than for females. However, the number of tumour markers per request is greater in women than in men. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  6. Periodontal and endodontic pathology delays extraction socket healing in a canine model

    Science.gov (United States)

    2017-01-01

    Purpose The aim of the present exploratory study was to evaluate extraction socket healing at sites with a history of periodontal and endodontic pathology. Methods The mandibular 4th premolar teeth in 5 adult beagle dogs served as experimental units. Periodontal and endodontic lesions were induced in 1 premolar site in each animal using wire ligatures and pulpal exposure over 3 months (diseased sites). The contralateral premolar sites served as healthy controls. The mandibular 4th premolar teeth were then extracted with minimal trauma, followed by careful wound debridement. The animals were sacrificed at days 1, 7, 30, 60, and 90 post-extraction for analysis, and the healing patterns at the healthy and diseased extraction sites were compared using radiography, scanning electron microscopy, histology, and histometry. Results During the first 7 days of healing, a significant presence of inflammatory granulation tissue was noted at the diseased sites (day 1), along with a slightly accelerated rate of fibrin clot resolution on day 7. On day 30, the diseased extraction sites showed a greater percentage of persistent fibrous connective tissue, and an absence of bone marrow formation. In contrast, healthy sites showed initial signs of bone marrow formation on day 30, and subsequently a significantly greater proportion of mature bone marrow formation on both days 60 and 90. Radiographs exhibited sclerotic changes adjoining apical endodontic lesions, with scanning electron microscopy showing collapsed Volkmann canals protruding from these regions in the diseased sites. Furthermore, periodontal ligament fibers exhibited a parallel orientation to the alveolar walls of the diseased sites, in contrast to a perpendicular arrangement in the healthy sites. Conclusions Within the limitations of this study, it appears that a history of periodontal and endodontic pathology may critically affect bone formation and maturation, leading to delayed and compromised extraction socket

  7. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease

    Directory of Open Access Journals (Sweden)

    Heike Wolf

    2016-09-01

    Full Text Available Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1 was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6-GlcNAc(β1-N-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS. On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis.

  8. Application of boron-entrapped stealth liposomes to inhibition of growth of tumour cells in the in vivo boron neutron-capture therapy model.

    Science.gov (United States)

    Yanagie, H; Maruyama, K; Takizawa, T; Ishida, O; Ogura, K; Matsumoto, T; Sakurai, Y; Kobayashi, T; Shinohara, A; Rant, J; Skvarc, J; Ilic, R; Kuhne, G; Chiba, M; Furuya, Y; Sugiyama, H; Hisa, T; Ono, K; Kobayashi, H; Eriguchi, M

    2006-01-01

    Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons. It is necessary for effective BNCT therapy to accumulate (10)B atoms in the tumour cells. The delivery system consisted of polyethylene-glycol (PEG) binding liposomes (DPPC/cholesterol/DSPC-PEG2000) with an entrapped (10)B-compound and we evaluated the cytotoxic effects of intravenously injected (10)B-PEG-liposomes on human pancreatic carcinoma xenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with (10)B-PEG-liposomes, growth of AsPC-1 tumours was suppressed relative to controls. Injection of (10)B-PEG-liposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of (10)B-PEG-liposomes can increase the retention of (10)B atoms by tumour cells, causing suppression of tumour growth in vivo, after thermal neutron irradiation.

  9. Presence of Cx43 in extracellular vesicles reduces the cardiotoxicity of the anti-tumour therapeutic approach with doxorubicin

    Directory of Open Access Journals (Sweden)

    Tania Martins-Marques

    2016-09-01

    Full Text Available Extracellular vesicles (EVs are major conveyors of biological information, mediating local and systemic cell-to-cell communication under physiological and pathological conditions. These endogenous vesicles have been recognized as prominent drug delivery vehicles of several therapeutic cargoes, including doxorubicin (dox, presenting major advantages over the classical approaches. Although dox is one of the most effective anti-tumour agents in the clinical practice, its use is very often hindered by its consequent dramatic cardiotoxicity. Despite significant advances witnessed in the past few years, more comprehensive studies, supporting the therapeutic efficacy of EVs, with decreased side effects, are still scarce. The main objective of this study was to evaluate the role of the gap junction protein connexin43 (Cx43 in mediating the release of EV content into tumour cells. Moreover, we investigated whether Cx43 improves the efficiency of dox-based anti-tumour treatment, with a concomitant decrease of cardiotoxicity. In the present report, we demonstrate that the presence of Cx43 in EVs increases the release of luciferin from EVs into tumour cells in vitro and in vivo. In addition, using cell-based approaches and a subcutaneous mouse tumour model, we show that the anti-tumour effect of dox incorporated into EVs is similar to the administration of the free drug, regardless the presence of Cx43. Strikingly, we demonstrate that the presence of Cx43 in dox-loaded EVs reduces the cardiotoxicity of the drug. Altogether, these results bring new insights into the concrete potential of EVs as therapeutic vehicles and open new avenues toward the development of strategies that help to reduce unwanted side effects.

  10. High-Risk Breast Lesions: A Machine Learning Model to Predict Pathologic Upgrade and Reduce Unnecessary Surgical Excision.

    Science.gov (United States)

    Bahl, Manisha; Barzilay, Regina; Yedidia, Adam B; Locascio, Nicholas J; Yu, Lili; Lehman, Constance D

    2018-03-01

    Purpose To develop a machine learning model that allows high-risk breast lesions (HRLs) diagnosed with image-guided needle biopsy that require surgical excision to be distinguished from HRLs that are at low risk for upgrade to cancer at surgery and thus could be surveilled. Materials and Methods Consecutive patients with biopsy-proven HRLs who underwent surgery or at least 2 years of imaging follow-up from June 2006 to April 2015 were identified. A random forest machine learning model was developed to identify HRLs at low risk for upgrade to cancer. Traditional features such as age and HRL histologic results were used in the model, as were text features from the biopsy pathologic report. Results One thousand six HRLs were identified, with a cancer upgrade rate of 11.4% (115 of 1006). A machine learning random forest model was developed with 671 HRLs and tested with an independent set of 335 HRLs. Among the most important traditional features were age and HRL histologic results (eg, atypical ductal hyperplasia). An important text feature from the pathologic reports was "severely atypical." Instead of surgical excision of all HRLs, if those categorized with the model to be at low risk for upgrade were surveilled and the remainder were excised, then 97.4% (37 of 38) of malignancies would have been diagnosed at surgery, and 30.6% (91 of 297) of surgeries of benign lesions could have been avoided. Conclusion This study provides proof of concept that a machine learning model can be applied to predict the risk of upgrade of HRLs to cancer. Use of this model could decrease unnecessary surgery by nearly one-third and could help guide clinical decision making with regard to surveillance versus surgical excision of HRLs. © RSNA, 2017.

  11. Augmented reality in bone tumour resection

    Science.gov (United States)

    Park, Y. K.; Gupta, S.; Yoon, C.; Han, I.; Kim, H-S.; Choi, H.; Hong, J.

    2017-01-01

    Objectives We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. Methods We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. Results The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137–143. PMID:28258117

  12. Pathological gambling and criminality.

    Science.gov (United States)

    Folino, Jorge Oscar; Abait, Patricia Estela

    2009-09-01

    To review research results on the relationship between pathological gambling and criminality, published in 2007 and 2008, in English and in Spanish. An important association between pathological gambling and criminality was confirmed in populations of anonymous gamblers, helpline callers and substance abusers. Helplines provide a timely service to gamblers who have not reached the maximum stages in the development of a pathological gambling pattern. Pathological gambling is associated with violence in couples and dysfunctional families. Inversely, violence is also an antecedent promoting vulnerability toward pathological gambling. Impulsiveness shows diverse relationships with pathological gambling and violence as well. A pathological gambler's involvement in crime is exceptionally considered without responsibility by justice, but it may be an indicator of the disorder severity and the need for special therapeutic tactics. While reviewing the present study, research work was published that contributed to a better understanding of the association between pathological gambling and criminality and went further into their complex relationship and the formulation of explanatory models related to impulsiveness.

  13. The dimethylhydrazine induced colorectal tumours in rat - experimental colorectal carcinogenesis

    International Nuclear Information System (INIS)

    Perse, M.; Cerar, A.

    2005-01-01

    Animal models of colorectal carcinogenesis represent invaluable research tool for investigating colorectal cancer (CRC). Experimentally induced tumours in laboratory animals provide opportunity for studying certain aspects of tumours that cannot be effectively studied in humans. Significant information on human CRC aetiology or factors influencing it has derived from studies using dimethylhydrazine (DMH) model that is one of the experimental models appreciated for its morphological similarity to human CRC. Today, DMH model represents useful research tool for the studies of colon carcinogens and chemopreventive agents. The review offers insight into morphogenesis and genetic alterations of DMH induced colorectal epithelial tumours in rats. (author)

  14. Anti-Tumor Action, Clinical Biochemistry Profile and Phytochemical Constituents of a Pharmacologically Active Fraction of S. crispus in NMU-Induced Rat Mammary Tumour Model.

    Directory of Open Access Journals (Sweden)

    Nik Soriani Yaacob

    Full Text Available Cancer patients seek alternative remedies such as traditional medicinal plants for safe and effective treatment and help overcome the side effects of conventional therapy. Current knowledge indicates that extracts of Strobilanthes crispus of the Acanthaceae family exhibit potent anticancer properties in vitro and are non-toxic in vivo. S. crispus was also reported to be protective against chemical hepatocarcinogenesis. We previously showed that a bioactive fraction of S. crispus leaves also synergized with tamoxifen to cause apoptosis of human breast cancer cell lines without damaging non-malignant epithelial cells. The present study aimed to evaluate the antitumor effect of S. crispus dichloromethane fraction (F3 using N-methyl-N-Nitrosourea (NMU-induced rat mammary tumor model. Tumor regression was observed in 75% of the rats following 8-week oral administration of F3 with no secondary tumour formation and no signs of anemia or infection. However, no improvement in the liver and renal function profiles was observed. Major constituents of F3 were identified as lutein, 131-hydroxy-132-oxo-pheophytin a, campesterol, stigmasterol, β-sitosterol, pheophytin a and 132-hydroxy-pheophytin a. These compounds however, may not significantly contribute to the antitumor effect of F3.

  15. Pathological gambling in patients with Parkinson's disease is associated with fronto-striatal disconnection: a path modeling analysis.

    Science.gov (United States)

    Cilia, Roberto; Cho, Sang Soo; van Eimeren, Thilo; Marotta, Giorgio; Siri, Chiara; Ko, Ji Hyun; Pellecchia, Giovanna; Pezzoli, Gianni; Antonini, Angelo; Strafella, Antonio P

    2011-02-01

    Pathological gambling may occur in Parkinson's disease (PD) as a complication of dopaminergic therapy. Neuroimaging studies have suggested an abnormal dopamine transmission within the reward system, but the changes in the neural network characterizing PD patients with pathological gambling have never been investigated. Thirty PD patients (15 with active gambling and 15 matched controls, on-medication) and 15 healthy subjects underwent brain perfusion single photon emission tomography at rest. The severity of gambling was assessed using the South Oaks Gambling Scale. Covariance analysis was applied to identify brain regions whose activity was associated with gambling severity. These regions were used as volume-of-interest to identify functionally interconnected areas using voxel-wise covariance analysis. A path model was defined by means of effective connectivity analysis within the Structural Equation Modeling framework. Gambling severity in PD was associated with a dysfunction of the brain network implicated in decision making, risk processing, and response inhibition, including the ventrolateral prefrontal cortex, anterior (ACC) and posterior cingulate cortex, medial prefrontal cortex, insula and striatum. PD gamblers showed a disconnection between the ACC and the striatum, while this interaction was very robust in both control groups. ACC-striatal disconnection may underlie a specific impairment of shifting behaviors after negative outcomes, possibly explaining why PD gamblers use to perseverate into risktaking behaviors despite self-destructive consequences. Copyright © 2011 Movement Disorder Society.

  16. Tumours following retinoblastoma radiotherapy

    International Nuclear Information System (INIS)

    Mollot, J.-P.

    1978-01-01

    Radioinduced tumours in young patients irradiated in childhood for retinoblastoma take on a particularly deadly aspect. The onset of this true clinical entity characterized by a long post-irradiation latency period induced by a dose above 6000 rads is a real tragedy. The vast majority of patients then enter into a long martyrdom ending in death. The only cure is surgical, but seldom possible. Treatment is limited to palliative radiotherapy, effective for a while, and chemiotherapy as a last resort but often difficult to prescribe. Prevention alone is the answer. The quality and reliability of the radiotherapeutic treatment depend not only on the personal talent of the radiotherapist but above all on the standard of the equipment. A strong reduction in the doses employed as well as recent technological progress improving the material, its precision and reproducibility appear already to have lowered the frequency curve of these fatal radioinduced tumours [fr

  17. Malignant mixed mullerian tumours of the body of the uterus: a clinicopathological study of 20 cases.

    Science.gov (United States)

    Muthuphei, M N; Maluleke, H J

    1998-02-01

    To review the clinical and histopathological data on malignant mixed mullerian tumours. A retrospective study of 20 cases of malignant mixed mullerian tumours seen over a period of five and half years. Departments of Obstetrics and Gynaecology and Anatomical Pathology at Garankuwa Acdemic Hospital. Clinical and histopathological records of patients with malignant mixed mullerian tumours of the body of the uterus. Clinical record and histopathological slides were reviewed. Age, clinical presentation and histological appearances of the cases were noted. The patient age ranged from 16 to 78 years with a median of 63 years (Q1 = 58.5, Q3 = 71.5). Of the 20 cases 14 died within 12 months of diagnosis. Clinical staging and histological staging had no effect on tumour behaviour and outcome of disease. Malignant mixed mullerian tumours are predominantly seen in post menopausal women. These tumours have a very poor prognosis irrespective of clinical stage, histological grade or the type of the stroma.

  18. Prognostic indicators in ovarian serous borderline tumours.

    Science.gov (United States)

    Malpica, Anais; Longacre, Teri A

    2018-02-01

    There have been great strides in our understanding of the serous group of borderline and malignant pelvic epithelial neoplasms in the past decade. While most serous borderline tumours have a favourable prognosis, recurrences and progression to carcinoma occur, often following a protracted clinical course. Clinical and pathological risk factors tend to co-vary, but the presence and type of extraovarian disease is the most important predictor for progression. Progression usually takes the form of low-grade serous carcinoma, although transformation to high-grade carcinoma is occasionally seen. A serous borderline - low-grade serous carcinoma pathway analogous to neoplastic transformation pathways seen in other organ systems has been proposed, based on global gene expression profiling, shared mutations in KRAS or BRAF, and in most cases, the presence of serous borderline tumour in de novo low-grade serous carcinoma. This discussion focuses on the key prognostic factors that predispose to disease progression and/or transformation to carcinoma in serous borderline tumours. Published by Elsevier B.V.

  19. Wilms tumour in Sudan.

    Science.gov (United States)

    Abuidris, Dafalla O; Elimam, Mohammed E; Nugud, Faisal M; Elgaili, Elgaili M; Ahmed, Mohamed E; Arora, Ramandeep S

    2008-06-01

    Wilms tumour is one of the commonest childhood solid tumours which has an excellent outlook in the developed world with 5-year overall survival exceeding 90%. There is little information from Sudan regarding Wilms tumour. Records of patients with Wilms tumour diagnosed and treated at Institute of Nuclear Medicine, Molecular Biology and Oncology (INMO) in the University of Gezira from May 1999 to June 2007 were reviewed. Thirty-seven children presented at a mean age of 4.1 years (range 2 months-13 years). The male to female ratio was 0.9-1. Abdominal swelling or mass was the commonest symptom. There was 1 child with Stage I (2.7%), 7 with stage II (18.9%), 25 with Stage III (67.6%) and 4 with Stage IV (10.8%). Following diagnosis 27% of children did not receive further treatment (5.4% died prior to treatment, 5.4% were not able to finance treatment and for the rest 16.2% no cause was identified). More than half of the children did not have a nephrectomy and only 4 (11%) completed treatment. The poor outlook is related to several factors. Delayed presentation, poor awareness of treatment options, lack of finances, no provision of food, lodging and transport, absence of paediatric trained staff are the obstacles to better outcomes. Empowering parents with information, giving chemotherapy prior to nephrectomy, training staff and establishing links with a tertiary cancer centre in the developed world are some of the options to improve survival. (c) 2007 Wiley-Liss, Inc.

  20. Treating tumours with radionuclides

    International Nuclear Information System (INIS)

    Nair, G.

    1993-01-01

    This article reviews the uses of radiopharmaceuticals in radiotherapy. After a discussion on the suitability of various isotopes for therapeutic use, some well-established examples of radiotherapy are described. These include the treatment of thyroid diseases with I-131, of polycythemia vera with P-32 and of neural crest tumours with 131 I-MIBG. New trends in therapy of bone diseases and in radioimmunotherapy are also considered

  1. Optimization of a 3D Dynamic Culturing System for In Vitro Modeling of Frontotemporal Neurodegeneration-Relevant Pathologic Features.

    Science.gov (United States)

    Tunesi, Marta; Fusco, Federica; Fiordaliso, Fabio; Corbelli, Alessandro; Biella, Gloria; Raimondi, Manuela T

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer's disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may be

  2. Normal and Pathological NCAT Image and Phantom Data Based on Physiologically Realistic Left Ventricle Finite-Element Models

    International Nuclear Information System (INIS)

    Veress, Alexander I.; Segars, W. Paul; Weiss, Jeffrey A.; Tsui, Benjamin M.W.; Gullberg, Grant T.

    2006-01-01

    The 4D NURBS-based Cardiac-Torso (NCAT) phantom, which provides a realistic model of the normal human anatomy and cardiac and respiratory motions, is used in medical imaging research to evaluate and improve imaging devices and techniques, especially dynamic cardiac applications. One limitation of the phantom is that it lacks the ability to accurately simulate altered functions of the heart that result from cardiac pathologies such as coronary artery disease (CAD). The goal of this work was to enhance the 4D NCAT phantom by incorporating a physiologically based, finite-element (FE) mechanical model of the left ventricle (LV) to simulate both normal and abnormal cardiac motions. The geometry of the FE mechanical model was based on gated high-resolution x-ray multi-slice computed tomography (MSCT) data of a healthy male subject. The myocardial wall was represented as transversely isotropichyperelastic material, with the fiber angle varying from -90 degrees at the epicardial surface, through 0 degrees at the mid-wall, to 90 degrees at the endocardial surface. A time varying elastance model was used to simulate fiber contraction, and physiological intraventricular systolic pressure-time curves were applied to simulate the cardiac motion over the entire cardiac cycle. To demonstrate the ability of the FE mechanical model to accurately simulate the normal cardiac motion as well abnormal motions indicative of CAD, a normal case and two pathologic cases were simulated and analyzed. In the first pathologic model, a subendocardial anterior ischemic region was defined. A second model was created with a transmural ischemic region defined in the same location. The FE based deformations were incorporated into the 4D NCAT cardiac model through the control points that define the cardiac structures in the phantom which were set to move according to the predictions of the mechanical model. A simulation study was performed using the FE-NCAT combination to investigate how the

  3. EVALUATION OF MEDIASTINAL TUMOURS: A STUDY OF 50 CASES

    Directory of Open Access Journals (Sweden)

    Prema K. R

    2016-06-01

    Full Text Available INTRODUCTION Mediastinum is a site for neoplastic and non-neoplastic lesions and many of them present as mediastinal mass. The location and composition of these lesions are critical in arriving at a clinical diagnosis. This study of different mediastinal masses is aimed to find out frequency of malignancy, their compartmental distribution and characteristics through computed tomography. MATERIALS AND METHODS A prospective study was conducted at Government Medical College, Thrissur, India, during the period 2010-2012 with a total of 50 patients with suspected mediastinal masses. All patients were subjected to investigations like chest X-ray, CT scan along with guided fine needle aspiration/biopsy for definite tissue diagnosis. The major variables were age, clinical symptoms, mass location, imaging studies, and tissue pathology. RESULT Fifty patients enrolled in this study were analysed and compared with existing studies in the literature. 34 cases (68% were malignant and 16 cases (32% were benign. Majority of the lesions were seen in the anterior compartment, followed by posterior compartment. Bronchogenic carcinoma and lymphoma were the common malignant tumours seen in the anterior and middle compartments of the mediastinum, whereas neurogenic tumours, mostly benign, were the common tumours in the posterior compartment. CONCLUSION CT scan is an effective tool in evaluating mediastinal masses. Moreover, sampling the mass is important in obtaining pathological diagnosis. Surgery, radiotherapy and chemotherapy either as single or in combination are the main modalities of treatment. Accurate preoperative pathological diagnosis, invasion and infiltration of the tumour were the key to successful treatment.

  4. Normal and Pathological NCAT Image and PhantomData Based onPhysiologically Realistic Left Ventricle Finite-Element Models

    Energy Technology Data Exchange (ETDEWEB)

    Veress, Alexander I.; Segars, W. Paul; Weiss, Jeffrey A.; Tsui,Benjamin M.W.; Gullberg, Grant T.

    2006-08-02

    The 4D NURBS-based Cardiac-Torso (NCAT) phantom, whichprovides a realistic model of the normal human anatomy and cardiac andrespiratory motions, is used in medical imaging research to evaluate andimprove imaging devices and techniques, especially dynamic cardiacapplications. One limitation of the phantom is that it lacks the abilityto accurately simulate altered functions of the heart that result fromcardiac pathologies such as coronary artery disease (CAD). The goal ofthis work was to enhance the 4D NCAT phantom by incorporating aphysiologically based, finite-element (FE) mechanical model of the leftventricle (LV) to simulate both normal and abnormal cardiac motions. Thegeometry of the FE mechanical model was based on gated high-resolutionx-ray multi-slice computed tomography (MSCT) data of a healthy malesubject. The myocardial wall was represented as transversely isotropichyperelastic material, with the fiber angle varying from -90 degrees atthe epicardial surface, through 0 degreesat the mid-wall, to 90 degreesat the endocardial surface. A time varying elastance model was used tosimulate fiber contraction, and physiological intraventricular systolicpressure-time curves were applied to simulate the cardiac motion over theentire cardiac cycle. To demonstrate the ability of the FE mechanicalmodel to accurately simulate the normal cardiac motion as well abnormalmotions indicative of CAD, a normal case and two pathologic cases weresimulated and analyzed. In the first pathologic model, a subendocardialanterior ischemic region was defined. A second model was created with atransmural ischemic region defined in the same location. The FE baseddeformations were incorporated into the 4D NCAT cardiac model through thecontrol points that define the cardiac structures in the phantom whichwere set to move according to the predictions of the mechanical model. Asimulation study was performed using the FE-NCAT combination toinvestigate how the differences in contractile function

  5. Neuromuscular hamartoma: imaging features of a rare paediatric craniofacial tumour

    International Nuclear Information System (INIS)

    Oeppen, Rachel S.; Harden, Stephen P.; Argent, Julie D.

    2003-01-01

    Neuromuscular hamartoma (also referred to as neuromuscular choristoma or benign triton tumour) has not previously been described in the radiological literature. It is a rare benign lesion composed of mature elements of striated muscle and neural tissue. We report a case of neuromuscular hamartoma involving the skull base, nasopharynx, orbit and maxilla in a 2.5-year-old child who presented with facial swelling. The CT and MRI appearances of this unusual soft-tissue tumour are emphasized, together with a discussion of the pathological findings, differential diagnosis and review of the literature. (orig.)

  6. Clinico-pathological analysis of malignant salivary gland tumours in ...

    African Journals Online (AJOL)

    Case files of these patients were retrieved and informations such as age, stage during surgery and site of occurrence were gotten from the files. Data was analyzed using simple statistical formulas to determine mean and frequency. Deductions and observed were then discussed. RESULTS A total of 74 malignant salivary ...

  7. Quantification of antiangiogenic treatment effects on tissue heterogeneity in glioma tumour xenograft model using a combination of DCE-MRI and 3D-ultramicroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Dominietto, Marco [University and ETH Zurich, Institute for Biomedical Engineering, Zurich (Switzerland); University of Basel, Biomaterials Science Center, Allschwil (Switzerland); Dobosz, Michael; Renner, Anja; Scheuer, Werner [Roche Innovation Center Penzberg, Discovery Oncology, Pharmaceutical Research and Early Development (pRED), Penzberg (Germany); Buergi, Sandra; Rudin, Markus [University and ETH Zurich, Institute for Biomedical Engineering, Zurich (Switzerland); Zahlmann, Gudrun [pRED, Oncology DTA, Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel (Switzerland)

    2017-07-15

    This study aimed at assessing the effects of an anti-angiogenic treatment, which neutralises vascular endothelial growth factor (VEGF), on tumour heterogeneity. Murine glioma cells have been inoculated into the right brain frontal lobe of 16 mice. Anti-VEGF antibody was administered to a first group (n = 8), while a second group (n = 8) received a placebo. Magnetic resonance acquisitions, performed at days 10, 12, 15 and 23 following the implantation, allowed the derivation of a three-dimensional features dataset characterising tumour heterogeneity. Three-dimensional ultramicroscopy and standard histochemistry analysis have been performed to verify in vivo results. Placebo-treated mice displayed a highly-vascularised area at the tumour periphery, a monolithic necrotic core and a chaotic dense vasculature across the entire tumour. In contrast, the B20-treated group did not show any highly vascularised regions and presents a fragmented necrotic core. A significant reduction of the number of vessel segments smaller than 17 μm has been observed. There was no difference in overall tumour volume and growth rate between the two groups. Region-specific analysis revealed that VEGF inhibition affects only: (1) highly angiogenic compartments expressing high levels of VEGF and characterised by small capillaries, and also (2) the formation and structure of necrotic regions. These effects appear to be transient and limited in time. (orig.)

  8. Catalytic antibodies in clinical and experimental pathology: human and mouse models.

    Science.gov (United States)

    Ponomarenko, Natalya A; Durova, Oxana M; Vorobiev, Ivan I; Aleksandrova, Elena S; Telegin, Georgy B; Chamborant, Olga G; Sidorik, Lyudmila L; Suchkov, Sergei V; Alekberova, Zemfira S; Gnuchev, Nikolay V; Gabibov, Alexander G

    2002-11-01

    Most of the data accumulated through studies on natural catalytic autoantibodies indicate that production scales up markedly in pathological abnormalities. We have previously described an increased level of DNA-hydrolyzing autoantibodies in the sera of patients with various autoimmune disorders [systemic lupus erythematosus (SLE), rheumatoid arthritis, scleroderma], HIV infection and lymphoproliferative diseases accompanied by autoimmune manifestations. In the present study, we show that an increased level of catalytic activity of autoantibodies can be observed in the sera of autoimmune mice, thus providing a fundamental insight into the medical relevance of abzymes. Polyclonal autoantibodies purified from sera of NZB/W, MRL-lpr/lpr and SJL/J mice show proteolytic and DNA-hydrolyzing activities, as opposed to those harvested from non-autoimmune BALB/c mice. The expressiveness of the catalytic activity was strongly dependent on the age of the animal. The highest levels of catalytic activity were found in the sera of mice aged between 8 and 12 months; the lowest level was typical of younger animals whose age ranged from 6 to 8 weeks. Specific inhibition assays of the catalytic activities were performed to throw light on the nature of the abzyme activity. Within a cohort of aging animals, a strong correlation between marked autoimmune abnormalities and levels of catalytic activities has been established. Nonimmunized SJL/J mice revealed specific immune responses to myelin basic protein (MBP), skeletal muscle myosin (skMyo) and cardiac myosin (Myo), and highly purified antibodies from their serum show specific proteolytic attack against the target antigens. This finding prompted us to undertake a more detailed study of specific antibody-mediated proteolysis in diseased humans. A targeted catalytic response was originally demonstrated against MBP and Myo in multiple sclerosis and myocarditis patients, respectively.

  9. Aggressive pituitary tumours and carcinomas: two sides of the same coin?

    Science.gov (United States)

    Trouillas, Jacqueline; Burman, Pia; McCormack, Ann I; Petersenn, Stephan; Popovic, Vera; Dekkers, Olaf; Raverot, Gerald

    2018-03-27

    The European Society of Endocrinology (ESE) survey reported on the largest cohort of 125 aggressive pituitary tumours (APT) and 40 pituitary carcinomas (PC). Whilst the survey focused on treatment effectiveness, all pathological data were not explored in detail. Here we comment on some interesting pathological findings, notably the difference between APT and PC.

  10. Alterations in spatial memory and anxiety in the MAM E17 rat model of hippocampal pathology in schizophrenia.

    Science.gov (United States)

    Gastambide, Francois; Taylor, Amy M; Palmer, Clare; Svard, Heta; Karjalainen, Maija; Janhunen, Sanna K; Tricklebank, Mark; Bannerman, David M

    2015-11-01

    Adult rats exposed to methylazoxymethanol acetate (MAM) at embryonic day 17 (E17) display robust pathological alterations in the hippocampus. However, discrepancies exist in the literature regarding the behavioural effects of this pre-natal manipulation. Therefore, a systematic assessment of MAM E17-induced behavioural alterations was conducted using a battery of dorsal and ventral hippocampus-dependent tests. Compared to saline controls, MAM E17-treated rats displayed deficits in spatial reference memory in both the aversive hidden platform watermaze task and an appetitive Y-maze task. Deficits in the spatial reference memory watermaze task were replicated across three different cohorts and two laboratories. In contrast, there was little, or no, effect on the non-spatial, visible platform watermaze task or an appetitive, non-spatial, visual discrimination task, respectively. MAM rats were also impaired in the spatial novelty preference task which assesses short-term memory, and displayed reduced anxiety levels in the elevated plus maze task. Thus, MAM E17 administration resulted in abnormal spatial information processing and reduced anxiety in a number of hippocampus-dependent behavioural tests, paralleling the effects of dorsal and ventral hippocampal lesions, respectively. These findings corroborate recent pathological and physiological studies, further highlighting the usefulness of MAM E17 as a model of hippocampal dysfunction in at least some aspects of schizophrenia.

  11. Dipotassium N-stearoyltyrosinate ameliorated pathological injuries in triple-transgenic mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Sha Liu

    2016-09-01

    Full Text Available Recently, anandamide (AEA analogues have been well recognized for its potent neuroprotective effects in counteracting the deterioration of Alzheimer's disease (AD brains through multiple pathological processes. In our previous studies, dipotassium N-stearoyltyrosinate (NSTK, an AEA analogue synthesized by our laboratory was reported to exert significant efficacy through multiple interventions. Within this study, the amyloid precursor protein (APPSWE/presenilin-1 (PS1M146V/TauP301L mouse (3×Tg-AD model was used to explore further the neuroprotective effects of NSTK and its underlying mechanisms. NSTK could increase spontaneous locomotor activity in the open field and low anxiety-like behavior in the elevated plus maze, and improve the spatial memory deficits in the Morris water maze. The biochemical analysis suggested that NSTK could decrease Aβ42 deposition, abnormal tau aggregation, and the expressions of p-APP Thr668, PS1 and p-tau Ser202/Thr205 in the hippocampus of 3×Tg-AD mice. Consistently, NSTK could reduce the level of malondialdehyde, increase the activity of superoxide dismutase and catalase. Up-regulation of Bcl-2, and down-regulation of BAX, caspase-3 and inflammatory cytokines also occurred in the hippocampus of 3×Tg-AD mice after treatment with NSTK. Thus, NSTK could intervene in multiple pathological processes of AD and would be a drug candidate against AD.

  12. Simvastatin restored vascular reactivity, endothelial function and reduced string vessel pathology in a mouse model of cerebrovascular disease

    Science.gov (United States)

    Tong, Xin-Kang; Hamel, Edith

    2015-01-01

    Cerebrovascular dysfunction seen in Alzheimer's disease (AD) and vascular dementia (VaD) is multifaceted and not limited to the amyloid-β (Aβ) pathology. It encompasses structural alterations in the vessel wall, degenerating capillaries (string vessels), vascular fibrosis and calcification, features recapitulated in transgenic mice that overexpress transforming growth factor-β1 (TGF mice). We recently found that simvastatin rescued Aβ-mediated cerebrovascular and cognitive deficits in a transgenic mouse model of AD. However, whether simvastatin can counteract Aβ-independent deficits remains unknown. Here, we evaluated the effects of simvastatin in aged TGF mice on cerebrovascular reactivity and structure, and on cognitive performance. Simvastatin restored baseline levels of nitric oxide (NO), NO-, and KATP channel-mediated dilations and endothelin-1-induced contractions. Simvastatin significantly reduced vasculopathy with arteriogenic remodeling and string vessel pathology in TGF mice. In contrast, simvastatin did not lessen gliosis, and the cerebrovascular levels of pro-fibrotic proteins and calcification markers remained elevated after treatment. The TGF mice displayed subtle cognitive decline that was not affected by simvastatin. Our results show potent benefits of simvastatin on endothelial- and smooth muscle cell-mediated vasomotor responses, endothelial NO synthesis and in preserving capillary integrity. We conclude that simvastatin could be indicated in the treatment of cerebrovascular dysfunction associated with VaD and AD. PMID:25564230

  13. In vivo modelling of normal and pathological human T-cell development

    NARCIS (Netherlands)

    Wiekmeijer, A.S.

    2016-01-01

    This thesis describes novel insights in human T-cell development by transplanting human HSPCs in severe immunodeficient NSG mice. First, an in vivo model was optimized to allow engraftment of hematopoietic stem cells derived from human bone marrow. This model was used to study aberrant human T-cell

  14. Automatic Voice Pathology Detection With Running Speech by Using Estimation of Auditory Spectrum and Cepstral Coefficients Based on the All-Pole Model.

    Science.gov (United States)

    Ali, Zulfiqar; Elamvazuthi, Irraivan; Alsulaiman, Mansour; Muhammad, Ghulam

    2016-11-01

    Automatic voice pathology detection using sustained vowels has been widely explored. Because of the stationary nature of the speech waveform, pathology detection with a sustained vowel is a comparatively easier task than that using a running speech. Some disorder detection systems with running speech have also been developed, although most of them are based on a voice activity detection (VAD), that is, itself a challenging task. Pathology detection with running speech needs more investigation, and systems with good accuracy (ACC) are required. Furthermore, pathology classification systems with running speech have not received any attention from the research community. In this article, automatic pathology detection and classification systems are developed using text-dependent running speech without adding a VAD module. A set of three psychophysics conditions of hearing (critical band spectral estimation, equal loudness hearing curve, and the intensity loudness power law of hearing) is used to estimate the auditory spectrum. The auditory spectrum and all-pole models of the auditory spectrums are computed and analyzed and used in a Gaussian mixture model for an automatic decision. In the experiments using the Massachusetts Eye & Ear Infirmary database, an ACC of 99.56% is obtained for pathology detection, and an ACC of 93.33% is obtained for the pathology classification system. The results of the proposed systems outperform the existing running-speech-based systems. The developed system can effectively be used in voice pathology detection and classification systems, and the proposed features can visually differentiate between normal and pathological samples. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  15. IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction.

    Science.gov (United States)

    Barbaux, S; Erwich, J J H M; Favaron, P O; Gil, S; Gallot, D; Golos, T G; Gonzalez-Bulnes, A; Guibourdenche, J; Heazell, A E P; Jansson, T; Laprévote, O; Lewis, R M; Miller, R K; Monk, D; Novakovic, B; Oudejans, C; Parast, M; Peugnet, P; Pfarrer, C; Pinar, H; Roberts, C T; Robinson, W; Saffery, R; Salomon, C; Sexton, A; Staff, A C; Suter, M; Tarrade, A; Wallace, J; Vaillancourt, C; Vaiman, D; Worton, S A; Lash, G E

    2015-04-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2014 there were six themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of animal models, xenobiotics, pathological biomarkers, genetics and epigenetics, and stillbirth and fetal growth restriction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. A 22-year Northern Irish experience of carotid body tumours.

    Science.gov (United States)

    O'Neill, Stephen; O'Donnell, Mark; Harkin, Denis; Loughrey, Maurice; Lee, Bernard; Blair, Paul

    2011-09-01

    Carotid body tumours (CBTs) are rare vascular neoplasms originating in paraganglionic cells of the carotid bifurcation. The aim of this study was to review all patients diagnosed with CBTs in Northern Ireland. A retrospective review was performed of all patients who had CBTs treated at our institutions between 1987 and 2009. Patient demographics, clinical symptomatology, investigative modality, therapeutic intervention, pathological analysis and long-term outcomes were assessed. Twenty-nine patients were identified with 33 CBTs and three glomus intravagale tumours (GITs). Six patients had bilateral CBTs (21%), one of whom had a synchronous GIT. Twenty-six patients underwent a total of 30 operative procedures for the resection of 28 CBTs and 3 GITs. Conventional operative treatment included subadventitial tumour excision. A vascular shunt facilitated arterial reconstruction following the removal of seven (23%) tumours and on six of these occasions (19%) continuity was restored with an interposition vein graft. For access the external carotid artery was ligated during the removal of four tumours (13%). Two tumours were considered malignant. No peri-operative mortalities were recorded. Immediate complications included peri-operative stroke secondary to an occluded vein graft (n=1), requirement of tracheostomy (n=2), emergency haematoma drainage (n=2) and transient cranial nerve damage (n=8). Late complications included pseudoaneurysm of vein graft with subsequent stoke (n=1), permanent cranial nerve damage (n=9), Horner's syndrome (n=1) and an asymptomatic vein graft occlusion (n=1). One patient had tumour recurrence two years post-operatively and died due to pulmonary metastases. Two other patients died of unrelated causes. All other patients remain well with no evidence of tumour recurrence at mean followup of 1801 days (range 159-9208 days). Our long-term experience is comparable with other reported case series where surgical intervention conferred a long

  17. Contribution of dysferlin deficiency to skeletal muscle pathology in asymptomatic and severe dystroglycanopathy models: generation of a new model for Fukuyama congenital muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Motoi Kanagawa

    Full Text Available Defects in dystroglycan glycosylation are associated with a group of muscular dystrophies, termed dystroglycanopathies, that include Fukuyama congenital muscular dystrophy (FCMD. It is widely believed that abnormal glycosylation of dystroglycan leads to disease-causing membrane fragility. We previously generated knock-in mice carrying a founder retrotransposal insertion in fukutin, the gene responsible for FCMD, but these mice did not develop muscular dystrophy, which hindered exploring therapeutic strategies. We hypothesized that dysferlin functions may contribute to muscle cell viability in the knock-in mice; however, pathological interactions between glycosylation abnormalities and dysferlin defects remain unexplored. To investigate contributions of dysferlin deficiency to the pathology of dystroglycanopathy, we have crossed dysferlin-deficient dysferlin(sjl/sjl mice to the fukutin-knock-in fukutin(Hp/- and Large-deficient Largemyd/myd mice, which are phenotypically distinct models of dystroglycanopathy. The fukutin(Hp/- mice do not show a dystrophic phenotype; however, (dysferlin(sjl/sjl: fukutin(Hp/- mice showed a deteriorated phenotype compared with (dysferlinsjl/sjl: fukutin(Hp/+ mice. These data indicate that the absence of functional dysferlin in the asymptomatic fukutin(Hp/- mice triggers disease manifestation and aggravates the dystrophic phenotype. A series of pathological analyses using double mutant mice for Large and dysferlin indicate that the protective effects of dysferlin appear diminished when the dystrophic pathology is severe and also may depend on the amount of dysferlin proteins. Together, our results show that dysferlin exerts protective effects on the fukutin(Hp/- FCMD mouse model, and the (dysferlin(sjl/sjl: fukutin(Hp/- mice will be useful as a novel model for a recently proposed antisense oligonucleotide therapy for FCMD.

  18. Distinct inflammatory phenotypes of microglia and monocyte-derived macrophages in Alzheimer's disease models: effects of aging and amyloid pathology.

    Science.gov (United States)

    Martin, Elodie; Boucher, Céline; Fontaine, Bertrand; Delarasse, Cécile

    2017-02-01

    Alzheimer's disease (AD) is a neurodegenerative disease characterized by formation of amyloid-β (Aβ) plaques, activated microglia, and neuronal cell death leading to progressive dementia. Recent data indicate that microglia and monocyte-derived macrophages (MDM) are key players in the initiation and progression of AD, yet their respective roles remain to be clarified. As AD occurs mostly in the elderly and aging impairs myeloid functions, we addressed the inflammatory profile of microglia and MDM during aging in TgAPP/PS1 and TgAPP/PS1dE9, two transgenic AD mouse models, compared to WT littermates. We only found MDM infiltration in very aged mice. We determined that MDM highly expressed activation markers at basal state. In contrast, microglia exhibited an activated phenotype only with normal aging and Aβ pathology. Our study showed that CD14 and CD36, two receptors involved in phagocytosis, were upregulated during Aβ pathogenesis. Moreover, we observed, at the protein levels in AD models, higher production of pro-inflammatory mediators: IL-1β, p40, iNOS, CCL-3, CCL-4, and CXCL-1. Taken together, our data indicate that microglia and MDM display distinct phenotypes in AD models and highlight the specific effects of normal aging vs Aβ peptides on inflammatory processes that occur during the disease progression. These precise phenotypes of different subpopulations of myeloid cells in normal and pathologic conditions may allow the design of pertinent therapeutic strategy for AD. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  19. Imaging and Pathological Features of Percutaneous Cryosurgery on Normal Lung Evaluated in a Porcine Model

    Directory of Open Access Journals (Sweden)

    Lizhi NIU

    2010-07-01

    Full Text Available Background and objective Lung cancer is one of the most commonly occurring malignancies and frequent causes of death in the world. Cryoablation is a safe and alternative treatment for unresectable lung cancer. Due to the lung being gas-containing organ and different from solid organs such as liver and pancreas, it is difficult to achieve the freezing range of beyond the tumor edge 1 cm safety border. The aim of this study is to examine the effect of different numbers of freeze cycles on the effectiveness of cryoablation on normal lung tissue and to create an operation guideline that gives the best effect. Methods Six healthy Tibetan miniature pigs were given a CT scan and histological investigation after percutaneous cryosurgery. Cryoablation was performed as 2 cycles of 10 min of active freezing in the left lung; each freeze followed by a 5 min thaw. In the right lung, we performed the same 2 cycles of 5 min of freezing followed by 5 min of thawing. However, for the right lung, we included a third cycle of consisting of 10 min of freezing followed by 5 min of thawing. Three cryoprobes were inserted into the left lung and three cryoprobes in the right lung per animal, one in the upper and two in the lower lobe, so as to be well away from each other. Comparison under the same experimental condition was necessary. During the experiment, observations were made regarding the imaging change of ice-ball. The lungs were removed postoperatively at 3 intervals: 4 h, 3 d of postoperation and 7 d of postoperation, respectively, to view microscopic and pathological change. Results The ice-ball grew gradually in relation to the increase in time, and the increase in number of cycles. The size of the cryolesion (hypothesis necrotic area in specimens, over time, became larger in size than the size of the ice-ball during operation, regardless of whether 2 or 3 freeze-thaw cycles were performed. The area of necrosis was gradually increased over the course of time

  20. Vaginal haemangioendothelioma: an unusual tumour.

    LENUS (Irish Health Repository)

    Mohan, H

    2012-02-01

    Vaginal tumours are uncommon and this is a particularly rare case of a vaginal haemangioendothelioma in a 38-year-old woman. Initial presentation consisted of symptoms similar to uterovaginal prolapse with "something coming down". Examination under anaesthesia demonstrated a necrotic anterior vaginal wall tumour. Histology of the lesion revealed a haemangioendothelioma which had some features of haemangiopericytoma. While the natural history of vaginal haemangioendothelioma is uncertain, as a group, they have a propensity for local recurrence. To our knowledge this is the third reported case of a vaginal haemangioendothelioma. Management of this tumour is challenging given the paucity of literature on this tumour. There is a need to add rare tumours to our "knowledge bank" to guide management of these unusual tumours.

  1. Quantification of antiangiogenic treatment effects on tissue heterogeneity in glioma tumour xenograft model using a combination of DCE-MRI and 3D-ultramicroscopy.

    Science.gov (United States)

    Dominietto, Marco; Dobosz, Michael; Bürgi, Sandra; Renner, Anja; Zahlmann, Gudrun; Scheuer, Werner; Rudin, Markus

    2017-07-01

    This study aimed at assessing the effects of an anti-angiogenic treatment, which neutralises vascular endothelial growth factor (VEGF), on tumour heterogeneity. Murine glioma cells have been inoculated into the right brain frontal lobe of 16 mice. Anti-VEGF antibody was administered to a first group (n = 8), while a second group (n = 8) received a placebo. Magnetic resonance acquisitions, performed at days 10, 12, 15 and 23 following the implantation, allowed the derivation of a three-dimensional features dataset characterising tumour heterogeneity. Three-dimensional ultramicroscopy and standard histochemistry analysis have been performed to verify in vivo results. Placebo-treated mice displayed a highly-vascularised area at the tumour periphery, a monolithic necrotic core and a chaotic dense vasculature across the entire tumour. In contrast, the B20-treated group did not show any highly vascularised regions and presents a fragmented necrotic core. A significant reduction of the number of vessel segments smaller than 17 μm has been observed. There was no difference in overall tumour volume and growth rate between the two groups. Region-specific analysis revealed that VEGF inhibition affects only: (1) highly angiogenic compartments expressing high levels of VEGF and characterised by small capillaries, and also (2) the formation and structure of necrotic regions. These effects appear to be transient and limited in time. • VEGF inhibition affects only the highly angiogenic region and small capillaries network • VEGF inhibition is transient in time • Tumour volume is not affected by anti-angiogenic treatment • VEGF inhibition also influences the architecture of necrotic regions.

  2. Orthotopic patient-derived xenografts of paediatric solid tumours.

    Science.gov (United States)

    Stewart, Elizabeth; Federico, Sara M; Chen, Xiang; Shelat, Anang A; Bradley, Cori; Gordon, Brittney; Karlstrom, Asa; Twarog, Nathaniel R; Clay, Michael R; Bahrami, Armita; Freeman, Burgess B; Xu, Beisi; Zhou, Xin; Wu, Jianrong; Honnell, Victoria; Ocarz, Monica; Blankenship, Kaley; Dapper, Jason; Mardis, Elaine R; Wilson, Richard K; Downing, James; Zhang, Jinghui; Easton, John; Pappo, Alberto; Dyer, Michael A

    2017-09-07

    Paediatric solid tumours arise from endodermal, ectodermal, or mesodermal lineages. Although the overall survival of children with solid tumours is 75%, that of children with recurrent disease is below 30%. To capture the complexity and diversity of paediatric solid tumours and establish new models of recurrent disease, here we develop a protocol to produce orthotopic patient-derived xenografts at diagnosis, recurrence, and autopsy. Tumour specimens were received from 168 patients, and 67 orthotopic patient-derived xenografts were established for 12 types of cancer. The origins of the patient-derived xenograft tumours were reflected in their gene-expression profiles and epigenomes. Genomic profiling of the tumours, including detailed clonal analysis, was performed to determine whether the clonal population in the xenograft recapitulated the patient's tumour. We identified several drug vulnerabilities and showed that the combination of a WEE1 inhibitor (AZD1775), irinotecan, and vincristine can lead to complete response in multiple rhabdomyosarcoma orthotopic patient-derived xenografts tumours in vivo.

  3. Primary bone tumours in infants

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Beluffi, G.; Cohen, D.H.; Padovani, J.; Tamaela, L.; Azouz, M.; Bale, P.; Martin, H.C.; Nayanar, V.V.; Arico, M.

    1985-09-01

    Ten cases of primary bone tumours in infants (1 osteosarcoma, 3 Ewing's sarcoma, 1 chondroblastoma and 5 angiomastosis) are reported. All cases of angiomatosis showed characteristic radiographic findings. In all the other tumours the X-ray appearances were different from those usually seen in older children and adolescents. In the auhtors' opinion the precise diagnosis of malignant bone tumours in infancy is very difficult as no characteristic X-ray features are present in this age period.

  4. Unsuccessful mitosis in multicellular tumour spheroids.

    Science.gov (United States)

    Molla, Annie; Couvet, Morgane; Coll, Jean-Luc

    2017-04-25

    Multicellular spheroids are very attractive models in oncology because they mimic the 3D organization of the tumour cells with their microenvironment. We show here using 3 different cell types (mammary TSA/pc, embryonic kidney Hek293 and cervical cancer HeLa), that when the cells are growing as spheroids the frequency of binucleated cells is augmented as occurs in some human tumours.We therefore describe mitosis in multicellular spheroids by following mitotic markers and by time-lapse experiments. Chromosomes alignment appears to be correct on the metaphasic plate and the passenger complex is well localized on centromere. Moreover aurora kinases are fully active and histone H3 is phosphorylated on Ser 10. Consequently, the mitotic spindle checkpoint is satisfied and, anaphase proceeds as illustrated by the transfer of survivin on the spindle and by the segregation of the two lots of chromosomes. However, the segregation plane is not well defined and oscillations of the dividing cells are observed. Finally, cytokinesis fails and the absence of separation of the two daughter cells gives rise to binucleated cells.Division orientation is specified during interphase and persists throughout mitosis. Our data indicate that the cancer cells, in multicellular spheroids, lose their ability to regulate their orientation, a feature commonly encountered in tumours.Moreover, multicellular spheroid expansion is still sensitive to mitotic drugs as pactlitaxel and aurora kinase inhibitors. The spheroids thus represent a highly relevant model for studying drug efficiency in tumours.

  5. Gastric schwannomas: radiological features with endoscopic and pathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Hong, H.S. [Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seodaemoon-gu, Seoul (Korea, Republic of); Ha, H.K. [Department of Radiology, University of Ulsan College of Medicine, Songpa-gu, Seoul (Korea, Republic of)], E-mail: hkha@amc.seoul.kr; Won, H.J.; Byun, J.H.; Shin, Y.M.; Kim, A.Y.; Kim, P.N.; Lee, M.-G. [Department of Radiology, University of Ulsan College of Medicine, Songpa-gu, Seoul (Korea, Republic of); Lee, G.H. [Internal Medicine, University of Ulsan College of Medicine, Songpa-gu, Seoul (Korea, Republic of); Kim, M.J. [Pathology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul (Korea, Republic of)

    2008-05-15

    Aim: To describe the radiological, endoscopic, and pathological findings of gastric schwannomas in 16 patients. Materials and methods: The radiological, endoscopic, and pathological findings of 16 surgically proven cases of gastric schwannoma were retrospectively reviewed. All patients underwent computed tomography (CT) and four patients were evaluated with upper gastrointestinal series. Two radiologists reviewed the CT and upper gastrointestinal series images by consensus with regard to tumour size, contour, margin, and growth pattern, the presence or absence of ulcer, cystic change, and the CT enhancement pattern. Endoscopy was performed in eight of these 16 patients. Six patients underwent endoscopic ultrasonography. Pathological specimens were obtained from and reviewed in all 16 patients. Immunohistochemistry was performed for c-kit, CD34, smooth muscle actin, and S-100 protein. Results: On radiographic examination, gastric schwannomas appeared as submucosal tumours with the CT features of well-demarcated, homogeneous, and uncommonly ulcerated masses. Endoscopy with endoscopic ultrasonography demonstrated homogeneous, submucosal masses contiguous with the muscularis propria in all six examined cases. On pathological examination, gastric schwannomas appeared as well-circumscribed and homogeneous tumours in the muscularis propria and consisted microscopically of interlacing bundles of spindle cells. Strong positivity for S-100 protein was demonstrated in all 16 cases on immunohistochemistry. Conclusion: Gastric schwannomas appear as submucosal tumours of the stomach and have well-demarcated and homogeneous features on CT, endoscopic ultrasonography, and gross pathology. Immunohistochemistry consistently reveals positivity for S-100 protein in the tumours.

  6. Animal tumour registry of two provinces in northern Italy: incidence of spontaneous tumours in dogs and cats

    Directory of Open Access Journals (Sweden)

    Carminato Antonio

    2009-10-01

    Full Text Available Abstract Background Cancer is a major cause of death in domestic animals. Furthermore, many forms of pet neoplasm resemble that of their human counterparts in biologic behaviour, pathologic expression, and recognised risk factors. In April 2005, a pilot project was activated so as to establish a dog and cat tumour registry living in the Venice and Vicenza provinces (Veneto Region, north-eastern Italy, with the aim of estimating the incidence of spontaneous tumours. Results Through a telephone survey, the estimates of canine and feline populations of the catchment area turned out to be of 296,318 (CI +/- 30,201 and 214,683 (CI +/- 21,755 subjects, respectively. During the first three years, overall 2,509 canine and 494 feline cases of neoplasia were diagnosed. In dogs, the estimated annual incidence rate (IR per 100,000 dogs for all tumours was 282 in all the catchment area, whereas in cats the IR was much lower (IR = 77. Malignant and benign tumours were equally distributed in male and female dogs, whereas cats had a 4.6-fold higher incidence of malignant tumours than benign. In both dogs and cats, purebreds had an almost 2-fold higher incidence of malignant tumours than mixed breeds. Tumour incidence increased with age in both dog and cat populations. Conclusion This study has provided estimates of incidence of spontaneous neoplasm in companion animals. Further attempts will be made to increase the accuracy in the population size assessment and to ascertain the real gap with the official regional canine demographic registry. Veterinary practitioners may also benefit from the tumour registry insofar they may obtain data for specific breeds, age groups or geographical areas.

  7. Does fixity affect prognosis in colorectal tumours?

    Science.gov (United States)

    Habib, N A; Peck, M A; Sawyer, C N; Blaxland, J W; Luck, R J

    1983-07-01

    In a retrospective series of 301 colorectal tumours, tumour fixity was assessed, and was found to be of prognostic significance in relation to 5-year survival. Fixity of the tumour was associated with low curative resection rate and advanced tumour state. Fixation did not correlate significantly with the site or differentiation of the tumour nor with operative mortality.

  8. Hostile takeover: how tumours hijack pre-existing vascular environments to thrive.

    Science.gov (United States)

    Winkler, Frank

    2017-07-01

    An increasing body of evidence suggests that solid tumours do not require the generation of new blood vessels, i.e. angiogenesis, to successfully grow, and to colonize normal tissue. Instead, many tumour cells make the best use of what they find: pre-existing blood vessels of the host. In these cases, the host vasculature is incorporated by the growing tumour, resulting in a new organ consisting of malignant and non-malignant cell types. In consequence, pre-existing vessels are exploited by the tumour for optimal access to oxygen and nutrients. In this perspective article, the argument is made that tumour cells might gain even more: that is, access to the very special microenvironment of the perivascular niche. Here, specific cues for invasion, metastasis, survival, stem-like features, dormancy and, potentially, also immune escape exist - for non-malignant and malignant cells alike. The consequence of the hijacking of normal blood vessels and their perivascular niches by tumours is that antiangiogenic agents have little chance to work, and that tumour cells are better protected from the adverse effects of cytotoxic and targeted therapies. Thus, disturbing vascular hijacking could make tumours less resistant to established therapies. Concepts of how to do this are just starting to be explored. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. Askin Tumour: Case Report

    International Nuclear Information System (INIS)

    Gomez, Carolina; Ramirez, Sandra Milena; Quesada, Diana Constanza; Unigarro Luz Adriana

    2011-01-01

    In this article we report a case of a 19 year-old woman with a final diagnosis of an extra skeletal Primitive Neuroectodermal Tumor/Ewing sarcoma of the chest, also known as Askin tumour. The histologic features and the immunohistochemical profile were consistent with this aggressive malignancy of the chest wall that affects young people. Because the low incidence of this entity, as well as the clear radiological findings, we considered it interesting to describe this documented case and undertake a review of the literature.

  10. A mouse model of pathological small intestinal epithelial cell apoptosis and shedding induced by systemic administration of lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Jonathan M. Williams

    2013-11-01

    The gut barrier, composed of a single layer of intestinal epithelial cells (IECs held together by tight junctions, prevents the entrance of harmful microorganisms, antigens and toxins from the gut lumen into the blood. Small intestinal homeostasis is normally maintained by the rate of shedding of senescent enterocytes from the villus tip exactly matching the rate of generation of new cells in the crypt. However, in various localized and systemic inflammatory conditions, intestinal homeostasis can be disturbed as a result of increased IEC shedding. Such pathological IEC shedding can cause transient gaps to develop in the epithelial barrier and result in increased intestinal permeability. Although pathological IEC shedding has been implicated in the pathogenesis of conditions such as inflammatory bowel disease, our understanding of the underlying mechanisms remains limited. We have therefore developed a murine model to study this phenomenon, because IEC shedding in this species is morphologically analogous to humans. IEC shedding was induced by systemic lipopolysaccharide (LPS administration in wild-type C57BL/6 mice, and in mice deficient in TNF-receptor 1 (Tnfr1−/−, Tnfr2 (Tnfr2−/−, nuclear factor kappa B1 (Nfκb1−/− or Nfĸb2 (Nfĸb2−/−. Apoptosis and cell shedding was quantified using immunohistochemistry for active caspase-3, and gut-to-circulation permeability was assessed by measuring plasma fluorescence following fluorescein-isothiocyanate–dextran gavage. LPS, at doses ≥0.125 mg/kg body weight, induced rapid villus IEC apoptosis, with peak cell shedding occurring at 1.5 hours after treatment. This coincided with significant villus shortening, fluid exudation into the gut lumen and diarrhea. A significant increase in gut-to-circulation permeability was observed at 5 hours. TNFR1 was essential for LPS-induced IEC apoptosis and shedding, and the fate of the IECs was also dependent on NFκB, with signaling via NFκB1 favoring cell survival and

  11. Pathology of Isfahan University of Medical Sciences based on Weisbord six box model and its relation with mental health.

    Science.gov (United States)

    Karimian, Jahangir; Taheri, Behjat; Sadeghpour, Masoumeh; Sadeghpour, Akram

    2015-01-01

    The aim of this research was to study the pathology of Isfahan University of Medical Sciences based on Weisbord six box model and to find its relation with mental health. The research method followed was a descriptive survey. The statistical society consisted of all staffs of the Isfahan University of Medical Sciences consisting of professors in the year 2012 (personnel of deputy of treatment, deputy of training, cultural-student deputy, supporting deputy, deputy of food and drugs, health deputy, and deputy of research). The number of subjects in the mentioned society was 1647, sample size was 332 Based on Cochrane's formula. They were selected by random sampling method in proportion with the statistical society. The measurement instruments included organizational pathology questionnaire (ODQ) with 35 questions and the questionnaire of mental health standard [General Health Questionnaire (GHQ)] with 28 questions. The validity of the questionnaires obtained from reviews by faculties and experts, and the reliability of the questionnaire assessed through Cronbach's coefficient were 0.86, 0.85, and 0.76, respectively. To analyze data, the statistical methods such as single-variance t-test, regression analysis, correlation coefficient, Kolmogorov-Smirnov test, and Multivariate Analysis of Variance (MANOVA) were used. The findings of research demonstrated that the organizational damage based on six box model was seen only in the reward component at the Isfahan University of Medical Sciences. Mental health of persons in the sample group of Isfahan University of Medical Sciences was in the suitable status. There was a meaningful and positive interrelation between mental health and attitude toward the organizational damages in the dimensions of communications, useful merchandises, and attitude to change. However, no meaningful interrelation was seen between aims, structure, leadership, and reward and mental health. There was no meaningful difference between the averages of

  12. Brain and behavioral pathology in an animal model of Wernicke's encephalopathy and Wernicke-Korsakoff Syndrome.

    Science.gov (United States)

    Vetreno, Ryan P; Ramos, Raddy L; Anzalone, Steven; Savage, Lisa M

    2012-02-03

    Animal models provide the opportunity for in-depth and experimental investigation into the anatomical and physiological underpinnings of human neurological disorders. Rodent models of thiamine deficiency have yielded significant insight into the structural, neurochemical and cognitive deficits associated with thiamine deficiency as well as proven useful toward greater understanding of memory function in the intact brain. In this review, we discuss the anatomical, neurochemical and behavioral changes that occur during the acute and chronic phases of thiamine deficiency and describe how rodent models of Wernicke-Korsakoff Syndrome aid in developing a more detailed picture of brain structures involved in learning and memory. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model.

    Directory of Open Access Journals (Sweden)

    Habib Baghirov

    Full Text Available The treatment of brain diseases is hindered by the blood-brain barrier (BBB preventing most drugs from entering the brain. Focused ultrasound (FUS with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma.

  14. Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model

    Science.gov (United States)

    Baghirov, Habib; Snipstad, Sofie; Sulheim, Einar; Berg, Sigrid; Hansen, Rune; Thorsen, Frits; Mørch, Yrr; Åslund, Andreas K. O.

    2018-01-01

    The treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering the brain. Focused ultrasound (FUS) with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma. PMID:29338016

  15. Blood oxygen level dependent magnetic resonance imaging for detecting pathological patterns in lupus nephritis patients: a preliminary study using a decision tree model.

    Science.gov (United States)

    Shi, Huilan; Jia, Junya; Li, Dong; Wei, Li; Shang, Wenya; Zheng, Zhenfeng

    2018-02-09

    Precise renal histopathological diagnosis will guide therapy strategy in patients with lupus nephritis. Blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) has been applicable noninvasive technique in renal disease. This current study was performed to explore whether BOLD MRI could contribute to diagnose renal pathological pattern. Adult patients with lupus nephritis renal pathological diagnosis were recruited for this study. Renal biopsy tissues were assessed based on the lupus nephritis ISN/RPS 2003 classification. The Blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) was used to obtain functional magnetic resonance parameter, R2* values. Several functions of R2* values were calculated and used to construct algorithmic models for renal pathological patterns. In addition, the algorithmic models were compared as to their diagnostic capability. Both Histopathology and BOLD MRI were used to examine a total of twelve patients. Renal pathological patterns included five classes III (including 3 as class III + V) and seven classes IV (including 4 as class IV + V). Three algorithmic models, including decision tree, line discriminant, and logistic regression, were constructed to distinguish the renal pathological pattern of class III and class IV. The sensitivity of the decision tree model was better than that of the line discriminant model (71.87% vs 59.48%, P patterns.

  16. Pathological gambling

    OpenAIRE

    Hesselbarth, Ulrike

    2012-01-01

    The dissertation is divided into two parts. The subject of the first part was the collection of the demand gambling and the frequency of pathological gambling within specific person's groups (prisoners, guests of gambling halls, officials and medical students), to which a new psychometric instrument – the BIG (Berliner Inventar zum Glücksspielverhalten; Grüsser, Hesselbarth, Albrecht & Mörsen, 2006) – was introduced. Depression, anxiety, maladaptive coping strategies and sensation seeking ...

  17. Urban Pathology

    OpenAIRE

    Pitcher, Brian L.

    1997-01-01

    Urban theorists have long debated to what extend and how the social problems of the city have been brought about or exaggerated in some consistent way by the urban environments in which they occur. This presentation reviews theories of urbanism, and the features of cities which contribute to the augmentation and control of various types of social pathology. Special emphasis is given to some types and patterns of urban unrest, and the structural characteristics associated with deleterious urba...

  18. Complete and irreversible unilateral vestibular loss: A novel rat model of vestibular pathology.

    Science.gov (United States)

    Péricat, David; Farina, Anne; Agavnian-Couquiaud, Emilie; Chabbert, Christian; Tighilet, Brahim

    2017-05-01

    Both basic and applied studies on the pathophysiology of vestibular disorders are currently impaired by the lack of animal models of controlled vestibular damages. In the present study, we describe the procedure to achieve a surgical unilateral vestibular neurectomy (UVN) in the rat and evaluate its functional consequences. This procedure is suitable for reproducing a unilateral, sudden and definitive vestibular areflexia. Proper induction of a UVN induces a severe vestibular syndrome, which mimics vestibular disorders encountered in humans. This model is also used clinically in the surgical treatment of pharmacological intractable Meniere's disease. Comparison with existing methods unilateral vestibular neurectomy has been essentially used in other species such as cats, monkeys and humans. The current study describes this technique in rats. This experimental model is particularly adapted to study the restoration kinetics of vestibular function after removal of peripheral inputs. It is also suitable for determining the neurochemical and molecular mechanisms underlying central compensation processes, as well as to check for the efficacy of drugs with potent antivertigo properties. Finally, UVN is an acknowledged model of postlesional plasticity involving original processes such as reactive neurogenesis in the vestibular nuclei. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Nomogram for predicting pathologically complete response after neoadjuvant chemoradiotherapy for oesophageal cancer

    International Nuclear Information System (INIS)

    Toxopeus, Eelke Lucie Anne; Nieboer, Daan; Shapiro, Joel; Biermann, Katharina; Gaast, Ate van der; Rij, Carolien M. van; Steyerberg, Ewout Willem; Lanschot, Joseph Jan Baptiste van; Wijnhoven, Bas Peter Louis

    2015-01-01

    Background: A pathologically complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) is seen in 30% of the patients with oesophageal cancer. The aim is to identify patient and tumour characteristics associated with a pCR and to develop a nomogram for the prediction of pCR. Patients and methods: Patients who underwent nCRT followed by surgery were identified and response to nCRT was assessed according to a modified Mandard classification in the resection specimen. A model was developed with age, gender, histology and location of the tumour, differentiation grade, alcohol use, smoking, percentage weight loss, Charlson Comorbidity Index (CCI), cT-stage and cN-stage as potential predictors for pCR. Probability of pCR was studied via logistic regression. Performance of the prediction nomogram was quantified using the concordance statistic (c-statistic) and corrected for optimism. Results: A total of 381 patients were included. After surgery, 27.6% of the tumours showed a pCR. Female sex, squamous cell histology, poor differentiation grade, and low cT-stage were predictive for a pCR with a c-statistic of 0.64 (corrected for optimism). Conclusion: A nomogram for the prediction of pathologically complete response after neoadjuvant chemoradiotherapy was developed, with a reasonable predictive power. This nomogram needs external validation before it can be used for individualised clinical decision-making

  20. Branched chain amino acids attenuate major pathologies in mouse models of retinal degeneration and glaucoma.

    Science.gov (United States)

    Hasegawa, Tomoko; Ikeda, Hanako Ohashi; Iwai, Sachiko; Muraoka, Yuki; Tsuruyama, Tatsuaki; Okamoto-Furuta, Keiko; Kohda, Haruyasu; Kakizuka, Akira; Yoshimura, Nagahisa

    2018-02-01

    Retinal neuronal cell death underlies many incurable eye diseases such as retinitis pigmentosa (RP) and glaucoma, and causes adult blindness. We have shown that maintenance of ATP levels via inhibiting ATP consumption is a promising strategy for preventing neuronal cell death. Here, we show that branched chain amino acids (BCAAs) are able to increase ATP production by enhancing glycolysis. In cell culture, supplementation of the culture media with BCAAs, but not glucose alone, enhanced cellular ATP levels, which was canceled by a glycolysis inhibitor. Administration of BCAAs to RP mouse models, rd10 and rd12 , significantly attenuated photoreceptor cell death morphologically and functionally, even when administration was started at later stages. Administration of BCAAs in a glaucoma mouse model also showed significant attenuation of retinal ganglion cell death. These results suggest that administration of BCAAs could contribute to a comprehensive therapeutic strategy for retinal neurodegenerative diseases such as RP and glaucoma.

  1. Imaging noradrenergic influence on amyloid pathology in mouse models of Alzheimer's disease

    International Nuclear Information System (INIS)

    Winkeler, A.; Waerzeggers, Y.; Klose, A.; Monfared, P.; Thomas, A.V.; Jacobs, A.H.; Schubert, M.; Heneka, M.T.

    2008-01-01

    Molecular imaging aims towards the non-invasive characterization of disease-specific molecular alterations in the living organism in vivo. In that, molecular imaging opens a new dimension in our understanding of disease pathogenesis, as it allows the non-invasive determination of the dynamics of changes on the molecular level. The imaging technology being employed includes magnetic resonance imaging (MRI) and nuclear imaging as well as optical-based imaging technologies. These imaging modalities are employed together or alone for disease phenotyping, development of imaging-guided therapeutic strategies and in basic and translational research. In this study, we review recent investigations employing positron emission tomography and MRI for phenotyping mouse models of Alzheimers' disease by imaging. We demonstrate that imaging has an important role in the characterization of mouse models of neurodegenerative diseases. (orig.)

  2. Renal Pathology in a Nontraditional Aging Model: The Naked Mole-Rat (Heterocephalus glaber).

    Science.gov (United States)

    Delaney, M A; Kinsel, M J; Treuting, P M

    2016-03-01

    The naked mole-rat (NMR; Heterocephalus glaber) is growing in popularity as a model for aging research due to its extreme longevity (up to 30 years), highly adapted physiology, and resistance to cancer, particularly when compared with traditional aging models such as laboratory mice and rats. Despite the NMR's seemingly lengthy health span, several age-related lesions have been documented. During a 15-year retrospective evaluation of a zoo-housed population, histologic changes in the kidneys were reported in 127 of 138 (92%) adult NMRs. Of these, renal tubular mineralization was very common (115 of 127; 90.6%) and found in NMRs without concurrent renal lesions (36 of 127; 28.3%). Many of the other described lesions were considered progressive stages of a single process, generally referred to as chronic nephritis or nephropathy, and diagnosed in 73 of 127 (57.5%), while end-stage renal disease was reported in only 12 (9.4%) NMRs. Renal lesions of these NMRs were comparable to disease entities reported in laboratory rats and certain strains of inbred and noninbred mice. Although many lesions of NMR kidneys were similar to those found in aged laboratory rodents, some common urinary diseases were not represented in the examined colonies. The goal of this study was to describe renal lesions in NMRs from a zoologic setting to familiarize investigators and pathologists with an apparently common and presumably age-related disease in this nontraditional model. © The Author(s) 2015.

  3. Radiotherapy in ocular tumours

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, J.M.

    1982-07-01

    Ocular tumours at the Tata Memorial Hospital, Bombay, form about 0.14% of all the proved cancer cases. In case of unilateral retinoblastoma with the other eye being not non-seeing for any reason, enucleation is advised, as the diagnosis may sometimes be in doubt. If after enucleation, optic nerve and/or peribulbar tissues are found to be involved, post-operative irradiation is given to the whole orbit. In bilateral retinoblastoma the more affected eye is enucleated and an attempt is made to preserve vision in the other eye. A tumour dose of 3500 to 4000 rad in about 4 weeks is given with a cobalt beam using a direct anterior field. A cataract that may develop has to be taken care of. Lateral and/or medial fields are used with deep X-rays. In certain cases, an implant of cobalt-60 or gold-198 grain is done. For carcinoma of conjuctiva, small lesions or early lesions are excised and a beta radiation dose of 2000 rad weekly for about 4 to 5 weeks is given; larger lesions require enucleation or exenteration followed by irradiation with super-voltage radiation. Post-irradiation sarcomas may develop many years later. Irradiation is repeated for recurrences.

  4. Radiotherapy in ocular tumours

    International Nuclear Information System (INIS)

    Pinto, J.M.

    1982-01-01

    Ocular tumours at the Tata Memorial Hospital, Bombay, form about 0.14% of all the proved cancer cases. In case of unilateral retinoblastoma with the other eye being not non-seeing for any reason, enucleation is advised, as the diagnosis may sometimes be in doubt. If after enucleation, optic nerve and/or peribulbar tissues are found to be involved, post-operative irradiation is given to the whole orbit. In bilateral retinoblastoma the more affected eye is enucleated and an attempt is made to preserve vision in the other eye. A tumour dose of 3500 to 4000 rad in about 4 weeks is given with a cobalt beam using a direct anterior field. A cataract that may develop has to be taken care of. Lateral and/or medial fields are used with deep X-rays. In certain cases, an implant of cobalt-60 or gold-198 grain is done. For carcinoma of conjuctiva, small lesions or early lesions are excised and a beta radiation dose of 2000 rad weekly for about 4 to 5 weeks is given; larger lesions require enucleation or exenteration followed by irradiation with super-voltage radiation. Post-irradiation sarcomas may develop many years later. Irradiation is repeated for recurrences. (M.G.B.)

  5. Comparing the dependability and associations with functioning of the DSM-5 Section III trait model of personality pathology and the DSM-5 Section II personality disorder model.

    Science.gov (United States)

    Chmielewski, Michael; Ruggero, Camilo J; Kotov, Roman; Liu, Keke; Krueger, Robert F

    2017-07-01

    Two competing models of personality psychopathology are included in the fifth edition of the Diagnostic Statistical Manual of Mental Disorders ( DSM-5 ; American Psychiatric Association, 2013); the traditional personality disorder (PD) model included in Section II and an alternative trait-based model included in Section III. Numerous studies have examined the validity of the alternative trait model and its official assessment instrument, the Personality Inventory for DSM-5 (PID-5; Krueger, Derringer, Markon, Watson, & Skodol, 2012). However, few studies have directly compared the trait-based model to the traditional PD model empirically in the same dataset. Moreover, to our knowledge, only a single study (Suzuki, Griffin, & Samuel, 2015) has examined the dependability of the PID-5, which is an essential component of construct validity for traits (Chmielewski & Watson, 2009; McCrae, Kurtz, Yamagata, & Terracciano, 2011). The current study directly compared the dependability of the DSM-5 traits, as assessed by the PID-5, and the traditional PD model, as assessed by the Personality Diagnostic Questionnaire-4 (PDQ-4+), in a large undergraduate sample. In addition, it evaluated and compared their associations with functioning, another essential component of personality pathology. In general, our findings indicate that most DSM-5 traits demonstrate high levels of dependability that are superior to the traditional PD model; however, some of the constructs assessed by the PID-5 may be more state like. The models were roughly equivalent in terms of their associations with functioning. The current results provide additional support for the validity of PID-5 and the DSM-5 Section III personality pathology model. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  6. Modular endoprosthetic replacement for metastatic tumours of the proximal femur

    Directory of Open Access Journals (Sweden)

    Carter Simon R

    2008-11-01

    Full Text Available Abstract Background and aims Endoprosthetic replacements of the proximal femur are commonly required to treat destructive metastases with either impending or actual pathological fractures at this site. Modular prostheses provide an off the shelf availability and can be adapted to most reconstructive situations for proximal femoral replacements. The aim of this study was to assess the clinical and functional outcomes following modular tumour prosthesis reconstruction of the proximal femur in 100 consecutive patients with metastatic tumours and to compare them with the published results of patients with modular and custom made endoprosthetic replacements. Methods 100 consecutive patients who underwent modular tumour prosthetic reconstruction of the proximal femur for metastases using the METS system from 2001 to 2007 were studied. The patient, tumour and treatment factors in relation to overall survival, local control, implant survival and complications were analysed. Functional scores were obtained from surviving patients. Results and conclusion There were 45 male and 55 female patients. The mean age was 60.2 years. The indications were metastases. Seventy five patients presented with pathological fracture or with failed fixation and 25 patients were at a high risk of developing a fracture. The mean follow up was 15.9 months [range 0–77]. Three patients died within 2 weeks following surgery. 69 patients have died and 31 are alive. Of the 69 patients who were dead 68 did not need revision surgery indicating that the implant provided single definitive treatment which outlived the patient. There were three dislocations (2/5 with THR and 1/95 with unipolar femoral heads. 6 patients had deep infections. The estimated five year implant survival (Kaplan-Meier analysis was 83.1% with revision as end point. The mean TESS score was 64% (54%–82%. We conclude that METS modular tumour prosthesis for proximal femur provides versatility; low implant related

  7. Seladin-1 and testicular germ cell tumours: new insights into cisplatin responsiveness.

    Science.gov (United States)

    Nuti, Francesca; Luciani, Paola; Marinari, Eliana; Erdei, Edit; Bak, Mihaly; Deledda, Cristiana; Rosati, Fabiana; Mazzinghi, Benedetta; Danza, Giovanna; Stoop, Hans; Looijenga, Leendert H J; Peri, Alessandro; Serio, Mario; Krausz, Csilla

    2009-12-01

    The molecular basis for the exquisite sensitivity of testicular germ cell tumours of adolescents and adults (TGCTs), ie seminomas and non-seminomatous germ cell tumours, to chemo/radiotherapy has not been fully clarified so far. It has been suggested that it may be dependent on factors involved in the regulation of apoptosis. Seladin-1 is a multi-functional protein involved in various biological processes, including apoptosis. The aim of our study was to assess the expression of seladin-1 in different histological types of TGCTs, known to have varying treatment sensitivity, in order to establish whether this protein may influence cisplatin responsiveness in vitro. Seladin-1 expression levels, both at the mRNA and at the protein level, were higher in the adjacent normal parenchyma than in the pathological counterparts. In tumoural tissues, the level of expression differed among TGCT histological types. The highest tumour-expression level was found in teratoma, whereas the lowest was detected in seminoma, corresponding to the different chemo/and radiosensitivities of these tumour types. In common with other cancers, in TGCT-derived cell lines seladin-1 showed anti-apoptotic properties through inhibition of caspase-3 activation. We confirmed our results using a non-seminomatous cell line model (NT2) before and after differentiation with retinoic acid. Significantly higher seladin-1 expression was observed in the differentiated derivatives (teratoma) and an inverse relationship was found between seladin-1 expression and the amount of cleaved caspase-3. Seladin-1 silencing or overexpression in this cell line supports involvement of seladin-1 in cisplatin responsiveness. Seladin-1 silencing was associated with greater cisplatin responsiveness demonstrated by decreased cell viability and increased expression of apoptotic markers. In contrast, overexpression of seladin-1 was associated with a higher survival rate and a clear anti-apoptotic effect. In conclusion, we have

  8. SURGICAL-PATHOLOGY

    African Journals Online (AJOL)

    features of optic neuropathy and no obvious tumour recurrence Histology showed; nodular tissue measuring. 5x¢l.8x'3.8 centimetres and weighing 31 grams The cut surface revealed a solid tumour that is well encapsulated. light microscopy (figure 3) showed an encapsulated vascular tumour of fairly regular spindle cells ...

  9. Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies

    Science.gov (United States)

    Barber, Amelia E.; Norton, J. Paul; Wiles, Travis J.

    2016-01-01

    SUMMARY Urinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are a source of substantial morbidity among otherwise healthy women. UTIs can be caused by a variety of microbes, but the predominant etiologic agent of these infections is uropathogenic Escherichia coli (UPEC). An especially troubling feature of UPEC-associated UTIs is their high rate of recurrence. This problem is compounded by the drastic increase in the global incidence of antibiotic-resistant UPEC strains over the past 15 years. The need for more-effective treatments for UTIs is driving research aimed at bettering our understanding of the virulence mechanisms and host-pathogen interactions that occur during the course of these infections. Surrogate models of human infection, including cell culture systems and the use of murine, porcine, avian, teleost (zebrafish), and nematode hosts, are being employed to define host and bacterial factors that modulate the pathogenesis of UTIs. These model systems are revealing how UPEC strains can avoid or overcome host defenses and acquire scarce nutrients while also providing insight into the virulence mechanisms used by UPEC within compromised individuals, such as catheterized patients. Here, we summarize our current understanding of UTI pathogenesis while also giving an overview of the model systems used to study the initiation, persistence, and recurrence of UTIs and life-threatening sequelae like urosepsis. Although we focus on UPEC, the experimental systems described here can also provide valuable insight into the disease processes associated with other bacterial pathogens both within the urinary tract and elsewhere within the host. PMID:26935136

  10. Ketogenic diet improves motor performance but not cognition in two mouse models of Alzheimer's pathology.

    Directory of Open Access Journals (Sweden)

    Milene L Brownlow

    Full Text Available Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer's disease (AD patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs, widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition and Tg4510 (a model of tau deposition mice were offered either a ketogenic or a control (NIH-31 diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition.

  11. Radiological morphology and pathological anatomy of osteoblastomas

    Energy Technology Data Exchange (ETDEWEB)

    Lingg, G.; Roessner, A.; Telgmann, C.L.; Karbowski, A.; Peters, P.E.; Grundmann, E.

    1986-07-01

    Between 1974 and 1984, 24 patients with osteoblastomas were entered in the bone tumour registry of the Gerhard Domagk Institute of Pathology and Institute for Clinical Radiology of Westphalia. These cases are evaluated. Osteoblastoma is a benign primary bone tumour with a peak incidence between ten and 20 years and a sex ratio of 18 males to 4 females in our series. The site of predilection is the spine (59%) with long bones in second place (32%). The tumour is mostly situated in the medulla. Radiologically it usually appears as well demarcated translucency with a narrow rim and marginal sclerosis. Variations in radiological appearance and the histology and treatment are described. A malignant variant the 'aggressive osteoblastoma', is discussed and one case is described. The classification of these cases is considered.

  12. Does tumour location influence postoperative long-term survival in patients with oesophageal squamous cell carcinoma?

    Science.gov (United States)

    Shi, Hui; Zhang, Kun; Niu, Zhong-Xi; Wang, Wen-Ping; Gao, Qiang; Chen, Long-Qi

    2015-08-01

    The seventh edition of the American Joint Committee on Cancer (AJCC) staging system introduced tumour location for the first time as an determinant of stage grouping in pathological T2N0M0 and T3N0M0 (pT2-3N0M0) oesophageal squamous cell carcinoma (OSCC). However, the new modification remains controversial. The objective of this study was to investigate the correlation between tumour location and postoperative long-term survival in patients with OSCC in China. The clinicopathological data and over 10 years of follow-up results from a large cohort of 988 patients with OSCC undergoing radical-intent oesophagectomy from 1984 to 1995 without preoperative and postoperative chemoradiotherapy were reviewed, in which 632 patients were staged as pT2-3N0M0. Tumour location was redefined according to the seventh edition of the AJCC staging system. Survival was calculated by the Kaplan-Meier method; univariate log-rank and multivariate Cox proportional hazard models were used to further determine the impact of tumour location on long-term survival. Univariate analysis showed that OSCC tumour location was closely associated with long-term survival for the entire cohort of 988 patients (odds ratio [OR]: 0.82; 95% confidence interval [95% CI]: 0.67-0.99; P = 0.049), and for pT2-3N0M0 patients (OR: 0.63; 95% CI: 0.48-0.84; P = 0.001). The median survival times for patients with pT2-3N0M0 OSCC in the upper, middle and lower third of the oesophagus were 38.1, 46.6 and 66.0 months, respectively, with corresponding 5-year survival rates of 40.0, 51.8 and 66.2%, respectively. Overall survival rates among three categories of patients according to tumour location in the pT2-3N0M0 patients were statistically different (P = 0.004). Multivariate analysis demonstrated that tumour location was a significant independent predictor of long-term survival for pT2-3N0M0 patients (OR: 0.53; 95% CI: 0.42-0.67; P = 0.0001), but not for the entire cohort of 988 patients (OR: 0.99; 95% CI: 0.79-1.23; P

  13. Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours

    International Nuclear Information System (INIS)

    Lunt, Sarah Jane; Kalliomaki, Tuula MK; Brown, Allison; Yang, Victor X; Milosevic, Michael; Hill, Richard P

    2008-01-01

    High tumour interstitial fluid pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread. KHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m), sub-cutaneously (s/c) or orthotopically. Polyoma middle-T (MMTV-PyMT) transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging. Tumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion between ME180 tumours grown i/m versus orthotopically

  14. Different Paths to Core Pathology: The Equifinal Model of the Schizophrenia Syndrome.

    Science.gov (United States)

    Green, Isobel W; Glausier, Jill R

    2016-05-01

    Schizophrenia is a clinically heterogeneous disorder that is perhaps more accurately characterized as "the schizophrenia syndrome." This clinical heterogeneity is reflected in the heterogeneous neurobiological presentations associated with the illness. Moreover, even highly specific neural aberrations that are associated with distinct symptoms of schizophrenia are linked to a wide range of risk factors. As such, any individual with schizophrenia likely has a particular set of risk factors that interact and converge to cross the disease threshold, forming a particular etiology that ultimately generates a core pathophysiology. This core pathophysiology may then produce 1 or more symptoms of schizophrenia, leading to common symptoms across individuals in spite of disparate etiologies. As such, the schizophrenia syndrome can be considered as anequifinalentity: a state of dysfunction that can arise from different upstream etiologies. Moreover, schizophrenia etiologies are multifactorial and can involve the interactive effects of a broad range of genetic, environmental, and developmental risk factors. Through a consideration of how disparate etiologies, caused by different sets of risk factors, converge on the same net dysfunction, this paper aims to model the equifinal nature of schizophrenia symptoms. To demonstrate the equifinal model, we discuss how maternal infection and adolescent cannabis use, 2 recognized schizophrenia risk factors, may interact with other genetic, environmental, and/or developmental risk factors to cause the conserved clinical presentation of impaired working memory. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Eye Movement Deficits Are Consistent with a Staging Model of pTDP-43 Pathology in Amyotrophic Lateral Sclerosis.

    Directory of Open Access Journals (Sweden)

    Martin Gorges

    Full Text Available The neuropathological process underlying amyotrophic lateral sclerosis (ALS can be traced as a four-stage progression scheme of sequential corticofugal axonal spread. The examination of eye movement control gains deep insights into brain network pathology and provides the opportunity to detect both disturbance of the brainstem oculomotor circuitry as well as executive deficits of oculomotor function associated with higher brain networks.To study systematically oculomotor characteristics in ALS and its underlying network pathology in order to determine whether eye movement deterioration can be categorized within a staging system of oculomotor decline that corresponds to the neuropathological model.Sixty-eight ALS patients and 31 controls underwent video-oculographic, clinical and neuropsychological assessments.Oculomotor examinations revealed increased anti- and delayed saccades' errors, gaze-palsy and a cerebellary type of smooth pursuit disturbance. The oculomotor disturbances occurred in a sequential manner: Stage 1, only executive control of eye movements was affected. Stage 2 indicates disturbed executive control plus 'genuine' oculomotor dysfunctions such as gaze-paly. We found high correlations (p<0.001 between the oculomotor stages and both, the clinical presentation as assessed by the ALS Functional Rating Scale (ALSFRS score, and cognitive scores from the Edinburgh Cognitive and Behavioral ALS Screen (ECAS.Dysfunction of eye movement control in ALS can be characterized by a two-staged sequential pattern comprising executive deficits in Stage 1 and additional impaired infratentorial oculomotor control pathways in Stage 2. This pattern parallels the neuropathological staging of ALS and may serve as a technical marker of the neuropathological spreading.

  16. Pathological Changes in APP/PS-1 Transgenic Mouse Models of Alzheimer's Disease Treated with Ganoderma Lucidum Preparation.

    Science.gov (United States)

    Qin, Chuan; Wu, Shan-Qiu; Chen, Bao-Sheng; Wu, Xiao-Xian; Qu, Kun-Yao; Liu, Jun-Min; Zhang, Gui-Fang; Xu, Yan-Feng; Shu, Shunli; Sun, Lihua; Li, Yan-Yong; Zhu, Hua; Huang, Lan; Ma, Chun-Mei; Xu, Yu-Huan; Han, Yun-Lin; Lu, Yao-Zeng

    2017-08-20

    Objective To explore the efficacy of ganoderma lucidum preparation(Ling Zhi) in treating APP/PS-1 transgenic mouse models of Alzheimer's disease(AD).Methods APP/PS-1 transgenic mice of 4 months were randomly divided into model group,ganoderma lucidum treatment groups,including high [2250 mg/(kg·d)] and middle [750 mg/(kg·d)] dose groups,i.e.LZ-H and LZ-M groups,and the positive control group(treated with donepezil hydrochloride [2 mg/(kg·d)]).In addition,C57BL/6J wild mice were selected as normal group.The animals were administered for 4 months.Histopathological examinations including hematoxylin-eosin(HE) staining,immunohistochemistry,special staining,and electron microscopy were applied,and then the pathological morphology and structures in different groups were compared. Results The senile plaques and neurofibrillar tangles in the cerebrum and cerebellum were dissolved or disappeared in LZ-H and LZ-M groups.Decrease of amyloid angiopathy was found in LZ-H and LZ-M groups.The immature neurons appeared more in hippocampus and dentate nucleus of LZ-H and LZ-M groups than those in AD model and donepezil hydrochloride groups(hippcampus:F=1.738,P=0.016;dentate nucleus:F=1.924,P=0.026),and these immature neurons differentiated to be neurons.More Purkinje cells loss occurred in AD model mice than that in LZ-H and LZ-M groups(F=9.46,P=0.007;F=9.46,P=0.010).The LZ-H and LZ-M groups had more new neuron stem cells grown up in cerebellum.Electromicroscopic examination showed the hippocampal neurons in LZ-H and LZ-M group were integrated,the nuclear membrane was intact,and the mitochondria in the cytoplasm,endoplasmic reticulum,Golgi bodies,microtubules,and synapses were also complete.The microglial cell showed no abnormality.No toxicity appeared in the pathological specimens of mice treated with ganoderma lucidum preparation.Conclusion The ganoderma lucidum preparation can dissolve and decline or dismiss the senile plaques and neurofibrillar tangles in the brain of AD

  17. Imaging in unilateral Wilms tumour

    NARCIS (Netherlands)

    Brisse, Hervé J.; Smets, Anne M.; Kaste, Sue C.; Owens, Catherine M.

    2008-01-01

    Wilms tumour is one of the most common malignancies in children, with an excellent prognosis after therapy. There is a very diverse approach to treatment according to geographical location. This variation in therapeutic attitude toward Wilms tumour, particularly between the United States and Europe,

  18. Carcinoid Tumour of the Ovary

    African Journals Online (AJOL)

    Abstract. A case of bilateral carcinoid tumour of the ovary, with benign cystic teratoma in one ovary, in a 38 year old woman is presented. She had total abdominal hysterectomy, bilateral salpingoophorectomy, infracolic omentectomy and appendectomy. There was no macroscopic tumour in the vermiform appendix and the ...

  19. Are tumours angiogenesis-dependent?

    NARCIS (Netherlands)

    Verheul, H. M. W.; Voest, E. E.; Schlingemann, R. O.

    2004-01-01

    The final proof of principle that cancer patients can be effectively treated with angiogenesis inhibitors is eagerly awaited. Various preclinical in vivo experiments have proven that most tumours need new vessel formation in order to grow and to form metastases. First of all, tumours do not grow in

  20. Chronic Trichuris muris infection causes neoplastic change in the intestine and exacerbates tumour formation in APC min/+ mice.

    Science.gov (United States)

    Hayes, Kelly S; Cliffe, Laura J; Bancroft, Alison J; Forman, Simon P; Thompson, Seona; Booth, Cath; Grencis, Richard K

    2017-06-01

    Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+) mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.

  1. Chronic Trichuris muris infection causes neoplastic change in the intestine and exacerbates tumour formation in APC min/+ mice.

    Directory of Open Access Journals (Sweden)

    Kelly S Hayes

    2017-06-01

    Full Text Available Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+ mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.

  2. Pathology and biofilm formation in a porcine model of staphylococcal osteomyelitis

    DEFF Research Database (Denmark)

    Johansen, L K; Koch, J; Frees, D

    2012-01-01

    A porcine model was used to examine the potential of human and porcine Staphylococcus aureus isolates to induce haematogenously spread osteomyelitis. Pigs were inoculated in the right femoral artery with one of the following S. aureus strains: S54F9 (from a porcine lung abscess; n = 3 animals......), NCTC-8325-4 (a laboratory strain of human origin; n = 3 animals) and UAMS-1 (a human osteomyelitis isolate; n = 3 animals). Two pigs were sham inoculated with saline. At 11 or 15 days post infection the animals were scanned by computed tomography before being killed and subjected to necropsy...... examination. Osteomyelitis lesions were present in the right hind limb of all pigs inoculated with strain S54F9 and in one pig inoculated with strain NCTC-8325-4. Microscopically, there was extensive loss of bone tissue with surrounding granulation tissue. Sequestrated bone trabeculae were intermingled...

  3. Phenotypic and pathologic evaluation of the myd mouse. A candidate model for facioscapulohumeral dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, K.D.; Rapisarda, D.; Bailey, H.L. [Univ. of Iowa College of Medicine, Iowa City, IA (United States)] [and others

    1995-07-01

    Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant disease of unknown pathogenesis which is characterized by weakness of the face and shoulder girdle. It is associated with a sensorineural hearing loss which may be subclinical. FSHD has been mapped to the distalmost portion of 4q35, although the gene has not yet been identified. Distal 4q has homology with a region of mouse chromosome 8 to which a mouse mutant, myodystrophy (myd), has been mapped. Muscle from homozygotes for the myd mutation appears dystrophic, showing degenerating and regenerating fibers, inflammatory infiltrates, central nuclei, and variation in fiber size. Brainstem auditory evoked potentials reveal a sensorineural hearing loss in myd homozygotes. Based on the homologous genetic map locations, and the phenotypic syndrome of dystrophic muscle with sensorineural hearing loss, we suggest that myd represents an animal model for the human disease FSHD. 28 refs., 4 figs.

  4. Helicobacter suis causes severe gastric pathology in mouse and mongolian gerbil models of human gastric disease.

    Directory of Open Access Journals (Sweden)

    Bram Flahou

    Full Text Available BACKGROUND: "Helicobacter (H. heilmannii" type 1 is the most prevalent gastric non-H. pylori Helicobacter species in humans suffering from gastric disease. It has been shown to be identical to H. suis, a bacterium which is mainly associated with pigs. To obtain better insights into the long-term pathogenesis of infections with this micro-organism, experimental infections were carried out in different rodent models. METHODOLOGY/PRINCIPAL FINDINGS: Mongolian gerbils and mice of two strains (BALB/c and C57BL/6 were infected with H. suis and sacrificed at 3 weeks, 9 weeks and 8 months after infection. Gastric tissue samples were collected for PCR analysis, histological and ultrastructural examination. In gerbils, bacteria mainly colonized the antrum and a narrow zone in the fundus near the forestomach/stomach transition zone. In both mice strains, bacteria colonized the entire glandular stomach. Colonization with H. suis was associated with necrosis of parietal cells in all three animal strains. From 9 weeks after infection onwards, an increased proliferation rate of mucosal epithelial cells was detected in the stomach regions colonized with H. suis. Most gerbils showed a marked lymphocytic infiltration in the antrum and in the forestomach/stomach transition zone, becoming more pronounced in the course of time. At 8 months post infection, severe destruction of the normal antral architecture at the inflamed sites and development of mucosa-associated lymphoid tissue (MALT lymphoma-like lesions were observed in some gerbils. In mice, the inflammatory response was less pronounced than in gerbils, consisting mainly of mononuclear cell infiltration and being most severe in the fundus. CONCLUSIONS/SIGNIFICANCE: H. suis causes death of parietal cells, epithelial cell hyperproliferation and severe inflammation in mice and Mongolian gerbil models of human gastric disease. Moreover, MALT lymphoma-like lesions were induced in H. suis-infected Mongolian gerbils

  5. Helicobacter suis causes severe gastric pathology in mouse and mongolian gerbil models of human gastric disease.

    Science.gov (United States)

    Flahou, Bram; Haesebrouck, Freddy; Pasmans, Frank; D'Herde, Katharina; Driessen, Ann; Van Deun, Kim; Smet, Annemieke; Duchateau, Luc; Chiers, Koen; Ducatelle, Richard

    2010-11-22

    "Helicobacter (H.) heilmannii" type 1 is the most prevalent gastric non-H. pylori Helicobacter species in humans suffering from gastric disease. It has been shown to be identical to H. suis, a bacterium which is mainly associated with pigs. To obtain better insights into the long-term pathogenesis of infections with this micro-organism, experimental infections were carried out in different rodent models. Mongolian gerbils and mice of two strains (BALB/c and C57BL/6) were infected with H. suis and sacrificed at 3 weeks, 9 weeks and 8 months after infection. Gastric tissue samples were collected for PCR analysis, histological and ultrastructural examination. In gerbils, bacteria mainly colonized the antrum and a narrow zone in the fundus near the forestomach/stomach transition zone. In both mice strains, bacteria colonized the entire glandular stomach. Colonization with H. suis was associated with necrosis of parietal cells in all three animal strains. From 9 weeks after infection onwards, an increased proliferation rate of mucosal epithelial cells was detected in the stomach regions colonized with H. suis. Most gerbils showed a marked lymphocytic infiltration in the antrum and in the forestomach/stomach transition zone, becoming more pronounced in the course of time. At 8 months post infection, severe destruction of the normal antral architecture at the inflamed sites and development of mucosa-associated lymphoid tissue (MALT) lymphoma-like lesions were observed in some gerbils. In mice, the inflammatory response was less pronounced than in gerbils, consisting mainly of mononuclear cell infiltration and being most severe in the fundus. H. suis causes death of parietal cells, epithelial cell hyperproliferation and severe inflammation in mice and Mongolian gerbil models of human gastric disease. Moreover, MALT lymphoma-like lesions were induced in H. suis-infected Mongolian gerbils. Therefore, the possible involvement of this micro-organism in human gastric disease

  6. [Primary sub-mandibular gland tumours: experience based on 68 cases].

    Science.gov (United States)

    Oudidi, A; El-Alami, M N; Boulaich, M; Jazouli, N; Kzadri, M

    2006-01-01

    Sub-mandibulary gland tumours are less common than tumours of the parotid and pose many clinical and therapeutic challengers. We report our experience of sub-mandibular tumours and review the literature. Retrospective studies of sub-mandibular gland tumours presenting to our department between 1986 and 2000. 68 cases were reviewed comprising 37 benign and 31 malignant tumours (15 females and 33 males). Average age of patient was 46 years and all presented with a sub-mandibular swelling. Clinical suspicion of malignancy was associated with symptom of pain, cervical adenopathy, nerve palsy, skin and/or bone invasion. CAT Scans were performedd to assess tumour extent / invasion. Definitive diagnosis was by complete excision and pathological examination. Pleomorphic adenoma (n= 32) were the most frequent benign tumours. For malignant lesions (n= 31) the most frequent were: Adenoid cystic carcinoma (n= 10), epidermoid carcinoma (n= 5), adenocarcinoma (n= 5), mucoepidermoid carcinoma (n= 3), malignant non Hodgkinien lymphoma (n= 5). Treatment was by total surgical excision of the submandibular gland for the begnin tumours. For the malignant lesions it was associated acording to their extension with other anatomical region or in case of adenopathy with neck dissection. Radiotherapy was performed in 24 cases and chemotherapy in 10 cases. Malignity in sub-mandibular gland tumours is more frequent than in the parotid gland. Any delay in diagnosis or inappropriate management may result in a poor prognosis for the patient.

  7. Adapting radiotherapy to hypoxic tumours

    International Nuclear Information System (INIS)

    Malinen, Eirik; Soevik, Aste; Hristov, Dimitre; Bruland, Oeyvind S; Olsen, Dag Rune

    2006-01-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO 2 -related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO 2 -related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO 2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO 2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure

  8. Adapting radiotherapy to hypoxic tumours

    Science.gov (United States)

    Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag

    2006-10-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields

  9. Development of pathological anthropomorphic models using 3D modelling techniques for numerical dosimetry; Desenvolvimento de modelos antropomorficos patologicos usando tecnicas de modelagem 3D para dosimetria numerica

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Kleber Souza Silva [Faculdade Integrada de Pernambuco (FACIPE), Recife, PE (Brazil); Barbosa, Antonio Konrado de Santana; Vieira, Jose Wilson [Instituto Federal de Educacao, Ciencia e Tecnologia de Pernambuco, Recife, PE (Brazil); Lima, Fernando Roberto de Andrade, E-mail: falima@cnen.gov.b [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2011-10-26

    Computational exposure models can be used to estimate human body absorbed dose in a series of situations such as X-Ray exams for diagnosis, accidents and medical treatments. These models are fundamentally composed of an anthropomorphic simulator (phantom), an algorithm that simulates a radioactive source and a Monte Carlo Code. The accuracy of data obtained in the simulation is strongly connected to the adequacy of such simulation to the real situation. The phantoms are one of the key factors for the researcher manipulation. They are generally developed in supine position and its anatomy is patronized by compiled data from international institutions such as ICRP or ICRU. Several pathologies modify the structure of organs and body tissues. In order to measure how significant these alterations are, an anthropomorphic model was developed for this study: patient mastectomies. This model was developed using voxel phantom FASH and then coupled with EGSnrc Monte Carlo code

  10. Clonal nature of odontogenic tumours.

    Science.gov (United States)

    Gomes, Carolina Cavaliéri; Oliveira, Carla da Silveira; Castro, Wagner Henriques; de Lacerda, Júlio César Tanos; Gomez, Ricardo Santiago

    2009-04-01

    Although clonal origin is an essential step in the comprehension of neoplasias, there have been no studies to examine whether odontogenic tumours are derived from a single somatic progenitor cell. The purpose of this study was to investigate the clonal origin of odontogenic tumours. Fresh samples of seven ameloblastomas, two odontogenic mixomas, two adenomatoid odontogenic tumour, one calcifying odontogenic cyst, one calcifying epithelial odontogenic tumour (CEOT) and six odontogenic keratocyst (OKC) of female patients were included in this study. After DNA extraction, the HUMARA gene polymorphism assay was performed. Most of the informative odontogenic lesions studied (12 out of 16) showed a monoclonal pattern. Among the polyclonal cases, two were OKC, one CEOT and one odontogenic mixoma. Our results suggest that most odontogenic tumours are monoclonal.

  11. Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity.

    Science.gov (United States)

    Marusyk, Andriy; Tabassum, Doris P; Altrock, Philipp M; Almendro, Vanessa; Michor, Franziska; Polyak, Kornelia

    2014-10-02

    Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumours. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity on tumour phenotypes and the competitive expansion of individual clones. We found that tumour growth can be driven by a minor cell subpopulation, which enhances the proliferation of all cells within a tumour by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumour collapse. We developed a mathematical modelling framework to identify the rules underlying the generation of intra-tumour clonal heterogeneity. We found that non-cell-autonomous driving of tumour growth, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits.

  12. Molecular pathology and thyroid FNA.

    Science.gov (United States)

    Poller, D N; Glaysher, S

    2017-12-01

    This review summarises molecular pathological techniques applicable to thyroid FNA. The molecular pathology of thyroid tumours is now fairly well understood. Molecular methods may be used as a rule-in test for diagnosis of malignancy in thyroid nodules, eg BRAF V600E point mutation, use of a seven-gene mutational panel (BRAF V600E, RAS genes, RET/PTC or PAX8/PPARG rearrangement), or as a comprehensive multigene next-generation sequencing panel, eg ThyroSeq v2. Molecular methods can also be applied as rule-out tests for malignancy in thyroid nodules, eg Afirma or ThyroSeq v2 or as markers of prognosis, eg TERT promoter mutation or other gene mutations including BRAF V600E, TP53 and AKT1, and as tests for newly defined tumour entities such as non-invasive follicular thyroid neoplasm with papillary like nuclei, or as a molecular marker(s) for targeted therapies. This review describes practical examples of molecular techniques as applied to thyroid FNA in routine clinical practice and the value of molecular diagnostics in thyroid FNA. It describes the range of molecular abnormalities identified in thyroid nodules and thyroid cancers with some practical applications of molecular methods to diagnosis and prognosis of thyroid nodules and thyroid cancer. © 2017 John Wiley & Sons Ltd.

  13. Improving tumour response

    International Nuclear Information System (INIS)

    Bentzen, S.

    2003-01-01

    Radiation oncology is in the middle of the most exciting developments in its 100-year history. Progress in treatment planning and delivery, in medical imaging and in basic cancer and normal tissue biology is likely to change the indication for radiotherapy as well as the way it is prescribed and delivered. Technological and conceptual advances, in particular the development of the multi-leaf collimator and the concept of inverse treatment planning, have led to the introduction of intensity modulated radiation therapy (IMRT) with its capability to plan and deliver non-uniform dose distributions in the clinic. This has forced us to re-think radiation oncology: refining the indication for radiotherapy, optimizing the prescription of dose distributions and considering how, based on clinical evidence, radiation can best be combined with other treatment modalities, surgery, cytotoxic chemotherapy and biologically targeted therapies. The attraction of radiation therapy as an element of multi-modality cancer therapy is that it induces DNA damage that can be modulated in space and time. Progress in basic cancer biology, genomics and proteomics, as well as biological imaging provides novel avenues for individualization of cancer therapy and for biological optimization of radiotherapy. In improving cancer care, it is the therapeutic ratio, rather than tumour control per se, that must be optimised. Interestingly, the two main avenues for improving the effectiveness of radiotherapy currently being actively pursued in the clinic generally aim at different sides of the therapeutic ratio: 3D conformal radiotherapy and IMRT predominantly aim to reduce normal-tissue side effects - and by doing this, open the way for dose escalation that may lead to increased tumour control rates - whereas combined radio-chemotherapy aims to improve tumour response - while keeping the fingers crossed that this will not increase normal-tissue complications to the same extent. In parallel with these

  14. Using a visual discrimination model for the detection of compression artifacts in virtual pathology images.

    Science.gov (United States)

    Johnson, Jeffrey P; Krupinski, Elizabeth A; Yan, Michelle; Roehrig, Hans; Graham, Anna R; Weinstein, Ronald S

    2011-02-01

    A major issue in telepathology is the extremely large and growing size of digitized "virtual" slides, which can require several gigabytes of storage and cause significant delays in data transmission for remote image interpretation and interactive visualization by pathologists. Compression can reduce this massive amount of virtual slide data, but reversible (lossless) methods limit data reduction to less than 50%, while lossy compression can degrade image quality and diagnostic accuracy. "Visually lossless" compression offers the potential for using higher compression levels without noticeable artifacts, but requires a rate-control strategy that adapts to image content and loss visibility. We investigated the utility of a visual discrimination model (VDM) and other distortion metrics for predicting JPEG 2000 bit rates corresponding to visually lossless compression of virtual slides for breast biopsy specimens. Threshold bit rates were determined experimentally with human observers for a variety of tissue regions cropped from virtual slides. For test images compressed to their visually lossless thresholds, just-noticeable difference (JND) metrics computed by the VDM were nearly constant at the 95th percentile level or higher, and were significantly less variable than peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) metrics. Our results suggest that VDM metrics could be used to guide the compression of virtual slides to achieve visually lossless compression while providing 5-12 times the data reduction of reversible methods.

  15. ANTI-ERGOTYPIC RESPONSE: ROLE IN NORMAL IMMUNE RESPONSE AND AUTOIMMUNE PATHOLOGY IN EXPERIMENTAL MODEL

    Directory of Open Access Journals (Sweden)

    N. A. Ilyina

    2011-01-01

    Full Text Available Abstract. Anti-ergotypic cells are a part of peripheral regulatory network, and they are thought to control autoreactive T cells by recognition of certain clonotypic and ergotypic determinants on the surface of activated T cells. The aim of our study was to investigate ability of anti-CD3 activated syngeneic splenocytes to induce anti-ergotypic  response  and  to  assess  immune  response  in  delayed-type hypersensitivity (DTH reaction.DTH response in experimental group was significantly greater than in control and intact groups. Upon crossadministration, DTH response was minimal and there were no significant differences between the groups. No changes in cellular and humoral immune response were observed under such conditions. These results suggest a development of immune response to activated antigen-nonspecific cells. In a model of chronic GvHD, donor immunization was shown to exert a protective effect, with regard of proteinuria dynamics in recipients, whereas immunization of recipients did not alter the GvHD dynamics. (Med. Immunol., 2011, vol. 13, N 1, pp 29-34

  16. Computed chest tomography in an animal model for decompression sickness: radiologic, physiologic, and pathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Reuter, M.; Struck, N.; Heller, M. [Dept. of Diagnostic Radiology, Christian Albrechts Univ., Kiel (Germany); Tetzlaff, K. [Dept. of Medicine, Christian Albrechts Univ., Kiel (Germany); Brasch, F.; Mueller, K.M. [Inst. of Pathology, Hospital Bergmannsheil, Bochum (Germany); Gerriets, T. [Dept. of Neurology, Medical Univ. at Luebeck (Germany); Weiher, M.; Hansen, J. [Dept. of Anaesthesiology and Hyperbaric Centre Northern Germany, Friedrich Ebert Hospital, Neumuenster (Germany); Hirt, S. [Dept. of Medicine, Cardiac and Vascular Surgery, Christian Albrechts University, Kiel (Germany)

    2000-03-01

    This study was conducted to investigate the early pulmonary effects of acute decompression in an animal model for human decompression sickness by CT and light microscopy. Ten test pigs were exposed to severe decompression stress in a chamber dive. Three pigs were kept at ambient pressure to serve as controls. Decompression stress was monitored by measurement of pulmonary artery pressure and arterial and venous Doppler recording of bubbles of inert gas. Chest CT was performed pre- and postdive and in addition the inflated lungs were examined after resection. Each lung was investigated by light microscopy. Hemodynamic data and bubble recordings reflected severe decompression stress in the ten test pigs. Computed tomography revealed large quantities of ectopic gas, predominantly intravascular, in three of ten pigs. These findings corresponded to maximum bubble counts in the Doppler study. The remaining test pigs showed lower bubble grades and no ectopic gas by CT. Sporadic interstitial edema was demonstrated in all animals - both test and control pigs - by CT of resected lungs and on histologic examination. A severe compression-decompression schedule can liberate large volumes of inert gas which are detectable by CT. Despite this severe decompression stress, which led to venous microembolism, CT and light microscopy did not demonstrate changes in lung structure related to the experimental dive. Increased extravascular lung water found in all animals may be due to infusion therapy. (orig.)

  17. The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.

    Science.gov (United States)

    Dorchies, Olivier M; Reutenauer-Patte, Julie; Dahmane, Elyes; Ismail, Heham M; Petermann, Olivier; Patthey- Vuadens, Ophélie; Comyn, Sophie A; Gayi, Elinam; Piacenza, Tony; Handa, Robert J; Décosterd, Laurent A; Ruegg, Urs T

    2013-02-01

    Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofiber membranes, normalized whole body force, and increased force production and resistance to repeated contractions of the triceps muscle above normal values. Tamoxifen improved the structure of leg muscles and diminished cardiac fibrosis by~ 50%. Tamoxifen also reduced fibrosis in the diaphragm, while increasing its thickness,myofiber count, and myofiber diameter, thereby augmenting by 72% the amount of contractile tissue available for respiratory function. Tamoxifen conferred a markedly slower phenotype to the muscles.Tamoxifen and its metabolites were present in nanomolar concentrations in plasma and muscles,suggesting signaling through high-affinity targets. Interestingly, the estrogen receptors ERa and ERb were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalized the relative abundance of ERb isoforms. Our findings suggest that tamoxifen might be a useful therapy for DMD.

  18. Computed chest tomography in an animal model for decompression sickness: radiologic, physiologic, and pathologic findings

    International Nuclear Information System (INIS)

    Reuter, M.; Struck, N.; Heller, M.; Tetzlaff, K.; Brasch, F.; Mueller, K.M.; Gerriets, T.; Weiher, M.; Hansen, J.; Hirt, S.

    2000-01-01

    This study was conducted to investigate the early pulmonary effects of acute decompression in an animal model for human decompression sickness by CT and light microscopy. Ten test pigs were exposed to severe decompression stress in a chamber dive. Three pigs were kept at ambient pressure to serve as controls. Decompression stress was monitored by measurement of pulmonary artery pressure and arterial and venous Doppler recording of bubbles of inert gas. Chest CT was performed pre- and postdive and in addition the inflated lungs were examined after resection. Each lung was investigated by light microscopy. Hemodynamic data and bubble recordings reflected severe decompression stress in the ten test pigs. Computed tomography revealed large quantities of ectopic gas, predominantly intravascular, in three of ten pigs. These findings corresponded to maximum bubble counts in the Doppler study. The remaining test pigs showed lower bubble grades and no ectopic gas by CT. Sporadic interstitial edema was demonstrated in all animals - both test and control pigs - by CT of resected lungs and on histologic examination. A severe compression-decompression schedule can liberate large volumes of inert gas which are detectable by CT. Despite this severe decompression stress, which led to venous microembolism, CT and light microscopy did not demonstrate changes in lung structure related to the experimental dive. Increased extravascular lung water found in all animals may be due to infusion therapy. (orig.)

  19. Accurate prostate tumour detection with multiparametric magnetic resonance imaging: dependence on histological properties.

    Science.gov (United States)

    Borren, Alie; Groenendaal, Greetje; Moman, Maaike R; Boeken Kruger, Arto E; van Diest, Paul J; van Vulpen, Marco; Philippens, Marielle E P; van der Heide, Uulke A

    2014-01-01

    To benefit most of focal treatment of prostate tumours, detection with high precision of all tumour voxels is needed. Although diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have good diagnostic performance, perfect tumour detection is challenging. In this study, we investigated the variation in prostate tissue characteristics Gleason score (GS), cell density (CD) and microvessel density (MVD) to explain the limitations in tumour voxel detection with a MRI-based logistic regression model. Twelve radical prostatectomy patients underwent a pre-operative 3.0T DWI and DCE-MRI exam. The MRI scans were used to calculate voxel-wise tumour probability with a logistic regression model for the peripheral zone (PZ) of the prostate. Tumour probability maps were correlated and validated with whole-mount histology. Additionally, from the whole-mount histological sections CD, MVD and GS were retrieved for every single voxel. GS, CD and MVD of true- and false-positive voxels and of true- and false-negative voxels were compared using Mann-Whitney U-tests. False-negative tumour voxels had significantly lower CD and MVD (p < 0.0001) and were similar to non-tumour PZ. True-positive detected tumour voxels had high CDs and MVDs (p < 0.0001). In addition, tumour voxels with higher GS showed a trend towards more frequent detection (p = 0.06). Tumour voxels with GS ≥ 3 + 4 showed higher CD and MVD compared to tumour voxels with GS 3 + 3 (p < 0.0001). Tumour voxels with low CD and MVD resemble healthy tissue and are limiting tumour voxel detection using DWI and DCE-MRI. Nevertheless, the most aggressive tumour voxels, containing high CD, MVD and GS, are more likely to be detected and can therefore be treated with high dose using focal therapy or focal boosting.

  20. Sperm protein 17 is expressed in human nervous system tumours

    International Nuclear Information System (INIS)

    Grizzi, Fabio; Baena, Riccardo Rodriguez y; Dioguardi, Nicola; Chiriva-Internati, Maurizio; Gaetani, Paolo; Franceschini, Barbara; Di Ieva, Antonio; Colombo, Piergiuseppe; Ceva-Grimaldi, Giorgia; Bollati, Angelo; Frezza, Eldo E; Cobos, E

    2006-01-01

    Human sperm protein 17 (Sp17) is a highly conserved protein that was originally isolated from a rabbit epididymal sperm membrane and testis membrane pellet. It has recently been included in the cancer/testis (CT) antigen family, and shown to be expressed in multiple myeloma and ovarian cancer. We investigated its immunolocalisation in specimens of nervous system (NS) malignancies, in order to establish its usefulness as a target for tumour-vaccine strategies. The expression of Sp17 was assessed by means of a standardised immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral nerve sheath tumours (4 schwannomas, and 1 neurofibroma),. A number of neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously immunopositive for Sp17. None of the peripheral nerve sheath tumours was immunopositive for Sp17. The expression pattern was heterogeneous in all of the positive samples, and did not correlate with the degree of malignancy. The frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells

  1. Proximal fibula resection in the treatment of bone tumours.

    Science.gov (United States)

    Dieckmann, Ralf; Gebert, Carsten; Streitbürger, Arne; Henrichs, Marcel-Philipp; Dirksen, Uta; Rödl, Robert; Gosheger, Georg; Hardes, Jendrik

    2011-11-01

    We present a large study of patients with proximal fibula resection. Moreover we describe a new classification system for tumour resection of the proximal fibula independent of the tumour differentiation. In 57 patients the functional and clinical outcomes were evaluated. The follow-up ranged between six months and 22.2 years (median 7.2 years). The indication for surgery was benign tumours in ten cases and malignant tumours in 47 cases. In 13 of 45 patients, where a resection of the lateral ligament complex was done, knee instability occurred. In 32 patients a resection of the peroneal nerve with resulting peroneal palsy was necessary. Patients with peroneal resection had significantly worse functional outcome than patients without peroneal resection. An ankle foot orthosis was tolerated well by these patients. Three of four patients with pathological tibia fracture had local radiation therapy. There was no higher risk of tibia fracture in patients with partial tibial resection. Resection of tumours in the proximal fibula can cause knee instability, peroneal palsy and in cases of local radiation therapy, a higher risk of delayed wound healing and fracture. Despite the risks of proximal fibula resection, good functional results can be achieved.

  2. Compressing pathology whole-slide images using a human and model observer evaluation

    Directory of Open Access Journals (Sweden)

    Elizabeth A Krupinski

    2012-01-01

    Full Text Available Introduction: We aim to determine to what degree whole-slide images (WSI can be compressed without impacting the ability of the pathologist to distinguish benign from malignant tissues. An underlying goal is to demonstrate the utility of a visual discrimination model (VDM for predicting observer performance. Materials and Methods: A total of 100 regions of interest (ROIs from a breast biopsy whole-slide images at five levels of JPEG 2000 compression (8:1, 16:1, 32:1, 64:1, and 128:1 plus the uncompressed version were shown to six pathologists to determine benign versus malignant status. Results: There was a significant decrease in performance as a function of compression ratio (F = 14.58, P < 0.0001. The visibility of compression artifacts in the test images was predicted using a VDM. Just-noticeable difference (JND metrics were computed for each image, including the mean, median, ≥90th percentiles, and maximum values. For comparison, PSNR (peak signal-to-noise ratio and Structural Similarity (SSIM were also computed. Image distortion metrics were computed as a function of compression ratio and averaged across test images. All of the JND metrics were found to be highly correlated and differed primarily in magnitude. Both PSNR and SSIM decreased with bit rate, correctly reflecting a loss of image fidelity with increasing compression. Observer performance as measured by the Receiver Operating Characteristic area under the curve (ROC Az was nearly constant up to a compression ratio of 32:1, then decreased significantly for 64:1 and 128:1 compression levels. The initial decline in Az occurred around a mean JND of 3, Minkowski JND of 4, and 99th percentile JND of 6.5. Conclusion: Whole-slide images may be compressible to relatively high levels before impacting WSI interpretation performance. The VDM metrics correlated well with artifact conspicuity and human performance.