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Sample records for brain tumours metabolite

  1. Linear discriminant analysis of brain tumour (1)H MR spectra: a comparison of classification using whole spectra versus metabolite quantification.

    Science.gov (United States)

    Opstad, K S; Ladroue, C; Bell, B A; Griffiths, J R; Howe, F A

    2007-12-01

    (1)H MRS is an attractive choice for non-invasively diagnosing brain tumours. Many studies have been performed to create an objective decision support system, but there is not yet a consensus as to the best techniques of MRS acquisition or data processing to be used for optimum classification. In this study, we investigate whether LCModel analysis of short-TE (30 ms), single-voxel tumour spectra provide a better input for classification than the use of the original spectra. A total of 145 histologically diagnosed brain tumour spectra were acquired [14 astrocytoma grade II (AS2), 15 astrocytoma grade III (AS3), 42 glioblastoma (GBM), 41 metastases (MET) and 33 meningioma (MNG)], and linear discriminant analyses (LDA) were performed on the LCModel analysis of the spectra and the original spectra. The results consistently suggest improvement in classification when the LCModel concentrations are used. LDA of AS2, MNG and high-grade tumours (HG, comprising GBM and MET) correctly classified 94% using the LCModel dataset compared with 93% using the spectral dataset. The inclusion of AS3 reduced the accuracy to 82% and 78% for LCModel analysis and the original spectra, respectively, and further separating HG into GBM and MET gave 70% compared with 60%. Generally MNG spectra have profiles that are visually distinct from those of the other tumour types, but the classification accuracy was typically about 80%, with MNG with substantial lipid/macromolecule signals being classified as HG. Omission of the lipid/macromolecule concentrations in the LCModel dataset provided an improvement in classification of MNG (91% compared with 76%). In conclusion, there appears to be an advantage to performing pattern recognition on the quantitative analysis of tumour spectra rather than using the whole spectra. However, the results suggest that a two-step LDA process may help in classifying the five tumour groups to provide optimum classification of MNG with high lipid

  2. of brain tumours

    African Journals Online (AJOL)

    Also, tumours in the frontal and temporal lobes are more likely to cause psychiatric symptoms than those in parietal or occipital lobes. Left-sided, frontal tumours also seem to be associated with higher rates of depression, while those in the frontal lobe of the right hemisphere may be associated with features that may be.

  3. 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").

  4. Neurofibromatosis type 1: brain stem tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bilaniuk, L.T. [Department of Radiology, The Children`s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA (United States); Molloy, P.T. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Zimmerman, R.A. [Department of Radiology, The Children`s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA (United States); Phillips, P.C. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Vaughan, S.N. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Liu, G.T. [Division of Neuro-Ophthalmology, Children`s Hospital of Philadelphia, PA (United States); Sutton, L.N. [Division of Neurosurgery, Children`s Hospital of Philadelphia, PA (United States); Needle, M. [Division of Oncology, The Children`s Hospital of Philadelphia. PA (United States)

    1997-09-01

    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.

  5. Symptoms and time to diagnosis in children with brain tumours

    DEFF Research Database (Denmark)

    Klitbo, Ditte Marie; Nielsen, Rine; Illum, Niels Ove

    2011-01-01

    Clinical symptoms in brain tumours in children are variable at onset and diagnosis is often delayed. Symptoms were investigated with regard to brain tumour localisation, prediagnostic symptomatic intervals and malignancy.......Clinical symptoms in brain tumours in children are variable at onset and diagnosis is often delayed. Symptoms were investigated with regard to brain tumour localisation, prediagnostic symptomatic intervals and malignancy....

  6. Primary brain tumours, meningiomas and brain metastases in pregnancy

    DEFF Research Database (Denmark)

    Verheecke, Magali; Halaska, Michael J; Lok, Christianne A

    2014-01-01

    to obtain better insight into outcome and possibilities of treatment in pregnancy. METHODS: We collected all intracranial tumours (primary brain tumour, cerebral metastasis, or meningioma) diagnosed during pregnancy, registered prospectively and retrospectively by international collaboration since 1973....... Patients diagnosed postpartum were excluded. We summarised the demographic features, treatment decisions, obstetrical and neonatal outcomes. RESULTS: The mean age of the 27 eligible patients was 31years (range 23-41years), of which 13 and 12 patients were diagnosed in the second and third trimesters...... were reassuring. CONCLUSION: Adherence to standard protocol for the treatment of brain tumours during pregnancy appears to allow a term delivery and a higher probability of a vaginal delivery....

  7. The feasibility of a brain tumour website

    DEFF Research Database (Denmark)

    Piil, K; Jakobsen, J; Juhler, M

    2015-01-01

    PURPOSE: Patients with a high-grade glioma (HGG) and their caregivers have imminent and changing informational and supportive care needs. The purpose of this study was to investigate the feasibility and safety of a Danish brain tumour website (BTW) in patients with HGG and their caregivers. We...

  8. Imaging biomarkers in primary brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)

    2015-04-01

    We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

  9. {sup 1}H magnetic resonance spectroscopy in the diagnosis of paediatric low grade brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Orphanidou-Vlachou, E., E-mail: eleni.orphanidou@googlemail.com [School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT (United Kingdom); Birmingham Children' s Hospital NHS Foundation Trust, Whittall Street, Birmingham, B4 6NH (United Kingdom); Auer, D., E-mail: dorothee.auer@nottingham.ac.uk [Division of Academic Radiology, School of Medical and Surgical Sciences, The University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom); Children' s Brain Tumour Research Centre, Queens Medical Centre, University of Nottingham (United Kingdom); Brundler, M.A., E-mail: marie-anne.brundler@bch.nhs.uk [Birmingham Children' s Hospital NHS Foundation Trust, Whittall Street, Birmingham, B4 6NH (United Kingdom); Davies, N.P., E-mail: nigel.davies@nhs.net [School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT (United Kingdom); Birmingham Children' s Hospital NHS Foundation Trust, Whittall Street, Birmingham, B4 6NH (United Kingdom); Department of Medical Physics, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB (United Kingdom); Jaspan, T., E-mail: tim.jaspan@nuh.nhs.uk [Children' s Brain Tumour Research Centre, Queens Medical Centre, University of Nottingham (United Kingdom); MacPherson, L., E-mail: Lesley.MacPherson@bch.nhs.uk [Birmingham Children' s Hospital NHS Foundation Trust, Whittall Street, Birmingham, B4 6NH (United Kingdom); Natarajan, K., E-mail: Kal.Natarajan@uhb.nhs.uk [Birmingham Children' s Hospital NHS Foundation Trust, Whittall Street, Birmingham, B4 6NH (United Kingdom); Department of Medical Physics, University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB (United Kingdom); and others

    2013-06-15

    Introduction: Low grade gliomas are the commonest brain tumours in children but present in a myriad of ways, each with its own treatment challenges. Conventional MRI scans play an important role in their management but have limited ability to identify likely clinical behaviour. The aim of this study is to investigate {sup 1}H magnetic resonance spectroscopy (MRS) as a method for detecting differences between the various low grade gliomas and related tumours in children. Patients and methods: Short echo time single voxel {sup 1}H MRS at 1.5 or 3.0 T was performed prior to treatment on children with low grade brain tumours at two centres and five MR scanners, 69 cases had data which passed quality control. MRS data was processed using LCModel to give mean spectra and metabolite concentrations which were compared using T-tests, ANOVA, Receiver Operator Characteristic curves and logistic regression in SPSS. Results: Significant differences were found in concentrations of key metabolites between glioneuronal and glial tumours (T-test p < 0.05) and between most of the individual histological subtypes of low grade gliomas. The discriminatory metabolites identified, such as choline and myoinositol, are known tumour biomarkers. In the set of pilocytic astrocytomas and unbiopsied optic pathway gliomas, significant differences (p < 0.05, ANOVA) were found in metabolite profiles of tumours depending on location and patient neurofibromatosis type 1 status. Logistic regression analyses yielded equations which could be used to assess the probability of a tumour being of a specific type. Conclusions: MRS can detect subtle differences between low grade brain tumours in children and should form part of the clinical assessment of these tumours.

  10. High resolution magic angle spinning 1H NMR of childhood brain and nervous system tumours

    Directory of Open Access Journals (Sweden)

    Davies Nigel P

    2009-02-01

    Full Text Available Abstract Background Brain and nervous system tumours are the most common solid cancers in children. Molecular characterisation of these tumours is important for providing novel biomarkers of disease and identifying molecular pathways which may provide putative targets for new therapies. 1H magic angle spinning NMR spectroscopy (1H HR-MAS is a powerful tool for determining metabolite profiles from small pieces of intact tissue and could potentially provide important molecular information. Methods Forty tissue samples from 29 children with glial and primitive neuro-ectodermal tumours were analysed using HR-MAS (600 MHz Varian gHX nanoprobe. Tumour spectra were fitted to a library of individual metabolite spectra to provide metabolite values. These values were then used in a two tailed t-test and multi-variate analysis employing a principal component analysis and a linear discriminant analysis. Classification accuracy was estimated using a leave-one-out analysis and B632+ bootstrapping. Results Glial tumours had significantly (two tailed t-test p Conclusion HR-MAS identified key differences in the metabolite profiles of childhood brain and nervous system improving the molecular characterisation of these tumours. Further investigation of the underlying molecular pathways is required to assess their potential as targets for new agents.

  11. DIAGNOSTIC ABILITY OF MRI IN CHARACTERISATION OF SUPRATENTORIAL BRAIN TUMOURS

    Directory of Open Access Journals (Sweden)

    Indira Sri Sailaja Rednam

    2017-04-01

    Full Text Available BACKGROUND Brain tumours arise from the normal constituents of brain and its coverings; 80% of all the intracranial tumours are supratentorial. Imaging plays a crucial function in the management of patients with brain tumours. Magnetic Resonance Imaging (MRI has earned recognition as the optimal screening technique for the detection of most intracranial tumours. MRI using conventional Spin-Echo sequences like axial T1, T2 and Fluid-Attenuated Inversion Recovery (FLAIR, coronal T2, sagittal T1, post contrast SE T1 axial, sagittal and coronal sequences were taken which provides inherently illustrious contrast resolution between structural abnormalities and adjacent brain parenchyma and has proved to be more sensitive in identification of focal lesions of the brain. MATERIALS AND METHODS The present study was conducted in 50 patients who all were clinically suspected of supratentorial brain tumour cases and underwent MRI in the Department of Radiodiagnosis, Konaseema Institute of Medical Sciences and Research Foundation, Amalapuram, during the period of 18 months from July 2015 to December 2016. RESULTS The MRI features of 50 supratentorial tumours were reviewed, out of which 72% were found to be extra-axial tumours and 28% intra-axial tumours. About 48% were found to be glial tumours and 52% were found to be non-glial tumours. CONCLUSION MRI proves to be a valuable modality of imaging in evaluating the characteristics, distribution, location and assessing the extent of various intra- and extra-axial tumours in the supratentorial region.

  12. The neuropsychiatry of brain tumours | Oosthuizen | South African ...

    African Journals Online (AJOL)

    Every psychiatrist who has worked in the clinical field for some time will be able to relate a story of a patient who presented with psychiatric symptoms but eventually turned out to have a brain tumour. We all fear that someday we will misdiagnose a brain tumour and therefore fail to save a patient's life. The purpose of this ...

  13. Psychiatric manifestations of brain tumours: a review | Magoha | East ...

    African Journals Online (AJOL)

    Objective: To carry out a current review of psychiatric manifestations of brain tumours. Data Source: To carry out a review of psychiatric manifestations of brain tumours utilizing electronic databases in the internet including Google Scholar, PubMed, Medline, MedScape and Psych Info Searches. Data Extraction: Abstracts of ...

  14. PP13. CHERNOBYL, BREXIT AND BRAIN TUMOURS

    Science.gov (United States)

    chia, Dr kazumi; Davies, Ms Rhiannon; Brazil, Dr Lucy

    2017-01-01

    Abstract Following the 2004 enlargement of the European Union, many hundreds of thousands of people from the newly ascended states travelled to the UK to look for work. Polish workers were by far the largest group and today, Polish is the second most commonly spoken language in the UK. In central London, the multidisciplinary, neuro-oncology team at Guy’s and St. Thomas’ NHS Foundation Trust (GSTFT) and Kings College Hospital serves a catchment area of nearly 3.5 million, 1% (32,253) of whom are recorded to have been born in Poland at the last 2011 census. Over the past few years, we have observed a relatively large number of Polish-born UK residents presenting with primary brain and central nervous system (CNS) tumours. Data collection is ongoing but we believe that the numbers of newly diagnosed cases far exceeds the published age standardized incidence rate for brain and CNS tumors in Poland which is 10 per 100,000. If a higher than expected incidence of brain and CNS tumors in our local Polish population is observed this could be explained by a number of socioeconomic/health factors. However, as we mark the 30th anniversary of the Chernobyl accident this year, we should also keep in mind geohistorical factors that may be relevant to this particular immigrant population. Poland neighbours Ukraine where the Chernobyl accident occurred, and was affected by the radioactive fallout that followed the disaster. The main health impact from Chernobyl has so far been the increased incidence of thyroid cancer but there is now increasing concern about the increased risk of non-thyroid, solid tumors. An increased incidence in CNS tumours has been seen in atomic bomb survivors where even a low exposures (<1Sv) was associated with an increased risk. Cohort studies in Belarus and Ukraine, two countries with the most radiation contamination, have so far not demonstrated any significant increase in non-thyroid cancers but it may still be early days. We know from long term

  15. Residential Radon and Brain Tumour Incidence in a Danish Cohort

    DEFF Research Database (Denmark)

    Bräuner, Elvira V.; Andersen, Zorana J.; Andersen, Claus Erik

    2013-01-01

    of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort. Methods: During 1993–1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced......Background: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective: To investigate the long-term effect...... (CI) for the risk of primary brain tumours associated with residential radon exposure with adjustment for age, sex, occupation, fruit and vegetable consumption and traffic-related air pollution. Effect modification by air pollution was assessed. Results: Median estimated radon was 40.5 Bq/m3...

  16. Brain tumours in children: importance of early identification.

    Science.gov (United States)

    Fry, Charles William; Perrow, Rachel; Paul, Siba Prosad

    A Brain tumours account for a quarter of all childhood cancers in the UK but are the leading cause of cancer-related deaths in children. Studies have previously shown that there is a delay in diagnosing brain tumours in children in the UK. The HeadSmart campaign was launched to increase awareness among health professionals working in different settings regarding brain tumour symptoms in children. Although headache is considered to be one of the most important symptoms, it is not often reported in paediatric practice, especially if the child is young. The HeadSmart symptom card is a useful resource and should be used when dealing with a child with symptoms suggestive of brain tumours. Nurses working in different settings play a vital role in early identification of brain tumours and also in supporting the child and his/her family through the child's journey following diagnosis of a brain tumour. The HeadSmart campaign has led to a reduction in the total diagnostic interval, to 7 weeks, and the ultimate aim is to reduce it further to 5 weeks which will be on a par with the time taken to diagnose brain tumours in children in other developed countries.

  17. MicroRNA Regulation of Brain Tumour Initiating Cells in Central Nervous System Tumours

    Directory of Open Access Journals (Sweden)

    Neha Garg

    2015-01-01

    Full Text Available CNS tumours occur in both pediatric and adult patients and many of these tumours are associated with poor clinical outcome. Due to a paradigm shift in thinking for the last several years, these tumours are now considered to originate from a small population of stem-like cells within the bulk tumour tissue. These cells, termed as brain tumour initiating cells (BTICs, are perceived to be regulated by microRNAs at the posttranscriptional/translational levels. Proliferation, stemness, differentiation, invasion, angiogenesis, metastasis, apoptosis, and cell cycle constitute some of the significant processes modulated by microRNAs in cancer initiation and progression. Characterization and functional studies on oncogenic or tumour suppressive microRNAs are made possible because of developments in sequencing and microarray techniques. In the current review, we bring recent knowledge of the role of microRNAs in BTIC formation and therapy. Special attention is paid to two highly aggressive and well-characterized brain tumours: gliomas and medulloblastoma. As microRNA seems to be altered in the pathogenesis of many human diseases, “microRNA therapy” may now have potential to improve outcomes for brain tumour patients. In this rapidly evolving field, further understanding of miRNA biology and its contribution towards cancer can be mined for new therapeutic tools.

  18. Incidence of Brain Tumours at an Academic Centre in Western ...

    African Journals Online (AJOL)

    Objective: To determine the incidence of brain tumours at King AbdulAziz University Hospital (KAUH) in Jeddah, Saudi Arabia, over eight year period. Design: Retrospective study. Sitting: King Abdul Aziz University Hospital in Jeddah Saudi Arabia. Subjects: Patients with intracranial tumours. Results: The overall average ...

  19. Quantitation of glial fibrillary acidic protein in human brain tumours

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...... amounts of GFA, up to 85 times the concentration in parietal grey substance of normal human brain. GFA was not found in neurinomas, meningiomas, adenomas of the hypophysis, or in a single case of metastasis of adenocarcinoma. Non-glial tumours of craniopharyngioma and haemangioblastoma were infiltrated...

  20. Intracerebral haemorrhage in primary and metastatic brain tumours.

    Science.gov (United States)

    Salmaggi, Andrea; Erbetta, Alessandra; Silvani, Antonio; Maderna, Emanuela; Pollo, Bianca

    2008-09-01

    Intracerebral haemorrhage may both be a presenting manifestation in unrecognised brain tumour or--more frequently--take place in the disease course of known/suspected brain tumour due to diagnostic/therapeutic procedures, including biopsy, locoregional treatments and anti-angiogenic therapies. Apart from the difficulties inherent to accurate neuroradiological diagnosis in selected cases with small tumour volume, the main clinical problem that neurologists face is represented by decision making in prophylaxis/treatment of venous thromboembolism in these patients. These points are briefly discussed and available evidence on the last point is commented on.

  1. Spectral and lifetime domain measurements of rat brain tumours

    Science.gov (United States)

    Abi Haidar, D.; Leh, B.; Allaoua, K.; Genoux, A.; Siebert, R.; Steffenhagen, M.; Peyrot, D.; Sandeau, N.; Vever-Bizet, C.; Bourg-Heckly, G.; Chebbi, I.; Collado-Hilly, M.

    2012-02-01

    During glioblastoma surgery, delineation of the brain tumour margins remains difficult especially since infiltrated and normal tissues have the same visual appearance. This problematic constitutes our research interest. We developed a fibre-optical fluorescence probe for spectroscopic and time domain measurements. First measurements of endogenous tissue fluorescence were performed on fresh and fixed rat tumour brain slices. Spectral characteristics, fluorescence redox ratios and fluorescence lifetime measurements were analysed. Fluorescence information collected from both, lifetime and spectroscopic experiments, appeared promising for tumour tissue discrimination. Two photon measurements were performed on the same fixed tissue. Different wavelengths are used to acquire two-photon excitation-fluorescence of tumorous and healthy sites.

  2. A rare metastasis from a rare brain tumour

    DEFF Research Database (Denmark)

    Aabenhus, Kristine; Hahn, Christoffer Holst

    2014-01-01

    This case report presents the story of a patient with an oligodendroglioma metastasizing to the bone marrow and to lymph nodes of the neck. The patient had undergone primary brain surgery 13 years prior to the discovery of metastases and radiotherapy directed at the brain tumour two months prior........ Oligodendroglioma are rare primary brain tumours of which extraneural metastasis is even more rare. The incidence of cases like this may be increasing because of better treatment and thus longer survival of patients with oligodendroglioma....

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

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    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.

  4. Predicting parenting stress in caregivers of children with brain tumours.

    Science.gov (United States)

    Bennett, Emily; English, Martin William; Rennoldson, Michael; Starza-Smith, Arleta

    2013-03-01

    The purpose of the study was to identify factors that contribute to parenting stress in caregivers of children diagnosed with brain tumours. The study was cross-sectional and recruited 37 participants from a clinical database at a specialist children's hospital. Parents were sent questionnaires, which were used to measure factors related to stress in caregivers of children diagnosed with a brain tumour. Stress levels were measured using the Parenting Stress Index-Short Form (PSI/SF). Correlation analysis and multiple linear regression were used to examine the associations between parenting stress and coping styles, locus of control, parent-perceived child disability and time since diagnosis. Results revealed that 51% of parents were experiencing clinically significant levels of stress. The mean stress level of parents in the study was significantly higher than the PSI/SF norms (t = 4.7, p coping by accepting responsibility accounted for 67% of the variance in parenting stress. Other styles of coping, child behaviour problems and the amount of time since diagnosis were not found to be predictive of levels of parenting stress. There was a high prevalence of parenting stress in caregivers of children with a brain tumour. An external locus of control and coping by accepting responsibility increased the likelihood of elevated levels of stress. Results emphasised the importance of ongoing support for parents of children with brain tumours. Intervention might helpfully be centred on strategies to increase parents' internal locus of control. Copyright © 2012 John Wiley & Sons, Ltd.

  5. Targeting DNA-PKcs and telomerase in brain tumour cells.

    Science.gov (United States)

    Gurung, Resham Lal; Lim, Hui Kheng; Venkatesan, Shriram; Lee, Phoebe Su Wen; Hande, M Prakash

    2014-10-13

    Patients suffering from brain tumours such as glioblastoma and medulloblastoma have poor prognosis with a median survival of less than a year. Identifying alternative molecular targets would enable us to develop different therapeutic strategies for better management of these tumours. Glioblastoma (MO59K and KNS60) and medulloblastoma cells (ONS76) were used in this study. Telomerase inhibitory effects of MST-312, a chemically modified-derivative of epigallocatechin gallate, in the cells were assessed using telomere repeat amplification protocol. Gene expression analysis following MST-312 treatment was done by microarray. Telomere length was measured by telomere restriction fragments analysis. Effects of MST-312 on DNA integrity were evaluated by single cell gel electrophoresis, immunofluorescence assay and cytogenetic analysis. Phosphorylation status of DNA-PKcs was measured with immunoblotting and effects on cell proliferation were monitored with cell titre glow and trypan blue exclusion following dual inhibition. MST-312 showed strong binding affinity to DNA and displayed reversible telomerase inhibitory effects in brain tumour cells. In addition to the disruption of telomere length maintenance, MST-312 treatment decreased brain tumour cell viability, induced cell cycle arrest and double strand breaks (DSBs). DNA-PKcs activation was observed in telomerase-inhibited cells presumably as a response to DNA damage. Impaired DNA-PKcs in MO59J cells or in MO59K cells treated with DNA-PKcs inhibitor, NU7026, caused a delay in the repair of DSBs. In contrast, MST-312 did not induce DSBs in telomerase negative osteosarcoma cells (U2OS). Combined inhibition of DNA-PKcs and telomerase resulted in an increase in telomere signal-free chromosomal ends in brain tumour cells as well. Interestingly, continual exposure of brain tumour cells to telomerase inhibitor led to population of cells, which displayed resistance to telomerase inhibition-mediated cell arrest. DNA-PKcs ablation

  6. Mobile phone use and risk of brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lahkola, A.

    2010-05-15

    Mobile phone use has increased rapidly worldwide since the 1990's. As mobile telephones are used close to the head, the exposure to the radiofrequency radiation emitted by mobile phones has been suggested as a possible risk factor for brain tumours. The effect of mobile phone use on risk of brain tumours, particularly gliomas and meningiomas as well as acoustic neuromas, was evaluated using both a case-control approach and a meta-analysis. In addition, one of the most important sources of error in a case-control study, selection bias due to differential participation, was assessed in a subset of the case-control data. The risk of glioma and meningioma in relation to mobile phone use was investigated in population-based case-control studies conducted in five North European countries. All these countries used a common protocol and were included in a multinational study on mobile phone use and brain tumours, the INTERPHONE study, coordinated by the International Agency for Research on Cancer (IARC). Cases (1,521 gliomas and 1,209 meningiomas) were identified mostly from hospitals and controls (3,299) from national population registers or general practitioners' patient lists. Detailed history of mobile phone use was obtained in personal interviews. Mobile phone use was assessed using several exposure indicators, such as regular use (phone use at least once a week for at least six months), duration of use as well as cumulative number of hours and calls. To comprehensively evaluate the effect of mobile phone use on risk of brain tumours, the existing evidence from the epidemiological studies published on the issue was combined using meta-analysis. In the analysis, a pooled estimate was calculated for all brain tumours combined, and also separately for the three most common tumour types, glioma, meningioma and acoustic neuroma using inverse variance-weighted method. Pooled estimate was also obtained for different telephone types (NMT and GSM) and by the location

  7. Iodine-125 brachytherapy for brain tumours - a review

    Science.gov (United States)

    2012-01-01

    Iodine-125 brachytherapy has been applied to brain tumours since 1979. Even though the physical and biological characteristics make these implants particularly attractive for minimal invasive treatment, the place for stereotactic brachytherapy is still poorly defined. An extensive review of the literature has been performed, especially concerning indications, results and complications. Iodine-125 seeds have been implanted in astrocytomas I-III, glioblastomas, metastases and several other tumour entities. Outcome data given in the literature are summarized. Complications are rare in carefully selected patients. All in all, for highly selected patients with newly diagnosed or recurrent primary or metastatic tumours, this method provides encouraging survival rates with relatively low complication rates and a good quality of life. PMID:22394548

  8. Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells

    DEFF Research Database (Denmark)

    Cheng, Chang; Edin, Nina F Jeppesen; Lauritzen, Knut H

    2012-01-01

    Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which favours tum...... tumour cell survival and metastases. Brain metastases frequently occur in patients with advanced breast cancer.Effective treatment strategies are therefore needed against brain metastasis from breast carcinoma.......Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which favours...

  9. Mobile phones, cordless phones and the risk for brain tumours.

    Science.gov (United States)

    Hardell, Lennart; Carlberg, Michael

    2009-07-01

    The Hardell-group conducted during 1997-2003 two case control studies on brain tumours including assessment of use of mobile phones and cordless phones. The questionnaire was answered by 905 (90%) cases with malignant brain tumours, 1,254 (88%) cases with benign tumours and 2,162 (89%) population-based controls. Cases were reported from the Swedish Cancer Registries. Anatomical area in the brain for the tumour was assessed and related to side of the head used for both types of wireless phones. In the current analysis we defined ipsilateral use (same side as the tumour) as >or=50% of the use and contralateral use (opposite side) as phones. Regarding astrocytoma we found highest risk for ipsilateral mobile phone use in the >10 year latency group, OR=3.3, 95% CI=2.0-5.4 and for cordless phone use OR=5.0, 95% CI=2.3-11. In total, the risk was highest for cases with first use phone OR=5.2, 95% CI=2.2-12 and for cordless phone OR=4.4, 95% CI=1.9-10. For acoustic neuroma, the highest OR was found for ipsilateral use and >10 year latency, for mobile phone OR=3.0, 95% CI=1.4-6.2 and cordless phone OR=2.3, 95% CI=0.6-8.8. Overall highest OR for mobile phone use was found in subjects with first use at age phone in that group, but based on only one exposed case. The annual age-adjusted incidence of astrocytoma for the age group >19 years increased significantly by +2.16%, 95% CI +0.25 to +4.10 during 2000-2007 in Sweden in spite of seemingly underreporting of cases to the Swedish Cancer Registry. A decreasing incidence was found for acoustic neuroma during the same period. However, the medical diagnosis and treatment of this tumour type has changed during recent years and underreporting from a single center would have a large impact for such a rare tumour.

  10. NANOTECHNOLOGY - NEW TRENDS IN THE TREATMENT OF BRAIN TUMOURS.

    Science.gov (United States)

    Krůpa, Petr; Řehák, Svatopluk; Diaz-Garcia, Daniel; Filip, Stanislav

    2014-01-01

    High grade gliomas are some of the deadliest human tumours. Conventional treatments such as surgery, radiotherapy and chemotherapy have only a limited effect. Nowadays, resection is the common treatment of choice and although new approaches, such as perioperative magnetic resonance imaging or fluorescent microscopy have been developed, the survival rate of diagnosed patients is still very low. The inefficacy of conventional methods has led to the development of new strategies and the significant progress of nanotechnology in recent years. These platforms can be used either as novel imaging tools or to improve anticancer drug delivery into tumours while minimizing its distribution and toxicity in healthy tissues. Amongst the new nanotechnology platforms used for delivery into the brain tissue are: polymeric nanoparticles, liposomes, dendrimers, nanoshells, carbon nanotubes, superparamagnetic nanoparticles and nucleic acid based nanoparticles (DNA, RNA interference [RNAi] and antisense oligonucleotides [ASO]). These nanoparticles have been applied in the delivery of small molecular weight drugs as well as macromolecules - proteins, peptides and genes. The unique properties of these nanoparticles, such as surface charge, particle size, composition and ability to modify their surface with tissue recognition ligands and antibodies, improve their biodistribution and pharmacokinetics. All of the above mentioned characteristics make of nanoplatforms a very suitable tool for its use in targeted, personalized medicine, where they could possibly carry large doses of therapeutic agents specifically into malignant cells while avoiding healthy cells. This review poses new possibilities in the large field of nanotechnology with special interest in the treatment of high grade brain tumours.

  11. Functional MRI and intraoperative brain mapping to evaluate brain plasticity in patients with brain tumours and hemiparesis

    OpenAIRE

    Roux, F.; Boulanouar, K; Ibarrola, D; Tremoulet, M.; Chollet, F; BERRY, I.

    2000-01-01

    OBJECTIVE—To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours.
METHODS—Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation—that is, movements of the paretic hand activated predominately ...

  12. 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

  13. Narrative skills of children treated for brain tumours: The impact of tumour and treatment related variables on microstructure and macrostructure.

    Science.gov (United States)

    Docking, Kimberley; Munro, Natalie; Marshall, Tara; Togher, Leanne

    2016-01-01

    The narrative skills of children with brain tumours were examined. Influence of tumour location, radiotherapy, time post-treatment and presence of hydrocephalus was also investigated, as well as associations between narrative and language abilities. Seventeen children (aged 5;6-14;11) treated for brain tumour and their matched controls completed a narrative assessment and comprehensive language testing. Audio recorded narratives were analysed for microstructure and macrostructure elements. Between-group comparisons were conducted. Narrative elements were explored in association with tumour and treatment-related variables. Correlation analysis examined relationships between narrative scores and language test performance. While significant differences were not found between two groups of children across narrative elements, sub-group comparisons revealed marginal differences in macrostructure related to tumour location and hydrocephalus. Children treated with methods other than radiotherapy showed a significant increase in number of mazes in their narratives compared to children who received radiotherapy. Strong positive correlations also existed between narrative elements and language performance. Preliminary findings highlight the importance of investigating narrative abilities as part of a comprehensive language assessment. Macrostructure should be routinely examined where children are diagnosed with either posterior fossa tumour or hydrocephalus or have undergone surgery and/or chemotherapy for brain tumour.

  14. Characterisation of tumour vasculature in mouse brain by USPIO contrast-enhanced MRI.

    NARCIS (Netherlands)

    Gambarota, G.; Leenders, W.P.J.; Maass, C.; Wesseling, P.; Kogel, A.J. van der; Tellingen, O van; Heerschap, A.

    2008-01-01

    To enhance the success rate of antiangiogenic therapies in the clinic, it is crucial to identify parameters for tumour angiogenesis that can predict response to these therapies. In brain tumours, one such parameter is vascular leakage, which is a response to tumour-derived vascular endothelial

  15. Metastatic brain tumour in pregnancy: A case report

    Directory of Open Access Journals (Sweden)

    Pantović Sveto

    2012-01-01

    Full Text Available Introduction. Malignant tumours of the central nervous system in pregnancy are rare and are most frequently diagnosed in the second part of pregnancy Of all malignant tumours which may occur in pregnancy, intracranial tumours bear the highest risk of maternal and foetal morbidity and mortality. Case Outline. A 29-year-old primipara was admitted to our hospital as an emergency in the twenty-ninth week of pregnancy due to headache, right eye sight disorders (double vision, nausea and vomiting. The patient had a total thyroidectomy and a dissection of lymph glands of the neck at the age of seven years due to papillary carcinoma of the thyroid glands. The clinical and sonographic test revealed regular foetal growth and morphology. The MRI showed expansive changes in the brain parenchyma corresponding to metastatic lesion with the subtentorial herniation of the uncus of the hippocampus by compressive effect onto the right cerebral peduncle of the mesencephalon. Emergent neurosurgical intervention was indicated. Having in mind the age at pregnancy, it was decided to perform a caesarean operation. Alive female child was born weighing 1,370 grams. The post-operative procedure was normal. The patient was transferred to the neurosurgery department on the first post-operative day, where she underwent emergent surgery. Immunohistochemistry confirmed the metastatic tumour originating from the primary papillary adenocarcinoma of the thyroid gland. Conclusion. Neurosurgical diseases in pregnancy simultaneously jeopardize two lives and represent both medical and ethical problem. Upon confirming the presence of intracranial malignancy in pregnancy, further procedure is very individual and it implies cooperation of gynaecologists, neurologists, neurosurgeons, oncologists, anaesthesiologists and neonatologists.

  16. Thallium uptake and biological behaviour in childhood brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, E.J.; Howman-Giles, R.; Kellie, S.; Uren, R.F. [Royal Alexandra Hospital for Children, Sydney, NSW (Australia)

    1998-03-01

    Full text: The histopathological grade and radiological appearance of the diverse cerebral neoplasms in childhood frequently poorly reflect their biological behaviour. We examined thallium accumulation prior to treatment (and in several cases, at intervals there after) in 13 children to determine its usefulness as a tumour marker. 23 SPECT studies were acquired 20 minutes after the injection of 1-3 mCi of {sup 201}TI. Thallium index (TI), the ratio of counts in tumour/normal brain, was calculated. No uptake was seen in two patients (pts) with a Grade 1 cerebellar astrocytomas (disease free at 4/12 f/u). Three pts with medulloblastomas were studied. One pt showed intense uptake (Tl =12). His tumour (proliferative antigen stain Ki67 = 50%) recurred early after debulking surgery (Tl +ve prior to CT or MRI changes). The second pt was imaged at relapse (Ki67 = 60%) and showed intense uptake, Tl = 17. The third pt showed lower level uptake (Tl = 2), Ki67 = 5%, and is disease-free at 5/12 (as per {sup 201}TI and MRI). One pt with a Grade 1 brainstem glioma showed Tl = 5 and has progressed rapidly despite low grade histology. Four pts with chiasmatic-hypothalamic gliomas have been studied. Although these neoplasms are usually low grade histologically, their growth properties vary greatly. Two pts with Tl<2.5 have been conservatively managed because of slow tumour growth. The other two pts have Tl>3.5 and have required aggressive treatment for rapid disease progression. One pt with a large pilocytic astrocytoma of the optic chiasm showed Tl = 9.5. Active treatment was not undertaken. One pt with a pineal germ cell tumour showed avid {sup 201}TI uptake (Tl not performed) and has had two normal studies, and is clinically well, since BMT. Avid {sup 201}TI uptake also seen in one pt with cerebral neuroblastoma. (Died at 8/12 after Dx.) Thus, {sup 201}TI accumulates in histologically diverse paediatric neoplasms. The Tl appears to reflect biological behaviour in the limited

  17. Long-term exposure to ambient air pollution and incidence of brain tumours

    DEFF Research Database (Denmark)

    Jørgensen, Jeanette Therming; Johansen, Martin Søes; Ravnskjær, Line

    2016-01-01

    is sparse, with no data on exposure to particles. In this study we aim to examine associations between long-term exposure to ambient air pollution and risk for development of brain tumours. METHODS: We used the Danish Nurse Cohort with 28,731 female nurses (age≥44years) recruited in 1993 or 1999 when self...... dioxide (NO2) at the residence since 1990 using an atmospheric integrated chemistry-transport models system, and examined the association between the 3-year running mean of pollutants and brain tumour incidence using time-varying Cox regression, separately for total brain tumours, and for tumour subtypes...

  18. Volumetric brain tumour detection from MRI using visual saliency.

    Science.gov (United States)

    Mitra, Somosmita; Banerjee, Subhashis; Hayashi, Yoichi

    2017-01-01

    Medical image processing has become a major player in the world of automatic tumour region detection and is tantamount to the incipient stages of computer aided design. Saliency detection is a crucial application of medical image processing, and serves in its potential aid to medical practitioners by making the affected area stand out in the foreground from the rest of the background image. The algorithm developed here is a new approach to the detection of saliency in a three dimensional multi channel MR image sequence for the glioblastoma multiforme (a form of malignant brain tumour). First we enhance the three channels, FLAIR (Fluid Attenuated Inversion Recovery), T2 and T1C (contrast enhanced with gadolinium) to generate a pseudo coloured RGB image. This is then converted to the CIE L*a*b* color space. Processing on cubes of sizes k = 4, 8, 16, the L*a*b* 3D image is then compressed into volumetric units; each representing the neighbourhood information of the surrounding 64 voxels for k = 4, 512 voxels for k = 8 and 4096 voxels for k = 16, respectively. The spatial distance of these voxels are then compared along the three major axes to generate the novel 3D saliency map of a 3D image, which unambiguously highlights the tumour region. The algorithm operates along the three major axes to maximise the computation efficiency while minimising loss of valuable 3D information. Thus the 3D multichannel MR image saliency detection algorithm is useful in generating a uniform and logistically correct 3D saliency map with pragmatic applicability in Computer Aided Detection (CADe). Assignment of uniform importance to all three axes proves to be an important factor in volumetric processing, which helps in noise reduction and reduces the possibility of compromising essential information. The effectiveness of the algorithm was evaluated over the BRATS MICCAI 2015 dataset having 274 glioma cases, consisting both of high grade and low grade GBM. The results were compared with

  19. Neuro-ophthalmic and clinical characteristics of brain tumours in a ...

    African Journals Online (AJOL)

    Background: Anecdotally, increasing number of patients are seen at Korle Bu Teaching Hospital (KBTH) with brain tumour. Neuro-ophthalmic symptoms and signs may help in timely diagnosis and intervention. Objective: To evaluate the neuro-ophthalmic and clinical characteristics of brain tumour in patients presenting at a ...

  20. Value of C-11-methionine PET in imaging brain tumours and metastases

    NARCIS (Netherlands)

    Glaudemans, Andor W J M; Enting, Roeline; Heesters, Martinus; Dierckx, Rudi A J O; van Rheenen, Ronald W J; Walenkamp, Annemiek M E; Slart, Riemer H J A

    C-11-methionine (MET) is the most popular amino acid tracer used in PET imaging of brain tumours. Because of its characteristics, MET PET provides a high detection rate of brain tumours and good lesion delineation. This review focuses on the role of MET PET in imaging cerebral gliomas. The

  1. A PROSPECTIVE HISTOPATHOLOGICAL-BASED STUDY OF BRAIN TUMOURS IN A REFERRAL CENTRE

    Directory of Open Access Journals (Sweden)

    Prathima Gujjaru

    2016-07-01

    Full Text Available BACKGROUND Brain neoplasms occur at all ages and account for around 2-3 percent of all deaths in adults. In children, the frequency increases to more than twenty percent. In children, it forms the second most common type of malignancy. Most of the tumours encountered are not related to any identifiable risk factors except for irradiation and some hereditary syndromes like subependymal giant cell astrocytoma, glioblastoma multiforme, cerebellar haemangioblastoma, meningioma, Schwannoma of 7 th cranial nerve. Gliomas constitute fifty percent of the brain tumours and sixty percent of all gliomas are glioblastoma multiforme. Meningiomas constitute twenty percent and cerebral metastasis is seen in fifteen percent of the cases. Seventy percent of supratentorial tumours are found in adults and seventy percent of brain tumours in children are infratentorial. The three common tumours of cerebellum are medulloblastoma, haemangioblastoma and juvenile pilocytic astrocytoma. Brain tumours are space occupying lesions and cause compression and destruction of adjacent structures, brain oedema (Peritumoural tissue, infarction and ischaemia of brain by compressing/infiltrating cerebral blood vessels, obstruction of CSF flow causing hydrocephalus, and rise in intracranial pressure with herniations. Tumours can undergo ischaemic necrosis and necrotic tumours tend to bleed. Brain tumours generally do not metastasise. Schwannoma and meningioma are benign tumours. Medulloblastoma of childhood may have drop metastasis via CSF. A sincere effort has been put in this study to identify the incidence of each variety of brain tumour among the fifty confirmed and identified cases of brain tumours. METHODS The age range of the cases in present study was 5-72 years with a mean age of occurrence of 44.11 years and the peak age group affected were in the 3 rd and 4 th decades. Cerebral hemisphere was the commonest site for intracranial tumours. RESULT In the present study, fifty

  2. Microbleeds and cavernomas after radiotherapy for paediatric primary brain tumours.

    Science.gov (United States)

    Passos, João; Nzwalo, Hipólito; Valente, Mariana; Marques, Joana; Azevedo, Ana; Netto, Eduardo; Mota, António; Borges, Alexandra; Nunes, Sofia; Salgado, Duarte

    2017-01-15

    With the expected growth and aging of the population of primary central nervous system tumours (PCNST) survivors, attention to the radiation-induced late brain injury is fundamental. Late focal hemosiderin deposition (FHD) lesions, namely microbleeds and cavernomas, are among the presumable late cerebrovascular complications associated with radiotherapy for PCNST. To explore association between PCNST radiotherapy and the occurrence FHD lesions and to address the correlation between the topographic location of these microvascular lesions with the focal radiotherapy location. Retrospective cohort study of 190 paediatric patients being followed for PCNST in a single referral oncological centre. The frequency of FHD lesions was compared between paediatric PCNST treated (n=132) and not treated (n=58) with brain radiation. Microbleed Anatomical Rating Scale (MARS) was used for systematic identification of these cerebrovascular lesions and to address the consistency between the topographic location of each lesion and the location of the focal radiotherapy area. Univariate analysis to address the role of variables such as tumour histology, location, gender and age of children at the beginning of radiotherapy, duration of follow-up and chemotherapy was performed. FHD lesions (microbleeds and cavernomas) occurred exclusively and in a high percentage (41.6%) in PCNST survivors treated with brain radiation. Younger age at the diagnosis (p=0.031), duration of follow-up (p=0.010) and embryonal histology (p=0.003) positively correlated with the occurrence FHD lesions. FHD lesions were topographically concordant with the brain focal irradiation area in 3/19 (15.8%) patients from the focal RT subgroup and in 22/111 (19.8%) patients from the WBRT plus focal RT subgroup. Our study, which is one of the largest to date on the topic, shows that FHD lesions are a common complication after radiotherapy for childhood PCNST. The young brain is probably more susceptible to radiation

  3. Perioperative intensive care in patients with brain tumours

    Directory of Open Access Journals (Sweden)

    Mariana A. Aquafredda

    2011-04-01

    Full Text Available The surgery of brain tumours is not free from complications, above all taking into account that today the patients operated are even older and with multiple comorbidities associated. The multidisciplinary preoperative evaluation aims at minimising the risks; nevertheless this evaluation has not yet been defined and is not based on a strong evidence. The detailed clinical history, the physical examination including functional status and the neuroimaging are the fundamental pillars.The more critical complications occur in the immediate postoperative period: cerebral oedema, postoperative haemorrhage, intracranial hypertension and convulsions; other complications, such as pulmonary thromboembolism or infections, develop lately but are not less severe. Every surgical approach has its own complications in addition to the ones common to the whole neurosurgery.

  4. A COMPARISON OF THREE DIFFERENT DOSES OF MANNITOL ON BRAIN RELAXATION DURING SUPRATENTORIAL BRAIN TUMOUR CRANIOTOMY

    Directory of Open Access Journals (Sweden)

    Bala Krishna Duba

    2017-06-01

    Full Text Available BACKGROUND A comparison of three different doses of mannitol on brain relaxation during supratentorial brain tumour craniotomy. Supratentorial tumours produce significant mass effects in the brain and certain types are accompanied by significant peritumoral oedema that leads to increased intracranial pressure. Higher osmotic pressure in the blood vessels after the infusion of mannitol drives water molecules from the brain tissue to blood vessels and results in brain tissue dehydration. The point of my study is to determine a dose that leads to a beneficial effect without triggering negative effects. MATERIALS AND METHODS This is a prospective, randomised single-blinded study conducted in Konaseema Institute of Medical Sciences, Amalapuram, from March 2015 to March 2017. After getting ethical committee approval and informed consent, 48 patients of both sexes (male and female who underwent elective craniotomy for supratentorial tumour surgeries under general anaesthesia at were taken up for study. 48 patients were divided into three groups as group-A, group-B and group-C with 16 in each group. RESULTS There is significant change in brain relaxation score with increasing dose of mannitol. MAP and pH are significant with increasing dose of mannitol, serum sodium and potassium levels are also significant. Anion gap and urine output also showed significant change. Age, sex and BMI are not statistically significant. CONCLUSION From this study, it is concluded that 1.5 mg/kg of 20% mannitol gives better brain relaxation scores than 0.5 mg/kg of 20% mannitol and 1.0 mg/kg of 20% mannitol.

  5. Combined radiotherapy and chemotherapy for high-grade brain tumours

    Science.gov (United States)

    Barazzuol, Lara

    Glioblastoma (GBM) is the most common primary brain tumour in adults and among the most aggressive of all tumours. For several decades, the standard care of GBM was surgical resection followed by radiotherapy alone. In 2005, a landmark phase III clinical trial coordinated by the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) demonstrated the benefit of radiotherapy with concomitant and adjuvant temozolomide (TMZ) chemotherapy. With TMZ, the median life expectancy in optimally managed patients is still only 12-14 months, with only 25% surviving 24 months. There is an urgent need for new therapies in particular in those patients whose tumour has an unmethylated methylguanine methyltransferase gene (MGMT) promoter, which is a predictive factor of benefit from TMZ. In this dissertation, the nature of the interaction between TMZ and radiation is investigated using both a mathematical model, based on in vivo population statistics of survival, and in vitro experimentation on a panel of human GBM cell lines. The results show that TMZ has an additive effect in vitro and that the population-based model may be insufficient in predicting TMZ response. The combination of TMZ with particle therapy is also investigated. Very little preclinical data exists on the effects of charged particles on GBM cell lines as well as on the concomitant application of chemotherapy. In this study, human GBM cells are exposed to 3 MeV protons and 6 MeV alpha particles in concomitance with TMZ. The results suggest that the radiation quality does not affect the nature of the interaction between TMZ and radiation, showing reproducible additive cytotoxicity. Since TMZ and radiation cause DNA damage in cancer cells, there has been increased attention to the use of poly(ADP-ribose) polymerase (PARP) inhibitors. PARP is a family of enzymes that play a key role in the repair of DNA breaks. In this study, a novel PARP inhibitor, ABT-888

  6. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells.

    Science.gov (United States)

    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi; Shah, Khalid

    2015-06-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications. © The Author (2015). Published by Oxford University Press on

  7. Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm.

    Science.gov (United States)

    Rahman, Ruman; Heath, Rachel; Grundy, Richard

    2009-04-01

    Brain tumours are a diverse group of neoplasms that continue to present a formidable challenge in our attempt to achieve curable intervention. Our conceptual framework of human brain cancer has been redrawn in the current decade. There is a gathering acceptance that brain tumour formation is a phenotypic outcome of dysregulated neurogenesis, with tumours viewed as abnormally differentiated neural tissue. In relation, there is accumulating evidence that brain tumours, similar to leukaemia and many solid tumours, are organized as a developmental hierarchy which is maintained by a small fraction of cells endowed with many shared properties of tissue stem cells. Proof that neurogenesis persists throughout adult life, compliments this concept. Although the cancer cell of origin is unclear, the proliferative zones that harbour stem cells in the embryonic, post-natal and adult brain are attractive candidates within which tumour-initiation may ensue. Dysregulated, unlimited proliferation and an ability to bypass senescence are acquired capabilities of cancerous cells. These abilities in part require the establishment of a telomere maintenance mechanism for counteracting the shortening of chromosomal termini. A strategy based upon the synthesis of telomeric repeat sequences by the ribonucleoprotein telomerase, is prevalent in approximately 90% of human tumours studied, including the majority of brain tumours. This review will provide a developmental perspective with respect to normal (neurogenesis) and aberrant (tumourigenesis) cellular turnover, differentiation and function. Within this context our current knowledge of brain tumour telomere/telomerase biology will be discussed with respect to both its developmental and therapeutic relevance to the hierarchical model of brain tumourigenesis presented by the cancer stem cell paradigm.

  8. Damage to tumour and brain by interstitial photodynamic therapy in the 9L rat tumour model comparing intravenous and intratumoral administration of the photosensitiser

    NARCIS (Netherlands)

    Hebeda, K. M.; Kamphorst, W.; Sterenborg, H. J.; Wolbers, J. G.

    1998-01-01

    In the 9L rat brain tumour model the damage to tumour and normal brain by photodynamic therapy after intratumoural photosensitizer administration (intratumoural PDT) was studied. Twenty four rats received an intratumoural injection of 4 or 40 mm3 haematoporphyrin derivative (HpD, 5 mg ml-1),

  9. Medical exposure to ionising radiation and the risk of brain tumours

    DEFF Research Database (Denmark)

    Blettner, Maria; Schlehofer, Brigitte; Samkange-Zeeb, Florence

    2007-01-01

    BACKGROUND: The role of exposure to low doses of ionising radiation in the aetiology of brain tumours has yet to be clarified. The objective of this study was to investigate the association between medically or occupationally related exposure to ionising radiation and brain tumours. METHODS: We...... used self-reported medical and occupational data collected during the German part of a multinational case-control study on mobile phone use and the risk of brain tumours (Interphone study) for the analyses. RESULTS: For any exposure to medical ionising radiation we found odds ratios (ORs) of 0.63 (95...... regions. CONCLUSION: We did not find any significant increased risk of brain tumours for exposure to medical ionising radiation....

  10. Non-negative matrix factorisation methods for the spectral decomposition of MRS data from human brain tumours

    Directory of Open Access Journals (Sweden)

    Ortega-Martorell Sandra

    2012-03-01

    Full Text Available Abstract Background In-vivo single voxel proton magnetic resonance spectroscopy (SV 1H-MRS, coupled with supervised pattern recognition (PR methods, has been widely used in clinical studies of discrimination of brain tumour types and follow-up of patients bearing abnormal brain masses. SV 1H-MRS provides useful biochemical information about the metabolic state of tumours and can be performed at short ( 45 ms echo time (TE, each with particular advantages. Short-TE spectra are more adequate for detecting lipids, while the long-TE provides a much flatter signal baseline in between peaks but also negative signals for metabolites such as lactate. Both, lipids and lactate, are respectively indicative of specific metabolic processes taking place. Ideally, the information provided by both TE should be of use for clinical purposes. In this study, we characterise the performance of a range of Non-negative Matrix Factorisation (NMF methods in two respects: first, to derive sources correlated with the mean spectra of known tissue types (tumours and normal tissue; second, taking the best performing NMF method for source separation, we compare its accuracy for class assignment when using the mixing matrix directly as a basis for classification, as against using the method for dimensionality reduction (DR. For this, we used SV 1H-MRS data with positive and negative peaks, from a widely tested SV 1H-MRS human brain tumour database. Results The results reported in this paper reveal the advantage of using a recently described variant of NMF, namely Convex-NMF, as an unsupervised method of source extraction from SV1H-MRS. Most of the sources extracted in our experiments closely correspond to the mean spectra of some of the analysed tumour types. This similarity allows accurate diagnostic predictions to be made both in fully unsupervised mode and using Convex-NMF as a DR step previous to standard supervised classification. The obtained results are comparable to

  11. Automated EEG signal analysis for identification of epilepsy seizures and brain tumour.

    Science.gov (United States)

    Sharanreddy, M; Kulkarni, P K

    2013-11-01

    Abstract Electroencephalography (EEG) is a clinical test which records neuro-electrical activities generated by brain structures. EEG test results used to monitor brain diseases such as epilepsy seizure, brain tumours, toxic encephalopathies infections and cerebrovascular disorders. Due to the extreme variation in the EEG morphologies, manual analysis of the EEG signal is laborious, time consuming and requires skilled interpreters, who by the nature of the task are prone to subjective judegment and error. Further, manual analysis of the EEG results often fails to detect and uncover subtle features. This paper proposes an automated EEG analysis method by combining digital signal processing and neural network techniques, which will remove error and subjectivity associated with manual analysis and identifies the existence of epilepsy seizure and brain tumour diseases. The system uses multi-wavelet transform for feature extraction in which an input EEG signal is decomposed in a sub-signal. Irregularities and unpredictable fluctuations present in the decomposed signal are measured using approximate entropy. A feed-forward neural network is used to classify the EEG signal as a normal, epilepsy or brain tumour signal. The proposed technique is implemented and tested on data of 500 EEG signals for each disease. Results are promising, with classification accuracy of 98% for normal, 93% for epilepsy and 87% for brain tumour. Along with classification, the paper also highlights the EEG abnormalities associated with brain tumour and epilepsy seizure.

  12. Analysis of fluid in cysts accompanying various primary and metastatic brain tumours : Proteins, lactate and pH

    NARCIS (Netherlands)

    Lohle, PNM; Wurzer, HAL; Seelen, PJ; Kingma, LM; Go, KG

    1998-01-01

    There is a growing interest in cystic lesions of the brain. By examining the cyst content of brain tumours more insight into the pathogenesis of cyst formation has been found. In this study, 39 samples of cyst fluid of 34 patients with a cyst accompanying a brain tumour were collected and studied

  13. Brain metabolite values in children with breath-holding spells

    Directory of Open Access Journals (Sweden)

    Calik M

    2017-06-01

    Full Text Available Mustafa Calik,1 Dilek Sen Dokumaci,2 Suna Sarikaya,3 Mahmut Demir,4 Ilhan Isik,5 Halil Kazanasmaz,4 Cemil Kaya,4 Hasan Kandemir6 1Department of Pediatric Neurology, 2Department of Radiology, 3Department of Neurology, 4Department of Pediatrics, Harran University School of Medicine, 5Department of Pediatric Neurology, Eyyubiye Training and Research Hospital, 6Department of Child and Adolescent Psychiatry, Harran University School of Medicine, Sanliurfa, Turkey Abstract: Breath-holding spells are benign, paroxysmal events with apnea and postural tone changes after a crying episode in infants. The objective of this study was to investigate the pathologies in brain metabolite values in the absence of seizure in children with breath-holding spells by using magnetic resonance spectroscopy (MRS. Brain MRS examination was performed on 18 children with breath-holding spells and 13 neurologically normal children who were included as the control group. There was no significant difference in terms of N-acetyl aspartate (NAA, choline (Cho, creatine (Cr, and myoinositol (mI levels and also in terms of NAA/Cr, Cho/Cr, and mI/Cr ratios between the patients and the control group (all P>0.05. Our study suggested that there is no permanent neuronal damage in patients with breath-holding spells. This result confirms the previous studies, which reported no permanent neuronal damage in patients with breath-holding spells. Keywords: brain metabolite, children, breath holding, magnetic resonance spectroscopy 

  14. Pre-operative embolisation of internal carotid artery branches and pial vessels in hypervascular brain tumours.

    Science.gov (United States)

    Yoon, Y S; Ahn, J Y; Chang, J H; Cho, J H; Suh, S H; Lee, B H; Lee, K S

    2008-05-01

    Pre-operative embolisation is an effective method used to reduce intra-operative bleeding and operative difficulty in hypervascular brain tumour surgery. However, embolisation of the internal carotid artery (ICA) and pial tumour feeding branches has certain limitations. From March 2000 to November 2006, 8 patients underwent superselective embolisation for hypervascular brain tumour. Seven tumours were extra-axial (6 meningiomas, 1 solitary fibrous tumour) and 1 was intra-axial (metastatic hepatocellular carcinoma). In all patients, feeding vessels from ICA branches or pial arteries were successfully embolised using superselective microcatheterisation. A provocative test was applied in 4 patients who had tumours adjacent to the motor cortex. Angiographic devascularisation was slight to extensive. Mean devascularisation on post-embolisation MRI ranged from 40 to 80% (mean 63.8%). One patient (12.5%) suffered an embolisation-related complication (loss of choroidal brush), but was not clinically worse because of the pre-existing blindness. Superselective embolisation of ICA branches or pial vessels should be performed if several conditions are met, especially angiographic findings, pre-existing neurologic deficits, provocative test, and technical feasibility. If the ICA embolisation for hypervascular tumour is successfully achieved, the bleeding loss and operative risk can be reduced.

  15. Brain tumour presenting with burns: Case report and discussion.

    Science.gov (United States)

    Sawyer, Oliver; O'Boyle, Ciaran P

    2017-05-01

    Descriptions of burns as the presenting features of underlying neurological pathology are very rare, with only two previously published case reports available. Both of these reports featured meningioma as the pre-existing pathology and both described burn excision and wound healing, prior to surgical tumour ablation. The authors describe the case of a 35-year-old female, who presented with 25% total body surface area burns and recent global neurological deterioration. MRI imaging revealed a large intracranial tumour. Multidisciplinary management included rigorous non-surgical burn wound care and early craniotomy and tumour excision. This proceeded without complication. Burn excision and skin grafting was carried out successfully, two weeks later. This case differs from the previous two reported cases, which both described burn excision, as a pre-requisite to neurosurgery. This case establishes that the presence of a burn wound is not a total contra-indication to intracranial surgery. Copyright © 2016. Published by Elsevier Ltd.

  16. Active video gaming improves body coordination in survivors of childhood brain tumours

    DEFF Research Database (Denmark)

    Sabel, M.; Sjölund, A.; Broeren, J.

    2016-01-01

    Purpose: We investigated whether active video gaming (AVG) could bring about regular, enjoyable, physical exercise in children treated for brain tumours, what level of physical activity could be reached and if the children’s physical functioning improved. Methods: Thirteen children, aged 7–17 years...... survivors, home-based AVG, supported by a coach, was a feasible, enjoyable and moderately intense form of exercise that improved Body Coordination.Implications for Rehabilitation Childhood brain tumour survivors frequently have cognitive problems, inferior physical functioning and are less physically active...... compared to their healthy peers. Active video gaming (AVG), supported by Internet coaching, is a feasible home-based intervention in children treated for brain tumours, promoting enjoyable, regular physical exercise of moderate intensity. In this pilot study, AVG with Nintendo Wii improved Body...

  17. Multiscale biomechanics of brain tumours favours cancer invasion by cell softening and tissue stiffening

    Science.gov (United States)

    Kas, Josef; Fritsch, Anatol; Grosser, Steffen; Friebe, Sabrina; Reiss-Zimmermann, Martin; Müller, Wolf; Hoffmann, Karl-Titus; Sack, Ingolf

    Cancer progression needs two contradictory mechanical prerequisites. For metastasis individual cancer cells or small clusters have to flow through the microenvironment by overcoming the yield stress exerted by the surrounding. On the other hand a tumour has to behave as a solid to permit cell proliferation and spreading of the tumour mass against its surrounding. We determine that the high mechanical adaptability of cancer cells and the scale controlled viscoelastic properties of tissues reconcile both conflicting properties, fluid and solid, simultaneously in brain tumours. We resolve why different techniques that assess cell and tissue mechanics have produced apparently conflicting results by our finding that tumours generate different viscoelastic behaviours on different length scales, which are in concert optimal for tumour spreading and metastasis. Single cancer cells become very soft in their elastic behavior which promotes cell unjamming. On the level of direct cell-to-cell interactions cells feel their micro-environment as rigid elastic substrate that stimulates cancer on the molecular level. All over a tumour has predominately a stiff elastic character in terms of viscoelastic behaviour caused by a solid backbone. Simultaneously, the tumour mass is characterized by a large local variability in the storage and loss modulus that is caused by areas of a more fluid nature.

  18. I-123-lodo-alpha-methyl tyrosine SPECT in non-parenchymal brain tumours.

    Science.gov (United States)

    Matheja, P; Weckesser, M; Rickert, Ch; Franzius, Ch; Palkovic, St; Riemann, B; Schober, O

    2002-01-01

    Scintigraphy using I-123-iodo-alpha-methyl tyrosine (IMT) is useful in the preoperative characterization of gliomas, in detecting recurrent glioma and in the biological re-evaluation of residual or recurrent tumours. A systematic evaluation of non-parenchymal brain tumours has not yet been performed. The aim of the present study was to evaluate IMT SPECT in the management of intracerebral metastases and lymphomas. IMT uptake was analyzed in 31 patients with 28 metastases of extracerebral solid tumours and 7 cerebral lymphomas. Histology revealed high grade lymphomas, melanomas, and carcinomas of the following origin: lung, unknown primary, breast, colon, renal cell, ovary, vagina, frontal sinus. IMT uptake was quantified as ratio between maximal tumour accumulation and average uptake in the contralateral hemisphere. All tumours except two renal cell and one small cell lung carcinoma metastases accumulated IMT (91%). The highest IMT uptake was found in a metastasis of lung carcinoma. IMT uptake was highly variable and was similar in primary and in recurrent tumours. Significant accumulation of IMT is seen in the majority of tumours, so that this technique might be helpful for the management of cerebral metastases and lymphomas.

  19. In vivo magnetic resonance imaging and 31P spectroscopy of large human brain tumours at 1.5 tesla

    DEFF Research Database (Denmark)

    Thomsen, C; Jensen, K E; Achten, E

    1988-01-01

    31P MR spectroscopy of human brain tumours is one feature of magnetic resonance imaging. Eight patients with large superficial brain tumours and eight healthy volunteers were examined with 31P spectroscopy using an 8 cm surface coil for volume selection. Seven frequencies were resolved in our spe...

  20. Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade.

    Directory of Open Access Journals (Sweden)

    Sylwia Libard

    Full Text Available Human cytomegalovirus (HCMV has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.

  1. Study of bantam miRNA expression in brain tumour resulted due to ...

    Indian Academy of Sciences (India)

    2017-06-19

    Jun 19, 2017 ... Disturbance of delicate concordance between stem cell proliferation, specification and differentiation during brain development leads to several neural disorders including tumours. Accumulating evidences have demonstratedinvolvement of short noncoding microRNAs (miRNAs) in governing several ...

  2. Magnetic fields and brain tumour risks in UK electricity supply workers.

    Science.gov (United States)

    Sorahan, T

    2014-04-01

    To investigate whether brain tumour risks are related to occupational exposure to low-frequency magnetic fields. Brain tumour risks experienced by 73 051 employees of the former Central Electricity Generating Board of England and Wales were investigated for the period 1973-2010. All employees were hired in the period 1952-82 and were employed for at least 6 months with some employment in the period 1973-82. Detailed calculations had been performed by others to enable an assessment to be made of exposures to magnetic fields. Poisson regression was used to calculate relative risks (rate ratios) of developing a brain tumour (or glioma or meningioma) for categories of lifetime, distant (lagged) and recent (lugged) exposure. Findings for glioma and for the generality of all brain tumours were unexceptional; risks were close to (or below) unity for all exposure categories and there was no suggestion of risks increasing with cumulative (or recent or distant) magnetic field exposures. There were no statistically significant dose-response effects shown for meningioma, but there was some evidence of elevated risks in the three highest exposure categories for exposures received >10 years ago. This study found no evidence to support the hypothesis that exposure to magnetic fields is a risk factor for gliomas, and the findings are consistent with the hypotheses that both distant and recent magnetic field exposures are not causally related to gliomas. The limited positive findings for meningioma may be chance findings; national comparisons argue against a causal interpretation.

  3. The risk of brain tumours in hereditary non-polyposis colorectal cancer (HNPCC)

    NARCIS (Netherlands)

    Vasen, HFA; Sanders, EACM; Taal, BG; Nagengast, FM; Griffioen, G; Menko, FH; Kleibeuker, JH; HouwingDuistermaat, JJ; Khan, PM

    1996-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is known to be associated with several extracolonic cancers, e.g., cancers of the endometrium, stomach, urinary tract, small bowel and ovary. An association between HNPCC and brain tumours has also been reported, although previous risk analysis did

  4. (18)F-fluoro-L-thymidine-PET for the evaluation of primary brain tumours in children: a report of three cases.

    NARCIS (Netherlands)

    Gilles, R.; Vogel, W.V.; Gidding, C.E.M.; Janssens, G.O.; Vliet, A.M. van der; Oyen, W.J.G.

    2010-01-01

    BACKGROUND: F-fluoro-L-thymidine (FLT) has been shown to be a useful PET tracer in the evaluation of brain tumours in adults. No studies of this modality in children with brain tumours, however, have been published. OBJECTIVE: In this report three children with brain tumours are presented in which

  5. F-18-fluoro-L-thymidine-PET for the evaluation of primary brain tumours in children: a report of three cases

    NARCIS (Netherlands)

    Gilles, R.; Vogel, W.V.; Gidding, C.E.M.; Janssens, G.O.R.J.; van der Vliet, T.M.; Oyen, W.J.G.

    2010-01-01

    Background F-18-fluoro-L-thymidine (FLT) has been shown to be a useful PET tracer in the evaluation of brain tumours in adults. No studies of this modality in children with brain tumours, however, have been published. Objective In this report three children with brain tumours are presented in which

  6. Brain metabolite values in children with breath-holding spells.

    Science.gov (United States)

    Calik, Mustafa; Sen Dokumaci, Dilek; Sarikaya, Suna; Demir, Mahmut; Isik, Ilhan; Kazanasmaz, Halil; Kaya, Cemil; Kandemir, Hasan

    2017-01-01

    Breath-holding spells are benign, paroxysmal events with apnea and postural tone changes after a crying episode in infants. The objective of this study was to investigate the pathologies in brain metabolite values in the absence of seizure in children with breath-holding spells by using magnetic resonance spectroscopy (MRS). Brain MRS examination was performed on 18 children with breath-holding spells and 13 neurologically normal children who were included as the control group. There was no significant difference in terms of N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), and myoinositol (mI) levels and also in terms of NAA/Cr, Cho/Cr, and mI/Cr ratios between the patients and the control group (all P>0.05). Our study suggested that there is no permanent neuronal damage in patients with breath-holding spells. This result confirms the previous studies, which reported no permanent neuronal damage in patients with breath-holding spells.

  7. {sup 1}H MR spectroscopy of human brain tumours: a practical approach

    Energy Technology Data Exchange (ETDEWEB)

    Callot, Virginie [Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR 6612, CNRS - Universite de la Mediterranee, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05 (France)], E-mail: virginie.callot@univmed.fr; Galanaud, Damien [Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR 6612, CNRS - Universite de la Mediterranee, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05 (France); Departement de Neuroradiologie, Hopital La Pitie-Salpetriere, Paris (France); Le Fur, Yann; Confort-Gouny, Sylviane; Ranjeva, Jean-Philippe; Cozzone, Patrick J. [Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR 6612, CNRS - Universite de la Mediterranee, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05 (France)

    2008-08-15

    Magnetic resonance spectroscopy (MRS) is proposed in addition to magnetic resonance imaging (MRI) to help in the characterization of brain tumours by detecting metabolic alterations that may be indicative of the tumour class. MRS can be routinely performed on clinical magnets, within a reasonable acquisition time and if performed under adequate conditions, MRS is reproducible and thus can be used for longitudinal follow-up of treatment. MRS can also be performed in clinical practice to guide the neurosurgeon into the most aggressive part of the lesions or to avoid unnecessary surgery, which may furthermore decrease the risk of surgical morbidity.

  8. Early medical rehabilitation after neurosurgical treatment of malignant brain tumours in Slovenia

    Directory of Open Access Journals (Sweden)

    Kos Natasa

    2016-06-01

    Full Text Available The number of patients with malignant brain tumours is on the rise, but due to the novel treatment methods the survival rates are higher. Despite increased survival the consequences of tumour properties and treatment can have a significant negative effect on the patients’ quality of life. Providing timely and appropriate rehabilitation interventions is an important aspect of patient treatment and should be started immediately after surgery. The most important goal of rehabilitation is to prevent complications that could have a negative effect on the patients’ ability to function.

  9. Nutritional Status and Body Composition of Adult Patients with Brain Tumours Awaiting Surgical Resection.

    Science.gov (United States)

    McCall, Michele; Leone, Ashley; Cusimano, Michael D

    2014-09-01

    To measure the prevalence of malnutrition, risk factors for poor dietary intake and body composition in patients with brain tumours admitted to hospital for surgical resection. In this study, 316 patients admitted for brain tumour resection to the Neurosurgical service at St. Michael's Hospital were screened. Assessment tools included the Subjective Global Assessment (SGA) for nutritional status and Bioelectrical Impedance Analysis (BIA) for body composition. All measurements were performed by one research dietitian. Information regarding medical history, symptomology, and tumour pathology was recorded. One hundred and nine participants were recruited. Malnutrition was present in 17.6% of patients, of whom 94.7% were moderately malnourished (SGA-B) and 5.3% severely malnourished (SGA-C). Key symptoms contributing to malnutrition included weight loss, nausea, vomiting, dysphagia, headaches, and fatigue. Patients with malignant tumors were more likely to have weight loss and lower fat mass. This study demonstrated that patients admitted for brain tumour resection have a low prevalence of malnutrition compared with other cancer populations. Useful parameters for nutritional screening of inpatient admissions include weight loss >5% of usual weight, nausea, vomiting, dysphagia, and headaches.

  10. MR imaging-guided cryoablation of metastatic brain tumours: initial experience in six patients

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chengli; Wu, Lebin; Song, Jiqing; Liu, Ming; Lv, Yubo [Shandong University, Shandong Provincial Medical Imaging Research Institute, Jinan, Shandong (China); Sequeiros, Roberto Blanco [Shandong University, Shandong Provincial Medical Imaging Research Institute, Jinan, Shandong (China); Oulu University Hospital, Department of Radiology, Oulu (Finland)

    2010-02-15

    The objective was to evaluate the initial experience and safety of magnetic resonance imaging (MRI)-guided transcranial cryoablation in cystic metastatic brain tumours. Seven cystic metastatic brain tumours in six patients were treated with cryoablation. The approval from the local ethics committee and individual patient consent were acquired before the study. Before the procedure the tumours were detected with conventional CT or MRI. The procedure was performed under local anaesthesia and conscious sedation. A 0.23-T open MRI system with optical tracking was used for procedural planning, instrument guidance and procedural monitoring of the ice ball formation. An MR-compatible, argon-based cryoablation system was used. The schedule of follow-up imaging ranged from 12 days to 12 months. Seven treatment sessions were performed. All the cryoprobes were successfully inserted into the target with one pass. All the patients tolerated the procedure well without experiencing any neurological deficits during the treatment phase or during the immediate post-treatment period. One patient died 12 days after cryoablation. MR-guided and monitored metastasis brain tumour cryoablation is technically feasible and may represent an alternative treatment in selected patients. (orig.)

  11. Intra-operative 3-T MRI for paediatric brain tumours: challenges and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Abernethy, L.J.; Avula, S.; Hughes, G.M. [Alder Hey Children' s NHS Foundation Trust, Department of Radiology, Liverpool (United Kingdom); Wright, E.J. [Alder Hey Children' s Hospital, Department of Anaesthesia, Liverpool (United Kingdom); Mallucci, C.L. [Alder Hey Children' s Hospital, Department of Neurosurgery, Liverpool (United Kingdom)

    2012-02-15

    MRI is the ideal modality for imaging intracranial tumours. Intraoperative MRI (ioMRI) makes it possible to obtain scans during a neurosurgical operation that can aid complete macroscopic tumour resection - a major prognostic factor in the majority of brain tumours in children. Intra-operative MRI can also help limit damage to normal brain tissue. It therefore has the potential to improve the survival of children with brain tumours and to minimise morbidity, including neurological deficits. The use of ioMRI is also likely to reduce the need for second look surgery, and may reduce the need for chemotherapy and radiotherapy. High-field MRI systems provide better anatomical information and also enable effective utilisation of advanced MRI techniques such as perfusion imaging, diffusion tensor imaging, and magnetic resonance spectroscopy. However, high-field ioMRI facilities require substantial capital investment, and careful planning is required for optimal benefit. Safe ioMRI requires meticulous attention to detail and rigorous application of magnetic field safety precautions. Interpretation of ioMRI can be challenging and requires experience and understanding of artefacts that are common in the intra-operative setting. (orig.)

  12. 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.

  13. Walker 256 tumour cells increase substance P immunoreactivity locally and modify the properties of the blood-brain barrier during extravasation and brain invasion.

    Science.gov (United States)

    Lewis, Kate M; Harford-Wright, Elizabeth; Vink, Robert; Nimmo, Alan J; Ghabriel, Mounir N

    2013-01-01

    It is not yet known how tumour cells traverse the blood-brain barrier (BBB) to form brain metastases. Substance P (SP) release is a key component of neurogenic inflammation which has been recently shown to increase the permeability of the BBB following CNS insults, making it a possible candidate as a mediator of tumour cell extravasation into the brain. This study investigated the properties of the BBB in the early stages of tumour cell invasion into the brain, and the possible involvement of SP. Male Wistar rats were injected with Walker 256 breast carcinoma cells via the internal carotid artery and euthanised at 1, 3, 6 and 9 days post tumour inoculation. Culture medium-injected animals served as controls at 1 and 9 days. Evidence of tumour cell extravasation across the BBB was first observed at 3 days post-inoculation, which corresponded with significantly increased albumin (p tumoral area (p cerebral metastases may be a SP-mediated process.

  14. In vivo proton magnetic resonance spectroscopy of intraventricular tumours of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Majos, Carles; Aguilera, Carles [Hospital Universitari de Bellvitge, Institut de Diagnostic per la Imatge (IDI). Centre Bellvitge, L' Hospitalet de Llobregat, Barcelona (Spain); Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigacion Biomedica en Red en Bioingenieria, Cerdanyola del Valles (Spain); Cos, Monica; Camins, Angels; Samitier, Alex; Castaner, Sara; Sanchez, Juan J. [Hospital Universitari de Bellvitge, Institut de Diagnostic per la Imatge (IDI). Centre Bellvitge, L' Hospitalet de Llobregat, Barcelona (Spain); Candiota, Ana P.; Delgado-Goni, Teresa [Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigacion Biomedica en Red en Bioingenieria, Cerdanyola del Valles (Spain); Unitat de Bioquimica de Biociencies, Department de Bioquimica i Biologia Molecular, Cerdanyola del Valles (Spain); Mato, David [Hospital Universitari de Bellvitge, Department of Neurosurgery, L' Hospitalet de Llobregat, Barcelona (Spain); Acebes, Juan J. [Hospital Universitari de Bellvitge, Department of Neurosurgery, L' Hospitalet de Llobregat, Barcelona (Spain); Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigacion Biomedica en Red en Bioingenieria, Cerdanyola del Valles (Spain); Arus, Carles [Unitat de Bioquimica de Biociencies, Department de Bioquimica i Biologia Molecular, Cerdanyola del Valles (Spain); Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigacion Biomedica en Red en Bioingenieria, Cerdanyola del Valles (Spain)

    2009-08-15

    The aim of this study was to assess the usefulness of proton MR spectroscopy in the diagnosis of intraventricular tumours. Fifty-two intraventricular tumours pertaining to 16 different tumour types were derived from our database. All cases had single-voxel proton MR spectroscopy performed at TE at both 30 and 136 ms at 1.5 T. The Mann-Whitney U test was used to search for the most discriminative datapoints each tumour type. Characteristic trends were found for some groups: high Glx and Ala in meningiomas (p<0.001 and p<0.01, respectively), high mobile lipids in metastasis (p<0.001), high Cho in PNET (p<0.001), high mI+Gly in ependymoma (p<0.001), high NAC (p<0.01) in the absence of the normal brain parenchyma pattern in colloid cysts, and high mI/Gly and Ala in central neurocytoma. Proton MR spectroscopy provides additional metabolic information that could be useful in the diagnosis of intraventricular brain tumors. (orig.)

  15. Childhood brain tumour risk and its association with wireless phones: a commentary

    Directory of Open Access Journals (Sweden)

    Söderqvist Fredrik

    2011-12-01

    Full Text Available Abstract Case-control studies on adults point to an increased risk of brain tumours (glioma and acoustic neuroma associated with the long-term use of mobile phones. Recently, the first study on mobile phone use and the risk of brain tumours in children and adolescents, CEFALO, was published. It has been claimed that this relatively small study yielded reassuring results of no increased risk. We do not agree. We consider that the data contain several indications of increased risk, despite low exposure, short latency period, and limitations in the study design, analyses and interpretation. The information certainly cannot be used as reassuring evidence against an association, for reasons that we discuss in this commentary.

  16. Severe encephalopathy after high-dose chemotherapy with autologous stem cell support for brain tumours.

    Science.gov (United States)

    van den Berkmortel, F; Gidding, C; De Kanter, M; Punt, C J A

    2006-01-01

    Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The patient was treated with high-dose chemotherapy and autologous stem cell transplantation. She developed a severe treatment-related encephalopathy which affected her quality of life and neurocognitive functioning for the rest of her life. Possible causative factors are discussed and central nervous system toxicity by high-dose chemotherapy in brain tumour patients is reviewed. Case reports on severe central nervous system toxicity have been reported, but data from prospective studies on neurocognitive functioning are not available. These data strongly support a systematic long-term follow-up of brain tumour patients treated with high-dose chemotherapy with emphasis on neurocognitive function tests.

  17. Coping with a childhood brain tumour: A qualitative analysis of parents’ experiences

    OpenAIRE

    Lurie, P.

    2014-01-01

    Pre-existing research on the stress reactions of caregivers of children with brain tumours was reviewed. Four overarching stress reactions were notably present for parents: burden from adjusting to changes in routine, burnout from fatigue and emotional exhaustion, residual stress from diagnosis and treatment, and future-oriented uncertainty. There is evidence to suggest that psychosocial implications for parents are a concern and that they require support from professionals long into the surv...

  18. The Problems of Treatment and Rehabilitation of the Patients Operated for Brain Tumours

    OpenAIRE

    Medyanik I.А.; Fraerman А.P.; Ruina Е.А.

    2011-01-01

    There have been presented literature data and long-term experience of the authors in postoperative rehabilitation of patients with brain tumours (BT). The main causes of neurological disturbances and the ways of their overcoming have been demonstrated. There have been considered the problems of postoperative diagnosis (CT- and MRI-studies), radiation and chemotherapy, drug therapy (use of glucocorticosteroids, osmodiuretics, anticholinesterase drugs and symptomatic medications, antidepressant...

  19. Neural correlates of delayed visual-motor performance in children treated for brain tumours.

    Science.gov (United States)

    Dockstader, Colleen; Gaetz, William; Bouffet, Eric; Tabori, Uri; Wang, Frank; Bostan, Stefan R; Laughlin, Suzanne; Mabbott, Donald J

    2013-09-01

    Both structural and functional neural integrity is critical for healthy cognitive function and performance. Across studies, it is evident that children who are affected by neurological insult commonly demonstrate impaired cognitive abilities. Children treated with cranial radiation for brain tumours suffer substantial structural damage and exhibit a particularly high correlation between the degree of neural injury and cognitive deficits. However the pathophysiology underlying impaired cognitive performance in this population, and many other paediatric populations affected by neurological injury or disease, is unknown. We wished to investigate the characteristics of neuronal function during visual-motor task performance in a group of children who were treated with cranial radiation for brain tumours. We used Magnetoencephalography to investigate neural function during visual-motor reaction time (RT) task performance in 15 children treated with cranial radiation for Posterior Fossa malignant brain tumours and 17 healthy controls. We found that, relative to controls, the patient group showed: 1) delayed latencies for neural activation in both visual and motor cortices; 2) muted motor responses in the alpha (8-12Hz) and beta (13-29Hz) bandwidths, and 3) potentiated visual and motor responses in the gamma (30-100Hz) bandwidth. Collectively these observations indicate impaired neural processing during visual-motor RT performance in this population and that delays in the speed of visual and motor neuronal processing both contribute to the delays in the behavioural response. As increases in gamma activity are often observed with increases in attention and effort, increased gamma activities in the patient group may reflect compensatory neural activity during task performance. This is the first study to investigate neural function in real-time during cognitive performance in paediatric brain tumour patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Bevacizumab plus irinotecan in the treatment patients with progressive recurrent malignant brain tumours

    DEFF Research Database (Denmark)

    Poulsen, H.S.; Grunnet, K.; Sorensen, M.

    2009-01-01

    glioma and 32 weeks for grade III glioma. Four patients discontinued treatment because of unmanageable toxicity: cerebral haemorrhage, cardiac arrhythmia, intestinal perforation and diarrhoea, the latter resulting in death. DISCUSSION: We conclude that the combination of bevacizumab and irinotecan shows...... acceptable safety and is a clinically relevant choice of therapy in heavily pre-treated patients with recurrent high-grade brain tumours Udgivelsesdato: 2009...

  1. A PROSPECTIVE HISTOPATHOLOGICAL-BASED STUDY OF BRAIN TUMOURS IN A REFERRAL CENTRE

    OpenAIRE

    Prathima Gujjaru; N. Saila Rekha; Syam Sunder Rao Uttarakar

    2016-01-01

    BACKGROUND Brain neoplasms occur at all ages and account for around 2-3 percent of all deaths in adults. In children, the frequency increases to more than twenty percent. In children, it forms the second most common type of malignancy. Most of the tumours encountered are not related to any identifiable risk factors except for irradiation and some hereditary syndromes like subependymal giant cell astrocytoma, glioblastoma multiforme, cerebellar haemangioblastoma, meningioma, Sc...

  2. Known glioma risk loci are associated with glioma with a family history of brain tumours

    DEFF Research Database (Denmark)

    Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika

    2013-01-01

    family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies...... and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain...... tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically...

  3. Development and piloting of a brain tumour-specific question prompt list.

    Science.gov (United States)

    Langbecker, D; Janda, M; Yates, P

    2012-07-01

    The objective of this research was to develop a question prompt list aimed at increasing question asking and reducing the unmet information needs of adults with primary brain tumours, and to pilot the question prompt list to determine its suitability for the intended population. Thematic analysis of existing resources was used to create a draft which was refined via interviews with 12 brain tumour patients and six relatives, readability testing and review by health professionals. A non-randomised before-after pilot study with 20 brain tumour patients was used to assess the acceptability and usefulness of the question prompt list, compared with a 'standard brochure', and the feasibility of evaluation strategies. The question prompt list developed covered seven main topics (diagnosis, prognosis, symptoms and changes, treatment, support, after treatment finishes and the health professional team). Pilot study participants provided with the question prompt list agreed that it was helpful (7/7), contained questions that were useful to them (7/7) and prompted them to ask their medical oncologist questions (5/7). The question prompt list is acceptable to patients and contains questions relevant to them. Research is now needed to assess its effectiveness in increasing question asking and reducing unmet information needs. © 2012 Blackwell Publishing Ltd.

  4. Use of mobile phones and risk of brain tumours: update of Danish cohort study.

    Science.gov (United States)

    Frei, Patrizia; Poulsen, Aslak H; Johansen, Christoffer; Olsen, Jørgen H; Steding-Jessen, Marianne; Schüz, Joachim

    2011-10-19

    To investigate the risk of tumours in the central nervous system among Danish mobile phone subscribers. Nationwide cohort study. Denmark. All Danes aged ≥ 30 and born in Denmark after 1925, subdivided into subscribers and non-subscribers of mobile phones before 1995. Risk of tumours of the central nervous system, identified from the complete Danish Cancer Register. Sex specific incidence rate ratios estimated with log linear Poisson regression models adjusted for age, calendar period, education, and disposable income. 358,403 subscription holders accrued 3.8 million person years. In the follow-up period 1990-2007, there were 10,729 cases of tumours of the central nervous system. The risk of such tumours was close to unity for both men and women. When restricted to individuals with the longest mobile phone use--that is, ≥ 13 years of subscription--the incidence rate ratio was 1.03 (95% confidence interval 0.83 to 1.27) in men and 0.91 (0.41 to 2.04) in women. Among those with subscriptions of ≥ 10 years, ratios were 1.04 (0.85 to 1.26) in men and 1.04 (0.56 to 1.95) in women for glioma and 0.90 (0.57 to 1.42) in men and 0.93 (0.46 to 1.87) in women for meningioma. There was no indication of dose-response relation either by years since first subscription for a mobile phone or by anatomical location of the tumour--that is, in regions of the brain closest to where the handset is usually held to the head. In this update of a large nationwide cohort study of mobile phone use, there were no increased risks of tumours of the central nervous system, providing little evidence for a causal association.

  5. In vivo magnetic resonance imaging and 31P spectroscopy of large human brain tumours at 1.5 tesla

    DEFF Research Database (Denmark)

    Thomsen, C; Jensen, K E; Achten, E

    1988-01-01

    31P MR spectroscopy of human brain tumours is one feature of magnetic resonance imaging. Eight patients with large superficial brain tumours and eight healthy volunteers were examined with 31P spectroscopy using an 8 cm surface coil for volume selection. Seven frequencies were resolved in our...... and after chemotherapy. The spectra showed considerable changes during chemotherapy. It is concluded that 31P spectroscopy using surface coils is of limited value for tumour characterization, but may add useful information in monitoring the effect of chemotherapy....

  6. Intracavitary moderator balloon combined with (252)Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations.

    Science.gov (United States)

    Brandão, S F; Campos, T P R

    2015-07-01

    This article proposes a combination of californium-252 ((252)Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Dosimetric evaluations were performed on three protocol set-ups: (252)Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0-5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the (252)Cf source, sparing the normal brain tissue. Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis.

  7. Intracavitary moderator balloon combined with 252Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations

    Science.gov (United States)

    Brandão, S F

    2015-01-01

    Objective: This article proposes a combination of californium-252 (252Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Methods: Dosimetric evaluations were performed on three protocol set-ups: 252Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Results: Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0–5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Conclusion: Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the 252Cf source, sparing the normal brain tissue. Advances in knowledge: Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis. PMID:25927876

  8. Three-dimensional textural features of conventional MRI improve diagnostic classification of childhood brain tumours.

    Science.gov (United States)

    Fetit, Ahmed E; Novak, Jan; Peet, Andrew C; Arvanitits, Theodoros N

    2015-09-01

    The aim of this study was to assess the efficacy of three-dimensional texture analysis (3D TA) of conventional MR images for the classification of childhood brain tumours in a quantitative manner. The dataset comprised pre-contrast T1 - and T2-weighted MRI series obtained from 48 children diagnosed with brain tumours (medulloblastoma, pilocytic astrocytoma and ependymoma). 3D and 2D TA were carried out on the images using first-, second- and higher order statistical methods. Six supervised classification algorithms were trained with the most influential 3D and 2D textural features, and their performances in the classification of tumour types, using the two feature sets, were compared. Model validation was carried out using the leave-one-out cross-validation (LOOCV) approach, as well as stratified 10-fold cross-validation, in order to provide additional reassurance. McNemar's test was used to test the statistical significance of any improvements demonstrated by 3D-trained classifiers. Supervised learning models trained with 3D textural features showed improved classification performances to those trained with conventional 2D features. For instance, a neural network classifier showed 12% improvement in area under the receiver operator characteristics curve (AUC) and 19% in overall classification accuracy. These improvements were statistically significant for four of the tested classifiers, as per McNemar's tests. This study shows that 3D textural features extracted from conventional T1 - and T2-weighted images can improve the diagnostic classification of childhood brain tumours. Long-term benefits of accurate, yet non-invasive, diagnostic aids include a reduction in surgical procedures, improvement in surgical and therapy planning, and support of discussions with patients' families. It remains necessary, however, to extend the analysis to a multicentre cohort in order to assess the scalability of the techniques used. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Multimodal magnetic resonance imaging increases the overall diagnostic accuracy in brain tumours: Correlation with histopathology

    Directory of Open Access Journals (Sweden)

    Kasim Abul-Kasim

    2013-03-01

    Full Text Available Background: The aim of this retrospective study was to assess the contribution of multimodal MRI techniques, specifically perfusion-weighted imaging (PWI, and/or MR spectroscopy (MRS, in increasing the diagnostic accuracy of MRI in brain tumours.Methods: Forty-four patients with suspected brain tumours (27 (61% patients male, mean age 58±17 (mean±SD years were included in this retrospective analysis. Patients were examined with conventional MR sequences, DWI, and with PWI and/or MRS. The concordance between the diagnoses obtained with multimodal MRI and with the conventional MR sequences, and the final diagnosis obtained by biopsy, was estimated. Fisher’s exact test and/or chi-square test was performed to estimate the added utility of multimodal MRI. Statistical significance was set at p<0.05.Results: With multimodal MRI, the diagnosis in 41 (93% patients was the same as that obtained by biopsy, compared with 39% (17/44 patients when the readers were allowed to give one diagnostic possibility during the evaluation of the conventional MR sequences alone (p<0.001. The concordance between the diagnoses provided by evaluating the multimodal MRIs and the final diagnoses was almost perfect (κ value 0.92, 95% CI 0.82 - 1. PWI primarily helped to differentiate lymphomas from other solid tumours, whereas MRS helped to differentiate malignant glioma from metastasis. Both PWI and MRS helped in grading astrocytomas.Conclusion: Multimodal MRI increases diagnostic accuracy and should, wherever available, be performed in the work-up of brain tumours, although this entails increased examination cost and time.

  10. Imaging of brain oxygenation with magnetic resonance imaging: A validation with positron emission tomography in the healthy and tumoural brain.

    Science.gov (United States)

    Valable, Samuel; Corroyer-Dulmont, Aurélien; Chakhoyan, Ararat; Durand, Lucile; Toutain, Jérôme; Divoux, Didier; Barré, Louisa; MacKenzie, Eric T; Petit, Edwige; Bernaudin, Myriam; Touzani, Omar; Barbier, Emmanuel L

    2017-07-01

    The partial pressure in oxygen remains challenging to map in the brain. Two main strategies exist to obtain surrogate measures of tissue oxygenation: the tissue saturation studied by magnetic resonance imaging (S t O 2 -MRI) and the identification of hypoxia by a positron emission tomography (PET) biomarker with 3-[ 18 F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([ 18 F]-FMISO) as the leading radiopharmaceutical. Nonetheless, a formal validation of S t O 2 -MRI against FMISO-PET has not been performed. The objective of our studies was to compare the two approaches in (a) the normal rat brain when the rats were submitted to hypoxemia; (b) animals implanted with four tumour types differentiated by their oxygenation. Rats were submitted to normoxic and hypoxemic conditions. For the brain tumour experiments, U87-MG, U251-MG, 9L and C6 glioma cells were orthotopically inoculated in rats. For both experiments, S t O 2 -MRI and [ 18 F]-FMISO PET were performed sequentially. Under hypoxemia conditions, S t O 2 -MRI revealed a decrease in oxygen saturation in the brain. Nonetheless, [ 18 F]-FMISO PET, pimonidazole immunohistochemistry and molecular biology were insensitive to hypoxia. Within the context of tumours, S t O 2 -MRI was able to detect hypoxia in the hypoxic models, mimicking [ 18 F]-FMISO PET with high sensitivity/specificity. Altogether, our data clearly support that, in brain pathologies, S t O 2 -MRI could be a robust and specific imaging biomarker to assess hypoxia.

  11. Intraoperative probe detecting β{sup −} decays in brain tumour radio-guided surgery

    Energy Technology Data Exchange (ETDEWEB)

    Solfaroli Camillocci, E., E-mail: elena.solfaroli@roma1.infn.it [Dip. Fisica, Sapienza Univ. di Roma, Roma (Italy); INFN Sezione di Roma, Roma (Italy); Bocci, V.; Chiodi, G. [INFN Sezione di Roma, Roma (Italy); Collamati, F. [INFN Sezione di Roma, Roma (Italy); Dip. Scienze di Base e Applicate per l' Ingegneria, Sapienza Univ. di Roma, Roma (Italy); Donnarumma, R.; Faccini, R.; Mancini Terracciano, C. [Dip. Fisica, Sapienza Univ. di Roma, Roma (Italy); INFN Sezione di Roma, Roma (Italy); Marafini, M. [INFN Sezione di Roma, Roma (Italy); Museo Storico della Fisica e Centro Studi e Ricerche ‘E. Fermi’, Roma (Italy); Mattei, I.; Muraro, S. [Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Roma (Italy); Recchia, L. [INFN Sezione di Roma, Roma (Italy); Rucinski, A. [INFN Sezione di Roma, Roma (Italy); Dip. Scienze di Base e Applicate per l' Ingegneria, Sapienza Univ. di Roma, Roma (Italy); Russomando, A. [Dip. Fisica, Sapienza Univ. di Roma, Roma (Italy); INFN Sezione di Roma, Roma (Italy); Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Roma (Italy); Toppi, M. [Laboratori Nazionali di Frascati dell' INFN, Frascati (Italy); Traini, G. [Dip. Fisica, Sapienza Univ. di Roma, Roma (Italy); INFN Sezione di Roma, Roma (Italy); Morganti, S. [INFN Sezione di Roma, Roma (Italy)

    2017-02-11

    Radio-guided surgery (RGS) is a technique to intraoperatively detect tumour remnants, favouring a radical resection. Exploiting β{sup −} emitting tracers provides a higher signal to background ratio compared to the established technique with γ radiation, allowing the extension of the RGS applicability range. We developed and tested a detector based on para-terphenyl scintillator with high sensitivity to low energy electrons and almost transparent to γs to be used as intraoperative probe for RGS with β{sup −} emitting tracer. Portable read out electronics was customised to match the surgeon needs. This probe was used for preclinical test on specific phantoms and a test on “ex vivo” specimens from patients affected by meningioma showing very promising results for the application of this new technique on brain tumours. In this paper, the prototype of the intraoperative probe and the tests are discussed; then, the results on meningioma are used to make predictions on the performance of the probe detecting residuals of a more challenging and more interesting brain tumour: the glioma.

  12. Fast and accurate water content and T2{sup ⁎} mapping in brain tumours localised with FET-PET

    Energy Technology Data Exchange (ETDEWEB)

    Oros-Peusquens, A.-M., E-mail: a.m.oros-peusquens@fz-juelich.de [Institute of Neuroscience and Medicine – 4, Research Centre Juelich, 52425 Juelich (Germany); Keil, F.; Langen, K.J.; Herzog, H.; Stoffels, G. [Institute of Neuroscience and Medicine – 4, Research Centre Juelich, 52425 Juelich (Germany); Weiss, C. [Department of Neurosurgery, University Hospital Cologne, 50924 Cologne (Germany); Shah, N.J. [Institute of Neuroscience and Medicine – 4, Research Centre Juelich, 52425 Juelich (Germany); Department of Neurology, Faculty of Medicine, JARA, RWTH Aachen University, 52074 Aachen (Germany)

    2014-01-11

    The availability of combined MR-PET scanners opens new opportunities for the characterisation of tumour environment. In this study, water content and relaxation properties of glioblastoma were investigated in five patients using advanced MRI. The region containing metabolically active tumour tissue was defined by simultaneously measured FET-PET uptake. The mean value of water content in tumour tissue – obtained noninvasively with high precision and accuracy for the first time – amounted to 84.5%, similar to the value for normal grey matter. Constancy of water content contrasted with a large variability of T2{sup ⁎} values in tumour tissue, qualitatively related to the magnetic inhomogeneity of tissue created by blood vessels and/or microbleeds. The quantitative MRI protocol takes 71/2 min of measurement time and is proposed for extended clinical use. -- Highlights: • Quantitative MRI and simultaneous FET-PET used for the study of brain tumours. • Quantitative water content and T2{sup ⁎} of the brain are reported in five glioblastoma patients. • The qMRI method achieves whole brain coverage in 71/2 min. • Water content in normal appearing tissue as well as tumour is constant within 1% for each class. • T2{sup ⁎} is highly variable within tumour volume and from patient to patient.

  13. Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bueltmann, Eva; Lanfermann, Heinrich [Hannover Medical School, Institute of Diagnostic and Interventional Neuroradiology, Hannover (Germany); Naegele, Thomas [University of Tuebingen, Department of Diagnostic and Interventional Neuroradiology, Radiological University Hospital, Tuebingen (Germany); Klose, Uwe [University of Tuebingen, Section of Experimental MR of the CNS, Department of Neuroradiology, Radiological University Hospital, Tuebingen (Germany)

    2017-01-15

    We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic. (orig.)

  14. Childhood brain tumours and use of mobile phones: comparison of a case–control study with incidence data

    Directory of Open Access Journals (Sweden)

    Aydin Denis

    2012-05-01

    Full Text Available Abstract The first case–control study on mobile phone use and brain tumour risk among children and adolescents (CEFALO study has recently been published. In a commentary published in Environmental Health, Söderqvist and colleagues argued that CEFALO suggests an increased brain tumour risk in relation to wireless phone use. In this article, we respond and show why consistency checks of case–control study results with observed time trends of incidence rates are essential, given the well described limitations of case–control studies and the steep increase of mobile phone use among children and adolescents during the last decade. There is no plausible explanation of how a notably increased risk from use of wireless phones would correspond to the relatively stable incidence time trends for brain tumours among children and adolescents observed in the Nordic countries. Nevertheless, an increased risk restricted to heavy mobile phone use, to very early life exposure, or to rare subtypes of brain tumours may be compatible with stable incidence trends at this time and thus further monitoring of childhood brain tumour incidence rate time trends is warranted.

  15. Effect of ephedrine and phenylephrine on brain oxygenation and microcirculation in anaesthetised patients with cerebral tumours

    DEFF Research Database (Denmark)

    Koch, Klaus Ulrik; Tietze, Anna; Aanerud, Joel

    2017-01-01

    extraction fraction. Surgery is initiated after MRI/PET measurements and subdural intracranial pressure is measured. ETHICS AND DISSEMINATION: This study was approved by the Central Denmark Region Committee on Health Research Ethics (12 June 2015; 1-10-72-116-15). Results will be disseminated via peer......INTRODUCTION: During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arterial blood pressure with the aim of maintaining sufficient cerebral perfusion pressure. Studies of the commonly used vasopressors show that brain oxygen saturation is reduced after......, anaesthetised patients will be randomised to receive either phenylephrine or ephedrine infusion until mean arterial blood pressure increases to above 60 mm Hg or 20% above baseline. Twenty-four patients were allocated to MRI and another 24 patients to PET examination. MRI measurements include cerebral blood...

  16. Functional Magnetic Resonance Imaging for Preoperative Planning in Brain Tumour Surgery.

    Science.gov (United States)

    Lau, Jonathan C; Kosteniuk, Suzanne E; Bihari, Frank; Megyesi, Joseph F

    2017-01-01

    Functional magnetic resonance imaging (fMRI) is being increasingly used for the preoperative evaluation of patients with brain tumours. The study is a retrospective chart review investigating the use of clinical fMRI from 2002 through 2013 in the preoperative evaluation of brain tumour patients. Baseline demographic and clinical data were collected. The specific fMRI protocols used for each patient were recorded. Sixty patients were identified over the 12-year period. The tumour types most commonly investigated were high-grade glioma (World Health Organization grade III or IV), low-grade glioma (World Health Organization grade II), and meningioma. Most common presenting symptoms were seizures (69.6%), language deficits (23.2%), and headache (19.6%). There was a predominance of left hemispheric lesions investigated with fMRI (76.8% vs 23.2% for right). The most commonly involved lobes were frontal (64.3%), temporal (33.9%), parietal (21.4%), and insular (7.1%). The most common fMRI paradigms were language (83.9%), motor (75.0%), sensory (16.1%), and memory (10.7%). The majority of patients ultimately underwent a craniotomy (75.0%), whereas smaller groups underwent stereotactic biopsy (8.9%) and nonsurgical management (16.1%). Time from request for fMRI to actual fMRI acquisition was 3.1±2.3 weeks. Time from fMRI acquisition to intervention was 4.9±5.5 weeks. We have characterized patient demographics in a retrospective single-surgeon cohort undergoing preoperative clinical fMRI at a Canadian centre. Our experience suggests an acceptable wait time from scan request to scan completion/analysis and from scan to intervention.

  17. Frequency, clinical correlates and rating of behavioural changes in primary brain tumour patients: A preliminary investigation.

    Directory of Open Access Journals (Sweden)

    Grahame K Simpson

    2015-04-01

    Full Text Available PurposeFew studies have addressed the specific behavioural changes associated with primary brain tumour (PBT. This paper will report on the frequency and demographic/clinical correlates of such behaviours, and the reliability of rating such behaviours amongst people with PBT, family informants and clinicians. The association of behavioural changes and patient functional status will also be discussed.MethodsA total of 57 patients with 37 family informants were recruited from two large Australian metropolitan hospitals. Each completed three neuro-behavioural self-report measures. Patients also completed a depression symptom measure. Functional status was defined by clinician-rated Karnofsky Performance Status.ResultsPatients were on average 52 years old, a median of four months (range 1-82 post-diagnosis, with high grade (39%, low grade (22% or benign tumours (39%. Patients reported frequency rates of 7-40% across various behavioural domains including anger, inappropriate behaviour, apathy, inertia and executive impairment. The presence of epileptic seizures was associated with significantly higher levels of behavioural changes. Notably, behaviour did not correlate with tumour grade or treatment modality. There was moderate agreement between patients and relatives on the presence or absence of behavioural changes, and substantial agreement between relative and clinician ratings. Depressed patients did not generally report more changes than non-depressed patients. Increases in the relative and clinician-rated behaviour scores were significantly correlated with decreasing functional status in the patient.ConclusionsBehavioural changes were a common sequela of both benign and malignant PBT. Larger scale studies are required to confirm these results. The results suggest the importance of including behaviour in brain cancer psychosocial assessments and the need to develop interventions to treat these patients and reduce the burden of care on families.

  18. Isolating dividing neural and brain tumour cells for gene expression profiling.

    Science.gov (United States)

    Endaya, Berwini; Cavanagh, Brenton; Alowaidi, Faisal; Walker, Tom; de Pennington, Nicholas; Ng, Jin-Ming A; Lam, Paula Y P; Mackay-Sim, Alan; Neuzil, Jiri; Meedeniya, Adrian C B

    2016-01-15

    The characterisation of dividing brain cells is fundamental for studies ranging from developmental and stem cell biology, to brain cancers. Whilst there is extensive anatomical data on these dividing cells, limited gene transcription data is available due to technical constraints. We focally isolated dividing cells whilst conserving RNA, from culture, primary neural tissue and xenografted glioma tumours, using a thymidine analogue that enables gene transcription analysis. 5-ethynyl-2-deoxyuridine labels the replicating DNA of dividing cells. Once labelled, cultured cells and tissues were dissociated, fluorescently tagged with a revised click chemistry technique and the dividing cells isolated using fluorescence-assisted cell sorting. RNA was extracted and analysed using real time PCR. Proliferation and maturation related gene expression in neurogenic tissues was demonstrated in acutely and 3 day old labelled cells, respectively. An elevated expression of marker and pathway genes was demonstrated in the dividing cells of xenografted brain tumours, with the non-dividing cells showing relatively low levels of expression. BrdU "immune-labelling", the most frequently used protocol for detecting cell proliferation, causes complete denaturation of RNA, precluding gene transcription analysis. This EdU labelling technique, maintained cell integrity during dissociation, minimized copper exposure during labelling and used a cell isolation protocol that avoided cell lysis, thus conserving RNA. The technique conserves RNA, enabling the definition of cell proliferation-related changes in gene transcription of neural and pathological brain cells in cells harvested immediately after division, or following a period of maturation. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Detection of comorbidities and synchronous primary tumours via thoracic radiography and abdominal ultrasonography and their influence on treatment outcome in dogs with soft tissue sarcomas, primary brain tumours and intranasal tumours.

    Science.gov (United States)

    Bigio Marcello, A; Gieger, T L; Jiménez, D A; Granger, L Abbigail

    2015-12-01

    Canine soft tissue sarcomas (STS), primary brain tumours and intranasal tumours are commonly treated with radiotherapy (RT). Given the low metastatic potential of these tumours, recommendations regarding imaging tests as staging are variable among institutions. The purpose of our study was to describe thoracic radiographic and abdominal ultrasonographic findings in dogs with these neoplasms and to investigate association of abnormal findings with alterations in recommended treatment. Medical records from 101 dogs, each having thoracic radiographs and abdominal ultrasound performed as part of their staging, were reviewed. In 98 of 101 (97%), imaging abnormalities were detected, 27% of which were further investigated with fine needle aspiration cytology or biopsy. Nine percent of the detected abnormalities were considered serious comorbidities that altered treatment recommendations, including 3 (3%) which were confirmed as synchronous primary neoplasms. These findings may influence recommendations regarding the decision to perform thoracic radiographs and abdominal ultrasound prior to initiation of RT. © 2013 John Wiley & Sons Ltd.

  20. Acute Ethanol-Induced Changes in Edema and Metabolite Concentrations in Rat Brain

    Directory of Open Access Journals (Sweden)

    Huimin Liu

    2014-01-01

    Full Text Available The aim of this study is to describe the acute effects of EtOH on brain edema and cerebral metabolites, using diffusion weight imaging (DWI and proton magnetic resonance spectroscopy (1H-MRS at a 7.0T MR and to define changes in apparent diffusion coefficient (ADC values and the concentration of metabolites in the rat brain after acute EtOH intoxication. ADC values in each ROI decreased significantly at 1 h and 3 h after ethanol administration. ADC values in frontal lobe were decreased significantly compared with other regions at 3 h. For EtOH/Cr+PCr and cerebral metabolites (Cho, Tau, and Glu differing over time, no significant differences for Ins, NAA, and Cr were observed in frontal lobes. Regression analysis revealed a significant association between TSEtOH/Cr+PCr and TSCho, TSTau, TSGlu, and TSADC. The changes of ADC values in different brain regions reflect the process of the cytotoxic edema in vivo. The characterization of frontal lobes metabolites changes and the correlations between TSEtOH/Cr+PCr and TSCho, TSTau, and TSGlu provide a better understanding for the biological mechanisms in neurotoxic effects of EtOH on the brain. In addition, the correlations between TSEtOH/Cr+PCr and TSADC will help us to understand development of the ethanol-induced brain cytotoxic edema.

  1. A novel brain tumour model in zebrafish reveals the role of YAP activation in MAPK- and PI3K-induced malignant growth

    Directory of Open Access Journals (Sweden)

    Marie Mayrhofer

    2017-01-01

    Full Text Available Somatic mutations activating MAPK and PI3K signalling play a pivotal role in both tumours and brain developmental disorders. We developed a zebrafish model of brain tumours based on somatic expression of oncogenes that activate MAPK and PI3K signalling in neural progenitor cells and found that HRASV12 was the most effective in inducing both heterotopia and invasive tumours. Tumours, but not heterotopias, require persistent activation of phospho (p-ERK and express a gene signature similar to the mesenchymal glioblastoma subtype, with a strong YAP component. Application of an eight-gene signature to human brain tumours establishes that YAP activation distinguishes between mesenchymal glioblastoma and low grade glioma in a wide The Cancer Genome Atlas (TCGA sample set including gliomas and glioblastomas (GBMs. This suggests that the activation of YAP might be an important event in brain tumour development, promoting malignant versus benign brain lesions. Indeed, co-expression of dominant-active YAP (YAPS5A and HRASV12 abolishes the development of heterotopias and leads to the sole development of aggressive tumours. Thus, we have developed a model proving that neurodevelopmental disorders and brain tumours might originate from the same activation of oncogenes through somatic mutations, and established that YAP activation is a hallmark of malignant brain tumours.

  2. Automated identification of brain tumours from single MR images based on segmentation with refined patient-specific priors

    Directory of Open Access Journals (Sweden)

    Ana eSanjuán

    2013-12-01

    Full Text Available Brain tumours can have different shapes or locations, making their identification very challenging. In functional MRI, it is not unusual that patients have only one anatomical image due to time and financial constraints. Here, we provide a modified automatic lesion identification (ALI procedure which enables brain tumour identification from single MR images. Our method rests on (A a modified segmentation-normalisation procedure with an explicit extra prior for the tumour and (B an outlier detection procedure for abnormal voxel (i.e. tumour classification. To minimise tissue misclassification, the segmentation-normalisation procedure requires prior information of the tumour location and extent. We therefore propose that ALI is run iteratively so that the output of Step B is used as a patient-specific prior in Step A. We test this procedure on real T1-weighted images from 18 patients, and the results were validated in comparison to two independent observers’ manual tracings. The automated procedure identified the tumours successfully with an excellent agreement with the manual segmentation (area under the ROC curve = 0.97 ± 0.03. The proposed procedure increases the flexibility and robustness of the ALI tool and will be particularly useful for lesion-behaviour mapping studies, or when lesion identification and/or spatial normalisation are problematic.

  3. The INTERPRET Decision-Support System version 3.0 for evaluation of Magnetic Resonance Spectroscopy data from human brain tumours and other abnormal brain masses

    Directory of Open Access Journals (Sweden)

    Mercadal Guillem

    2010-11-01

    Full Text Available Abstract Background Proton Magnetic Resonance (MR Spectroscopy (MRS is a widely available technique for those clinical centres equipped with MR scanners. Unlike the rest of MR-based techniques, MRS yields not images but spectra of metabolites in the tissues. In pathological situations, the MRS profile changes and this has been particularly described for brain tumours. However, radiologists are frequently not familiar to the interpretation of MRS data and for this reason, the usefulness of decision-support systems (DSS in MRS data analysis has been explored. Results This work presents the INTERPRET DSS version 3.0, analysing the improvements made from its first release in 2002. Version 3.0 is aimed to be a program that 1st, can be easily used with any new case from any MR scanner manufacturer and 2nd, improves the initial analysis capabilities of the first version. The main improvements are an embedded database, user accounts, more diagnostic discrimination capabilities and the possibility to analyse data acquired under additional data acquisition conditions. Other improvements include a customisable graphical user interface (GUI. Most diagnostic problems included have been addressed through a pattern-recognition based approach, in which classifiers based on linear discriminant analysis (LDA were trained and tested. Conclusions The INTERPRET DSS 3.0 allows radiologists, medical physicists, biochemists or, generally speaking, any person with a minimum knowledge of what an MR spectrum is, to enter their own SV raw data, acquired at 1.5 T, and to analyse them. The system is expected to help in the categorisation of MR Spectra from abnormal brain masses.

  4. The role of CXC chemokine ligand (CXCL)12-CXC chemokine receptor (CXCR)4 signalling in the migration of neural stem cells towards a brain tumour

    NARCIS (Netherlands)

    van der Meulen, A. A. E.; Biber, K.; Lukovac, S.; Balasubramaniyan, V.; den Dunnen, W. F. A.; Boddeke, H. W. G. M.; Mooij, J. J. A.

    2009-01-01

    Aims: It has been shown that neural stem cells (NSCs) migrate towards areas of brain injury or brain tumours and that NSCs have the capacity to track infiltrating tumour cells. The possible mechanism behind the migratory behaviour of NSCs is not yet completely understood. As chemokines are involved

  5. Metabolite concentrations in the developing brain estimated with proton MR spectroscopy

    DEFF Research Database (Denmark)

    Toft, P B; Leth, H; Lou, H C

    1995-01-01

    The purpose of the present study was to estimate absolute concentrations and relaxation time constants of metabolites that were detectable with proton magnetic resonance (MR) spectroscopy in the healthy preterm, term, and infant brain. Five MR spectra were recorded for each infant by using STEAM ...... concentration. The concentration of PCr+Cr increased rapidly and reached adolescent values at approximately 4 months of age....

  6. Brain and ocular metastases from a transmissible venereal tumour in a dog.

    Science.gov (United States)

    Ferreira, A J; Jaggy, A; Varejão, A P; Ferreira, M L; Correia, J M; Mulas, J M; Almeida, O; Oliveira, P; Prada, J

    2000-04-01

    A five-year-old crossbred dog was referred with rapidly growing masses over its penis and right popliteal lymph node. The dog had severe blepharospasm, congestion of episcleral vessels and rubeosis iridis of the left eye. A presumptive diagnosis of transmissible venereal tumour (TVT) and iridocyclitis was made based on the results of fine needle aspiration. Chemotherapy with vincristine and prednisolone was initiated and after four months the dog made a complete recovery. However, the dog subsequently relapsed, showing miosis, blepharospasm and a well defined mass within the anterior chamber of the left eye. In addition, the dog exhibited generalised 'grand mal' type seizures. Computed tomographic (CT) examination of the brain revealed two distinct masses in the left frontal lobe. Because of the poor prognosis, the owners elected to have the dog euthanased. On histopathology, metastases of TVT in the left eye and left cerebral hemisphere were found, showing no specific staining for CD3, immunoglobulin (Ig) G, IgM and lambda light chains. It was therefore concluded that the tumour growth was progressive, and that there was an absence of local humoral immune response against TVT in this case.

  7. Measuring the volume of brain tumour and determining its location in T2-weighted MRI images using hidden Markov random field: expectation maximization algorithm

    Science.gov (United States)

    Mat Jafri, Mohd. Zubir; Abdulbaqi, Hayder Saad; Mutter, Kussay N.; Mustapha, Iskandar Shahrim; Omar, Ahmad Fairuz

    2017-06-01

    A brain tumour is an abnormal growth of tissue in the brain. Most tumour volume measurement processes are carried out manually by the radiographer and radiologist without relying on any auto program. This manual method is a timeconsuming task and may give inaccurate results. Treatment, diagnosis, signs and symptoms of the brain tumours mainly depend on the tumour volume and its location. In this paper, an approach is proposed to improve volume measurement of brain tumors as well as using a new method to determine the brain tumour location. The current study presents a hybrid method that includes two methods. One method is hidden Markov random field - expectation maximization (HMRFEM), which employs a positive initial classification of the image. The other method employs the threshold, which enables the final segmentation. In this method, the tumour volume is calculated using voxel dimension measurements. The brain tumour location was determined accurately in T2- weighted MRI image using a new algorithm. According to the results, this process was proven to be more useful compared to the manual method. Thus, it provides the possibility of calculating the volume and determining location of a brain tumour.

  8. Day surgery awake craniotomy for removing brain tumours: technical note describing a simple protocol.

    Science.gov (United States)

    Carrabba, G; Venkatraghavan, L; Bernstein, M

    2008-08-01

    Day surgery awake craniotomy has been recently proposed for patients harbouring supratentorial brain tumours. This technique has been demonstrated to be safe and effective in a large cohort of patients operated by one neurosurgeon at the University of Toronto. The aim of this paper is to present a technical description of the protocol that has been adopted for these patients and a discussion of relevant practical issues which may arise. In particular, patient eligibility criteria are briefly discussed and intra- and post-operative management are presented. Key messages for those who are going to start to perform day surgery awake craniotomies include the preparation of a fast, simple and standardized protocol for the treatment of these patients and cooperation among patients and their care-givers (surgeon, anesthetist, nurses, family members).

  9. Lipopolysaccharide induces expression of tumour necrosis factor alpha in rat brain : inhibition by methylprednisolone and by rolipram

    NARCIS (Netherlands)

    Buttini, M; Mir, A; Appel, K; Wiederhold, KH; Limonta, S; GebickeHaerter, PJ; Boddeke, HWGM

    1997-01-01

    1 We have investigated the effects of the phosphodiesterase (PDE) type TV inhibitor rolipram and of the glucocorticoid methylprednisolone on the induction of tumour necrosis factor alpha (TNF-alpha) mRNA and protein in brains of rats after peripheral administration of lipopolysaccharide (LPS). 2

  10. Semi-autonomous image-guided brain tumour resection using an integrated robotic system: A bench-top study.

    Science.gov (United States)

    Hu, Danying; Gong, Yuanzheng; Seibel, Eric J; Sekhar, Laligam N; Hannaford, Blake

    2018-02-01

    Complete brain tumour resection is an extremely critical factor for patients' survival rate and long-term quality of life. This paper introduces a prototype medical robotic system that aims to automatically detect and clean up brain tumour residues after the removal of tumour bulk through conventional surgery. We focus on the development of an integrated surgical robotic system for image-guided robotic brain surgery. The Behavior Tree framework is explored to coordinate cross-platform medical subtasks. The integrated system was tested on a simulated laboratory platform. Results and performance indicate the feasibility of supervised semi-automation for residual brain tumour ablation in a simulated surgical cavity with sub-millimetre accuracy. The modularity in the control architecture allows straightforward integration of further medical devices. This work presents a semi-automated laboratory setup, simulating an intraoperative robotic neurosurgical procedure with real-time endoscopic image guidance and provides a foundation for the future transition from engineering approaches to clinical application. Copyright © 2017 John Wiley & Sons, Ltd.

  11. The oxidation states and chemical environments of iron and zinc as potential indicators of brain tumour malignancy grade - preliminary results.

    Science.gov (United States)

    Wandzilak, Aleksandra; Czyzycki, Mateusz; Wrobel, Pawel; Szczerbowska-Boruchowska, Magdalena; Radwanska, Edyta; Adamek, Dariusz; Lankosz, Marek

    2013-11-01

    Despite the enormous advances in medicine, brain tumours are still among the lesser-known types of tumours and carry the worst prognoses. Transition metals are believed to play an essential role in carcinogenesis. The aim of this study was to determine differences in the average oxidation state and trends in the changes in the chemical environment of iron and zinc contained in healthy and neoplastic tissues of the human brain. For this purpose, X-ray Absorption Spectroscopy was used, which enables the study of disordered matter. The samples were taken intraoperatively and then immediately frozen to slow down chemical processes. Sixteen tumour samples with various malignancy grades were studied as well as one control sample. For each sample four to eight spectra were recorded, with a shift between them not greater than 0.2 eV. In all of the samples, iron occurred in compounds with both Fe(2+) and Fe(3+). However, the ratio of Fe(ii) to Fe(iii) content in the tissue visibly increased with the tumour malignancy grade. The change in the oxidation state of iron did not correlate with the hypoxia level of the tissues. Analysis of EXAFS spectra of zinc atoms showed that the chemical environment of zinc atoms differed with the tumour malignancy grade. Additionally, cryogenic conditions were found to produce positive results in studies of biological samples, whose form under such conditions is close to their native state, without preparation-caused artefacts.

  12. Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression

    DEFF Research Database (Denmark)

    Jørgensen, A.; Magnusson, P.; Hanson, Lars G.

    2016-01-01

    , and metabolite changes in 19 patients receiving ECT for severe depression. Other regions of interest included the amygdala, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex, and hypothalamus. Patients received a 3T MR scan before ECT (TP1), 1 week (TP2), and 4 weeks (TP3) after ECT. Results......: Hippocampal and amygdala volume increased significantly at TP2 and continued to be increased at TP3. DLPFC exhibited a transient volume reduction at TP2. DTI revealed a reduced anisotropy and diffusivity of the hippocampus at TP2. We found no significant post-ECT changes in brain metabolite concentrations...

  13. Texture analysis in quantitative MR imaging. Tissue characterisation of normal brain and intracranial tumours at 1.5 T

    DEFF Research Database (Denmark)

    Kjaer, L; Ring, P; Thomsen, C

    1995-01-01

    The diagnostic potential of texture analysis in quantitative tissue characterisation by MR imaging at 1.5 T was evaluated in the brain of 6 healthy volunteers and in 88 patients with intracranial tumours. Texture images were computed from calculated T1 and T2 parameter images by applying groups...... to be successful in some cases of clinical importance. However, no discrimination between benign and malignant tumour growth was possible. Much texture information seems to be contained in MR images, which may prove useful for classification and image segmentation....

  14. Increasing Rates of Brain Tumours in the Swedish National Inpatient Register and the Causes of Death Register

    Directory of Open Access Journals (Sweden)

    Lennart Hardell

    2015-04-01

    Full Text Available Radiofrequency emissions in the frequency range 30 kHz–300 GHz were evaluated to be Group 2B, i.e., “possibly”, carcinogenic to humans by the International Agency for Research on Cancer (IARC at WHO in May 2011. The Swedish Cancer Register has not shown increasing incidence of brain tumours in recent years and has been used to dismiss epidemiological evidence on a risk. In this study we used the Swedish National Inpatient Register (IPR and Causes of Death Register (CDR to further study the incidence comparing with the Cancer Register data for the time period 1998–2013 using joinpoint regression analysis. In the IPR we found a joinpoint in 2007 with Annual Percentage Change (APC +4.25%, 95% CI +1.98, +6.57% during 2007–2013 for tumours of unknown type in the brain or CNS. In the CDR joinpoint regression found one joinpoint in 2008 with APC during 2008–2013 +22.60%, 95% CI +9.68, +37.03%. These tumour diagnoses would be based on clinical examination, mainly CT and/or MRI, but without histopathology or cytology. No statistically significant increasing incidence was found in the Swedish Cancer Register during these years. We postulate that a large part of brain tumours of unknown type are never reported to the Cancer Register. Furthermore, the frequency of diagnosis based on autopsy has declined substantially due to a general decline of autopsies in Sweden adding further to missing cases. We conclude that the Swedish Cancer Register is not reliable to be used to dismiss results in epidemiological studies on the use of wireless phones and brain tumour risk.

  15. Faster metabolite (1H transverse relaxation in the elder human brain.

    Directory of Open Access Journals (Sweden)

    Małgorzata Marjańska

    Full Text Available (1H magnetic resonance spectroscopy (MRS is unique among imaging modalities because signals from several metabolites are measured during a single examination period. Each metabolite reflects a distinct intracellular process. Furthermore transverse (T2 relaxation times probe the viability of the cell microenvironment, e.g., the viscosity of the cellular fluids, the microscopic susceptibility distribution within the cells, and the iron content. In this study, T2s of brain metabolites were measured in the occipital lobe of eighteen young and fourteen elderly subjects at a field strength of 4 tesla. The T2s of N-acetylaspartate, total creatine, and total choline were 23%, 16% and 10% shorter in elderly than in young subjects. The findings of this study suggest that noninvasive detection of T2 provides useful biological information on changes in the cellular microenvironment that take place during aging.

  16. Reproducibility of brain metabolite concentration measurements in lesion free white matter at 1.5 T.

    Science.gov (United States)

    Busch, Martin H J; Vollmann, Wolfgang; Mateiescu, Serban; Stolze, Manuel; Deli, Martin; Garmer, Marietta; Grönemeyer, Dietrich H W

    2015-09-29

    Post processing for brain spectra has a great influence on the fit quality of individual spectra, as well as on the reproducibility of results from comparable spectra. This investigation used pairs of spectra, identical in system parameters, position and time assumed to differ only in noise. The metabolite amplitudes of fitted time domain spectroscopic data were tested on reproducibility for the main brain metabolites. Proton spectra of white matter brain tissue were acquired with a short spin echo time of 30 ms and a moderate repetition time of 1500 ms at 1.5 T. The pairs were investigated with one time domain post-processing algorithm using different parameters. The number of metabolites, the use of prior knowledge, base line parameters and common or individual damping were varied to evaluate the best reproducibility. The protocols with most reproducible amplitudes for N-acetylaspartate, creatine, choline, myo-inositol and the combined Glx line of glutamate and glutamine in lesion free white matter have the following common features: common damping of the main metabolites, a baseline using only the points of the first 10 ms, no additional lipid/macromolecule lines and Glx is taken as the sum of separately fitted glutamate and glutamine. This parameter set is different to the one delivering the best individual fit results. All spectra were acquired in "lesion free" (no lesion signs found in MR imaging) white matter. Spectra of brain lesions, for example tumors, can be drastically different. Thus the results are limited to lesion free brain tissue. Nevertheless the application to studies is broad, because small alterations in brain biochemistry of lesion free areas had been detected nearby tumors, in patients with multiple sclerosis, drug abuse or psychiatric disorders. Main metabolite amplitudes inside healthy brain can be quantified with a normalized root mean square deviation around 5 % using CH3 of creatine as reference. Only the reproducibility of myo

  17. In vivo quantitation of metabolite concentrations in the brain by means of proton MRS

    DEFF Research Database (Denmark)

    Henriksen, O

    1995-01-01

    MRS offers unique possibilities for non-invasive studies of biochemistry in the human brain in vivo. A growing body of evidence suggests that proton MRS may contribute to the clinical evaluation of a number of pathologies including ischaemia, tumours, epilepsy, metabolic and neuropaediatric......, selection efficiency, outer volume depression and signal contamination is essential for validation of the measurements. Furthermore, corrections for the influence of relaxation behavior are necessary. The results published so far indicate that the concentrations of NAA, total creatine, Cho and Ins in mmoles...

  18. A case series discussing the anaesthetic management of pregnant patients with brain tumours [v2; ref status: indexed, http://f1000r.es/2hn

    Directory of Open Access Journals (Sweden)

    Alaa A Abd-Elsayed

    2013-12-01

    Full Text Available Pregnancy may aggravate the natural history of an intracranial tumour, and may even unmask a previously unknown diagnosis. Here we present a series of seven patients who had brain tumours during pregnancy. The aim of this case series is to characterize the current perioperative management and to suggest evidence based guidelines for the anaesthetic management of pregnant females with brain tumours. This is a retrospective study. Information on pregnant patients diagnosed with brain tumours that underwent caesarean section (CS and/or brain tumour resection from May 2003 through June 2008 was obtained from the Department of General Anaesthesia and the Rose Ella Burkhardt Brain Tumour & Neuro-Oncology Centre (BBTC at the Cleveland Clinic, OH, USA. The mean age was 34.5 years (range 29-40 years old. Six patients had glioma, two of whom had concomitant craniotomy and CS. Six cases had the tumour in the frontal lobe. Four cases were operated on under general anaesthesia and three underwent awake craniotomy. The neonatal outcomes of the six patients with elective or emergent delivery were six viable infants with normal Apgar scores. Pregnancy was terminated in the 7th patient. In conclusion, good knowledge of the variable anesthetic agents and their effects on the fetus is very important in managing those patients.

  19. A PROSPECTIVE HISTOPATHOLOGICAL-BASED STUDY OF BRAIN TUMOURS IN A REFERRAL CENTRE

    National Research Council Canada - National Science Library

    Prathima Gujjaru; N. Saila Rekha; Syam Sunder Rao Uttarakar

    2016-01-01

    .... Most of the tumours encountered are not related to any identifiable risk factors except for irradiation and some hereditary syndromes like subependymal giant cell astrocytoma, glioblastoma multiforme...

  20. In-vivo imaging of the morphology and blood perfusion of brain tumours in rats with UHR-OCT (Conference Presentation)

    Science.gov (United States)

    Bizheva, Kostadinka; Tan, Bingyao; Fisher, Carl J.; Mason, Erik; Lilge, Lothar D.

    2017-02-01

    Brain tumors are characterized with morphological changes at cellular level such as enlarged, non-spherical nuclei, microcalcifications, cysts, etc., and are highly vascularized. In this study, two research-grade optical coherence tomography (OCT) systems operating at 800 nm and 1060 nm with axial resolution of 0.95 µm and 3.5 µm in biological tissue respectively, were used to image in vivo and ex vivo the structure of brain tumours in rats. Female Fischer 344 rats were used for this study, which has received ethics clearance by the Animal Research Ethics Committees of the University of Waterloo and the University Health Network, Toronto. Brain tumours were induced by injection of rat brain cancer cell line (RG2 glioma) through a small craniotomy. Presence of brain tumours was verified by MRI imaging on day 7 post tumour cells injection. The in vivo OCT imaging session was conducted on day 14 of the study with the 1060 nm OCT system and both morphological OCT, Doppler OCT and OMAG images were acquired from the brain tumour and the surrounding healthy brain tissue. After completion of the imaging procedure, the brains were harvested, fixed in formalin and reimaged after 2 weeks with the 800 nm OCT system. The in vivo and ex vivo OCT morphological images were correlated with H and E histology. Results from this study demonstrate that UHR-OCT can distinguish between healthy and cancerous brain tissue based on differences in structural and vascular pattern.

  1. Influence of X-rays on early response gene expression in rat astrocytes and brain tumour cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Vrdoljak, E.; Borchardt, P.E.; Bill, C.A.; Stephens, L.C.; Tofilon, P.J. [Anderson (M.D.) Cancer Center, Houston, TX (United States)

    1994-12-01

    The effects of ionizing radiation on c-fos, c-jun and jun-B mRNA levels were determined in cultures of rat perinatal type 1 astrocytes and two rat brain tumour cell lines, 175A and 9L. In astrocyte cultures X-ray doses as low as 1 Gy induced the expression of c-fos and jun-B but had essentially no effect on c-jun. The maximum increase in expression was found 1 h after irradiation, which then rapidly returned to control levels. These findings suggest that astrocytes may play a role in mediating the radiation response of the central nervous system via X-ray-induced changes in gene expression. In contrast, doses of up to 20 Gy had no effect on c-fos, c-jun and jun-B mRNA levels in the two brain tumour cell lines. In addition, whereas 12-0-tetradecanoylphorbol-13-acetate induced the expression of these genes in astrocytes, it had little or no effect on fos or jun expression in 9L or 175A cells. These results suggest that the signal transduction pathways mediating radiation-induced genes expression may be different in normal astrocytes and brain tumour cells. (author).

  2. A multinational case-control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures

    DEFF Research Database (Denmark)

    Vienneau, Danielle; Infanger, Denis; Feychting, Maria

    2016-01-01

    complemented with data from birth registries and validated by assessing agreement (Cohen's Kappa). We used conditional logistic regression models matched on age, sex and geographical region (adjusted for maternal age and parental education) to explore associations between birth factors and childhood brain...... during pregnancy was indicative of a protective effect (OR 0.75, 95%-CI: 0.56-1.01). No association was seen for maternal smoking during pregnancy or working during pregnancy. We found little evidence that the considered birth factors were related to brain tumour risk among children and adolescents....

  3. The Prognostic Value of Brain Extracellular Fluid Nitric Oxide Metabolites After Traumatic Brain Injury

    NARCIS (Netherlands)

    Tisdall, M.M.; Rejdak, K.; Kitchen, N.D.; Smith, M.; Petzold, A.

    2013-01-01

    Background: Nitric oxide (NO) is a compound with both protective and damaging effects on neurons. Quantification of NO metabolites in humans is limited by sample contamination with blood. In vivo cerebral microdialysis may offer an alternative approach as sampling of extracellular fluid (ECF)

  4. Cerebellar mutism syndrome in children with brain tumours of the posterior fossa

    DEFF Research Database (Denmark)

    Wibroe, Morten; Cappelen, Johan; Castor, Charlotte

    2017-01-01

    Background: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has ...

  5. Pharmacokinetics of thioridazine and its metabolites in blood plasma and the brain of rats after acute and chronic treatment.

    Science.gov (United States)

    Daniel, W A; Syrek, M; Mach, A; Wójcikowski, J; Boksa, J

    1997-01-01

    This study was aimed at investigation of the pharmacokinetics of thioridazine and its metabolites after a single and repeated administrations. Male Wistar rats received thioridazine as a single dose (10 mg/kg i.p.) or they were treated chronically with the neuroleptic (10 mg/kg i.p., twice a day for two weeks). Plasma and brain concentrations of thioridazine and its metabolites (N-desmethylthioridazine, mesoridazine, sulforidazine, and the ring sulfoxide) were determined using the HPLC method. The obtained data showed that sulfoxidation in position 2 of the thiomethyl substituent and in the thiazine ring are main metabolic pathways of thioridazine, and showed that, in contrast to humans, in the rat N-desmethylthioridazine is formed in appreciable amount. The biotransformation of thioridazine was rather fast yielding plasma peak concentrations of metabolites lower than that of the parent compound. The maximum concentrations of thioridazine and its metabolites in the brain appeared later than in plasma. The peak concentrations and AUC values of thioridazine and its metabolites were higher in the brain than in plasma and this corresponded well with their longer half-lives in the brain as compared to plasma. The drug was not taken up by the brain as efficiently as other phenothiazines. Chronic treatment with thioridazine produced significant increases (with the exception of thioridazine ring sulfoxide) in the plasma concentrations of the parent compound and its metabolites which was accompanied with the prolongation of their plasma half-lives. The observed plasma levels of thioridazine were within 'therapeutic range' while the concentrations of its metabolites were relatively lower as compared to those observed in psychiatric patients. The increased plasma concentrations of thioridazine and its metabolites observed in plasma after chronic treatment were not followed by parallel changes in the brain.

  6. Pharmaco-thermodynamics of deuterium-induced oedema in living rat brain via 1H2O MRI: implications for boron neutron capture therapy of malignant brain tumours

    Science.gov (United States)

    Medina, Daniel C.; Li, Xin; Springer, Charles S., Jr.

    2005-05-01

    In addition to its common usage as a tracer in metabolic and physiological studies, deuterium possesses anti-tumoural activity and confers protection against γ-irradiation. A more recent interest in deuterium emanates from the search for alternatives capable of improving neutron penetrance whilst reducing healthy tissue radiation dose deposition in boron neutron capture therapy of malignant brain tumours. Despite this potential clinical application, deuterium induces brain oedema, which is detrimental to neutron capture therapy. In this study, five adult male rats were titrated with deuterated drinking water while brain oedema was monitored via water proton magnetic resonance imaging. This report concludes that deuterium, as well as deuterium-induced brain oedema, possesses a uniform brain bio-distribution. At a steady-state blood fluid deuteration value of 16%, when the deuterium isotope fraction in drinking water was 25%, a mean oedematous volume change of 9 ± 2% (p-value body fluid deuteration enhances thermal neutron flux penetrance and reduces dose deposition, oedema has the opposite effect because it increases the volume of interest, e.g., the brain volume. Thermal neutron enhancement and effective dose reduction factors could be reduced by as much as ~10% in the presence of a 9% water volume increase (oedema). All three authors have contributed equally to this work.

  7. Simultaneous determination of monoamine transmitters, precursors and metabolites in a single mouse brain.

    Science.gov (United States)

    Ishikawa, K; McGaugh, J L

    1982-04-16

    A simple and sensitive procedure for simultaneous determination of monoamine transmitters and related substances including precursors and metabolites has been developed for a single mouse brain. The proposed procedure involves (1) primary butanol extraction, (2) separation of the substances into either acid or alkaline aqueous layers according to their physicochemical properties, and (3) determination by means of high-performance liquid chromatography with electrochemical detection. Three transmitters (noradrenaline, dopamine and 5-hydroxytryptamine) and their precursors (tyrosine, 3,4-dihydroxyphenylalanine and tryptophan) and major metabolites (normethanephrine, 3-methoxy-4-hydroxyphenylethylene glycol, 3-methoxytyramine, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylacetic acid and 5-hydroxyindoleacetic acid) were selectively separated and sensitively detected in mouse whole brain sample. Although 3-methoxy-4-hydroxymandelic acid was also separated from other substances by authentic chromatography, the substance was not detected in mouse brain. Changes in levels of these substances were examined for drugs whose effects had been previously confirmed. These changes reflected putative effects of the drugs and confirmed that the procedure is effective for neurochemical research into the transmitter system.

  8. Postmortem Brain and Blood Reference Concentrations of Alprazolam, Bromazepam, Chlordiazepoxide, Diazepam, and their Metabolites and a Review of the Literature

    DEFF Research Database (Denmark)

    Skov, Louise; Holm, Karen Marie Dollerup; Johansen, Sys Stybe

    2016-01-01

    , the brain, might be considered. Here we present reference concentrations of femoral blood and brain tissue of selected benzodiazepines (BZDs). Using LC-MS/MS, we quantified alprazolam, bromazepam, chlordiazepoxide, diazepam, and the metabolites desmethyldiazepam, oxazepam and temazepam in postmortem femoral...

  9. Misdiagnosis of Child Abuse Related to Delay in Diagnosing a Paediatric Brain Tumour

    Directory of Open Access Journals (Sweden)

    Lynne Wrennall Ph.D.

    2008-01-01

    Full Text Available Conflicting opinion regarding the relative weight that should be allocated to the investigation of organic causes of child illness, compared to the pursuit of suspicions of child abuse, has generated considerable public debate. The discourse of Munchausen Syndrome by Proxy/Fabricated and Induced Illness is at the centre of contention. In particular, concern has arisen that children's medical needs are being neglected when their conditions are misdiagnosed as child abuse. This paper documents a case study in which the use of Child Protection procedures was linked to the belief that the child's illness had “no organic cause.” The case study is contextualised in a review of literature relevant to the diagnostic process. The deployment of the Child Protection perspective resulted in significant delay in the diagnosis of the child's brain tumour. The child was ultimately found to be suffering from an optic chasm mass lesion involving the hypothalamus and the medial temporal regions, resulting in Diencephalic Syndrome. The evidence in this case is that erring on the side of suspecting Munchausen Syndrome by Proxy/Fabricated and Induced Illness, was not “erring on the side of the child.” Several lessons need to be learned from the case. The importance of ensuring that the Child Protection perspective does not displace adequate assessment of alternative explanations for the child's condition is emphasised, as is the need for good communication in medical relationships. Strategies involving empathy, mediation, negotiation and conflict resolution may provide a more appropriate and therapeutic alternative to the use of Child Protection procedures in cases where the diagnosis is contentious. The need to re-write relevant policy, protocols and guidance is imperative.

  10. Misdiagnosis of Child Abuse Related to Delay in Diagnosing a Paediatric Brain Tumour

    Directory of Open Access Journals (Sweden)

    Lynne Wrennall

    2008-01-01

    Full Text Available Conflicting opinion regarding the relative weight that should be allocated to the investigation of organic causes of child illness, compared to the pursuit of suspicions of child abuse, has generated considerable public debate. The discourse of Munchausen Syndrome by Proxy/Fabricated and Induced Illness is at the centre of contention. In particular, concern has arisen that children’s medical needs are being neglected when their conditions are misdiagnosed as child abuse. This paper documents a case study in which the use of Child Protection procedures was linked to the belief that the child’s illness had “no organic cause.” The case study is contextualised in a review of literature relevant to the diagnostic process. The deployment of the Child Protection perspective resulted in significant delay in the diagnosis of the child’s brain tumour. The child was ultimately found to be suffering from an optic chasm mass lesion involving the hypothalamus and the medial temporal regions, resulting in Diencephalic Syndrome. The evidence in this case is that erring on the side of suspecting Munchausen Syndrome by Proxy/Fabricated and Induced Illness, was not “erring on the side of the child.” Several lessons need to be learned from the case. The importance of ensuring that the Child Protection perspective does not displace adequate assessment of alternative explanations for the child’s condition is emphasised, as is the need for good communication in medical relationships. Strategies involving empathy, mediation, negotiation and conflict resolution may provide a more appropriate and therapeutic alternative to the use of Child Protection procedures in cases where the diagnosis is contentious. The need to re-write relevant policy, protocols and guidance is imperative.

  11. Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Gredal, O; Rosenbaum, S; Topp, S

    1997-01-01

    20-mm3 voxel placed in the motor cortex and in the cerebellum from seven patients with clinically probable or definite amyotrophic lateral sclerosis (ALS) according to the El Escorial criteria, from three patients with suspected ALS (progressive muscular atrophy), and from eight normal control...... subjects. We estimated the concentrations of the metabolites using the water signal as an internal standard. The concentrations of Cho and Cr/PCr in both brain regions, as well as the concentration of NAA in the cerebellum, were unaltered in the MND patients compared with the controls. Only MND patients...

  12. A case series discussing the anaesthetic management of pregnant patients with brain tumours [v1; ref status: indexed, http://f1000r.es/y7

    Directory of Open Access Journals (Sweden)

    Alaa A Abd-Elsayed

    2013-03-01

    Full Text Available Pregnancy may aggravate the natural history of an intracranial tumour, and may even unmask a previously unknown diagnosis. Here we present a series of seven patients who had brain tumours during pregnancy. The aim of this case series is to characterize the current perioperative management and to suggest evidence based guidelines for the anaesthetic management of pregnant females with brain tumours. This is a retrospective study. Information on pregnant patients diagnosed with brain tumours that underwent caesarean section (CS and/or brain tumour resection from May 2003 through June 2008 was obtained from the Department of General Anaesthesia and the Rose Ella Burkhardt Brain Tumour & Neuro-Oncology Centre (BBTC at the Cleveland Clinic, OH, USA. The mean age was 34.5 years (range 29-40 years old. Six patients had glioma, two of whom had concomitant craniotomy and CS. Six cases had the tumour in the frontal lobe. Four cases were operated on under general anaesthesia and three underwent awake craniotomy. The neonatal outcomes of the six patients with elective or emergent delivery were six viable infants with normal Apgar scores. Pregnancy was terminated in the 7th patient. In conclusion, management of brain tumours in pregnant women is mainly reliant on case reports and the doctor’s personal experience. Therefore, close communication between the neurosurgeon, neuroanaesthetist, obstetrician and the patient is crucial. General anaesthesia, propofol, dexmedetomidine and remifentanil were used in our study and were safe. Although this may not agree with previous studies, desflurane and isoflurane were used in our patients with no detectable complications.

  13. Metabolite concentrations in the developing brain estimated with proton MR spectroscopy

    DEFF Research Database (Denmark)

    Toft, P B; Leth, H; Lou, H C

    1995-01-01

    The purpose of the present study was to estimate absolute concentrations and relaxation time constants of metabolites that were detectable with proton magnetic resonance (MR) spectroscopy in the healthy preterm, term, and infant brain. Five MR spectra were recorded for each infant by using STEAM...... of a relatively larger signal overlap with glutamate in the most immature brains. The concentration of NAA almost doubled, whereas the Cho concentration showed only a nonsignificant tendency to decrease; therefore, the well-known increase in the ratio of NAA to Cho appears to be due mostly to an increase in NAA...... concentration. The concentration of PCr+Cr increased rapidly and reached adolescent values at approximately 4 months of age....

  14. Human Serum Metabolites Associate With Severity and Patient Outcomes in Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Matej Orešič

    2016-10-01

    Full Text Available Traumatic brain injury (TBI is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n = 22, moderate (moTBI; n = 14 or mild TBI (mTBI; n = 108 according to Glasgow Coma Scale. The control group (n = 28 comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n = 23, moTBI (n = 7, mTBI (n = 37 patients and controls (n = 27. We show that two medium-chain fatty acids (decanoic and octanoic acids and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC = 0.84 in validation cohort. Addition of the metabolites to the established clinical model (CRASH, comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified ‘TBI metabotype’ in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new avenue for the development of diagnostic and prognostic markers of broad spectrum of TBIs.

  15. Protection of Brain Injury by Amniotic Mesenchymal Stromal Cell-Secreted Metabolites.

    Science.gov (United States)

    Pischiutta, Francesca; Brunelli, Laura; Romele, Pietro; Silini, Antonietta; Sammali, Eliana; Paracchini, Lara; Marchini, Sergio; Talamini, Laura; Bigini, Paolo; Boncoraglio, Giorgio B; Pastorelli, Roberta; De Simoni, Maria-Grazia; Parolini, Ornella; Zanier, Elisa R

    2016-11-01

    To define the features of human amniotic mesenchymal stromal cell secretome and its protective properties in experimental models of acute brain injury. Prospective experimental study. Laboratory research. C57Bl/6 mice. Mice subjected to sham or traumatic brain injury by controlled cortical impact received human amniotic mesenchymal stromal cells or phosphate-buffered saline infused intracerebroventricularly or intravenously 24 hours after injury. Organotypic cortical brain slices exposed to ischemic injury by oxygen-glucose deprivation were treated with human amniotic mesenchymal stromal cells or with their secretome (conditioned medium) in a transwell system. Traumatic brain injured mice receiving human amniotic mesenchymal stromal cells intravenously or intracerebroventricularly showed early and lasting functional and anatomical brain protection. cortical slices injured by oxigen-glucose deprivation and treated with human amniotic mesenchymal stromal cells or conditioned medium showed comparable protective effects (neuronal rescue, promotion of M2 microglia polarization, induction of trophic factors) indicating that the exposure of human amniotic mesenchymal stromal cells to the injured tissue is not necessary for the release of bioactive factors. Using sequential size-exclusion and gel-filtration chromatography, we identified a conditioned medium subfraction, which specifically displays these highly protective properties and we found that this fraction was rich in bioactive molecules with molecular weight smaller than 700 Da. Quantitative RNA analysis and mass spectrometry-based peptidomics showed that the active factors are not proteins or RNAs. The metabolomic profiling of six metabolic classes identified a list of molecules whose abundance was selectively elevated in the active conditioned medium fraction. Human amniotic mesenchymal stromal cell-secreted factors protect the brain after acute injury. Importantly, a fraction rich in metabolites, and

  16. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Local tumour control and survival

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, Oliver; Wucherpfennig, David; Prokic, Vesna [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Fels, Franziska [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); St. Josefs Hospital, Department of Radiation Oncology, Offenburg (Germany); Frings, Lars [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); University Hospital Freiburg, Department of Geriatrics and Gerontology, Freiburg (Germany); University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Egger, Karl [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Weyerbrock, Astrid [University Medical Center Freiburg, Department of Neurosurgery, Freiburg (Germany); Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Grosu, Anca-Ligia [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK), Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2015-01-16

    Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D{sub 98} {sub %} to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. D{sub mean} to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration. (orig.) [German] Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusaetzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie praesentieren wir erste Ergebnisse

  17. Failure of the PTEN/aPKC/Lgl Axis Primes Formation of Adult Brain Tumours in Drosophila

    Directory of Open Access Journals (Sweden)

    Simona Paglia

    2017-01-01

    Full Text Available Different regions in the mammalian adult brain contain immature precursors, reinforcing the concept that brain cancers, such as glioblastoma multiforme (GBM, may originate from cells endowed with stem-like properties. Alterations of the tumour suppressor gene PTEN are very common in primary GBMs. Very recently, PTEN loss was shown to undermine a specific molecular axis, whose failure is associated with the maintenance of the GBM stem cells in mammals. This axis is composed of PTEN, aPKC, and the polarity determinant Lethal giant larvae (Lgl: PTEN loss promotes aPKC activation through the PI3K pathway, which in turn leads to Lgl inhibition, ultimately preventing stem cell differentiation. To find the neural precursors responding to perturbations of this molecular axis, we targeted different neurogenic regions of the Drosophila brain. Here we show that PTEN mutation impacts aPKC and Lgl protein levels also in Drosophila. Moreover, we demonstrate that PI3K activation is not sufficient to trigger tumourigenesis, while aPKC promotes hyperplastic growth of the neuroepithelium and a noticeable expansion of the type II neuroblasts. Finally, we show that these neuroblasts form invasive tumours that persist and keep growing in the adult, leading the affected animals to untimely death, thus displaying frankly malignant behaviours.

  18. Advance care planning in patients with primary malignant brain tumours: a systematic review

    Directory of Open Access Journals (Sweden)

    Krystal Song

    2016-10-01

    Full Text Available Advance care planning (ACP is a process of reflection and communication of a person’s future health care preferences, and has been shown to improve end-of-life care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumours (pmBT. A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus and Web of Science up to July 2016. Manual search of bibliographies of articles and grey literature search were also conducted. Two independent reviewers selected studies, extracted data and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program’s appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included (1 RCT, 17 cohort studies, 1 qualitative study with 4686 participants. All studies scored low to moderate on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision–making. However, the effect of the intervention on quality of life and care at the end-of-life were unclear. There was a low rate of use of ACP discussions at the end-of-life. Advance Directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with lack of

  19. Preoperative mapping of cortical language areas in adult brain tumour patients using PET and individual non-normalised SPM analyses

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Philipp T. [Department of Nuclear Medicine, Aachen University of Technology, Aachen (Germany); Department of Nuclear Medicine, University of Leipzig, Leipzig (Germany); Institute of Medicine, Research Centre Juelich, 52425, Juelich (Germany); Sturz, Laszlo; Schreckenberger, Mathias; Setani, Keyvan S.; Buell, Udalrich [Department of Nuclear Medicine, Aachen University of Technology, Aachen (Germany); Spetzger, Uwe [Department of Neurosurgery, Aachen University of Technology, Aachen (Germany); Meyer, Georg F. [MacKay Institute of Communication and Neuroscience, Keele University (United Kingdom); Sabri, Osama [Department of Nuclear Medicine, Aachen University of Technology, Aachen (Germany); Department of Nuclear Medicine, University of Leipzig, Leipzig (Germany)

    2003-07-01

    In patients scheduled for the resection of perisylvian brain tumours, knowledge of the cortical topography of language functions is crucial in order to avoid neurological deficits. We investigated the applicability of statistical parametric mapping (SPM) without stereotactic normalisation for individual preoperative language function brain mapping using positron emission tomography (PET). Seven right-handed adult patients with left-sided brain tumours (six frontal and one temporal) underwent 12 oxygen-15 labelled water PET scans during overt verb generation and rest. Individual activation maps were calculated for P<0.005 and P<0.001 without anatomical normalisation and overlaid onto the individuals' magnetic resonance images for preoperative planning. Activations corresponding to Broca's and Wernicke's areas were found in five and six cases, respectively, for P<0.005 and in three and six cases, respectively, for P<0.001. One patient with a glioma located in the classical Broca's area without aphasic symptoms presented an activation of the adjacent inferior frontal cortex and of a right-sided area homologous to Broca's area. Four additional patients with left frontal tumours also presented activations of the right-sided Broca's homologue; two of these showed aphasic symptoms and two only a weak or no activation of Broca's area. Other frequently observed activations included bilaterally the superior temporal gyri, prefrontal cortices, anterior insulae, motor areas and the cerebellum. The middle and inferior temporal gyri were activated predominantly on the left. An SPM group analysis (P<0.05, corrected) in patients with left frontal tumours confirmed the activation pattern shown by the individual analyses. We conclude that SPM analyses without stereotactic normalisation offer a promising alternative for analysing individual preoperative language function brain mapping studies. The observed right frontal activations agree with

  20. Multimodal imaging utilising integrated MR-PET for human brain tumour assessment

    Energy Technology Data Exchange (ETDEWEB)

    Neuner, Irene [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); RWTH Aachen University, Department of Psychiatry, Psychotherapy and Psychosomatics, Aachen (Germany); JARA-BRAIN-Translational Medicine, Aachen (Germany); Kaffanke, Joachim B. [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); MR-Transfer e.K., Wuppertal (Germany); Langen, Karl-Josef; Kops, Elena Rota; Tellmann, Lutz; Stoffels, Gabriele; Weirich, Christoph; Filss, Christian; Scheins, Juergen; Herzog, Hans [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); Shah, N. Jon [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); RWTH Aachen University, Department of Neurology, Aachen (Germany); JARA-BRAIN-Translational Medicine, Aachen (Germany)

    2012-12-15

    The development of integrated magnetic resonance (MR)-positron emission tomography (PET) hybrid imaging opens up new horizons for imaging in neuro-oncology. In cerebral gliomas the definition of tumour extent may be difficult to ascertain using standard MR imaging (MRI) only. The differentiation of post-therapeutic scar tissue, tumour rests and tumour recurrence is challenging. The relationship to structures such as the pyramidal tract to the tumour mass influences the therapeutic neurosurgical approach. The diagnostic information may be enriched by sophisticated MR techniques such as diffusion tensor imaging (DTI), multiple-volume proton MR spectroscopic imaging (MRSI) and functional MRI (fMRI). Metabolic imaging with PET, especially using amino acid tracers such as {sup 18}F-fluoroethyl-l-tyrosine (FET) or {sup 11}C-l-methionine (MET) will indicate tumour extent and response to treatment. The new technologies comprising MR-PET hybrid systems have the advantage of providing comprehensive answers by a one-stop-job of 40-50 min. The combined approach provides data of different modalities using the same iso-centre, resulting in optimal spatial and temporal realignment. All images are acquired exactly under the same physiological conditions. We describe the imaging protocol in detail and provide patient examples for the different imaging modalities such as FET-PET, standard structural imaging (T1-weighted, T2-weighted, T1-weighted contrast agent enhanced), DTI, MRSI and fMRI. (orig.)

  1. Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumour stem cells

    OpenAIRE

    Martín, V.; Sanchez-Sanchez, A M; Herrera, F.; Gomez-Manzano, C; Fueyo, J; Alvarez-Vega, M A; Antolín, I; Rodriguez, C.

    2013-01-01

    Background: Current evidence indicates that a stem cell-like sub-population within malignant glioblastomas, that overexpress members of the adenosine triphosphate-binding cassette (ABC) family transporters, is responsible for multidrug resistance and tumour relapse. Eradication of the brain tumour stem cell (BTSC) compartment is therefore essential to achieve a stable and long-lasting remission. Methods: Melatonin actions were analysed by viability cell assays, flow cytometry, quantitative PC...

  2. Cerebellar mutism syndrome in children with brain tumours of the posterior fossa

    DEFF Research Database (Denmark)

    Wibroe, Morten; Cappelen, Johan; Castor, Charlotte

    2017-01-01

    Background: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has...... standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre- operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally...

  3. Prognostic factors and survival according to tumour subtype in women presenting with breast cancer brain metastases at initial diagnosis.

    Science.gov (United States)

    Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro

    2017-03-01

    The presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is uncommon. Hence, the prognostic assessment and management of these patients is very challenging. The aim of this study was to analyse the influence of tumour subtype compared with other prognostic factors in the survival of patients with BMIBCD. We evaluated women with BMIBCD, reported to Surveillance, Epidemiology and End Results program from 2010 to 2013. Patients with other primary malignancy were excluded. Univariate and multivariate analyses were performed to determine the effects of each variable on overall survival (OS). We included 740 patients. Median OS for the whole population was 10 months, and 20.7% of patients were alive at 36 months. Tumour subtype distribution was: 46.6% hormone receptor (HR)+/HER2-, 17% HR+/HER2+, 14.1% HR-/HER2+ and 22.3% triple-negative. Univariate analysis showed that the presence of liver metastases, lung metastases and triple-negative patients (median OS 6 months) had worse prognosis. The HR+/HER2+ subtype had the longest OS with a median of 22 months. In multivariate analysis, older age (hazard ratio 1.8), lobular histology (hazard ratio 2.08), triple-negative subtype (hazard ratio 2.25), liver metastases (hazard ratio 1.6) and unmarried patients (hazard ratio 1.39) had significantly shorter OS. Although the prognosis of patients with BMIBCD is generally poor, 20.7% were still alive 3 years after the diagnosis. There were substantial differences in OS according to tumour subtype. In addition to tumour subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Cigarette smoking exacerbates chronic alcohol-induced brain damage: a preliminary metabolite imaging study.

    Science.gov (United States)

    Durazzo, Timothy C; Gazdzinski, Stefan; Banys, Peter; Meyerhoff, Dieter J

    2004-12-01

    Cigarette smoking is common among alcohol-dependent individuals. Nevertheless, previous research has typically not accounted for the potential independent or compounding effects of cigarette smoking on alcohol-induced brain injury and neurocognition. Twenty-four 1-week-abstinent recovering alcoholics (RAs; 14 smokers and 10 nonsmokers) in treatment and 26 light-drinking controls (7 smokers and 19 nonsmokers) were compared on measures of common brain metabolites in gray matter and white matter of the major lobes, basal ganglia, midbrain, and cerebellar vermis, obtained via multislice short-echo time proton magnetic resonance spectroscopic imaging. Smoking and nonsmoking RAs were also contrasted on measures of neurocognitive functioning, as well as laboratory markers of drinking severity and nutritional status. Chronic alcohol dependence, independent of smoking, was associated with lower concentrations of frontal N-acetylaspartate (NAA) and frontal choline-containing compounds, as well as lower parietal and thalamic choline. Smoking RAs had lower NAA concentrations in frontal white matter and midbrain and lower midbrain choline than nonsmoking RAs. A four-group analysis of covariance also demonstrated that chronic cigarette smoking was associated with lower midbrain NAA and choline and with lower vermian choline. In smoking RAs, heavier drinking was associated with heavier smoking, which correlated with numerous subcortical metabolite abnormalities. The 1-week-abstinent smoking and nonsmoking RAs did not differ significantly on a brief neurocognitive battery. In smoking RAs, lower cerebellar vermis NAA was associated with poorer visuomotor scanning speed and incidental learning, and in nonsmoking RAs lower vermis NAA was related to poorer visuospatial learning and memory. These human in vivo proton magnetic resonance spectroscopic imaging findings indicate that chronic cigarette smoking exacerbates chronic alcohol-induced neuronal injury and cell membrane damage in

  5. Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria-related appendicitis

    DEFF Research Database (Denmark)

    Kaemmerer, Elke; Schneider, Ursula; Klaus, Christina

    2012-01-01

    Kaemmerer E, Schneider U, Klaus C, Plum P, Reinartz A, Adolf M, Renner M, Wolfs T G A M, Kramer B W, Wagner N, Mollenhauer J & Gassler N (2012) Histopathology Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria-related appendicitis Aims:  Deleted in malignant brain...... in bacteria-related active intestinal inflammation such as appendicitis. Methods and results:  mRNA and protein levels of DMBT1 were analysed in surgical resections of 50 appendices (active inflammation: n = 25). In non-actively inflamed appendices, inter-individual differences in basal DMBT1 levels...... of enterocytes and some non-epithelial cells were found. In active appendicitis, enterocytic DMBT1 mRNA expression was increased approximately fivefold, which was paralleled by a corresponding increase of cytoplasmic and secreted DMBT1 protein levels. Increased DMBT1 expression was predominant in enterocytes...

  6. Mir-34a mimics are potential therapeutic agents for p53-mutated and chemo-resistant brain tumour cells.

    Directory of Open Access Journals (Sweden)

    Yuen Ngan Fan

    Full Text Available Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma and adult (glioblastoma brain tumour treatment. Medulloblastoma tumours and cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive to DNA damaging agents. The aim of this study was to investigate the potential of triggering cell death in p53 mutated medulloblastoma cells by a direct activation of pro-death signalling downstream of p53 activation. Since non-coding microRNAs (miRNAs have the ability to fine tune the expression of a variety of target genes, orchestrating multiple downstream effects, we hypothesised that triggering the expression of a p53 target miRNA could induce cell death in chemo-resistant cells. Treatment with etoposide, increased miR-34a levels in a p53-dependent fashion and the level of miR-34a transcription was correlated with the cell sensitivity to etoposide. miR-34a activity was validated by measuring the expression levels of one of its well described target: the NADH dependent sirtuin1 (SIRT1. Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines. Our results show that the need of a functional p53 signaling pathway can be bypassed by direct activation of miR-34a in brain tumour cells.

  7. Neurotransmitter and their metabolite concentrations in different areas of the HPRT knockout mouse brain.

    Science.gov (United States)

    Tschirner, Sarah K; Gutzki, Frank; Schneider, Erich H; Seifert, Roland; Kaever, Volkhard

    2016-06-15

    Lesch-Nyhan syndrome (LNS) is characterized by uric acid overproduction and severe neurobehavioral symptoms, such as recurrent self-mutilative behavior. To learn more about the pathophysiology of the disease, we quantified neurotransmitters and their metabolites in the cerebral hemisphere, cerebellum and the medulla oblongata of HPRT knockout mice, an animal model for LNS, in comparison to the corresponding wild-type. Our analyses included l-glutamate, 4-aminobutanoic acid (GABA), acetylcholine, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, l-normetanephrine, epinephrine and l-metanephrine and were conducted via high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS). Among these neurotransmitter systems, we did not find any abnormalities in the HPRT knockout mouse brains. On one side, this might indicate that HPRT deficiency most severely affects dopamine signaling, while brain functioning based on other neurotransmitters is more or less spared. On the other hand, our findings may reflect a compensating mechanism for impaired purine salvage that protects the brain in HPRT-deficient mice but not in LNS patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Study of bantam miRNA expression in brain tumour resulted due to ...

    Indian Academy of Sciences (India)

    ANIMESH BANERJEE

    2017-06-19

    Jun 19, 2017 ... ... in governing several biological as well as pathological processes, including tumourigenesis across various species. Drosophila bantam miRNA, known to regulate critical physiological functions is reported to have elevated expression in ovarian tumour. Here, we provide an update on the expression of.

  9. incidence of brain tumours at an academic centre in western saudi ...

    African Journals Online (AJOL)

    2012-04-04

    Apr 4, 2012 ... most common presenting symptom was headache. (68%), followed by nausea and vomiting (32%). The most common sign was weakness (37.6%), followed by cranial nerve abnormalities (29.8%) and abnormal reflexes (27.2%). The frequency of tumours with regard to location showed that the frontal lobe ...

  10. Imaging of adult astrocytic brain tumours with 7 T MRI: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Moenninghoff, Christoph; Forsting, Michael; Wanke, Isabel [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Maderwald, Stefan; Theysohn, Jens M.; Kraff, Oliver; Ladd, Mark E. [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); El Hindy, Nicolai [University Hospital Essen, Department of Neurosurgery, Essen (Germany); Nes, Johannes van de [University Hospital Essen, Department of Neuropathology, Essen (Germany)

    2010-03-15

    In this study tumour vascularity and necrosis of intracranial astrocytomas were compared using 7 T and 1.5 T magnetic resonance imaging (MRI). Fifteen patients with histologically proven astrocytomas (WHO grades II-IV) were prospectively examined at 1.5 T (Magnetom Espree or Sonata) and 7 T (Magnetom 7 T, Siemens, Erlangen, Germany) with T2*-w (weighted), T1-w with (only a subset of five patients at 7 T) and without contrast medium, T2-w and proton-density (PD)-w MRI. Clinically used 1.5 T sequences were adapted to 7 T. Histological findings and T2*-w MR images at both field strengths were compared for the presence of assumed tumour microvascularity and necrosis. Two diffusely infiltrating astrocytomas, four anaplastic astrocytomas and nine glioblastomas were included. T2*-w images depicted susceptibility patterns representing presumed tumour microvascularity in 8 out of 15 (53%) gliomas at 7 T compared with 5 out of 15 (33%) gliomas at 1.5 T. Compared with 1.5 T MRI three additional necrotic tumour areas were depicted only on 7 T T2- and T2*-w images of one glioblastoma. On T1-w MR images, contrast enhancement of five out of five glioblastomas was similar at both field strengths. 7 T gradient-echo sequences provide excellent image contrast of presumed microvasculature and necrosis in astrocytomas. (orig.)

  11. Diagnostic benefits of presurgical fMRI in patients with brain tumours in the primary sensorimotor cortex

    Energy Technology Data Exchange (ETDEWEB)

    Wengenroth, Martina; Blatow, M.; Guenther, J. [University of Heidelberg Medical School, Department of Neuroradiology, Heidelberg (Germany); Akbar, M. [University of Heidelberg Medical School, Department of Orthopaedics, Heidelberg (Germany); Tronnier, V.M. [University of Schleswig-Holstein, Department of Neurosurgery, Luebeck (Germany); Stippich, C. [University Hospital Basle, Department of Diagnostic and Interventional Neuroradiology, Basle (Switzerland)

    2011-07-15

    Reliable imaging of eloquent tumour-adjacent brain areas is necessary for planning function-preserving neurosurgery. This study evaluates the potential diagnostic benefits of presurgical functional magnetic resonance imaging (fMRI) in comparison to a detailed analysis of morphological MRI data. Standardised preoperative functional and structural neuroimaging was performed on 77 patients with rolandic mass lesions at 1.5 Tesla. The central region of both hemispheres was allocated using six morphological and three functional landmarks. fMRI enabled localisation of the motor hand area in 76/77 patients, which was significantly superior to analysis of structural MRI (confident localisation of motor hand area in 66/77 patients; p < 0.002). FMRI provided additional diagnostic information in 96% (tongue representation) and 97% (foot representation) of patients. FMRI-based presurgical risk assessment correlated in 88% with a positive postoperative clinical outcome. Routine presurgical FMRI allows for superior assessment of the spatial relationship between brain tumour and motor cortex compared with a very detailed analysis of structural 3D MRI, thus significantly facilitating the preoperative risk-benefit assessment and function-preserving surgery. The additional imaging time seems justified. FMRI has the potential to reduce postoperative morbidity and therefore hospitalisation time. (orig.)

  12. Role of Multivoxel Intermediate TE 2D CSI MR Spectroscopy and 2D Echoplanar Diffusion Imaging in Grading of Primary Glial Brain Tumours.

    Science.gov (United States)

    Aggarwal, Abhishek; Das, Pankaj Kumar; Shukla, Arvind; Parashar, Sagar; Choudhary, Mohini; Kumar, Arpit; Kumar, Narendra; Dutta, Shyamoli

    2017-06-01

    Preoperative tumour grading is imperative owing to difference in invasive, aggressive tendencies of different grades of glial tumours implying varied prognosis, therapeutic options. Histopathological examination has inherent sampling errors. Magnetic Resonance Spectroscopy (MRS) and Diffusion Weighted Imaging (DWI) can provide non invasive information about internal mileu hence, aiding in tumour grading by adding to information provided by conventional MRI sequences. To evaluate the role of multivoxel intermediate TE 2D CSI MRS and 2D echoplanar diffusion imaging in grading of primary glial brain tumours. A prospective study was conducted in Department of Radiology, Teerthanker Mahaveer Medical College and Research Centre, Uttar Pradesh, India, from April 2015 to August 2016 after obtaining necessary approvals from Institutional Ethical Committee and written informed consent from all participants on histopathological proven cases of glial brain tumours that underwent multivoxel MRS using intermediate TE 2D chemical shift imaging and DWI using 2D echoplanar imaging. Tumour grade calculated on MRI using MRS and DWI was compared with histopathological grading. Positive Predictive Value (PPV), Negative Predictive Value (NPV), Sensitivity, specificity and accuracy were calculated for each parameter and statistical significance was evaluated using two tailed Pearson test. Choline: N Acetyl aspartate (Cho: NAA) and Choline: creatinine (Cho: Cr) ratios from MRS as well as Apparent Diffusion Coffecient (ADC) values from DWI were significantly higher with increasing severity of tumour grade. Accuracy of 58.6% was obtained with DWI while it was 83% with MRS. MRS and DWI used together provided 88.4% accuracy. All parameters evaluated showed statistical significance. Both DWI as well as MRS were found to have statistically significant roles in grading of glial brain tumours. MRS was found to be more useful than DWI.

  13. Brain metabolism and Alzheimer's disease: the prospect of a metabolite-based therapy.

    Science.gov (United States)

    Thomas, S C; Alhasawi, A; Appanna, V P; Auger, C; Appanna, V D

    2015-01-01

    The brain is one of the most energy-demanding organs in the body. It has evolved intricate metabolic networks to fulfill this need and utilizes a variety of substrates to generate ATP, the universal energy currency. Any disruption in the supply of energy results in various abnormalities including Alzheimer's disease (AD), a condition with markedly diminished cognitive ability. Astrocytes are an important participant in maintaining the cerebral ATP budget. However, under oxidative stress induced by numerous factors including aluminum toxicity, the ability of astroctyes to generate ATP is impaired due to dysfunctional mitochondria. This leads to globular, glycolytic, lipogenic and ATP-deficient astrocytes, cerebral characteristics common in AD patients. The reversal of these perturbations by such natural metabolites as pyruvate, α-ketoglutarate, acetoacetate and L-carnitine provides valuable therapeutic cues against AD.

  14. Patterns of exposure to infectious diseases and social contacts in early life and risk of brain tumours in children and adolescents

    DEFF Research Database (Denmark)

    Andersen, T V; Schmidt, L S; Poulsen, A H

    2013-01-01

    BACKGROUND: Infectious diseases and social contacts in early life have been proposed to modulate brain tumour risk during late childhood and adolescence. METHODS: CEFALO is an interview-based case-control study in Denmark, Norway, Sweden and Switzerland, including children and adolescents aged 7......% confidence interval: 1.57-5.50) and 4.21 (95% confidence interval: 1.24-14.30). INTERPRETATION: There was little support for the hypothesis that social contacts influence childhood and adolescent brain tumour risk. The association between reported sick days due to infections and risk of glioma and embryonal...

  15. Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study

    Science.gov (United States)

    Oommen, Anup M.; Varma, Sudhir; Casanova, Ramon; An, Yang; O’Brien, Richard; Pletnikova, Olga; Kastenmueller, Gabi; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima; Thambisetty, Madhav

    2018-01-01

    Background The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression. Methods and findings Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180) assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15), control (CN; N = 14), and “asymptomatic Alzheimer’s disease” (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15) participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes—sphingolipids and glycerophospholipids—that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer’s Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, % female = 42.63) AD, in which we tested their associations with magnetic resonance imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF) biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that

  16. Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

    Directory of Open Access Journals (Sweden)

    Varsha Agarwal

    2008-06-01

    Full Text Available Cytochrome P450 (P450 is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

  17. The effect of ethanol on human brain metabolites longitudinally characterized by proton MR spectroscopy.

    Science.gov (United States)

    Biller, Armin; Bartsch, Andreas J; Homola, György; Solymosi, László; Bendszus, Martin

    2009-05-01

    The effect ethanol exerts on the human brain has not yet been addressed by longitudinal magnetic resonance (MR) spectroscopic experiments. Therefore, we longitudinally characterized cerebral metabolite changes in 15 healthy individuals by proton magnetic resonance spectroscopy ((1)H-MRS) subsequent to the ingestion of a standard beverage (mean peak blood alcohol concentration (BAC): 51.43 +/- 10.27 mg/dL). Each participant was examined before, over 93.71 +/- 11.17 mins immediately after and 726.36 +/- 94.96 mins (12.11 +/ -1.58 h) past per os alcohol exposure. Fronto-mesial and cerebellar ethanol concentrations over time were similar as determined by the LCModel analysis of spectral data. Alcohol-induced changes of fronto-mesial creatine, choline, glucose, inositol and aspartate levels at 5.79 +/- 2.94 [corrected] mins upon ingestion as well as cerebellar choline and inositol levels at 8.64 +/- 2.98 [corrected] mins past exposure. Closely associated with ethanol concentrations, supratentorial creatine, choline, inositol and aspartate levels decreased after ethanol administration, whereas glucose levels increased. Similarly, infratentorial choline and inositol concentrations were negatively correlated with ethanol levels over time. There were no changes in N-acetyl-aspartate levels upon alcohol exposure. Furthermore, no influence of ethanol on brain water integrals was detected. Ethanol consumption may directly increase oxidative stress and the neuronal vulnerability to it. In addition, our results are compatible with ethanol-induced cell membrane modifications and alternative energy substrate usage upon alcohol exposure.

  18. DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours

    DEFF Research Database (Denmark)

    Mollenhauer, J; Wiemann, S; Scheurlen, W

    1997-01-01

    Loss of sequences from human chromosome 10q has been associated with the progression of human cancer. Medulloblastoma and glioblastoma multiforme are the most common malignant brain tumours in children and adults, respectively. In glioblastoma multiforme, the most aggressive form, 80% of the tumo......Loss of sequences from human chromosome 10q has been associated with the progression of human cancer. Medulloblastoma and glioblastoma multiforme are the most common malignant brain tumours in children and adults, respectively. In glioblastoma multiforme, the most aggressive form, 80......% of the tumours show loss of 10q. We have used representational difference analysis to identify a homozygous deletion at 10q25.3-26.1 in a medulloblastoma cell line and have cloned a novel gene, DMBT1, spanning this deletion. DMBT1 shows homology to the scavenger receptor cysteine-rich (SRCR) superfamily...

  19. Are cranial germ cell tumours really tumours of germ cells?

    Science.gov (United States)

    Scotting, P J

    2006-12-01

    Germ cell tumours of the brain and those that occur in the gonads are believed to share a common origin from germ cell progenitors. This 'germ cell theory' rests upon similar histopathology between these tumours in different locations and the belief that endogenous somatic cells of the brain could not give rise to the range of cell types seen in germ cell tumours. An alternative 'embryonic cell theory' has been proposed for some classes of cranial germ cell tumours, but this still relies on the misplacement of cells in the brain (in this case the earliest embryonic stem cells) during early embryonic development. Recent evidence has demonstrated that neural stem cells of the brain can also give rise to many of the cell types seen in germ cell tumours. These data suggest that endogenous progenitor cells of the brain are a plausible alternative origin for these tumours. This idea is of central importance for studies aiming to elucidate the mechanisms of tumour development. The application of modern molecular analyses to reveal how tumour cells have altered with respect to their cell of origin relies on the certain identification of the cell from which the particular tumour arose. If the identity of this cell is mistaken, then studies to elucidate the mechanisms by which the progenitor cell has been subverted from its normal behaviour will not yield useful information. In addition, it will prove impossible to generate an appropriate animal model in which to study the underlying causes of those tumours. This article makes the case that current assumptions of the origins of cranial germ cell tumours are unreliable. It reviews the evidence in favour of the 'germ cell theory' and argues in favour of a 'brain cell theory' in which endogenous neural progenitor cells of the brain are the likely origin for these tumours. Thus, the case is made that cranial germ cell tumours, like other brain tumours, arise by the transformation of progenitor cells normally resident in the

  20. Brain tumours at 7T MRI compared to 3T - contrast effect after half and full standard contrast agent dose: initial results

    Energy Technology Data Exchange (ETDEWEB)

    Noebauer-Huhmann, Iris-Melanie; Weber, M. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Vienna, Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Szomolanyi, P.; Juras, V. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Slovak Academy of Sciences, Department of Imaging Methods, Institute of Measurement Science, Bratislava (Slovakia); Kronnerwetter, C. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Widhalm, G. [Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Nemec, S.; Prayer, D. [Medical University of Vienna, Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Ladd, M.E. [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); German Cancer Research Center (DKFZ), Division of Medical Physics in Radiology, Heidelberg (Germany); Trattnig, S. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Vienna (Austria)

    2015-01-15

    To compare the contrast agent effect of a full dose and half the dose of gadobenate dimeglumine in brain tumours at 7 Tesla (7T) MR versus 3 Tesla (3T). Ten patients with primary brain tumours or metastases were examined. Signal intensities were assessed in the lesion and normal brain. Tumour-to-brain contrast and lesion enhancement were calculated. Additionally, two independent readers subjectively graded the image quality and artefacts. The enhanced mean tumour-to-brain contrast and lesion enhancement were significantly higher at 7T than at 3T for both half the dose (91.8 ± 45.8 vs. 43.9 ± 25.3 [p = 0.010], 128.1 ± 53.7 vs. 75.5 ± 32.4 [p = 0.004]) and the full dose (129.2 ± 50.9 vs. 66.6 ± 33.1 [p = 0.002], 165.4 ± 54.2 vs. 102.6 ± 45.4 [p = 0.004]). Differences between dosages at each field strength were also significant. Lesion enhancement was higher with half the dose at 7T than with the full dose at 3T (p =.037), while the tumour-to-brain contrast was not significantly different. Subjectively, contrast enhancement, visibility, and lesion delineation were better at 7T and with the full dose. All parameters were rated as good, at the least. Half the routine contrast agent dose at 7T provided higher lesion enhancement than the full dose at 3T which indicates the possibility of dose reduction at 7T. (orig.)

  1. 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.

  2. Exercise training improves physical function and fitness in long-term paediatric brain tumour survivors treated with cranial irradiation.

    Science.gov (United States)

    Piscione, P J; Bouffet, E; Timmons, B; Courneya, K S; Tetzlaff, D; Schneiderman, J E; de Medeiros, C B; Bartels, U; Mabbott, D J

    2017-07-01

    We examined the efficacy of exercise training for improving physical functioning and cardiopulmonary fitness in survivors of paediatric brain tumours (BTs) treated with cranial irradiation. We conducted a controlled clinical trial with crossover of exercise training versus no training in the community in either a group or combined group/home setting. A volunteer sample of 28 children treated with cranial irradiation for brain tumours completed training (mean age = 11.53 years; mean time since diagnosis = 5.25 years). end-points were physical functioning assessed by four subtests from the Bruininks-Oseretsky Test of motor performance (BOT-2) and pro-rated work rate from a cycle ergometer. Linear mixed modelling was used to evaluate time, training, training setting, and carryover effects. Adherence to training was 84%. Performance on the BOT-2 was below average for all assessments. However, training resulted in improvement in bilateral coordination (F (1, 30) = 6.59, p = 0.02), irrespective of training setting and improved performance was maintained even approximately 12°weeks after training had ended (F (1, 24) = 9.60, p = 0.005). Training resulted in increased pro-rated work rate for participants in the group training setting only (F (1, 25) = 4.57, p = 0.04) and these participants maintained their improved work rate approximately 12°weeks after training had ended (F (1, 20) = 8.38, p = 0.01). Exercise training improves physical functioning and fitness in paediatric BT survivors. Exercise interventions that ameliorate adverse physical effects and promote health in long-term survivors are highly recommended in this vulnerable population. (ClinicalTrials.gov, NCT01944761). Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Clinical trial design for systemic agents in patients with brain metastases from solid tumours: a guideline by the Response Assessment in Neuro-Oncology Brain Metastases working group.

    Science.gov (United States)

    Camidge, D Ross; Lee, Eudocia Q; Lin, Nancy U; Margolin, Kim; Ahluwalia, Manmeet S; Bendszus, Martin; Chang, Susan M; Dancey, Janet; de Vries, Elisabeth G E; Harris, Gordon J; Hodi, F Stephen; Lassman, Andrew B; Macdonald, David R; Peereboom, David M; Schiff, David; Soffietti, Ricardo; van den Bent, Martin J; Wefel, Jeffrey S; Wen, Patrick Y

    2018-01-01

    Patients with active CNS disease are often excluded from clinical trials, and data regarding the CNS efficacy of systemic agents are usually obtained late in the drug development process or not at all. In this guideline from the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group, we provide detailed recommendations on when patients with brain metastases from solid tumours should be included or excluded in clinical trials of systemic agents. We also discuss the limitations of retrospective studies in determining the CNS efficacy of systemic drugs. Inclusion of patients with brain metastases early on in the clinical development of a drug or a regimen is needed to generate appropriate CNS efficacy or non-efficacy signals. We consider how to optimally incorporate or exclude such patients in systemic therapy trials depending on the likelihood of CNS activity of the agent by considering three scenarios: drugs that are considered very unlikely to have CNS antitumour activity or efficacy; drugs that are considered very likely to have CNS activity or efficacy; and drugs with minimal baseline information on CNS activity or efficacy. We also address trial design issues unique to patients with brain metastases, including the selection of appropriate CNS endpoints in systemic therapy trials. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. [Effects of amitriptyline, fluoxetine, and tianeptine on the content of monoamines and their metabolites in Wistar rat brain structures].

    Science.gov (United States)

    Kudrin, V S; Mosin, V M; Klodt, P M; Narkevich, V B; Molodavkin, G M; Voronina, T A

    2010-03-01

    The effects of antidepressant drugs belonging to different pharmacological groups--amitriptyline, fluoxetine (prozac), and tianeptine (coaxyl)--on the content of monoamines and their metabolites in Wistar rat brain structures (frontal cortex, hypothalamus, nucleus accumbens, striatum, and hippocamp) has been studied using HPLC with electrochemical detection. Tricyclic antidepressant amitriptyline (10 mg/kg) was found to produce a moderate increase in the DOPAC/dopamine turnover index in nucleus accumbens, but did not influence the levels of serotonin (5-HT), dopamine, and its metabolites (5-HIAA, DOPAC, and HVA) in other brain structures studied (frontal cortex, hypothalamus, striatum, hippocamp). Fluoxetine (Prozac) (20 mg/kg) decreased both the 5-HIAA content and the 5-HIAA/5-HT (5-HT turnover index) in all brain structures of Wistar rats. In contrast, the effects of Prozac on the level of catecholamines and their metabolites in various brain regions was more complex. Tianeptine (Coaxyl) was demonstrated to increase both the 5-HIAA content and the 5-HIAA/5-HT ratio in all the structures studied (except for nucleus accumbens), in good agreement with the hypothesis concerning a two-phase mode of tianeptine action with enhanced 5-HT secretion in the synaptic gap in the first stage of pharmacological response.

  5. Comparison of LCModel and SAGE in Analysis of Brain Metabolite Concentrations-A study of Patients with Mild Cognitive Impairment.

    Science.gov (United States)

    Shih, Chiu-Ming; Lai, Jui-Jen; Chang, Chin-Ching; Chen, Cheng-Sheng; Yeh, Yi-Chun; Jaw, Twei-Shiun; Hsu, Jui-Sheng; Li, Chun-Wei

    2017-03-15

    The purpose of this study was to compare brain metabolite concentration ratios determined by LCModel and Spectroscopy Analysis by General Electric (SAGE) quantitative methods to elucidate the advantages and disadvantages of each method. A total of 10 healthy volunteers and 10 patients with mild cognitive impairment (MCI) were recruited in this study. A point-resolved spectroscopy (PRESS) sequence was used to obtain the brain magnetic resonance spectroscopy (MRS) spectra of the volunteers and patients, as well as the General Electric (GE) MRS-HD-sphere phantom. The brain metabolite concentration ratios were estimated based on the peak area obtained from both LCModel and SAGE software. Three brain regions were sampled for each volunteer or patient, and 20 replicates were acquired at different times for the phantom analysis. The metabolite ratios of the GE phantom were estimated to be myo-inositol (mI)/creatine (Cr): 0.70 ± 0.01, choline (Cho)/Cr: 0.37 ± 0.00, N-acetylaspartate (NAA)/Cr: 1.26 ± 0.02, and NAA/mI: 1.81 ± 0.04 by LCModel, and mI/Cr: 0.88 ± 0.15, Cho/Cr: 0.35 ± 0.01, NAA/Cr: 1.33 ± 0.03, and NAA/mI: 1.55 ± 0.26 by SAGE. In the healthy volunteers and MCI patients, the ratios of mI/Cr and Cho/Cr estimated by LCModel were higher than those estimated by SAGE. In contrast, the ratio of NAA/Cr estimated by LCModel was lower than that estimated by SAGE. Both methods were acceptable in estimating brain metabolite concentration ratios. However, LCModel was marginally more accurate than SAGE because of its full automation, basis set, and user independency.

  6. Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases.

    Science.gov (United States)

    Mendelsohn, Andrew R; Larrick, James W

    2013-12-01

    Decline of cognition and increasing risk of neurodegenerative diseases are major problems associated with aging in humans. Of particular importance is how the brain removes potentially toxic biomolecules that accumulate with normal neuronal function. Recently, a biomolecule clearance system using convective flow between the cerebrospinal fluid (CSF) and interstitial fluid (ISF) to remove toxic metabolites in the brain was described. Xie and colleagues now report that in mice the clearance activity of this so-called "glymphatic system" is strongly stimulated by sleep and is associated with an increase in interstitial volume, possibly by shrinkage of astroglial cells. Moreover, anesthesia and attenuation of adrenergic signaling can activate the glymphatic system to clear potentially toxic proteins known to contribute to the pathology of Alzheimer disease (AD) such as beta-amyloid (Abeta). Clearance during sleep is as much as two-fold faster than during waking hours. These results support a new hypothesis to answer the age-old question of why sleep is necessary. Glymphatic dysfunction may pay a hitherto unsuspected role in the pathogenesis of neurodegenerative diseases as well as maintenance of cognition. Furthermore, clinical studies suggest that quality and duration of sleep may be predictive of the onset of AD, and that quality sleep may significantly reduce the risk of AD for apolipoprotein E (ApoE) ɛ4 carriers, who have significantly greater chances of developing AD. Further characterization of the glymphatic system in humans may lead to new therapies and methods of prevention of neurodegenerative diseases. A public health initiative to ensure adequate sleep among middle-aged and older people may prove useful in preventing AD, especially in apolipoprotein E (ApoE) ɛ4 carriers.

  7. Comparison of the prevalence of KRAS-LCS6 polymorphism (rs61764370) within different tumour types (colorectal, breast, non-small cell lung cancer and brain tumours). A study of the Czech population.

    Science.gov (United States)

    Uvirova, Magdalena; Simova, Jarmila; Kubova, Barbora; Dvorackova, Nina; Tomaskova, Hana; Sedivcova, Monika; Dite, Petr

    2015-09-01

    A germline SNP (rs61764370) is located in a let-7 complementary site (LCS6) in the 3'UTR of KRAS oncogene, and it was found to alter the binding capability of the mature let-7 microRNA to the KRAS mRNA. The aim of the study was to evaluate the frequency of the KRAS-LCS6 variant allele in different cancer types that included patients with colorectal cancer (CRC), breast cancer (BC), non-small cell lung cancer (NSCLC) and brain tumour patient subgroups from the Czech Republic. The occurrence of this genetic variant was correlated with the presence of selected somatic mutations representing predictive biomarkers in the respective tumours. DNA of tumour tissues was isolated from 428 colorectal cancer samples, 311 non-small cell lung cancer samples, 195 breast cancer samples and 151 samples with brain tumour. Analysis of SNP (rs61764370) was performed by the PCR+RFLP method and direct sequencing. KRAS, BRAF and EGFR mutation status was assessed using real-time PCR. The status of the HER2 gene was assessed using the FISH method. The KRAS-LCS6 TG genotype has been detected in 16.4% (32/195) of breast cancer cases (in HER2 positive breast cancer 3.3%, in HER2 negative breast cancer 20.1%), in 12.4% (53/428) of CRC cases (KRAS/BRAF wild type CRC in 10.6%, KRAS mutant CRC in 10.1%, BRAF V600E mutant CRC in 18.5%), in 13.2% (41/311) of NSCLC samples, (EGFR mutant NSCLC patients in 8%, EGFR wild type NSCLC in 12.9%), and 17.9% (27/151) of brain tumour cases. The KRAS-LCS6 TG genotype was not significantly different across the studied tumours. In our study, the GG genotype has not been found among the cancer samples. Based on the findings, it is concluded that the occurrence of the KRAS-LCS6 TG genotype was statistically significantly different in association with status of the HER2 gene in breast cancer. Furthermore, significant association between the mutation status of analysed somatic variants in genes of the EGFR signalling pathway (KRAS, BRAF, EGFR) and the KRAS-LCS6

  8. Comparison of human brain metabolite levels using 1H MRS at 1.5T and 3.0T

    Directory of Open Access Journals (Sweden)

    Fernando Fernandes Paiva

    Full Text Available ABSTRACT Proton magnetic resonance spectroscopy (MRS of the human brain has proven to be a useful technique in several neurological and psychiatric disorders and benefits from higher field scanners as signal intensity and spectral resolution are proportional to the magnetic field strength. Objective: To investigate the effects of the magnetic field on the measurement of brain metabolites in a typical routine clinical setting. Methods: Single voxel spectra were acquired from the posterior cingulate cortex in 26 healthy subjects. Each subject was scanned consecutively at 1.5T and 3.0T in a randomly distributed order. Results: SNR and peak width improvements were observed at higher fields. However, SNR improvement was lower than the theoretical two-fold improvement. Other than the values obtained for creatine (Cre and myo-Inositol (mI, which were both higher at 3.0T, all metabolite concentrations obtained were roughly the same at both field strengths. All the metabolite concentrations were estimated with a Cramer Rao lower bounds (CRLB lower than 15% of the calculated concentrations. Conclusions: Even though the present study supports the expected benefits of higher field strength for MRS, there are several factors that can lead to different quantitative results when comparing 1.5T to 3.0T MRS. Future comparative studies are necessary to refine the metabolite thresholds for early detection and quantification of distinct neurological and psychiatric disorders using 3.0T MRS.

  9. UK case control study of brain tumours in children, teenagers and young adults: a pilot study.

    Science.gov (United States)

    Feltbower, Richard G; Fleming, Sarah J; Picton, Susan V; Alston, Robert D; Morgan, Diana; Achilles, Janice; McKinney, Patricia A; Birch, Jillian M

    2014-01-08

    Tumours of the central nervous system are the second most common group of childhood cancers in 0-14 year olds (24% of total cancers) and represent a major diagnostic group in 15-24 year olds. The pilot case-control study aimed to establish methodologies for a future comprehensive aetiological investigation among children and young adults. Eligible cases were newly diagnosed with an intracranial tumour of neuroepithelial tissue aged 0-24 years. The pilot recruited patients through Leeds and Manchester Principal Treatment Centres. Controls were drawn from general practice lists. Controls were frequency matched by age and gender. We interviewed 49 cases and 78 controls comprising 85% of the target sample size. Response rates were 52% for cases and 32% for controls. Completion of the questionnaire was successful, with a very small proportion of missing data being reported (5-10%). The age distribution of cases and controls was similar with around three-quarters of interviewed subjects aged 0-14. Half of cases and almost two-thirds of controls reported using a mobile phone with the majority starting between 10-14 years of age. Prevalence of breastfeeding was lower in cases than controls (Odds Ratio 0.4; 95% CI 0.2-1.2), whilst cases were more likely to be delivered by caesarean section (OR 1.6; 95% CI 0.6-4.4). Cases were significantly more likely to have a birthweight > 3.5 kg compared to controls. Cases were also more likely to come from a family with 3 or more siblings than controls (OR 3.0; 95% CI 0.7-13.6). The majority of participants (>80%) were in favour of taking either blood or saliva to aid molecular epidemiological research. Successful methods were established for identifying and recruiting a high proportion of case subjects, exploiting strong links with the clinical teams at the treatment centres. Control procedures proved more difficult to implement. However, working closely with national clinical and professional research networks will enable improved

  10. In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of Intrauterine Growth Restriction (IUGR.

    Directory of Open Access Journals (Sweden)

    Rui V Simões

    Full Text Available Intrauterine growth restriction (IUGR is a risk factor for abnormal neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging (MRI and spectroscopy (MRS, to assess in vivo brain structural and metabolic consequences, and identify potential metabolic biomarkers for clinical translation.IUGR was induced in 3 pregnant rabbits at gestational day 25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn was used as control. Fetuses were delivered at day 30 and weighted. A total of 6 controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the first 8 hours of life, at 7T. Changes in brain tissue volumes and respective contributions to each MRS voxel were estimated by semi-automated registration of MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i absolute metabolite quantifications, using linear fitting; (ii local temperature estimations, based on the water chemical shift; and (iii classification, using spectral pattern analysis.Lower birth weight was associated with (i smaller brain sizes, (ii slightly lower brain temperatures, and (iii differential metabolite profile changes in specific regions of the brain parenchyma. Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA in the cerebral cortex and hippocampus (suggesting neuronal impairment, and higher glycine levels in the striatum (possible marker of brain injury. Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.IUGR was associated with brain metabolic changes in vivo, which correlate well with the neurostructural changes and neurodevelopment problems described in IUGR. Metabolic parameters could constitute non invasive biomarkers for the diagnosis and abnormal neurodevelopment of perinatal origin.

  11. In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of Intrauterine Growth Restriction (IUGR).

    Science.gov (United States)

    Simões, Rui V; Muñoz-Moreno, Emma; Carbajo, Rodrigo J; González-Tendero, Anna; Illa, Miriam; Sanz-Cortés, Magdalena; Pineda-Lucena, Antonio; Gratacós, Eduard

    2015-01-01

    Intrauterine growth restriction (IUGR) is a risk factor for abnormal neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging (MRI) and spectroscopy (MRS), to assess in vivo brain structural and metabolic consequences, and identify potential metabolic biomarkers for clinical translation. IUGR was induced in 3 pregnant rabbits at gestational day 25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn was used as control. Fetuses were delivered at day 30 and weighted. A total of 6 controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the first 8 hours of life, at 7T. Changes in brain tissue volumes and respective contributions to each MRS voxel were estimated by semi-automated registration of MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i) absolute metabolite quantifications, using linear fitting; (ii) local temperature estimations, based on the water chemical shift; and (iii) classification, using spectral pattern analysis. Lower birth weight was associated with (i) smaller brain sizes, (ii) slightly lower brain temperatures, and (iii) differential metabolite profile changes in specific regions of the brain parenchyma. Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA) in the cerebral cortex and hippocampus (suggesting neuronal impairment), and higher glycine levels in the striatum (possible marker of brain injury). Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum. IUGR was associated with brain metabolic changes in vivo, which correlate well with the neurostructural changes and neurodevelopment problems described in IUGR. Metabolic parameters could constitute non invasive biomarkers for the diagnosis and abnormal neurodevelopment of perinatal origin.

  12. Assessing the performance of four different categories of histological criteria in brain tumours grading by means of a computer-aided diagnosis image analysis system.

    Science.gov (United States)

    Kostopoulos, S; Konstandinou, C; Sidiropoulos, K; Ravazoula, P; Kalatzis, I; Asvestas, P; Cavouras, D; Glotsos, D

    2015-10-01

    Brain tumours are considered one of the most lethal and difficult to treat forms of cancer, with unknown aetiology and lack of any realistic screening. In this study, we examine, whether the combination of descriptive criteria, used by expert histopathologists in assessing histologic tissue samples, and quantitative image analysis features may improve the diagnostic accuracy of brain tumour grading. Data comprised 61 cases of brain cancers (astrocytomas, oligodendrogliomas, meningiomas) collected from the archives of the University Hospital of Patras, Greece. Incorporating physician's descriptive criteria and image analysis's quantitative features into a discriminant function, a computer-aided diagnosis system was designed for discriminating low-grade from high-grade brain tumours. Physician's descriptive features, when solely used in the system, proved of high discrimination accuracy (93.4%). When verbal descriptive features were combined with quantitative image analysis features in the system, discrimination accuracy improved to 98.4%. The generalization of the proposed system to unseen data converged to an overall prediction accuracy of 86.7% ± 5.4%. Considering that histological grading affects treatment selection and diagnostic errors may be notable in clinical practice, the utilization of the proposed system may safeguard against diagnostic misinterpretations in every day clinical practice. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  13. Urinary profile of catecholamines and metabolites in Parkinson patients with deep brain stimulation.

    Science.gov (United States)

    Guimarães, J; Vieira-Coelho, M A; Moura, E; Afonso, J; Rosas, M J; Vaz, R; Garrett, C

    2014-02-01

    Deep brain stimulation of the subthalamic nucleus (DBS-STN) is thought to continuously alter the activity of STN neurons in Parkinson's disease (PD). A chronic decrease in the levodopa dose with continuous STN stimulation may induce plastic neuronal changes. The objective of this work was to study urinary excretion of catecholamines in patients with PD before and after DBS-STN. Twenty-three patients were submitted to DBS-STN, and evaluated before and after surgery with respect to catecholamines and metabolites in 24-h urine measured by high-performance liquid chromatography with electrochemical detection. Of the 23 patients evaluated, a significant decrease of about 60% in the urinary excretion of L-3,4-dihydroxyphenylalanine (L-DOPA; in nmol/mg creatinine/24 h) was observed 1 week after DBS-STN. Moreover, in 17 patients with a follow-up of 8 weeks after surgery, there was a further 50% decrease in urinary L-DOPA levels, dropping to about 75% of the values before surgery. There was also a significant decrease in dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels 1 week after DBS-STN that was no longer present 8 weeks after. A significant increase in the DA/l-DOPA ratio was observed 1 week after surgery, with a further increase 8 weeks after surgery. After DBS-STN, the DA/l-DOPA ratio, an indirect measure of DA synthesis, increased. These results show that DBS-STN may improve the efficacy of oral levodopa. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

  14. A numerical model for the study of photoacoustic imaging of brain tumours

    CERN Document Server

    Firouzi, Kamyar

    2015-01-01

    Photoacoustic imaging has shown great promise for medical imaging, where optical energy absorption by blood haemoglobin is used as the contrast mechanism. A numerical method was developed for the in-silico assessment of the photoacoustic image reconstruction of the brain. Image segmentation techniques were used to prepare a digital phantom from MR images. Light transport through brain tissue was modelled using a Finite Element approach. The resulting acoustic pressure was then estimated by pulsed photoacoustics considerations. The forward acoustic wave propagation was modelled by the linearized coupled first order wave equations and solved by an acoustic k-space method. Since skull bone is an elastic solid and strongly attenuates ultrasound (due to both scattering and absorption), a k-space method was developed for elastic media. To model scattering effects, a new approach was applied based on propagation in random media. In addition, absorption effects were incorporated using a power law. Finally, the acoust...

  15. Pre-operative neutrophil count and neutrophil-lymphocyte count ratio (NLCR) in predicting the histological grade of paediatric brain tumours: a preliminary study.

    Science.gov (United States)

    Wilson, J R F; Saeed, F; Tyagi, A K; Goodden, J R; Sivakumar, G; Crimmins, D; Elliott, M; Picton, S; Chumas, P D

    2017-11-29

    -grade group (p = 0.033, p = 0.002). Post-operative NC was significantly higher in the high-grade tumours (p = 0.034), but no difference was observed for NLCR (p = 0.28). No evidence exists to support the correlation of pre-operative NC or NLCR to histological diagnosis in paediatric intracranial tumours. Our results indicate that a higher pre-operative NC/NLCR correlates with a higher histological grade of tumour. This suggests that immunological mechanisms may be involved in the pathogenesis of paediatric brain tumours, and a further prospective study is required to substantiate and expand these findings.

  16. Understanding the challenges to improve transition to palliative care: An issue for the primary malignant brain tumour population.

    Science.gov (United States)

    Sabo, Brenda; Johnston, Grace

    2016-01-01

    Reports highlight the growing unmet need for palliative care as it applies to all cancers, yet the system and health care professionals (HCP) appear slow to respond. The following discussion paper highlights the current state of palliative care within the context of the primary malignant brain tumour (PMBT) population and argues for a shift in the current health care system's approach, which continues to place greater emphasis on cure over care. An exploration of extant literature over the past 10 years. The current literature demonstrates that timely referrals to palliative care consult teams and access to community-based resources have been associated with fewer hospitalizations and visits to emergency departments and a decrease in the initiation of invasive, aggressive treatment at end of life. Timely referral to palliative care has also been shown to reduce distress, enhance quality of life and, in some cases, increase life expectancy. Earlier referral to palliative care has yet to become a reality for many patients diagnosed with life-limiting illnesses and, in particular, those with a PMBT. More research is needed to uncover and challenge the barriers to early transition including communication issues among professionals, patients and families around palliative care.

  17. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an {sup 1}H-MR spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, H.; Harada, M.; Hisaoka, S.; Nishitani, H. [Dept. of Radiology, Univ. of Tokushima, Tokushima City (Japan); Mori, K. [Dept. of Pediatrics, Univ. of Tokushima (Japan)

    1999-07-01

    Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

  18. Brain metabolite levels assessed by lactate-edited MR spectroscopy in premature neonates with and without pentobarbital sedation.

    Science.gov (United States)

    Wang, Z J; Vigneron, D B; Miller, S P; Mukherjee, P; Charlton, N N; Lu, Y; Barkovich, A J

    2008-04-01

    Pentobarbital is known to affect cerebral metabolism; pentobarbital sedation is, however, frequently used for MR imaging and MR spectroscopy, especially in children. Accurate assessment of the brain metabolite levels is important, particularly in neonates with suspected brain injury. We investigated whether pentobarbital sedation has any effect on the ratios of spectral metabolites lactate, N-acetylaspartate, or choline in a group of premature neonates. MR spectroscopy was performed in 43 premature neonates, all with normal concurrent MR imaging and normal neurodevelopmental outcome at 12 months of age. Of those neonates, 14 (33%) required pentobarbital (Nembutal 1 mg/kg) sedation during MR spectroscopy; the remaining 29 neonates did not receive any sedation. Ratios of lactate, choline, and N-acetylaspartate were calculated in the basal ganglia, thalami, and corticospinal tracts and compared between those neonates with and without sedation. Small amounts of brain lactate were detected in all of the premature neonates. The basal ganglia lactate/choline and lactate/N-acetylaspartate ratios were significantly lower, by 17% and 25% respectively, in the neonates with pentobarbital sedation compared with the age-matched neonates without sedation (P Sedation did not affect the lactate level in the thalami or the corticospinal tracts. The N-acetylaspartate/choline ratios were unaffected by pentobarbital sedation. Pentobarbital sedation is associated with lower lactate/choline and lactate/N-acetylaspartate ratios in the basal ganglia of premature neonates, as determined by proton MR spectroscopy. Investigators should be aware of this phenomenon for accurate interpretation of their MR spectroscopy results.

  19. Primary postoperative chemotherapy without radiotherapy for treatment of brain tumours other than ependymoma in children under 3 years: results of the first UKCCSG/SIOP CNS 9204 trial.

    Science.gov (United States)

    Grundy, R G; Wilne, S H; Robinson, K J; Ironside, J W; Cox, T; Chong, W K; Michalski, A; Campbell, R H A; Bailey, C C; Thorp, N; Pizer, B; Punt, J; Walker, D A; Ellison, D W; Machin, D

    2010-01-01

    Radiotherapy is an effective adjuvant treatment for brain tumours arising in very young children, but it has the potential to damage the child's developing nervous system at a crucial time - with a resultant reduction in IQ leading to cognitive impairment, associated endocrinopathy and risk of second malignancy. We aimed to assess the role of a primary chemotherapy strategy in avoiding or delaying radiotherapy in children younger than 3 years with malignant brain tumours other than ependymoma, the results of which have already been published. Ninety-seven children were enrolled between March 1993 and July 2003 and, following diagnostic review, comprised: medulloblastoma (n=31), astrocytoma (26), choroid plexus carcinoma [CPC] (15), CNS PNET (11), atypical teratoid/rhabdoid tumours [AT/RT] (6) and ineligible (6). Following maximal surgical resection, chemotherapy was delivered every 14 d for 1 year or until disease progression. Radiotherapy was withheld in the absence of progression. Over all diagnostic groups the cumulative progression rate was 80.9% at 5 years while the corresponding need-for-radiotherapy rate for progression was 54.6%, but both rates varied by tumour type. There was no clear relationship between chemotherapy dose intensity and outcome. Patients with medulloblastoma presented as a high-risk group, 83.9% having residual disease and/or metastases at diagnosis. For these patients, outcome was related to histology. The 5-year OS for desmoplastic/nodular medulloblastoma was 52.9% (95% confidence interval (CI): 27.6-73.0) and for classic medulloblastoma 33.3% (CI: 4.6-67.6); the 5-year EFS were 35.3% (CI: 14.5-57.0) and 33.3% (CI: 4.6-67.6), respectively. All children with large cell or anaplastic variants of medulloblastoma died within 2 years of diagnosis. The 5-year EFS for non-brainstem high-grade gliomas [HGGs] was 13.0% (CI: 2.2-33.4) and the OS was 30.9% (CI: 11.5-52.8). For CPC the 5-year OS was 26.67% (CI: 8.3-49.6) without RT. This treatment

  20. Simultaneous evaluation of brain tumour metabolism, structure and blood volume using [{sup 18}F]-fluoroethyltyrosine (FET) PET/MRI: feasibility, agreement and initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Henriksen, Otto M.; Hansen, Adam E.; Law, Ian [Copenhagen University Hospital Rigshospitalet Blegdamsvej, Department of Clinical Physiology Nuclear Medicine and PET, Copenhagen (Denmark); Larsen, Vibeke A. [Copenhagen University Hospital Rigshospitalet Blegdamsvej, Department of Radiology, Copenhagen (Denmark); Muhic, Aida; Poulsen, Hans S. [Copenhagen University Hospital Rigshospitalet Blegdamsvej, Department of Oncology, Copenhagen (Denmark); Larsson, Henrik B.W. [Copenhagen University Hospital Rigshospitalet Glostrup, Functional Imaging Unit, Department of Clinical Physiology Nuclear Medicine and PET, Glostrup (Denmark)

    2016-01-15

    imaging of brain tumour metabolism and perfusion using hybrid PET/MR systems may provide complementary information on tumour biology, but the potential clinical value remains to be determined in future trials. (orig.)

  1. Metabolic scaling in solid tumours

    Science.gov (United States)

    Milotti, E.; Vyshemirsky, V.; Sega, M.; Stella, S.; Chignola, R.

    2013-06-01

    Tumour metabolism is an outstanding topic of cancer research, as it determines the growth rate and the global activity of tumours. Recently, by combining the diffusion of oxygen, nutrients, and metabolites in the extracellular environment, and the internal motions that mix live and dead cells, we derived a growth law of solid tumours which is linked to parameters at the cellular level. Here we use this growth law to obtain a metabolic scaling law for solid tumours, which is obeyed by tumours of different histotypes both in vitro and in vivo, and we display its relation with the fractal dimension of the distribution of live cells in the tumour mass. The scaling behaviour is related to measurable parameters, with potential applications in the clinical practice.

  2. Neurofeedback ineffective in paediatric brain tumour survivors: Results of a double-blind randomised placebo-controlled trial.

    Science.gov (United States)

    de Ruiter, Marieke Anna; Oosterlaan, Jaap; Schouten-van Meeteren, Antoinette Yvonne Narda; Maurice-Stam, Heleen; van Vuurden, Dannis Gilbert; Gidding, Corrie; Beek, Laura Rachel; Granzen, Bernd; Caron, Huib N; Grootenhuis, Martha Alexandra

    2016-09-01

    Many paediatric brain tumour survivors (PBTS) suffer from neurocognitive impairments. Promising effects of neurofeedback (NF) on neurocognitive functioning have been reported, however research into NF for PBTS has not been conducted. We investigated the effects of NF on neurocognitive functioning in PBTS using a double-blind randomised placebo-controlled trial with a parallel-group design (Pediatric Research on Improving Speed, Memory, and Attention; the PRISMA study). Eligible for inclusion were PBTS with neurocognitive complaints, aged 8-18 years, >2 years post-treatment. They were recruited from five medical centres in the Netherlands. A randomisation table assigned participants to 30 sessions (two per week) of either NF or placebo feedback (PF) (ratio 1:1). Participants, parents, trainers, and researchers handling the data were blinded to group assignment. Participants were assessed pre-, post- and 6 months post-training to determine whether NF training would lead to improved functioning as compared with PF training. Primary outcome measures were attention, processing speed, memory, executive functioning, visuomotor integration, and intelligence. Linear mixed models analyses were used to test differences between NF and PF training over time. A total of 82 children were enrolled (mean age 13.9 years, standard deviation = 3.2, 49% males); 80 participants were randomised (NF: n = 40, PF n = 40); 71 participants completed the training (NF: n = 34, PF: n = 37); 68 participants completed training and 6 months post-training assessment (NF: n = 33, PF: n = 35). Similar improvements were found over time for the two treatment groups on the primary outcomes (all p's > 0.15). Results indicated no specific treatment-effects of NF on neurocognitive functioning of PBTS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Simultaneous evaluation of brain tumour metabolism, structure and blood volume using [(18)F]-fluoroethyltyrosine (FET) PET/MRI: feasibility, agreement and initial experience.

    Science.gov (United States)

    Henriksen, Otto M; Larsen, Vibeke A; Muhic, Aida; Hansen, Adam E; Larsson, Henrik B W; Poulsen, Hans S; Law, Ian

    2016-01-01

    Both [(18)F]-fluoroethyltyrosine (FET) PET and blood volume (BV) MRI supplement routine T1-weighted contrast-enhanced MRI in gliomas, but whether the two modalities provide identical or complementary information is unresolved. The aims of the study were to investigate the feasibility of simultaneous structural MRI, BV MRI and FET PET of gliomas using an integrated PET/MRI scanner and to assess the spatial and quantitative agreement in tumour imaging between BV MRI and FET PET. A total of 32 glioma patients underwent a 20-min static simultaneous PET/MRI acquisition on a Siemens mMR system 20 min after injection of 200 MBq FET. The MRI protocol included standard structural MRI and dynamic susceptibility contrast (DSC) imaging for BV measurements. Maximal relative tumour FET uptake (TBRmax) and BV (rBVmax), and Dice coefficients were calculated to assess the quantitative and spatial congruence in the tumour volumes determined by FET PET, BV MRI and contrast-enhanced MRI. FET volume and TBRmax were higher in BV-positive than in BV-negative scans, and both VOLBV and rBVmax were higher in FET-positive than in FET-negative scans. TBRmax and rBVmax were positively correlated (R (2) = 0.59, p PET were quantitatively correlated, their spatial congruence in a mixed population of treated glioma patients was generally poor, and the modalities did not provide the same information in this population of patients. Combined imaging of brain tumour metabolism and perfusion using hybrid PET/MR systems may provide complementary information on tumour biology, but the potential clinical value remains to be determined in future trials.

  4. [Increase of brain serotonin and its metabolite in rats caused by meclofenoxate].

    Science.gov (United States)

    Koga, T

    1976-05-01

    Influence of meclofenoxate (MF) on the 5-HT and 5-HIAA contents in the cortex, diencephalon and brain stem of the rat was studied with the following results. MF caused a dose-dependent elevation of 5-HIAA level in the three different brain regions and particularly in the brain stem. An increase of 5-HT was also noted in the brain stem, whereas 5-HT in the diencephalon tended to decrease. The increase of 5-HT after pargyline was accelerated and the pargyline-induced decrease of 5-HIAA was equally inhibited by MF and probenecid, which suggests that MF blocks the efflux of 5-HIAA from the brain. The effects of MF on the brain 5-HT and 5-HIAA contents were identical with those of its hydrolysate, p-chlorophenoxyacetic acid.

  5. Fatty acid amide hydrolase-dependent generation of antinociceptive drug metabolites acting on TRPV1 in the brain.

    Directory of Open Access Journals (Sweden)

    David A Barrière

    Full Text Available The discovery that paracetamol is metabolized to the potent TRPV1 activator N-(4-hydroxyphenyl-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404 and that this metabolite contributes to paracetamol's antinociceptive effect in rodents via activation of TRPV1 in the central nervous system (CNS has provided a potential strategy for developing novel analgesics. Here we validated this strategy by examining the metabolism and antinociceptive activity of the de-acetylated paracetamol metabolite 4-aminophenol and 4-hydroxy-3-methoxybenzylamine (HMBA, both of which may undergo a fatty acid amide hydrolase (FAAH-dependent biotransformation to potent TRPV1 activators in the brain. Systemic administration of 4-aminophenol and HMBA led to a dose-dependent formation of AM404 plus N-(4-hydroxyphenyl-9Z-octadecenamide (HPODA and arvanil plus olvanil in the mouse brain, respectively. The order of potency of these lipid metabolites as TRPV1 activators was arvanil = olvanil>>AM404> HPODA. Both 4-aminophenol and HMBA displayed antinociceptive activity in various rodent pain tests. The formation of AM404, arvanil and olvanil, but not HPODA, and the antinociceptive effects of 4-aminophenol and HMBA were substantially reduced or disappeared in FAAH null mice. The activity of 4-aminophenol in the mouse formalin, von Frey and tail immersion tests was also lost in TRPV1 null mice. Intracerebroventricular injection of the TRPV1 blocker capsazepine eliminated the antinociceptive effects of 4-aminophenol and HMBA in the mouse formalin test. In the rat, pharmacological inhibition of FAAH, TRPV1, cannabinoid CB1 receptors and spinal 5-HT3 or 5-HT1A receptors, and chemical deletion of bulbospinal serotonergic pathways prevented the antinociceptive action of 4-aminophenol. Thus, the pharmacological profile of 4-aminophenol was identical to that previously reported for paracetamol, supporting our suggestion that this drug metabolite contributes to paracetamol's analgesic activity via

  6. Simultaneous evaluation of brain tumour metabolism, structure and blood volume using [18F]-fluoroethyltyrosine (FET) PET/MRI

    DEFF Research Database (Denmark)

    Henriksen, Otto M.; Larsen, Vibeke A; Muhic, Aida

    2016-01-01

    of simultaneous structural MRI, BV MRI and FET PET of gliomas using an integrated PET/MRI scanner and to assess the spatial and quantitative agreement in tumour imaging between BV MRI and FET PET. METHODS: A total of 32 glioma patients underwent a 20-min static simultaneous PET/MRI acquisition on a Siemens m......MR system 20 min after injection of 200 MBq FET. The MRI protocol included standard structural MRI and dynamic susceptibility contrast (DSC) imaging for BV measurements. Maximal relative tumour FET uptake (TBRmax) and BV (rBVmax), and Dice coefficients were calculated to assess the quantitative and spatial...

  7. Transient Changes in Brain Metabolites after Transcranial Direct Current Stimulation in Spastic Cerebral Palsy: A Pilot Study.

    Science.gov (United States)

    Auvichayapat, Paradee; Aree-Uea, Benchaporn; Auvichayapat, Narong; Phuttharak, Warinthorn; Janyacharoen, Taweesak; Tunkamnerdthai, Orathai; Boonphongsathian, Wuttisak; Ngernyam, Niran; Keeratitanont, Keattichai

    2017-01-01

    Muscle spasticity is a disability caused by damage to the pyramidal system. Standard treatments for spasticity include muscle stretching, antispastic medications, and tendon release surgeries, but treatment outcomes remain unsatisfactory. Anodal transcranial direct current stimulation (tDCS) in patients with muscle spasticity is known to result in significant improvement in spastic tone (p spasticity remains unclear. This pilot study aimed to investigate the effect of anodal tDCS upon brain metabolites in the left basal ganglia and ipsilateral primary motor cortex (M1) in children with spastic cerebral palsy (CP). This study consisted of three steps: a baseline evaluation, a treatment period, and a follow-up period. During the treatment period, patients were given 20 min of 1 mA anodal tDCS over the left M1 for five consecutive days. Outcomes were compared between pre- and immediate posttreatment in terms of brain metabolites, Tardieu scales, and the quality of upper extremity skills test. Ten patients with spastic CP were enrolled. Following tDCS, there were significant increases in the ratio of N-acetylaspartate (NAA)/creatine (Cr) (p = 0.030), choline (Cho)/Cr (p = 0.043), and myoinositol (mI)/Cr (p = 0.035) in the basal ganglia. Moreover, increased glutamine-glutamate (Glx)/Cr ratio in the left M1 (p = 0.008) was found. In addition, we also observed improvements in the extent of spasticity and hand function (p = 0.028). Five consecutive days of anodal tDCS over the left M1 appeared statistically to reduce the degree of spasticity and increase NAA, Cho, mI, and Glx. Future research studies, involving a larger sample size of spastic CP patients undergoing tDCS is now warranted.

  8. Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Sarac, K.; Alkan, A.; Baysal, T. [Inonu University School of Medicine, Department of Radiology, Malatya (Turkey); Akinci, A.; Aslan, M. [Inonu University School of Medicine, Department of Paediatric Endocrinology, Malatya (Turkey); Oezcan, C. [Inonu University School of Medicine, Department of Neurology, Malatya (Turkey)

    2005-07-01

    The metabolite changes in the brains of children with poorly controlled type 1 diabetes mellitus (DM) were investigated by proton magnetic resonance spectroscopy (MRS). A total of 30 subjects and 14 age-matched healthy volunteers underwent single-voxel MRS (TE: 136). The duration of disease, medication, presence of hypoglycaemia episodes and the level of haemoglobin A1C (HbA1C) in the patients were noted. Voxels were placed in the pons, left basal ganglion (LBG) and left posterior parietal white matter (PPWM). N-acetylaspartate (NAA)/creatinine (Cr) and choline (Cho)/Cr ratios were calculated. The average HbA1c level was 11.9{+-}3.4 (8.2-19.4). The average number of keto-acidosis episodes was 1.9{+-}2.2 (0-9) and the average number of daily insulin injections was 2.8{+-}0.97 (2-4). MRS revealed lower NAA/Cr and Cho/Cr ratios in the pons and lower NAA/Cr ratio in the PPWM of patients with DM than in control subjects. No significant correlation was observed between the number of hypoglycaemia episodes and metabolite ratios. Metabolic abnormalities have been observed by MRS in the brain of poorly controlled type 1 DM children. These metabolic changes, in particular in the pons region, include a decrease in NAA, indicating neuronal loss or functional impairment, and likely explanations for a decrease in Cho may be dynamic changes in membrane lipids and/or decreased membrane turnover. (orig.)

  9. In vivo 1H spectroscopy of the human brain at 1.5 tesla. Preliminary experience at a clinical installation

    DEFF Research Database (Denmark)

    Henriksen, O; Larsson, H; Jensen, K M

    1990-01-01

    technique. Our preliminary results indicate that it is possible to detect a number of metabolites in the brain within a total measurement time of one hour. The dominant peaks in the spectra from healthy volunteers are N-acetyl aspartate, choline and creatine/phosphocreatine. The spectra obtained from......In vivo localized water suppressed proton spectroscopy of human brain was carried out on 15 healthy volunteers and 2 patients suffering from a brain tumour and an infarction, respectively. The measurements were performed on a whole body MR system, operating at 1.5 tesla using the stimulated echo...... the brain tumour and the infarct, respectively, differed very much from those obtained in healthy brain tissue. Our preliminary results indicate that localized proton spectroscopy may contribute to non-invasive brain tumour classification and possibly also to the differentiation between tumours and infarcts...

  10. Understanding the protective effects of wine components and their metabolites in the brain function

    Directory of Open Access Journals (Sweden)

    Esteban-Fernández A.

    2016-01-01

    Full Text Available Moderate wine consumption has been suggested to exert a positive effect in prevention of neurodegenerative process and cognitive impairment. With the ultimate aim of achieving a better understanding of the molecular mechanisms behind this benefit, we have investigated the role of certain wine- derived phenolic metabolites and aroma compounds in the MAPK cascade (including ERK1/2, p38, one of the routes directly related to inflammation in neuronal cells. Some of the tested phenolic compounds, especially in the case of 3,4-dihydroxyphenylacetic acid, showed a significant neuroprotective effect against SIN-1-induced neuronal death. Regarding their effect over MAPK phosphorylation, inmunoblotting technique revealed a beneficial and significant decrease on the phosphorylation of p38 and ERK1/2 kinases after incubation with wine constituents. In addition, activity of caspase3-like protease, an executor of neuronal apoptosis and a downstream signal of MAPK, was significantly diminished by 3-(3-hydroxyphenyl propionic acid and linalool, counterbalancing the increase produced by SIN-1. Altogether, these results suggest that wine aroma, phenolic compounds and their gut metabolites could exert neuroprotective actions by modulating MAPK signalling and caspase-3 proteases activation, which are known to play a key role in oxidative/ nitrosative stress-induced response.

  11. Decrease of deleted in malignant brain tumour-1 (DMBT-1) expression is a crucial late event in intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Sasaki, M; Huang, S-F; Chen, M-F

    2003-01-01

    AIMS: To investigate the participation of DMBT-1, a candidate tumour suppressor gene, in the development of intrahepatic cholangiocarcinoma via intraductal papillary neoplasm of the liver (IPN-L) arising in hepatolithiasis. DMBT-1 plays a role in mucosal immune defence. METHODS AND RESULTS: The e...

  12. Case-control study of the association between malignant brain tumours diagnosed between 2007 and 2009 and mobile and cordless phone use

    Science.gov (United States)

    HARDELL, LENNART; CARLBERG, MICHAEL; SÖDERQVIST, FREDRIK; MILD, KJELL HANSSON

    2013-01-01

    Previous studies have shown a consistent association between long-term use of mobile and cordless phones and glioma and acoustic neuroma, but not for meningioma. When used these phones emit radiofrequency electromagnetic fields (RF-EMFs) and the brain is the main target organ for the hand-held phone. The International Agency for Research on Cancer (IARC) classified in May, 2011 RF-EMF as a group 2B, i.e. a ‘possible’ human carcinogen. The aim of this study was to further explore the relationship between especially long-term (>10 years) use of wireless phones and the development of malignant brain tumours. We conducted a new case-control study of brain tumour cases of both genders aged 18–75 years and diagnosed during 2007–2009. One population-based control matched on gender and age (within 5 years) was used to each case. Here, we report on malignant cases including all available controls. Exposures on e.g. use of mobile phones and cordless phones were assessed by a self-administered questionnaire. Unconditional logistic regression analysis was performed, adjusting for age, gender, year of diagnosis and socio-economic index using the whole control sample. Of the cases with a malignant brain tumour, 87% (n=593) participated, and 85% (n=1,368) of controls in the whole study answered the questionnaire. The odds ratio (OR) for mobile phone use of the analogue type was 1.8, 95% confidence interval (CI)=1.04–3.3, increasing with >25 years of latency (time since first exposure) to an OR=3.3, 95% CI=1.6–6.9. Digital 2G mobile phone use rendered an OR=1.6, 95% CI=0.996–2.7, increasing with latency >15–20 years to an OR=2.1, 95% CI=1.2–3.6. The results for cordless phone use were OR=1.7, 95% CI=1.1–2.9, and, for latency of 15–20 years, the OR=2.1, 95% CI=1.2–3.8. Few participants had used a cordless phone for >20–25 years. Digital type of wireless phones (2G and 3G mobile phones, cordless phones) gave increased risk with latency >1–5 years, then a

  13. Human Serum Metabolites Associate With Severity and Patient Outcomes in Traumatic Brain Injury

    NARCIS (Netherlands)

    M. Oresic (Matej); Posti, J.P. (Jussi P.); Kamstrup-Nielsen, M.H. (Maja H.); Takala, R.S.K. (Riikka S.K.); H.F. Lingsma (Hester); Mattila, I. (Ismo); Jäntti, S. (Sirkku); A. Katila (Ari); K.L.H. Carpenter (Keri L.H.); Ala-Seppälä, H. (Henna); Kyllönen, A. (Anna); Maanpää, H.-R. (Henna-Riikka); Tallus, J. (Jussi); J.P. Coles (Jonathan P.); Heino, I. (Iiro); J. Frantzén (Janek); P.J. Hutchinson (Peter J.); D.K. Menon (David ); O. Tenovuo (Olli); Hyötyläinen, T. (Tuulia)

    2016-01-01

    textabstractTraumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of

  14. Brain metabolites in definite amyotrophic lateral sclerosis. A longitudinal proton magnetic resonance spectroscopy study.

    Science.gov (United States)

    Unrath, Alexander; Ludolph, Albert C; Kassubek, Jan

    2007-08-01

    Biomarkers beyond clinical assessment are needed in patients who suffer from amyotrophic lateral sclerosis (ALS). Here, single-voxel proton magnetic resonance spectroscopy ((1)H MRS) of the gray matter of the motor cortex and the white matter including the pyramidal tracts was used to investigate concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myoinositol, glutamate, and glutamine in patients with definite ALS in a longitudinal design (three measurements at study inclusion, after 3 and 6 months). A volume-corrected analysis of gray and white matter fractions within the volumes of interest (VOI) was performed for the identification of the absolute metabolite concentrations. The patient group showed a significant decline of the compound NAA over time in the motor cortex areas both of the clinically more and less affected hemisphere between first measurement and month 6 and for the less affected side additionally between first measurement and month 3. For the NAA/(Cr + Cho) ratio, significant decline in the less affected hemisphere was observed from the first measurement to month 3 and to month 6 as well as from month 3 to month 6. In contrast, neither NAA nor the NAA/(Cr + Cho) ratios in the white matter areas showed any significant alterations. All other compounds showed no significant changes over time. In summary, the longitudinal changes of cortical metabolite concentrations in the course of ALS could be assessed by optimized (1)H MRS techniques at group level, so that (1)H MRS parameters, in particular volume-corrected values of NAA in the clinically less affected hemisphere, seem to have the potential to serve as a surrogate marker for monitoring ALS disease progression.

  15. Amiodarone biokinetics, the formation of its major oxidative metabolite and neurotoxicity after acute and repeated exposure of brain cell cultures.

    Science.gov (United States)

    Pomponio, Giuliana; Zurich, Marie-Gabrielle; Schultz, Luise; Weiss, Dieter G; Romanelli, Luca; Gramowski-Voss, Alexandra; Di Consiglio, Emma; Testai, Emanuela

    2015-12-25

    The difficulty in mimicking nervous system complexity and cell-cell interactions as well as the lack of kinetics information has limited the use of in vitro neurotoxicity data. Here, we assessed the biokinetic profile as well as the neurotoxicity of Amiodarone after acute and repeated exposure in two advanced rodent brain cell culture models, consisting of both neurons and glial cells organized in 2 or 3 dimensions to mimic the brain histiotypic structure and function. A strategy was applied to evidence the abiotic processes possibly affecting Amiodarone in vitro bioavailability, showing its ability to adsorb to the plastic devices. At clinically relevant Amiodarone concentrations, known to induce neurotoxicity in some patients during therapeutic treatment, a complete uptake was observed in both models in 24 h, after single exposure. After repeated treatments, bioaccumulation was observed, especially in the 3D cell model, together with a greater alteration of neurotoxicity markers. After 14 days, Amiodarone major oxidative metabolite (mono-N-desethylamiodarone) was detected at limited levels, indicating the presence of active drug metabolism enzymes (i.e. cytochrome P450) in both models. The assessment of biokinetics provides useful information on the relevance of in vitro toxicity data and should be considered in the design of an Integrated Testing Strategy aimed to identify specific neurotoxic alerts, and to improve the neurotoxicity assay predictivity for human acute and repeated exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Somatic transposition in the brain has the potential to influence the biosynthesis of metabolites involved in Parkinson’s disease and schizophrenia

    Directory of Open Access Journals (Sweden)

    Abrusán György

    2012-11-01

    Full Text Available Abstract It has been recently discovered that transposable elements show high activity in the brain of mammals, however, the magnitude of their influence on its functioning is unclear so far. In this paper, I use flux balance analysis to examine the influence of somatic retrotransposition on brain metabolism, and the biosynthesis of its key metabolites, including neurotransmitters. The analysis shows that somatic transposition in the human brain can influence the biosynthesis of more than 250 metabolites, including dopamine, serotonin and glutamate, shows large inter-individual variability in metabolic effects, and may contribute to the development of Parkinson’s disease and schizophrenia. Reviewers This article was reviewed by Dr Kenji Kojima (nominated by Dr Jerzy Jurka and Dr Eugene Koonin.

  17. Quantitative multivoxel proton MR spectroscopy study of brain metabolites in patients with amnestic mild cognitive impairment: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Zhong-Xian; Cheng, Xiao-Fang; Xu, Zhi-Feng; Cao, Zhen; Xiao, Ye-Yu; You, Ke-Zeng; Liu, Yan-Yan [Medical College of Shantou University, Department of Medical Imaging, The Second Affiliated Hospital, Shantou (China); Huo, Shan-Shan [Science College of Shantou University, Department of Physics, Shantou (China); Zeng, Jie-Xia; Chen, Wei [Medical College of Shantou University, Department of Neurology, The Second Affiliated Hospital, Shantou (China); Wu, Ren-Hua [Medical College of Shantou University, Department of Medical Imaging, The Second Affiliated Hospital, Shantou (China); Medical College of Shantou University, Provincial Key Laboratory of Medical Molecular Imaging, Guangdong, Shantou (China)

    2012-05-15

    The purpose of this study is to investigate brain metabolic changes in patients with amnestic mild cognitive impairment (aMCI) using multivoxel proton MR spectroscopy ({sup 1}H-MVS). Fourteen aMCI patients and fifteen healthy control subjects participated in this experiment. All MR measurements were acquired using a 1.5-T GE scanner. {sup 1}H-MVS point resolved spectroscopy (2D PROBE-CSI PRESS) pulse sequence (TE = 35 ms; TR = 1,500 ms; phase x frequency, 18 x 18) was used for acquiring MRS data. All data were post-processed using Spectroscopy Analysis by General Electric software and linear combination of model (LCModel). The absolute concentrations of N-acetylaspartate (NAA), choline (Cho), myoinositol (MI), creatine (Cr), and the metabolite ratios of NAA/Cr, Cho/Cr, MI/Cr, and NAA/MI were measured bilaterally in the posterior cingulate gyrus (PCG), inferior precuneus (Pr), paratrigonal white matter (PWM), dorsal thalamus (DT), and lentiform nucleus (LN). Patients with aMCI displayed significantly lower NAA levels in the bilateral PCG (p < 0.01), PWM (p < 0.05), and left inferior Pr (p < 0.05). The metabolite ratio of NAA/MI was decreased in the bilateral PCG (p < 0.01) and PWM (p < 0.05) and in the left DT (p < 0.01). NAA/Cr was decreased in the left PCG (p < 0.01), DT (p < 0.05), right PWM (p < 0.05), and LN (p < 0.05). However, MI/Cr was elevated in the right PCG (p < 0.01) and left PWM (p < 0.05). Significantly increased Cho level was also evident in the left PWM (p < 0.05). Our observations of decreased NAA, NAA/Cr, and NAA/MI, in parallel with increased Cho and MI/Cr might be characteristic of aMCI patients. (orig.)

  18. Brain metabolite changes in alcoholism: Localized proton magnetic resonance spectroscopy study of the occipital lobe

    Energy Technology Data Exchange (ETDEWEB)

    Modi, Shilpi; Bhattacharya, Manisha; Kumar, Pawan [NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (DRDO), Lucknow Road, Timarpur, Delhi 110054 (India); Deshpande, Smita N. [Department of Psychiatry, Dr. Ram Manohar Lohia Hospital, New Delhi (India); Tripathi, Rajendra Prasad [NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (DRDO), Lucknow Road, Timarpur, Delhi 110054 (India); Khushu, Subash, E-mail: skhushu@yahoo.com [NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (DRDO), Lucknow Road, Timarpur, Delhi 110054 (India)

    2011-07-15

    Chronic alcoholism is associated with altered brain metabolism, morphology and cognitive abilities. Besides deficits in higher order cognitive functions, alcoholics also show a deficit in the processing of basic sensory information viz. visual stimulation. To assess the metabolic changes associated with this deficit, {sup 1}H MRS was carried out in the occipital lobe of alcohol dependents. A significant increase in Cho/Cr ratio (p < 0.015) was observed in occipital lobe in the alcoholic group indicating altered cell membrane metabolism, which may probably be associated with the alterations in the cognitive abilities associated with vision.

  19. MR spectroscopy-based brain metabolite profiling in propionic acidaemia: metabolic changes in the basal ganglia during acute decompensation and effect of liver transplantation

    Directory of Open Access Journals (Sweden)

    McKiernan Patrick J

    2011-05-01

    Full Text Available Abstract Background Propionic acidaemia (PA results from deficiency of Propionyl CoA carboxylase, the commonest form presenting in the neonatal period. Despite best current management, PA is associated with severe neurological sequelae, in particular movement disorders resulting from basal ganglia infarction, although the pathogenesis remains poorly understood. The role of liver transplantation remains controversial but may confer some neuro-protection. The present study utilises quantitative magnetic resonance spectroscopy (MRS to investigate brain metabolite alterations in propionic acidaemia during metabolic stability and acute encephalopathic episodes. Methods Quantitative MRS was used to evaluate brain metabolites in eight children with neonatal onset propionic acidaemia, with six elective studies acquired during metabolic stability and five studies during acute encephalopathic episodes. MRS studies were acquired concurrently with clinically indicated MR imaging studies at 1.5 Tesla. LCModel software was used to provide metabolite quantification. Comparison was made with a dataset of MRS metabolite concentrations from a cohort of children with normal appearing MR imaging. Results MRI findings confirm the vulnerability of basal ganglia to infarction during acute encephalopathy. We identified statistically significant decreases in basal ganglia glutamate+glutamine and N-Acetylaspartate, and increase in lactate, during encephalopathic episodes. In white matter lactate was significantly elevated but other metabolites not significantly altered. Metabolite data from two children who had received liver transplantation were not significantly different from the comparator group. Conclusions The metabolite alterations seen in propionic acidaemia in the basal ganglia during acute encephalopathy reflect loss of viable neurons, and a switch to anaerobic respiration. The decrease in glutamine + glutamate supports the hypothesis that they are consumed to

  20. Transient Changes in Brain Metabolites after Transcranial Direct Current Stimulation in Spastic Cerebral Palsy: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Paradee Auvichayapat

    2017-07-01

    Full Text Available BackgroundMuscle spasticity is a disability caused by damage to the pyramidal system. Standard treatments for spasticity include muscle stretching, antispastic medications, and tendon release surgeries, but treatment outcomes remain unsatisfactory. Anodal transcranial direct current stimulation (tDCS in patients with muscle spasticity is known to result in significant improvement in spastic tone (p < 0.001. However, the mechanism of action by which tDCS treatment affects spasticity remains unclear. This pilot study aimed to investigate the effect of anodal tDCS upon brain metabolites in the left basal ganglia and ipsilateral primary motor cortex (M1 in children with spastic cerebral palsy (CP.Materials and methodsThis study consisted of three steps: a baseline evaluation, a treatment period, and a follow-up period. During the treatment period, patients were given 20 min of 1 mA anodal tDCS over the left M1 for five consecutive days. Outcomes were compared between pre- and immediate posttreatment in terms of brain metabolites, Tardieu scales, and the quality of upper extremity skills test.ResultsTen patients with spastic CP were enrolled. Following tDCS, there were significant increases in the ratio of N-acetylaspartate (NAA/creatine (Cr (p = 0.030, choline (Cho/Cr (p = 0.043, and myoinositol (mI/Cr (p = 0.035 in the basal ganglia. Moreover, increased glutamine–glutamate (Glx/Cr ratio in the left M1 (p = 0.008 was found. In addition, we also observed improvements in the extent of spasticity and hand function (p = 0.028.ConclusionFive consecutive days of anodal tDCS over the left M1 appeared statistically to reduce the degree of spasticity and increase NAA, Cho, mI, and Glx. Future research studies, involving a larger sample size of spastic CP patients undergoing tDCS is now warranted.

  1. Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumour stem cells.

    Science.gov (United States)

    Martín, V; Sanchez-Sanchez, A M; Herrera, F; Gomez-Manzano, C; Fueyo, J; Alvarez-Vega, M A; Antolín, I; Rodriguez, C

    2013-05-28

    Current evidence indicates that a stem cell-like sub-population within malignant glioblastomas, that overexpress members of the adenosine triphosphate-binding cassette (ABC) family transporters, is responsible for multidrug resistance and tumour relapse. Eradication of the brain tumour stem cell (BTSC) compartment is therefore essential to achieve a stable and long-lasting remission. Melatonin actions were analysed by viability cell assays, flow cytometry, quantitative PCR for mRNA expression, western blot for protein expression and quantitative and qualitative promoter methylation methods. Combinations of melatonin and chemotherapeutic drugs (including temozolomide, current treatment for malignant gliomas) have a synergistic toxic effect on BTSCs and A172 malignant glioma cells. This effect is correlated with a downregulation of the expression and function of the ABC transporter ABCG2/BCRP. Melatonin increased the methylation levels of the ABCG2/BCRP promoter and the effects on ABCG2/BCRP expression and function were prevented by preincubation with a DNA methyltransferase inhibitor. Our results point out a possible relationship between the downregulation of ABCG2/BCRP function and the synergistic toxic effect of melatonin and chemotherapeutic drugs. Melatonin could be a promising candidate to overcome multidrug resistance in the treatment of glioblastomas, and thus improve the efficiency of current therapies.

  2. Is it Possible to Extract Brain Metabolic Pathways Information from In Vivo H Nuclear Magnetic Resonance Spectroscopy Data?

    CERN Document Server

    de Lara, Alejandro Chinea Manrique

    2010-01-01

    In vivo H nuclear magnetic resonance (NMR) spectroscopy is an important tool for performing non-invasive quantitative assessments of brain tumour glucose metabolism. Brain tumours are considered as fast-growth tumours because of their high rate of proliferation. In addition, tumour cells exhibit profound genetic, biochemical and histological differences with respect to the original non-transformed cellular types. Therefore, there is a strong interest from the clinical investigator point of view in understanding the role of brain metabolites in normal and pathological conditions and especially on the development of early tumour detection techniques. Unfortunately, current diagnosis techniques ignore the dynamic aspects of these signals. It is largely believed that temporal variations of NMR Spectra are noisy or just simply do not carry enough information to be exploited by any reliable diagnosis procedure. Thus, current diagnosis procedures are mainly based on empirical observations extracted from single avera...

  3. Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

    Directory of Open Access Journals (Sweden)

    Giuliani Patricia

    2010-02-01

    Full Text Available Abstract Background Both hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. In the present study, quantitative proton magnetic resonance spectroscopy was used to evaluate regional metabolic alterations, following a 24-hour hypoxic or hyperoxic exposure on the background of ischemic brain insult, in two contrasting age-groups of rats: young - 3 months old and aged - 24 months old. Methods Cerebral ischemia was induced by ligation of the right common carotid artery. Concentrations of eight metabolites (alanine, choline-containing compounds, total creatine, γ-aminobutyric acid, glutamate, lactate, myo-inositol and N-acetylaspartate were quantified from extracts in three different brain regions (fronto-parietal and occipital cortices and the hippocampus from both hemispheres. Results In the control normoxic condition, there were significant increases in lactate and myo-inositol concentrations in the hippocampus of the aged rats, compared with the respective values in the young ones. In the ischemia-hypoxia condition, the most prevalent changes in the brain metabolites were found in the hippocampal regions of both young and aged rats; but the effects were more evident in the aged animals. The ischemia-hyperoxia procedure caused less dedicated changes in the brain metabolites, which may reflect more limited tissue damage. Conclusions We conclude that the hippocampus turns out to be particularly susceptible to hypoxia overlaid on cerebral ischemia and that old age further increases this susceptibility.

  4. The prognostic value of multivoxel magnetic resonance spectroscopy determined metabolite levels in white and grey matter brain tissue for adverse outcome in term newborns following perinatal asphyxia

    Energy Technology Data Exchange (ETDEWEB)

    Doormaal, Pieter Jan van [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Division of Neonatology, Groningen (Netherlands); Meander Medical Center Amersfoort, Department of Radiology, PO Box 1502, Amersfoort (Netherlands); Meiners, Linda C.; Sijens, Paul E. [University Medical Center Groningen and University of Groningen, Department of Radiology, Groningen (Netherlands); Horst, Hendrik J. ter; Veere, Christa N. van der [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Division of Neonatology, Groningen (Netherlands)

    2012-04-15

    Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia by providing ratios of metabolites, such as choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate (Lact) [Cho/Cr, Lact/NAA, etc.]. The purpose of this study was to quantify the separate white and grey matter metabolites in a slab cranial to the ventricles and relate these to the outcome. A standard 2D-chemical shift imaging protocol was used for measuring a transverse volume of interest located cranial to the ventricles allowing for direct comparison of the metabolites in white and grey matter brain tissue in 24 term asphyxiated newborns aged 3 to 16 days. Cho, NAA and Lact showed significant differences between four subgroups of asphyxiated infants with more and less favourable outcomes. High levels of Cho and Lact in the grey matter differentiated non-survivors from survivors (P = 0.003 and P = 0.017, respectively). In perinatal asphyxia the levels of Cho, NAA and Lact in both white and grey matter brain tissue are affected. The levels of Cho and Lact measured in the grey matter are the most indicative of survival. It is therefore advised to include grey matter brain tissue in the region of interest examined by multivoxel MR spectroscopy. (orig.)

  5. Morphine metabolites

    DEFF Research Database (Denmark)

    Christrup, Lona Louring

    1997-01-01

    Morphine is a potent opioid analgesic widely used for the treatment of acute pain and for long-term treatment of severe pain. Morphine is a member of the morphinan-framed alkaloids, which are present in the poppy plant. The drug is soluble in water, but its solubility in lipids is poor. In man...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...... systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear...

  6. Dosimetric and geometric evaluation of an open low-field magnetic resonance simulator for radiotherapy treatment planning of brain tumours

    DEFF Research Database (Denmark)

    Kristensen, B.H.; Laursen, F.J.; Logager, V.

    2008-01-01

    and bone segmented mediums are performed. Results: Mean MR and CT tumour volumes of approximately the same size ((V-MR) over bar = 55 +/- 34 cm(3) and (V-CT) over bar = 51 +/- 32 cm(3)) are observed, but for individual patients, small intersection volumes are observed. The MR images show negligible...... distortion within radial distances below 12 cm (observed in low dose areas. Monte Carlo simulations with 4 MV photons show large deviations in dose (>2%) just behind the skull if bone is not segmented. Conclusions: It is feasible to use an MR...

  7. New Zealand adolescents' cellphone and cordless phone user-habits: are they at increased risk of brain tumours already? A cross-sectional study.

    Science.gov (United States)

    Redmayne, Mary

    2013-01-10

    Cellphone and cordless phone use is very prevalent among early adolescents, but the extent and types of use is not well documented. This paper explores how, and to what extent, New Zealand adolescents are typically using and exposed to active cellphones and cordless phones, and considers implications of this in relation to brain tumour risk, with reference to current research findings. This cross-sectional study recruited 373 Year 7 and 8 school students with a mean age of 12.3 years (range 10.3-13.7 years) from the Wellington region of New Zealand. Participants completed a questionnaire and measured their normal body-to-phone texting distances. Main exposure-metrics included self-reported time spent with an active cellphone close to the body, estimated time and number of calls on both phone types, estimated and actual extent of SMS text-messaging, cellphone functions used and people texted. Statistical analyses used Pearson Chi2 tests and Pearson's correlation coefficient (r). Analyses were undertaken using SPSS version 19.0. Both cellphones and cordless phones were used by approximately 90% of students. A third of participants had already used a cordless phone for ≥ 7 years. In 4 years from the survey to mid-2013, the cordless phone use of 6% of participants would equal that of the highest Interphone decile (≥ 1640 hours), at the surveyed rate of use. High cellphone use was related to cellphone location at night, being woken regularly, and being tired at school. More than a third of parents thought cellphones carried a moderate-to-high health risk for their child. While cellphones were very popular for entertainment and social interaction via texting, cordless phones were most popular for calls. If their use continued at the reported rate, many would be at increased risk of specific brain tumours by their mid-teens, based on findings of the Interphone and Hardell-group studies.

  8. New Zealand adolescents’ cellphone and cordless phone user-habits: are they at increased risk of brain tumours already? A cross-sectional study

    Science.gov (United States)

    2013-01-01

    Background Cellphone and cordless phone use is very prevalent among early adolescents, but the extent and types of use is not well documented. This paper explores how, and to what extent, New Zealand adolescents are typically using and exposed to active cellphones and cordless phones, and considers implications of this in relation to brain tumour risk, with reference to current research findings. Methods This cross-sectional study recruited 373 Year 7 and 8 school students with a mean age of 12.3 years (range 10.3-13.7 years) from the Wellington region of New Zealand. Participants completed a questionnaire and measured their normal body-to-phone texting distances. Main exposure-metrics included self-reported time spent with an active cellphone close to the body, estimated time and number of calls on both phone types, estimated and actual extent of SMS text-messaging, cellphone functions used and people texted. Statistical analyses used Pearson Chi2 tests and Pearson’s correlation coefficient (r). Analyses were undertaken using SPSS version 19.0. Results Both cellphones and cordless phones were used by approximately 90% of students. A third of participants had already used a cordless phone for ≥ 7 years. In 4 years from the survey to mid-2013, the cordless phone use of 6% of participants would equal that of the highest Interphone decile (≥ 1640 hours), at the surveyed rate of use. High cellphone use was related to cellphone location at night, being woken regularly, and being tired at school. More than a third of parents thought cellphones carried a moderate-to-high health risk for their child. Conclusions While cellphones were very popular for entertainment and social interaction via texting, cordless phones were most popular for calls. If their use continued at the reported rate, many would be at increased risk of specific brain tumours by their mid-teens, based on findings of the Interphone and Hardell-group studies. PMID:23302218

  9. C1q-tumour necrosis factor-related protein 8 (CTRP8) is a novel interaction partner of relaxin receptor RXFP1 in human brain cancer cells.

    Science.gov (United States)

    Glogowska, Aleksandra; Kunanuvat, Usakorn; Stetefeld, Jörg; Patel, Trushar R; Thanasupawat, Thatchawan; Krcek, Jerry; Weber, Ekkehard; Wong, G William; Del Bigio, Marc R; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2013-12-01

    We report a novel ligand-receptor system composed of the leucine-rich G-protein-coupled relaxin receptor, RXFP1, and the C1q-tumour necrosis factor-related protein 8 (CTRP8) in human primary brain cancer, a tumour entity devoid of the classical RXFP1 ligands, RLN1-3. In structural homology studies and computational docking experiments we delineated the N-terminal region of the globular C1q region of CTRP8 and the leucine-rich repeat units 7 and 8 of RXFP1 to mediate this new ligand-receptor interaction. CTRP8 secreted from HEK293T cells, recombinant human (rh) CTRP8, and short synthetic peptides derived from the C1q globular domain of human CTRP8 caused the activation of RXFP1 as determined by elevated intracellular cAMP levels and the induction of a marked pro-migratory phenotype in established glioblastoma (GB) cell lines and primary cells from GB patients. Employing a small competitor peptide, we were able to disrupt the CTRP8-RXFP1-induced increased GB motility. The CTRP8-RXFP1-mediated migration in GB cells involves the activation of PI3K and specific protein kinase C pathways and the increased production/secretion of the potent lysosomal protease cathepsin B (cathB), a known prognostic marker of GB. Specific inhibition of CTRP8-induced cathB activity effectively blocked the ability of primary GB to invade laminin matrices. Finally, co-immunoprecipitation studies revealed the direct interaction of human CTRP8 with RXFP1. Our results support a therapeutic approach in GB aimed at targeting multiple steps of the CTRP8-RXFP1 signalling pathway by a combined inhibitor and peptide-based strategy to block GB dissemination within the brain. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  10. Early-life exercise may promote lasting brain and metabolic health through gut bacterial metabolites.

    Science.gov (United States)

    Mika, Agnieszka; Fleshner, Monika

    2016-02-01

    The 100 trillion microorganisms residing within our intestines contribute roughly 5 million additional genes to our genetic gestalt, thus posing the potential to influence many aspects of our physiology. Microbial colonization of the gut shortly after birth is vital for the proper development of immune, neural and metabolic systems, while sustaining a balanced, diverse gut flora populated with beneficial bacteria is necessary for maintaining optimal function of these systems. Although symbiotic host-microbial interactions are important throughout the lifespan, these interactions can have greater and longer lasting impacts during certain critical developmental periods. A better understanding of these sensitive periods is necessary to improve the impact and effectiveness of health-promoting interventions that target the microbial ecosystem. We have recently reported that exercise initiated in early life increases gut bacterial species involved in promoting psychological and metabolic health. In this review, we emphasize the ability of exercise during this developmentally receptive time to promote optimal brain and metabolic function across the lifespan through microbial signals.

  11. Long-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged rats.

    Science.gov (United States)

    O'Hagan, Caroline; Li, Jia V; Marchesi, Julian R; Plummer, Sue; Garaiova, Iveta; Good, Mark A

    2017-10-01

    Ageing is associated with changes in the gut microbiome that may contribute to age-related changes in cognition. Previous work has shown that dietary supplements with multi-species live microorganisms can influence brain function, including induction of hippocampal synaptic plasticity and production of brain derived neurotrophic factor, in both young and aged rodents. However, the effect of such dietary supplements on memory processes has been less well documented, particularly in the context of aging. The main aim of the present study was to examine the impact of a long-term dietary supplement with a multi-species live Lactobacillus and Bifidobacteria mixture (Lactobacillus acidophilus CUL60, L. acidophilus CUL21, Bifidobacterium bifidum CUL20 and B. lactis CUL34) on tests of memory and behavioural flexibility in 15-17-month-old male rats. Following behavioural testing, the hippocampus and prefrontal cortex was extracted and analysed ex vivo using (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy to examine brain metabolites. The results showed a small beneficial effect of the dietary supplement on watermaze spatial navigation and robust improvements in long-term object recognition memory and short-term memory for object-in-place associations. Short-term object novelty and object temporal order memory was not influenced by the dietary supplement in aging rats. (1)H NMR analysis revealed diet-related regional-specific changes in brain metabolites; which indicated changes in several pathways contributing to modulation of neural signaling. These data suggest that chronic dietary supplement with multi-species live microorganisms can alter brain metabolites in aging rats and have beneficial effects on memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Extended findings of Brain Metabolite Normalization in MA-Dependent Subjects Across Sustained Abstinence: A Proton MRS Study

    Science.gov (United States)

    Salo, Ruth; Buonocore, Michael H.; Leamon, Martin; Natsuaki, Yutaka; Waters, Christy; Moore, Charles D.; Galloway, Gantt P.; Nordahl, Thomas E.

    2010-01-01

    Objective The goal of the present study was to extend our previous findings on long-term methamphetamine (MA) use and drug abstinence on brain metabolite levels in an expanded group of MA-dependent individuals. Methods Seventeen MA abusers with sustained drug abstinence (1 year to 5 years), 30 MA abusers with short-term drug abstinence (1 month to 6 months) and 24 non-substance using controls were studied using MR spectroscopy (MRS). MRS measures of NAA/Cr, Cho/Cr and Cho/NAA were obtained in the anterior cingulate cortex (ACC) and in the primary visual cortex (PVC). Results ACC-Cho/NAA values were abnormally high in the short-term abstinent group compared to controls [F(1,52)=18.76, p<0.0001]. No differences were observed between controls and the long-term abstinent group [F(1,39)=0.97, p=0.97]. New evidence of lower ACC-NAA/Cr levels were observed in the short-term abstinent MA abusers compared to controls [F(1,52)=23.05, p<0.0001] and long-term abstinent MA abusers [F(1,45)=7.06, p=0.01]. No differences were observed between long-term abstinent MA abusers and controls [F(1,39)=0.48, p=0.49]. Conclusions The new findings of relative NAA/Cr normalization across periods of abstinence suggest that adaptive changes following cessation of MA abuse may be broader than initially thought. These changes may contribute to some degree of normalization of neuronal function in the ACC. PMID:20739127

  13. Total {sup 18}F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

    Energy Technology Data Exchange (ETDEWEB)

    Fiebrich, Helle-Brit; Walenkamp, Annemiek M.; Vries, Elisabeth G.E. de [University Medical Centre Groningen, Department of Medical Oncology, Groningen (Netherlands); Jong, Johan R. de; Koopmans, Klaas Pieter; Dierckx, Rudi A.J.O.; Brouwers, Adrienne H. [University Medical Centre Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Kema, Ido P. [University Medical Centre Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Sluiter, Wim; Links, Thera P. [University Medical Centre Groningen, Department of Endocrinology, Groningen (Netherlands)

    2011-10-15

    Positron emission tomography (PET) using 6-[{sup 18}F]fluoro-L-dihydroxyphenylalanine ({sup 18}F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. {sup 18}F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total {sup 18}F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an {sup 18}F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on {sup 18}F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. {sup 18}F-dopa PET detected 979 lesions. SUV{sub max} on {sup 18}F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with {sup 18}F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity. (orig.)

  14. New Zealand adolescents’ cellphone and cordless phone user-habits: are they at increased risk of brain tumours already? A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Redmayne Mary

    2013-01-01

    Full Text Available Abstract Background Cellphone and cordless phone use is very prevalent among early adolescents, but the extent and types of use is not well documented. This paper explores how, and to what extent, New Zealand adolescents are typically using and exposed to active cellphones and cordless phones, and considers implications of this in relation to brain tumour risk, with reference to current research findings. Methods This cross-sectional study recruited 373 Year 7 and 8 school students with a mean age of 12.3 years (range 10.3-13.7 years from the Wellington region of New Zealand. Participants completed a questionnaire and measured their normal body-to-phone texting distances. Main exposure-metrics included self-reported time spent with an active cellphone close to the body, estimated time and number of calls on both phone types, estimated and actual extent of SMS text-messaging, cellphone functions used and people texted. Statistical analyses used Pearson Chi2 tests and Pearson’s correlation coefficient (r. Analyses were undertaken using SPSS version 19.0. Results Both cellphones and cordless phones were used by approximately 90% of students. A third of participants had already used a cordless phone for ≥ 7 years. In 4 years from the survey to mid-2013, the cordless phone use of 6% of participants would equal that of the highest Interphone decile (≥ 1640 hours, at the surveyed rate of use. High cellphone use was related to cellphone location at night, being woken regularly, and being tired at school. More than a third of parents thought cellphones carried a moderate-to-high health risk for their child. Conclusions While cellphones were very popular for entertainment and social interaction via texting, cordless phones were most popular for calls. If their use continued at the reported rate, many would be at increased risk of specific brain tumours by their mid-teens, based on findings of the Interphone and Hardell-group studies.

  15. Transient postnatal fluoxetine decreases brain concentrations of 20-HETE and 15-epi-LXA4, arachidonic acid metabolites in adult mice.

    Science.gov (United States)

    Yuan, Zhi-Xin; Rapoport, Stanley I

    2015-10-01

    Transient postnatal exposure of rodents to the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine alters behavior and brain 5-HT neurotransmission during adulthood, and also reduces brain arachidonic (ARA) metabolic consumption and protein level of the ARA metabolizing enzyme, cytochrome P4504A (CYP4A). Brain 20-hydroxyeicosatetraenoic acid (20-HETE), converted by CYP4A from ARA, will be reduced in adult mice treated transiently and postnatally with fluoxetine. Male mice pups were injected i.p. daily with fluoxetine (10mg/kg) or saline during P4-P21. At P90 their brain was high-energy microwaved and analyzed for 20-HETE and six other ARA metabolites by enzyme immunoassay. Postnatal fluoxetine vs. saline significantly decreased brain concentrations of 20-HETE (-70.3%) and 15-epi-lipoxin A4 (-60%) in adult mice, but did not change other eicosanoid concentrations. Behavioral changes in adult mice treated postnatally with fluoxetine may be related to reduced brain ARA metabolism involving CYP4A and 20-HETE formation. Published by Elsevier Ltd.

  16. Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain.

    Science.gov (United States)

    Schou-Pedersen, Anne Marie V; Hansen, Stine N; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2016-08-15

    In the present paper, we describe a validated chromatographic method for the simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell culture and in sub-regions of the guinea pig brain. Electrochemical detection provided limits of quantifications (LOQs) between 3.6 and 12nM. Within the linear range, obtained recoveries were from 90.9±9.9 to 120±14% and intra-day and inter-day precisions found to be less than 5.5% and 12%, respectively. The analytical method was applicable for quantification of intracellular and extracellular amounts of monoamine neurotransmitters and their metabolites in guinea pig frontal cortex and hippocampal primary neuronal cell cultures. Noradrenaline, dopamine and serotonin were found to be in a range from 0.31 to 1.7pmol per 2 million cells intracellularly, but only the biogenic metabolites could be detected extracellularly. Distinct differences in monoamine concentrations were observed when comparing concentrations in guinea pig frontal cortex and cerebellum tissue with higher amounts of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid in frontal cortex, as compared to cerebellum. The chemical turnover in frontal cortex tissue of guinea pig was for serotonin successfully predicted from the turnover observed in the frontal cortex cell culture. In conclusion, the present analytical method shows high precision, accuracy and sensitivity and is broadly applicable to monoamine measurements in cell cultures as well as brain biopsies from animal models used in preclinical neurochemistry. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Estimating associations of mobile phone use and brain tumours taking into account laterality: a comparison and theoretical evaluation of applied methods.

    Science.gov (United States)

    Frederiksen, Kirsten; Deltour, Isabelle; Schüz, Joachim

    2012-12-10

    Estimating exposure-outcome associations using laterality information on exposure and on outcome is an issue, when estimating associations of mobile phone use and brain tumour risk. The exposure is localized; therefore, a potential risk is expected to exist primarily on the side of the head, where the phone is usually held (ipsilateral exposure), and to a lesser extent at the opposite side of the head (contralateral exposure). Several measures of the associations with ipsilateral and contralateral exposure, dealing with different sampling designs, have been presented in the literature. This paper presents a general framework for the analysis of such studies using a likelihood-based approach in a competing risks model setting. The approach clarifies the implicit assumptions required for the validity of the presented estimators, particularly that in some approaches the risk with contralateral exposure is assumed to be zero. The performance of the estimators is illustrated in a simulation study showing for instance that while in some scenarios there is a loss of statistical power, others - in case of a positive ipsilateral exposure-outcome association - would result in a negatively biased estimate of the contralateral exposure parameter, irrespective of any additional recall bias. In conclusion, our theoretical evaluations and results from the simulation study emphasize the importance of setting up a formal model, which furthermore allows for estimation in more complicated and perhaps more realistic exposure settings, such as taking into account exposure to both sides of the head. Copyright © 2012 John Wiley & Sons, Ltd.

  18. Multimodal optical imaging database from tumour brain human tissue: endogenous fluorescence from glioma, metastasis and control tissues

    Science.gov (United States)

    Poulon, Fanny; Ibrahim, Ali; Zanello, Marc; Pallud, Johan; Varlet, Pascale; Malouki, Fatima; Abi Lahoud, Georges; Devaux, Bertrand; Abi Haidar, Darine

    2017-02-01

    Eliminating time-consuming process of conventional biopsy is a practical improvement, as well as increasing the accuracy of tissue diagnoses and patient comfort. We addressed these needs by developing a multimodal nonlinear endomicroscope that allows real-time optical biopsies during surgical procedure. It will provide immediate information for diagnostic use without removal of tissue and will assist the choice of the optimal surgical strategy. This instrument will combine several means of contrast: non-linear fluorescence, second harmonic generation signal, reflectance, fluorescence lifetime and spectral analysis. Multimodality is crucial for reliable and comprehensive analysis of tissue. Parallel to the instrumental development, we currently improve our understanding of the endogeneous fluorescence signal with the different modalities that will be implemented in the stated. This endeavor will allow to create a database on the optical signature of the diseased and control brain tissues. This proceeding will present the preliminary results of this database on three types of tissues: cortex, metastasis and glioblastoma.

  19. Translation and pilot validation of Hindi translation of assessing quality of life in patients with primary brain tumours using EORTC brain module (BN-20

    Directory of Open Access Journals (Sweden)

    Budrukkar Ashwini

    2006-01-01

    Full Text Available Aim: To translate and validate the European Organisation for Research and Treatment for Cancer (EORTC brain cancer module (BN-20 into Hindi to make it available for patients and scientific community. Methods and Results: The EORTC BN-20 was translated into Hindi using standard guidelines by EORTC. The process included forward translation by two translators, discussion with the translators in case of discrepancies and formation of first intermediate questionnaire. This questionnaire was then given to two more translators who translated this questionnaire back into English. These 2 questionnaires were then compared with the original EORTC questionnaire and the second intermediate questionnaire was formed. The second intermediate questionnaire was subsequently administered in 10 patients with brain tumors who had never seen the questionnaire before, for pilot-testing. Each of these 10 patients after filling up the questionnaire themselves was then interviewed for any difficulty encountered during the filling up of the questionnaire. These were in the form of specific modules including difficulty in answering, confusion while answering and difficulty to understand, whether the questions were upsetting and if patients would have asked the question in any different way. There were major suggestions in three questions, which were incorporated into the second intermediate questionnaire to form the final Hindi BN-20 questionnaire. Conclusion: The final Hindi BN-20 has been approved by EORTC and can be used in clinical practice and studies for patients with brain tumors.

  20. Translation and pilot validation of Hindi translation of assessing quality of life in patients with primary brain tumours using EORTC brain module (BN-20).

    Science.gov (United States)

    Budrukkar, Ashwini; Jalali, Rakesh; Kamble, Rashmi; Parab, Sachin

    2006-01-01

    To translate and validate the European Organisation for Research and Treatment for Cancer (EORTC) brain cancer module (BN-20) into Hindi to make it available for patients and scientific community. The EORTC BN-20 was translated into Hindi using standard guidelines by EORTC. The process included forward translation by two translators, discussion with the translators in case of discrepancies and formation of first intermediate questionnaire. This questionnaire was then given to two more translators who translated this questionnaire back into English. These 2 questionnaires were then compared with the original EORTC questionnaire and the second intermediate questionnaire was formed. The second intermediate questionnaire was subsequently administered in 10 patients with brain tumors who had never seen the questionnaire before, for pilot-testing. Each of these 10 patients after filling up the questionnaire themselves was then interviewed for any difficulty encountered during the filling up of the questionnaire. These were in the form of specific modules including difficulty in answering, confusion while answering and difficulty to understand, whether the questions were upsetting and if patients would have asked the question in any different way. There were major suggestions in three questions, which were incorporated into the second intermediate questionnaire to form the final Hindi BN-20 questionnaire. The final Hindi BN-20 has been approved by EORTC and can be used in clinical practice and studies for patients with brain tumors.

  1. Toward an in Vivo Neurochemical Profile: Quantification of 18 Metabolites in Short-Echo-Time 1H NMR Spectra of the Rat Brain

    Science.gov (United States)

    Pfeuffer, Josef; Tkáč , Ivan; Provencher, Stephen W.; Gruetter, Rolf

    1999-11-01

    Localized in vivo1H NMR spectroscopy was performed with 2-ms echo time in the rat brain at 9.4 T. Frequency domain analysis with LCModel showed that the in vivo spectra can be explained by 18 metabolite model solution spectra and a highly structured background, which was attributed to resonances with fivefold shorter in vivo T1 than metabolites. The high spectral resolution (full width at half maximum approximately 0.025 ppm) and sensitivity (signal-to-noise ratio approximately 45 from a 63-μL volume, 512 scans) was used for the simultaneous measurement of the concentrations of metabolites previously difficult to quantify in 1H spectra. The strongly represented signals of N-acetylaspartate, glutamate, taurine, myo-inositol, creatine, phosphocreatine, glutamine, and lactate were quantified with Cramér-Rao lower bounds below 4%. Choline groups, phosphorylethanolamine, glucose, glutathione, γ-aminobutyric acid, N-acetylaspartylglutamate, and alanine were below 13%, whereas aspartate and scyllo-inositol were below 22%. Intra-assay variation was assessed from a time series of 3-min spectra, and the coefficient of variation was similar to the calculated Cramér-Rao lower bounds. Interassay variation was determined from 31 pooled spectra, and the coefficient of variation for total creatine was 7%. Tissue concentrations were found to be in very good agreement with neurochemical data from the literature.

  2. Effects of a high-caloric diet and physical exercise on brain metabolite levels: a combined proton MRS and histologic study.

    Science.gov (United States)

    Auer, Matthias K; Sack, Markus; Lenz, Jenny N; Jakovcevski, Mira; Biedermann, Sarah V; Falfán-Melgoza, Claudia; Deussing, Jan; Steinle, Jörg; Bielohuby, Maximilian; Bidlingmaier, Martin; Pfister, Frederik; Stalla, Günter K; Ende, Gabriele; Weber-Fahr, Wolfgang; Fuss, Johannes; Gass, Peter

    2015-03-31

    Excessive intake of high-caloric diets as well as subsequent development of obesity and diabetes mellitus may exert a wide range of unfavorable effects on the central nervous system (CNS). It has been suggested that one mechanism in this context is the promotion of neuroinflammation. The potentially harmful effects of such diets were suggested to be mitigated by physical exercise. Here, we conducted a study investigating the effects of physical exercise in a cafeteria-diet mouse model on CNS metabolites by means of in vivo proton magnetic resonance spectroscopy ((1)HMRS). In addition postmortem histologic and real-time (RT)-PCR analyses for inflammatory markers were performed. Cafeteria diet induced obesity and hyperglycemia, which was only partially moderated by exercise. It also induced several changes in CNS metabolites such as reduced hippocampal glutamate (Glu), choline-containing compounds (tCho) and N-acetylaspartate (NAA)+N-acetyl-aspartyl-glutamic acid (NAAG) (tNAA) levels, whereas opposite effects were seen for running. No association of these effects with markers of central inflammation could be observed. These findings suggest that while voluntary wheel running alone is insufficient to prevent the unfavorable peripheral sequelae of the diet, it counteracted many changes in brain metabolites. The observed effects seem to be independent of neuroinflammation.

  3. 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.

  4. Factors related to pregnancy and birth and the risk of childhood brain tumours: The ESTELLE and ESCALE studies (SFCE, France).

    Science.gov (United States)

    Bailey, Helen D; Rios, Paula; Lacour, Brigitte; Guerrini-Rousseau, Léa; Bertozzi, Anne-Isabelle; Leblond, Pierre; Faure-Conter, Cécile; Pellier, Isabelle; Freycon, Claire; Michon, Jean; Puget, Stéphanie; Ducassou, Stéphane; Orsi, Laurent; Clavel, Jacqueline

    2017-04-15

    Little is known of the causes of childhood brain tumors (CBT). The aims of this study were to investigate whether extremes of birth weight were associated with increased risk of CBT and whether maternal preconceptional folic acid supplementation or breastfeeding reduced the risk. In addition, other maternal characteristics and birth related factors were also investigated. We pooled data from two French national population-based case-control studies with similar designs conducted in 2003-2004 and 2010-2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender did a telephone interview, which focussed on demographic and perinatal characteristics, and maternal life style habits and reproductive history. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex, study of origin and relevant confounders. No association was found between CBT and birth weight or fetal growth. The use of preconceptional folic acid supplementation was rare (5.3% in cases and 7.8% in controls) and the OR was 0.8 (95% CI 0.5, 1.4). There was no association with breastfeeding, even prolonged (six months or more; OR 1.0, 95% CI 0.8, 1.4). Neither was there any association between CBT and other investigated factors (maternal body mass index, gestational weight gain, congenital abnormality, maternal reproductive history or use of fertility treatments. Although large, this study was underpowered for subtype analyses. Pooling data with other population-based studies may provide further insight into findings by CBT subtypes. © 2017 UICC.

  5. Data supporting the rat brain sample preparation and validation assays for simultaneous determination of 8 neurotransmitters and their metabolites using liquid chromatography–tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Aneta Wojnicz

    2016-06-01

    Full Text Available The data presented in this article supports the rat brain sample preparation procedure previous to its injection into the liquid chromatography–tandem mass spectrometry (LC–MS/MS system to monitor levels of adrenaline, noradrenaline, glutamic acid, γ-aminobutyric acid, dopamine, 5-hydroxytryptamine, 5-hydroxyindole acetic acid, and 3-methoxy-4-hydroxyphenylglycol. In addition, we describe the method validation assays (such as calibration curve, lower limit of quantification, precision and accuracy intra- and inter-day, selectivity, extraction recovery and matrix effect, stability, and carry-over effect according to the United States Food and Drug Administration and European Medicine Agency to measure in one step different neurotransmitters and their metabolites. The data supplied in this article is related to the research study entitled: “Simultaneous determination of 8 neurotransmitters and their metabolite levels in rat brain using liquid chromatography in tandem with mass spectrometry: application to the murine Nrf2 model of depression” (Wojnicz et al. 2016 [1].

  6. Comparison between Short and Long Echo Time Magnetic Resonance Spectroscopic Imaging at 3T and 7T for Evaluating Brain Metabolites in Patients with Glioma.

    Science.gov (United States)

    Li, Yan; Lafontaine, Marisa; Chang, Susan; Nelson, Sarah J

    2018-01-17

    Three-dimensional proton magnetic resonance spectroscopic imaging (MRSI) is a powerful non-invasive tool for characterizing spatial variations in metabolic profiles for patients with glioma. Metabolic parameters obtained using this technique have been shown to predict treatment response, disease progression, and transformation to a more malignant phenotype. The availability of ultra-high-field MR systems has the potential to improve the characterization of metabolites. The purpose of this study was to compare the metabolite profiles acquired with conventional long echo time (TE) MRSI at 3T with those obtained with short TE MRSI at 3T and 7T in patients with glioma. The data acquisition parameters were optimized separately for each echo time and field strength to obtain volumetric coverage within clinically feasible data acquisition times of 5-10 min. While a higher field strength did provide better detection of metabolites with overlapping peaks, spatial coverage was reduced and the use of inversion recovery to reduce lipid precluded the detection of lipid in regions of necrosis. For serial evaluation of large, heterogeneous lesions, the use of 3T short TE MRSI may thus be preferred. Despite the limited number of metabolites that it is able to detect, the use of 3T long TE MRSI gives the best contrast in choline/N-acetyl aspartate between normal appearing brain and tumor and also allows the separate detection of lactate and lipid. It may therefore be preferred for serial evaluation of patients with high-grade glioma and for detection of malignant transformation in patients with low-grade glioma.

  7. In vivo quantification of brain metabolites by 1H-MRS using water as an internal standard

    DEFF Research Database (Denmark)

    Christiansen, P; Henriksen, O; Stubgaard, M

    1993-01-01

    in quantification of N-acetyl aspartate (NAA) concentration was about 1-2 mM (6-12%). Also in vivo a good linearity between water signal and selected voxel size was seen. The same was true for the studied metabolites, N-acetyl aspartate (NAA), creatine/phosphocreatine (Cr/PCr), and choline (Cho). Calculated average...

  8. Development and validation of a high performance liquid chromatography quantification method of levo-tetrahydropalmatine and its metabolites in plasma and brain tissues: application to a pharmacokinetic study.

    Science.gov (United States)

    Abdallah, Inas A; Huang, Peng; Liu, Jing; Lee, David Y; Liu-Chen, Lee-Yuan; Hassan, Hazem E

    2017-04-01

    Levo-tetrahydropalmatine (l-THP) is an alkaloid isolated from Chinese medicinal herbs of the Corydalis and Stephania genera. It has been used in China for more than 40 years mainly as an analgesic with sedative/hypnotic effects. Despite its extensive use, its metabolism has not been quantitatively studied, nor there a sensitive reliable bioanalytical method for its quantification simultaneously with its metabolites. As such, the objective of this study was to develop and validate a sensitive and selective HPLC method for simultaneous quantification of l-THP and its desmethyl metabolites l-corydalmine (l-CD) and l-corypalmine (l-CP) in rat plasma and brain tissues. Rat plasma and brain samples were processed by liquid-liquid extraction using ethyl acetate. Chromatographic separation was achieved on a reversed-phase Symmetry® C18 column (4.6 × 150 mm, 5 μm) at 25°C. The mobile phase consisted of acetonitrile-methanol-10 mm ammonium phosphate (pH 3) (10:30:60, v/v) and was used at a flow rate of 0.8 mL/min. The column eluent was monitored at excitation and emission wavelengths of 230 and 315 nm, respectively. The calibration curves were linear over the concentration range of 1-10,000 ng/mL. The intra- and interday reproducibility studies demonstrated accuracy and precision within the acceptance criteria of bioanalytical guidelines. The validated HPLC method was successfully applied to analyze samples from a pharmacokinetic study of l-THP in rats. Taken together, the developed method can be applied for bioanalysis of l-THP and its metabolites in rodents and potentially can be transferred for bioanalysis of human samples. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Parents' perspectives of life challenges experienced by long-term paediatric brain tumour survivors: work and finances, daily and social functioning, and legal difficulties.

    Science.gov (United States)

    Howard, A Fuchsia; Hasan, Haroon; Bobinski, Mary Anne; Nurcombe, Wendy; Olson, Robert; Parkinson, Maureen; Goddard, Karen

    2014-09-01

    Paediatric brain tumour survivors (PBTS) are at high risk for medical, neurocognitive and psychological sequelea during adulthood. Details illustrating the types and breadth of these chronic sequelae are essential to fully comprehend their impact on daily living. This study describes Canadian parents of PBTS perspectives of life challenges experienced by their now adult son or daughter related to work and finances, daily and social functioning, and legal difficulties. Parents of PBTS completed an anonymous online exploratory survey. Forty-six of 60 invited parents completed the survey. Parents reported that PBTS experienced difficulty gaining or sustaining employment (65 %) because of their health and/or a disability and employers reticence to hire and adequately support PBTS. Independent living was considered unaffordable for PBTS who received a disability allowance (82 %) and those who were employed (50 %). Thirty percent indicated their family experienced hardship because of PBTS medical expenses, which were usually paid for out of pocket (76 %). Although the majority of PBTS were independent with daily tasks and social functioning, a subgroup required continuous support. Forty percent of employed PBTS received limited assistance to accommodate their special needs. Parents indicated their son or daughter had been the victim of theft, fraud or assault (37 %), and commonly considered them vulnerable, in need of protection and feared for their future safety. Research that further illuminates the hardships facing PBTS and informs the development of support and resources to address PBTS vulnerabilities is warranted. PBTS are at risk for unemployment, financial challenges and legal difficulties, which appear to be poorly addressed by health and social programs.

  10. Preventive brain radio-chemotherapy alters plasticity associated metabolite profile in the hippocampus but seems to not affect spatial memory in young leukemia patients.

    Science.gov (United States)

    Brandt, Moritz D; Brandt, Kalina; Werner, Annett; Schönfeld, Robby; Loewenbrück, Kai; Donix, Markus; Schaich, Markus; Bornhäuser, Martin; von Kummer, Rüdiger; Leplow, Bernd; Storch, Alexander

    2015-09-01

    Neuronal plasticity leading to evolving reorganization of the neuronal network during entire lifespan plays an important role for brain function especially memory performance. Adult neurogenesis occurring in the dentate gyrus of the hippocampus represents the maximal way of network reorganization. Brain radio-chemotherapy strongly inhibits adult hippocampal neurogenesis in mice leading to impaired spatial memory. To elucidate the effects of CNS radio-chemotherapy on hippocampal plasticity and function in humans, we performed a longitudinal pilot study using 3T proton magnetic resonance spectroscopy ((1)H-MRS) and virtual water-maze-tests in 10 de-novo patients with acute lymphoblastic leukemia undergoing preventive whole brain radio-chemotherapy. Patients were examined before, during and after treatment. CNS radio-chemotherapy did neither affect recall performance in probe trails nor flexible (reversal) relearning of a new target position over a time frame of 10 weeks measured by longitudinal virtual water-maze-testing, but provoked hippocampus-specific decrease in choline as a metabolite associated with cellular plasticity in (1)H-MRS. Albeit this pilot study needs to be followed up to definitely resolve the question about the functional role of adult human neurogenesis, the presented data suggest that (1)H-MRS allows the detection of neurogenesis-associated plasticity in the human brain.

  11. Dosimetry comparison of irradiation with conformal radiotherapy, intensity modulated radiotherapy, conformal radiotherapy in stereotactic conditions and robotic stereotactic radiotherapy for benign brain tumours; Comparaison dosimetrique de la radiotherapie conformationnelle, la radiotherapie conformationnelle avec modulation d'intensite, la radiotherapie conformationnelle en conditions stereotaxiques et la radiotherapie en conditions stereotaxiques robotisee des tumeurs cerebrales benignes

    Energy Technology Data Exchange (ETDEWEB)

    Spasic, E.; Noel, A. [Departement de radiophysique, centre Alexis-Vautrin, avenue de Bourgogne, 54511 Vandoeuvre-les-Nancy cedex (France); UMR 7039 CNRS, centre de recherche en automatique de Nancy (Cran), BP 239, 54506 Vandoeuvre-les-Nancy cedex (France); Cran UMR 7039, faculte des sciences et techniques, universite Henri-Poincare Nancy 1, BP 239, 54506 Vandoeuvre-les-Nancy cedex (France); Cran UMR 7039, institut national polytechnique de Lorraine, BP 239, 54506 Vandoeuvre-les-Nancy cedex (France); Buchheit, I.; Bernier, V. [Departement de radiophysique, centre Alexis-Vautrin, avenue de Bourgogne, 54511 Vandoeuvre-les-Nancy cedex (France)

    2011-07-15

    Purpose. - To compare several techniques in order to determine the best treatment for benign brain tumours. Methods and patients. - A retrospective study was performed for five patients who received 3D-conformal radiotherapy, intensity modulated radiotherapy or CyberKnife{sup R}. These patients had a meningioma, a pituitary tumour, a cranio-pharyngioma or a neurinoma. In each case, these treatment plans were optimised and compared with the three other dosimetries. Radiobiological or positioning parameters were evaluated, as well as dosimetric parameters, in order to compare treatments with different characteristics. Results. - The dosimetric parameters showed that the choice of treatment seemed to be determined mostly by tumour size, shape and proximity with organs at risk (not tumour localisation). Whereas the results showed no significant deviations with regards to the radiobiological parameters. Therefore, with these parameters, it was difficult to give priority to a treatment. Conclusions. - With regards to benign brain tumours of medium or large size, intensity modulated radiotherapy seemed the recommended treatment. It enabled to obtain a good ratio between efficacy and toxicity for tumours that are really close to organs at risk. Concerning small benign brain tumours, the CyberKnife{sup R} was probably the best treatment. (authors)

  12. A new clinical guideline from the Royal College of Paediatrics and Child Health with a national awareness campaign accelerates brain tumor diagnosis in UK children—“HeadSmart: Be Brain Tumour Aware”

    Science.gov (United States)

    2016-01-01

    Background A national survey in 2006 identified that UK referral practice for pediatric CNS tumors ranked poorly in international comparisons, which led to new National Health Service (NHS) Evidence accredited referral guidelines published in 2008 by the Royal College of Paediatrics and Child Health and a campaign to raise awareness of early features of CNS tumors and the need for timely imaging. Methods The “HeadSmart: Be Brain Tumour Aware” campaign was launched in June 2011 across the UK as a quality improvement strategy directed at reducing the total diagnostic interval (TDI) from a pre-campaign (2006) median of 14 (mean, 35.4) weeks to a target of 5 weeks in order to equal the best reported internationally. Professional and public awareness was measured by questionnaire surveys. TDI was collected by clinical champions in 18 regional children's cancer centers and the public campaign was coordinated by a national charity, working with a network of community champions. Results The guidelines and campaign raised awareness among pediatricians and were associated with reduction in TDI to a median of 6.7 (mean, 21.3) weeks by May 2013. This change in referral practice was most pronounced in the time from first medical contact to CNS imaging, for which the median was reduced from 3.3 to 1.4 weeks between January 2011 and May 2013 (P = .009). Conclusion This strategy to accelerate brain tumor diagnosis by the NHS using a public and professional awareness campaign is a “world first” in pediatric cancer and is being emulated internationally and acknowledged by a series of NHS and charity awards for excellence. PMID:26523066

  13. A new clinical guideline from the Royal College of Paediatrics and Child Health with a national awareness campaign accelerates brain tumor diagnosis in UK children--"HeadSmart: Be Brain Tumour Aware".

    Science.gov (United States)

    2016-03-01

    A national survey in 2006 identified that UK referral practice for pediatric CNS tumors ranked poorly in international comparisons, which led to new National Health Service (NHS) Evidence accredited referral guidelines published in 2008 by the Royal College of Paediatrics and Child Health and a campaign to raise awareness of early features of CNS tumors and the need for timely imaging. The "HeadSmart: Be Brain Tumour Aware" campaign was launched in June 2011 across the UK as a quality improvement strategy directed at reducing the total diagnostic interval (TDI) from a pre-campaign (2006) median of 14 (mean, 35.4) weeks to a target of 5 weeks in order to equal the best reported internationally. Professional and public awareness was measured by questionnaire surveys. TDI was collected by clinical champions in 18 regional children's cancer centers and the public campaign was coordinated by a national charity, working with a network of community champions. The guidelines and campaign raised awareness among pediatricians and were associated with reduction in TDI to a median of 6.7 (mean, 21.3) weeks by May 2013. This change in referral practice was most pronounced in the time from first medical contact to CNS imaging, for which the median was reduced from 3.3 to 1.4 weeks between January 2011 and May 2013 (P = .009). This strategy to accelerate brain tumor diagnosis by the NHS using a public and professional awareness campaign is a "world first" in pediatric cancer and is being emulated internationally and acknowledged by a series of NHS and charity awards for excellence. © Crown copyright 2015.

  14. The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Thomas Raymond H

    2012-07-01

    Full Text Available Abstract Gastrointestinal symptoms and altered blood phospholipid profiles have been reported in patients with autism spectrum disorders (ASD. Most of the phospholipid analyses have been conducted on the fatty acid composition of isolated phospholipid classes following hydrolysis. A paucity of information exists on how the intact phospholipid molecular species are altered in ASD. We applied ESI/MS to determine how brain and blood intact phospholipid species were altered during the induction of ASD-like behaviors in rats following intraventricular infusions with the enteric bacterial metabolite propionic acid. Animals were infused daily for 8 days, locomotor activity assessed, and animals killed during the induced behaviors. Propionic acid infusions increased locomotor activity. Lipid analysis revealed treatment altered 21 brain and 30 blood phospholipid molecular species. Notable alterations were observed in the composition of brain SM, diacyl mono and polyunsaturated PC, PI, PS, PE, and plasmalogen PC and PE molecular species. These alterations suggest that the propionic acid rat model is a useful tool to study aberrations in lipid metabolism known to affect membrane fluidity, peroxisomal function, gap junction coupling capacity, signaling, and neuroinflammation, all of which may be associated with the pathogenesis of ASD.

  15. Epidemiology of childhood cancer and the SACCSG tumour regis try

    African Journals Online (AJOL)

    In South Africa leukaemia is the most common malignancy in childhood, representing 25.35% of all cancers, which is similar to rates in other countries. While brain tumours and leukaemia comprise almost half of childhood malignancies in developed countries, in South Africa brain tumours represent only 13.44% of the total.

  16. Determination of monoamine neurotransmitters and their metabolites in a mouse brain microdialysate by coupling high-performance liquid chromatography with gold nanoparticle-initiated chemiluminescence

    Energy Technology Data Exchange (ETDEWEB)

    Li Na; Guo Jizhao; Liu Bo; Yu Yuqi [Department of Chemistry, University of Science and Technology of China (USTC), JinZhai Road No: 96, 230026 Hefei, Anhui (China); Cui Hua, E-mail: hcui@ustc.edu.cn [Department of Chemistry, University of Science and Technology of China (USTC), JinZhai Road No: 96, 230026 Hefei, Anhui (China); Mao Lanqun; Lin Yuqing [Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), 100080 Beijing (China)

    2009-07-10

    Our previous work showed that gold nanoparticles could trigger chemiluminescence (CL) between luminol and AgNO{sub 3}. In the present work, the effect of some biologically important reductive compounds, including monoamine neurotransmitters and their metabolites, reductive amino acids, ascorbic acid, uric acid, and glutathione, on the novel CL reaction were investigated for analytical purpose. It was found that all of them could inhibit the CL from the luminol-AgNO{sub 3}-Au colloid system. Among them, monoamine neurotransmitters and their metabolites exhibited strong inhibition effect. Taking dopamine as a model compound, the CL mechanism was studied by measuring absorption spectra during the CL reaction and the reaction kinetics via stopped-flow technique. The CL inhibition mechanism is proposed to be due to that these tested compounds competed with luminol for AgNO{sub 3} to inhibit the formation of luminol radicals and to accelerate deposition of Ag atoms on surface of gold nanoparticles, leading to a decrease in CL intensity. Based on the inhibited CL, a novel method for simultaneous determination of monoamine neurotransmitters and their metabolites was developed by coupling high-performance liquid chromatography with this CL reaction. The new method was successfully applied to determine the compounds in a mouse brain microdialysate. Compared with the reported HPLC-CL methods, the proposed method is simple, fast, and could determine more analytes. Moreover, the limits of linear ranges for NE, E, and DA using the proposed method were one order of magnitude lower than the luminol system without gold nanoparticles.

  17. The role of rehabilitation measures in reintegration of children with brain tumours or leukaemia and their families after completion of cancer treatment: a study protocol.

    Science.gov (United States)

    Peikert, Mona Leandra; Inhestern, Laura; Bergelt, Corinna

    2017-08-11

    For ill children as well as for their parents and siblings, childhood cancer poses a major challenge. Little is known about the reintegration into daily life of childhood cancer survivors and their families. The aim of this prospective observational study is to further the understanding of the role of rehabilitation measures in the reintegration process of childhood leukaemia or brain tumour survivors and their family members after the end of cancer treatment. This prospective observational study consists of three study arms: a quantitative study in cooperation with three German paediatric oncological study registries (study arm 1), a quantitative study in cooperation with a rehabilitation clinic that offers a family-oriented paediatric oncological rehabilitation programme (study arm 2) and a qualitative study at 12-month follow-up including families from the study arms 1 and 2 (study arm 3). In study arm 1, children, parents and siblings are surveyed after treatment (baseline), 4-6 months after baseline measurement and at 12-month follow-up. In study arm 2, data are collected at the beginning and at the end of the rehabilitation measure and at 12-month follow-up. Families are assessed with standardised questionnaires on quality of life, emotional and behavioural symptoms, depression, anxiety, fear of progression, coping and family functioning. Furthermore, self-developed items on rehabilitation aims and reintegration into daily life are used. Where applicable, users and non-users of rehabilitation measures will be compared regarding the outcome parameters. Longitudinal data will be analysed by means of multivariate analysis strategies. Reference values will be used for comparisons if applicable. Qualitative data will be analysed using thematic analysis. This study has been approved by the medical ethics committee of the Medical Chamber of Hamburg. Data will be published in peer-reviewed journals and presented at conferences. © Article author(s) (or their

  18. The interference of ethanol with heroin-stimulated psychomotor activation in mice is not related to changed brain concentrations of the active metabolites 6MAM or morphine.

    Science.gov (United States)

    Andersen, Jannike M; Haugen, Karianne S; Ripel, Ase; Mørland, Jørg

    2014-02-01

    It has been suggested that the potentiating effect observed in human beings when combining alcohol and heroin may be due to an interference of ethanol with the pharmacokinetics of heroin, leading to accumulation of the biologically active metabolites, 6-monoacetylmorphine (6MAM) and morphine. However, experimental evidence for this hypothesis is lacking. In this study, we used mice and examined the effect of ethanol on the metabolism of heroin by combining a locomotor activity test, which is a behaviour model representative of psychomotor stimulation, with pharmacokinetic studies in blood and brain tissue. Pre-treatment with ethanol (1 and 2.5 g/kg, po) affected heroin-stimulated (2.5 and 15 μmol/kg, sc) locomotor activation significantly, resulting in a dose-dependent reduction in run distance. However, the change in the activity profiles did not indicate any increase in the concentration of active metabolites. Pharmacokinetic studies in blood and brain supported the behavioural findings, showing no change in the time-versus-concentration curves of either 6MAM or morphine after administration of heroin (15 μmol/kg, sc) to mice pre-treated with ethanol (2.5 g/kg, po). The concentration of heroin itself was elevated, but is probably of minor importance because heroin has low biological activity by itself. The in vivo pharmacokinetic findings were supported by experiments in vitro. In conclusion, studies in mice do not support the hypothesis from epidemiological studies of a pharmacokinetic interaction between alcohol and heroin. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  19. Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain.

    Science.gov (United States)

    Keevil, S F; Barbiroli, B; Brooks, J C; Cady, E B; Canese, R; Carlier, P; Collins, D J; Gilligan, P; Gobbi, G; Hennig, J; Kügel, H; Leach, M O; Metzler, D; Mlynárik, V; Moser, E; Newbold, M C; Payne, G S; Ring, P; Roberts, J N; Rowland, I J; Thiel, T; Tkác, I; Topp, S; Wittsack, H J; Podo, F

    1998-11-01

    We have performed a multicentre trial to assess the performance of three techniques for absolute quantification of cerebral metabolites using in vivo proton nuclear magnetic resonance (NMR). The techniques included were 1) an internal water standard method, 2) an external standard method based on phantom replacement, and 3) a more sophisticated method incorporating elements of both the internal and external standard approaches, together with compartmental analysis of brain water. Only the internal water standard technique could be readily implemented at all participating sites and gave acceptable precision and interlaboratory reproducibility. This method was insensitive to many of the experimental factors affecting the performance of the alternative techniques, including effects related to loading, standing waves and B1 inhomogeneities; and practical issues of phantom positioning, user expertise and examination duration. However, the internal water standard method assumes a value for the concentration of NMR-visible water within the spectroscopic volume of interest. In general, it is necessary to modify this assumed concentration on the basis of the grey matter, white matter and cerebrospinal fluid (CSF) content of the volume, and the NMR-visible water content of the grey and white matter fractions. Combining data from 11 sites, the concentrations of the principal NMR-visible metabolites in the brains of healthy subjects (age range 20-35 years) determined using the internal water standard method were (mean+/-SD): [NAA]=10.0+/-3.4 mM (n=53), [tCho]=1.9+/-1.0 mM (n=51), [Cr + PCr]=6.5+/-3.7 mM (n=51). Evidence of system instability and other sources of error at some participating sites reinforces the need for rigorous quality assurance in quantitative spectroscopy.

  20. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in brain cells in vitro

    Science.gov (United States)

    The shift in equilibrium towards excess reactive oxygen or nitrogen species production from innate antioxidant defense in brain is a critical factor in the declining neural functions and cognitive deficits accompanying age. In aging, there are noticeable alterations in the membrane microenvironment,...

  1. Tumours and tumourous diseases; Tumoren, tumoraehnliche Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Winkelmann, W. (ed.)

    2005-07-01

    This book on tumours and tumourous diseases comprises two parts: 1. Bone tumours and tumourous lesions. 2. Soft tissue tumours and tumourous lesions. Details are presented on pathology, diagnosis, conservative and perioperative therapy, surgical therapy, complications after resection, indicators for amputation, recommendations for follow-up treatment, radiotherapy, radionuclide therapy, alternative therapies, therapy concepts in case of metastases, tissue engineering and plastic surgery. (uke) [German] Der vorliegende Band der Reihe Orthopaedie und orthopaedische Chirurgie behandelt das Thema Tumoren und tumoraehnliche Erkrankungen. Der Band teilt sich in zwei Kapitel: 1. Knochentumoren und tumorartige Laesionen und 2. Weichteiltumoren und tumorartige Laesionen. Dargestellt werden Pathologie, Diagnostik, konservative und perioperative Therapie, chirurgische Therapie, Komplikationen nach Resektion, Indikatoren zur Amputation, Nachsorgeempfehlung, Strahlentherapie, Radionuklidtherapie, alternative Therapieverfahren, Therapiekonzepte bei Metastasen, Tissue Engineering und plastisch-chirurgische Massnahmen. (uke)

  2. Corallocins A-C, Nerve Growth and Brain-Derived Neurotrophic Factor Inducing Metabolites from the Mushroom Hericium coralloides.

    Science.gov (United States)

    Wittstein, Kathrin; Rascher, Monique; Rupcic, Zeljka; Löwen, Eduard; Winter, Barbara; Köster, Reinhard W; Stadler, Marc

    2016-09-23

    Three new natural products, corallocins A-C (1-3), along with two known compounds were isolated from the mushroom Hericium coralloides. Their benzofuranone and isoindolinone structures were elucidated by spectral methods. All corallocins induced nerve growth factor and/or brain-derived neurotrophic factor expression in human 1321N1 astrocytes. Furthermore, corallocin B showed antiproliferative activity against HUVEC and human cancer cell lines MCF-7 and KB-3-1.

  3. Controversies in Odontogenic Tumours

    Science.gov (United States)

    Siwach, Pooja; Joy, Tabita; Tupkari, Jagdish; Thakur, Arush

    2017-01-01

    Odontogenic tumours are lesions that occur solely within the oral cavity and are so named because of their origin from the odontogenic (i.e. tooth-forming) apparatus. Odontogenic tumours comprise a variety of lesions ranging from non-neoplastic tissue proliferations to benign or malignant neoplasms. However, controversies exist regarding the pathogenesis, categorisation and clinical and histological variations of these tumours. The recent 2017 World Health Organization classification of odontogenic tumours included new entities such as primordial odontogenic tumours, sclerosing odontogenic carcinomas and odontogenic carcinosarcomas, while eliminating several previously included entities like keratocystic odontogenic tumours and calcifying cystic odonogenic tumours. The aim of the present review article was to discuss controversies and recent concepts regarding odontogenic tumours so as to increase understanding of these lesions. PMID:29062548

  4. Perinatal tumours: the contribution of radiology to management

    Energy Technology Data Exchange (ETDEWEB)

    Donoghue, Veronica; Ryan, Stephanie; Twomey, Eilish [Children' s University Hospital, Radiology Department, Dublin (Ireland)

    2008-06-15

    A formal classification does not exist and they are probably best classified by their location. Overall the most common neoplasms are - Extracranial teratoma - Neuroblastoma - Soft-tissue tumours - Brain tumours - Leukaemia - Renal tumours - Liver tumours - Retinoblastoma. The prognosis is generally poor, although there are some exceptions such as congenital neuroblastoma and hepatoblastoma. These tumours have a tendency to regress and have a benign clinical course despite a clear malignant histological picture. Other tumours, though histologically benign, may be fatal because of their size and location. Large benign masses may cause airway or cardiovascular compromise and death. Others may cause significant mass effect preventing normal organ development. As normal embryonic cells have a high mitotic rate it is not surprising that perinatal tumours may have a rapid growth rate and become enormous in size. (orig.)

  5. Determination of fluoxetine and its metabolite norfluoxetine in serum and brain areas using high-performance liquid chromatography with ultraviolet detection.

    Science.gov (United States)

    Alvarez, J C; Bothua, D; Collignon, I; Advenier, C; Spreux-Varoquaux, O

    1998-04-10

    A high-performance liquid chromatography (HPLC) method using only 0.1 ml of serum or homogenate from brain areas has been developed for the determination of fluoxetine (FLU) and its metabolite, norfluoxetine (N-FLU), with ultraviolet detection at 227 nm. The small volume of sample required in this method allows studies in small animals, such as mouse. The method provides recoveries of up to 90% for both compounds. Acceptable coefficients of variation were found for both within-run and day-to-day assays. The limit of detection was 5.0 ng/ml. No interferences were found with tricyclic antidepressant drugs and benzodiazepines, which allows this method to be used in clinical studies, Pharmacokinetic parameters for the two compounds are reported in mouse serum, frontal cortex and caudate nucleus. We also report the values of FLU and N-FLU in serum from humans who were treated once daily with 20 mg of FLU, obtained after 1, 14 and 28 days of treatment.

  6. Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Waldman, A.D.; Cordery, R.J.; Godbolt, A.; Rossor, M.N. [University College London, Dementia Research Group, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom); Imperial College of Science, Technology and Medicine, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, London (United Kingdom); MacManus, D.G. [University College London, NMR Research Unit, Department of Clinical Neurology, Institute of Neurology, London (United Kingdom); Collinge, J. [University College London, MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, London (United Kingdom)

    2006-06-15

    Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Straeussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. (orig.)

  7. Measuring levels of biogenic amines and their metabolites in rat brain tissue using high-performance liquid chromatography with photodiode array detection.

    Science.gov (United States)

    Gu, Min-Jung; Jeon, Ji-Hyun; Oh, Myung Sook; Hong, Seon-Pyo

    2016-01-01

    We developed a method to detect biogenic amines and their metabolites in rat brain tissue using simultaneous high-performance liquid chromatography and a photodiode array detection. Measurements were made using a Hypersil Gold C-18 column (250 × 2.1 mm, 5 µm). The mobile phase was 5 mM perchloric acid containing 5 % acetonitrile. The correlation coefficient was 0.9995-0.9999. LODs (S/N = 3) and LOQs (S/N = 10) were as follows: dopamine 0.4 and 1.3 pg, 3, 4-dihydroxyphenylacetic acid 8.4 and 28.0 pg, serotonin 0.4 and 1.3 pg, 5-hydroxyindolacetic acid 3.4 and 11.3 pg, and homovanillic acid 8.4 and 28.0 pg. This method does not require derivatization steps, and is more sensitive than the widely used HPLC-UV method.

  8. Target-based metabolomics for the quantitative measurement of 37 pathway metabolites in rat brain and serum using hydrophilic interaction ultra-high-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Chen, Jiahui; Hou, Waner; Han, Bo; Liu, Guanghui; Gong, Jin; Li, Yemeng; Zhong, Danmin; Liao, Qiongfeng; Xie, Zhiyong

    2016-04-01

    Amino acids, neurotransmitters, purines, and pyrimidines are bioactive molecules that play fundamental roles in maintaining various physiological functions. Their metabolism is closely related to the health, growth, development, reproduction, and homeostasis of organisms. Most recently, comprehensive measurements of these metabolites have shown their potential as innovative approaches in disease surveillance or drug intervention. However, simultaneous measurement of these metabolites presents great difficulties. Here, we report a novel quantitative method that uses hydrophilic interaction ultra-high-performance liquid chromatography-tandem mass spectrometry (HILIC-UPLC-MS/MS), which is highly selective, high throughput, and exhibits better chromatographic behavior than existing methods. The developed method enabled the rapid quantification of 37 metabolites, spanning amino acids, neurotransmitters, purines, and pyrimidines pathways, within 6.5 min. The compounds were separated on an ACQUITY UPLC® BEH Amide column. Serum and brain homogenate were extracted by protein precipitation. The intra- and interday precision of all of the analytes was less than 11.34 %, and the accuracy was between -11.74 and 11.51 % for all quality control (QC) levels. The extraction recoveries of serum ranged from 84.58 % to 116.43 % and those of brain samples from 80.80 % to 119.39 %, while the RSD was 14.61 % or less for all recoveries. This method was used to successfully characterize alterations in the rat brain and, in particular, their dynamics in serum. The following study was performed to simultaneously test global changes of these metabolites in a serotonin antagonist p-chlorophenylalanine (PCPA)-induced anxiety and insomnia rat model to understand the effect and mechanism of PCPA. Taken together, these results show that the method is able to simultaneously monitor a large panel of metabolites and that this protocol may represent a metabolomic method to diagnose toxicological and

  9. Spectrum of intracranial tumours in a tertiary health carefacility: Our ...

    African Journals Online (AJOL)

    Medulloblastoma accounted for 18%.(10).Of the cases of Gliomas, majority(52%) fell under WHO grade II. (38%)of the Meningioma were of the mixed type while 25% had transitional type. Conclusion: astrocytomas was the commonest brain tumour.

  10. Imaging of sacral tumours

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, S.; Ollivier, L.; Brisse, H.; Neuenschwander, S. [Institut Curie, Department of Radiology, Paris (France); Leclere, J. [Institut Gustave Roussy, Department of Radiology, Villejuif (France); Vanel, D. [The Rizzoli Institute, Department of Radiology, Bologna (Italy); Missenard, G. [Institut Gustave Roussy, Comite de pathologie tumorale de l' appareil locomoteur, Villejuif (France); Pinieux, G. de [CHRU de Tours, Department of Pathology, Hopital Trousseau, Tours (France)

    2008-04-15

    All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves, notochord remnants, etc.) can give rise to benign or malignant tumours. Bone metastases and intraosseous sites of haematological malignancies, lymphoma and multiple myeloma are the most frequent aetiologies, while primary bone tumours and meningeal or nerve tumours are less common. Some histological types have a predilection for the sacrum, especially chordoma and giant cell tumour. Clinical signs are usually minor, and sacral tumours are often discovered in the context of nerve root or pelvic organ compression. The roles of conventional radiology, CT and MRI are described and compared with the histological features of the main tumours. The impact of imaging on treatment decisions and follow-up is also reviewed. (orig.)

  11. Parapharyngeal space primary tumours.

    Science.gov (United States)

    Grilli, Gianluigi; Suarez, Vanessa; Muñoz, María Gabriela; Costales, María; Llorente, José Luis

    The aim of this study is to present our experience with the diagnostic and therapeutic approaches for parapharyngeal space tumours. This study is a retrospective review of 90 patients diagnosed with tumours of the parapharyngeal space and treated surgically between 1984 and 2015. Patients whose tumours were not primary but invaded the parapharyngeal space expanding from another region, tumours originating in the deep lobe of the parotid gland and head and neck metastasis were excluded from this study. 74% percent of the parapharyngeal space neoplasms were benign and 26% were malignant. Pleomorphic adenoma was the most common neoplasm (27%), followed by paragangliomas (25%), miscellaneous malignant tumours (16%), neurogenic tumours (12%), miscellaneous benign tumours (10%), and malignant salivary gland tumours (10%). The transcervical approach was used in 56 cases, cervical-transparotid approach in 15 cases, type A infratemporal fossa approach in 13 cases, transmandibular approach in 4 cases and transoral approach in 2 cases. The most common complications were those deriving from nervous injuries. Most parapharyngeal space tumours can be removed surgically with a low rate of complications and recurrence. The transcervical approach is the most frequently used. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  12. c-Fos immunoreactivity in prefrontal, basal ganglia and limbic areas of the rat brain after central and peripheral administration of ethanol and its metabolite acetaldehyde.

    Directory of Open Access Journals (Sweden)

    Kristen N. Segovia

    2013-05-01

    Full Text Available Considerable evidence indicates that the metabolite of ethanol (EtOH, acetaldehyde, is biologically active. Acetaldehyde can be formed from EtOH peripherally mainly by alcohol dehydrogenase, and also centrally by catalase. EtOH and acetaldehyde show differences in their behavioral effects depending upon the route of administration. In terms of their effects on motor activity and motivated behaviors, when administered peripherally acetaldehyde tends to be more potent than EtOH but shows very similar potency administered centrally. Since dopamine (DA rich areas have an important role in regulating both motor activity and motivation, the present studies were undertaken to compare the effects of central (intraventricular, ICV and peripheral (intraperitoneal, IP administration of EtOH and acetaldehyde on a cellular marker of brain activity, c-Fos immunoreactivity, in DA innervated areas. Male Sprague-Dawley rats received an IP injection of vehicle, EtOH (0.5 or 2.5 g/kg or acetaldehyde (0.1 or 0.5 g/kg or an ICV injection of vehicle, EtOH or acetaldehyde (2.8 or 14.0 µmoles. IP administration of EtOH minimally induced c-Fos in some regions of the prefrontal cortex and basal ganglia, mainly at the low dose (0.5 g/kg, while IP acetaldehyde induced c-Fos in virtually all the structures studied at both doses. Acetaldehyde administered centrally increased c-Fos in all areas studied, a pattern that was very similar to EtOH. Thus, IP administered acetaldehyde was more efficacious than EtOH at inducing c-Fos expression. However, the general pattern of c-Fos induction promoted by ICV EtOH and acetaldehyde was similar. These results are consistent with the pattern observed in behavioral studies in which both substances produced the same magnitude of effect when injected centrally, and produced differences in potency after peripheral administration.

  13. A simple and sensitive high-performance liquid chromatography-electrochemical detection assay for the quantitative determination of monoamines and respective metabolites in six discrete brain regions of mice.

    Science.gov (United States)

    Allen, Serena A; Rednour, Stephanie; Shepard, Samantha; Pond, Brooks Barnes

    2017-11-01

    A rapid, sensitive, and reproducible assay is described for the quantitative determination of the monoamine neurotransmitters dopamine, norepinephrine and serotonin, their metabolites, and the internal standard 3,4-dihydroxybenzlyamine hydro-bromide in mouse brain homogenate using high-performance liquid chromatography with electrochemical detection. The method was validated in the following brain areas: frontal cortex, striatum, nucleus accumbens, hippocampus, substantia nigra pars compacta and ventral tegmental area. Biogenic amines and relevant metabolites were extracted from discrete brain regions using a simple protein precipitation procedure, and the chromatography was achieved using a C18 column. The method was accurate over the linear range of 0.300-30 ng/mL (r = 0.999) for dopamine and 0.300-15 ng/mL (r = 0.999) for norepinephrine, 3,4-dihydroxybenzlyamine hydro-bromide, homovanillic acid and 5-hydroxyindolacetic acid, with detection limits of ~0.125 ng/mL (5 pg on column) for each of these analytes. Accuracy and linearity for serotonin were observed throughout the concentration range of 0.625-30 ng/mL (r = 0.998) with an analytical detection limit of ~0.300 ng/mL (12 pg on column). Relative recoveries for all analytes were approximately ≥90% and the analytical run time was analysis in small, discrete brain tissue samples. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Warthin's tumour and smoking

    NARCIS (Netherlands)

    de Ru, JA; Majoor, MHJM; van Benthem, PPG; Slootweg, PJ; Peeters, PHM; Hordijk, GJ

    2005-01-01

    Warthin's tumour and smoking. Objective: In an evaluation of our patients with parotid gland neoplasms, we noticed that patients with a Warthin's tumour were heavy smokers. The aim of this study was to confirm earlier findings in the literature concerning a possible association between smoking and

  15. Wilms' tumour (nephroblastoma)

    African Journals Online (AJOL)

    cancer cells throughout the body and affects fast-dividing cells. With radiation therapy high-energy X-rays reach cancer cells in a specific area of the body. In. Wilms' tumour, radiation is directed at the site of the tumour in the abdomen, and sometimes also at the lungs or the liver. Surgery. Total nephrectomy is the key step in.

  16. Determination of monoamine and amino acid neurotransmitters and their metabolites in rat brain samples by UFLC-MS/MS for the study of the sedative-hypnotic effects observed during treatment with S. chinensis.

    Science.gov (United States)

    Wei, Binbin; Li, Qing; Fan, Ronghua; Su, Dan; Chen, Xiaohui; Jia, Ying; Bi, Kaishun

    2014-01-01

    Schisandra chinensis (Turcz.) Baill. has been used as a sedative and hypnotic agent in traditional Chinese medicine for centuries. The purpose of this study was to reveal the influence of insomnia on the levels of the neurotransmitters: glutamate (Glu), γ-aminobutyric acid (GABA), noradrenaline (NE), dopamine (DA), serotonin (5-HT) and their metabolites (5-HIAA, DOPAC and HVA), and to study the role of S. chinensis in the treatment of insomnia. To achieve this goal, an efficient, sensitive and selective method was developed and validated for the simultaneous determination of these five neurotransmitters and their metabolites in rat brain samples using ultra fast liquid chromatography/tandem mass spectrometry (UFLC-MS/MS). The analysis was performed on a Synergi Fusion-RP 80A ODS column (150mm×2.0mm, 4.0μm) using gradient elution, with the mobile phase consisting of acetonitrile and 0.05% formic acid in water. The method was validated using rat brain homogenate samples and showed a good linearity over a wide concentration range (r(2)>0.99) with a lower limit of quantification (LLOQ) at 4-16ngmL(-1). The intra and inter-day assay variability was less than 15% for all analytes. The results indicated that the condition of insomnia elevated GABA, NE, DA, DOPAC and HVA, and reduced 5-HT, 5-HIAA levels in rat brain. The oral administration of S. chinensis (7.5gkg(-1)day(-1), eight days) influenced insomnia by significantly increasing or reducing the levels of the neurotransmitters parameters mentioned above. These results suggested that S. chinensis could alter the levels of these brain neurotransmitters and their metabolites through its sedative-hypnotic effects. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Possible roles of the dominant uncinate fasciculus in naming objects: a case report of intraoperative electrical stimulation on a patient with a brain tumour.

    Science.gov (United States)

    Nomura, Keiko; Kazui, Hiroaki; Tokunaga, Hiromasa; Hirata, Masayuki; Goto, Tetsu; Goto, Yuko; Hashimoto, Naoya; Yoshimine, Toshiki; Takeda, Masatoshi

    2013-01-01

    How the dominant uncinate fasciculus (UF) contributes to naming performance is uncertain. In this case report, a patient with an astrocytoma near the dominant UF was given a picture-naming task during intraoperative electrical stimulation in order to resect as much tumourous tissues as possible without impairing the dominant UF function. Here we report that the stimulations with the picture-naming task also provided some insights into how the dominant UF contributes to naming performance. The stimulation induced naming difficulty, verbal paraphasia, and recurrent and continuous perseveration. Moreover, just after producing the incorrect responses, the patient displayed continuous perseveration even though the stimulation had ended. The left UF connects to the inferior frontal lobe, which is necessary for word production, so that the naming difficulty appears to be the result of disrupted word production caused by electrical stimulation of the dominant UF. The verbal paraphasia appears to be due to the failure to select the correct word from semantic memory and the failure to suppress the incorrect word. The left UF is associated with working memory, which plays an important role in recurrent perseveration. The continuous perseveration appears to be due to disturbances in word production and a failure to inhibit an appropriate response. These findings in this case suggest that the dominant UF has multiple roles in the naming of objects.

  18. Method for simultaneous imaging of endogenous low molecular weight metabolites in mouse brain using TiO2 nanoparticles in nanoparticle-assisted laser desorption/ionization-imaging mass spectrometry.

    Science.gov (United States)

    Shrivas, Kamlesh; Hayasaka, Takahiro; Sugiura, Yuki; Setou, Mitsutoshi

    2011-10-01

    We report the detection of a group of endogenous low molecular weight metabolites (LMWM) in mouse brain (80-500 Da) using TiO(2) nanoparticles (NPs) in nanoparticle-assisted laser desorption/ionization-imaging mass spectrometry (Nano-PALDI-IMS) without any washing and separation step prior to MS analysis. The identification of metabolites using TiO(2) NPs was compared with a conventional organic matrix 2,5-dihydroxybenzoic acid (DHB) where signals of 179 molecules were specific to TiO(2) NPs, 4 were specific to DHB, and 21 were common to both TiO(2) NPs and DHB. The use of TiO(2) NPs enabled the detection of a higher number of LMWM as compared to DHB and gold NPs as a matrix. This approach is a simple, inexpensive, washing, and separation free for imaging and identification of LMWM in mouse brain. We believe that the biochemical information from distinct regions of the brain using a Nano-PALDI-IMS will be helpful in elucidating the imbalances linked with diseases in biomedical samples.

  19. Further evaluation of [11C]MP-10 as a radiotracer for phosphodiesterase 10A (PDE10A): PET imaging study in rhesus monkeys and brain tissue metabolite analysis

    Science.gov (United States)

    Lin, Shu-fei; Labaree, David; Chen, Ming-Kai; Holden, Daniel; Gallezot, Jean-Dominique; Kapinos, Michael; Teng, Jo-Ku; Najafzadeh, Soheila; Plisson, Christophe; Rabiner, Eugenii A.; Gunn, Roger N.; Carson, Richard E.; Huang, Yiyun

    2014-01-01

    [11C]MP-10 is a potent and specific PET tracer previously shown to be suitable for imaging the PDE10A in baboons with reversible kinetics and high specific binding. However, another report indicated that [11C]MP-10 displayed seemingly irreversible kinetics in rhesus monkeys, potentially due to the presence of a radiolabeled metabolite capable of penetrating the blood-brain-barrier (BBB) into the brain. This study was designed to address the discrepancies between the species by re-evaluating [11C]MP-10 in vivo in rhesus monkey with baseline scans to assess tissue uptake kinetics and self-blocking scans with unlabeled MP-10 to determine binding specificity. Ex vivo studies with one rhesus monkey and 4 Sprague-Dawley rats were also performed to investigate the presence of radiolabeled metabolites in the brain. Our results indicated that [11C]MP-10 displayed reversible uptake kinetics in rhesus monkeys, albeit slower than in baboons. Administration of unlabeled MP-10 reduced the binding of [11C]MP-10 in a dose-dependent manner in all brain regions including the cerebellum. Consequently, the cerebellum appeared not to be a suitable reference tissue in rhesus monkeys. Regional volume of distribution (VT) was mostly reliably derived with the multilinear analysis (MA1) method. In ex vivo studies in the monkey and rats only negligible (< 2.7%) amount of radiometabolites was seen in the brain of either species. In summary, results from the present study strongly support the suitability of [11C]MP-10 as a radiotracer for PET imaging and quantification of PDE10A in non-human primates. PMID:25450608

  20. Target volumes in radiation therapy of childhood brain tumours; La determination des volumes-cibles en radiotherapie pediatrique: application aux tumeurs cerebrales

    Energy Technology Data Exchange (ETDEWEB)

    Habrand, J.L.; Abdulkarim, B. [Institut Gustave Roussy, Dept. de Radiotherapie, 94 - Villejuif (France); Beaudre, A. [Institut Gustave Roussy, Unite de Radiophysique, 94 - Villejuif (France); El Khouri, M. [Institut Gustave Roussy, Dept. d' Imagerie Medicale, 94 - Villejuif (France); Kalifa, C. [Institut Gustave Roussy, Dept. de Pediatrie, 94 - Villejuif (France)

    2001-10-01

    Pediatric tumors have enjoyed considerable improvements for the past 30 years. This is mainly due to the extensive use of combined therapeutical modalities in which chemotherapy plays a prominent role. In many children, local treatment including radiotherapy, can nowadays be adapted in terms of target volume and dose to the 'response' to an initial course of chemotherapy almost on a case by case basis. This makes precise recommendation on local therapy highly difficult in this age group. We will concentrate in this paper on brain tumors in which chemotherapy is of limited value and radiotherapy still plays a key-role. (authors)

  1. Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain

    DEFF Research Database (Denmark)

    Schou-Pedersen, Anne Marie Voigt; Hansen, Stine Normann; Tveden-Nyborg, Pernille

    2016-01-01

    of intracellular and extracellular amounts of monoamine neurotransmitters and their metabolites in guinea pig frontal cortex and hippocampal primary neuronal cell cultures. Noradrenaline, dopamine and serotonin were found to be in a range from 0.31 to 1.7 pmol per 2 million cells intracellularly, but only...... the biogenic metabolites could be detected extracellularly. Distinct differences in monoamine concentrations were observed when comparing concentrations in guinea pig frontal cortex and cerebellum tissue with higher amounts of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid...... in frontal cortex, as compared to cerebellum. The chemical turnover in frontal cortex tissue of guinea pig was for serotonin successfully predicted from the turnover observed in the frontal cortex cell culture. In conclusion, the present analytical method shows high precision, accuracy and sensitivity...

  2. Intellectual disability, oncogenes and tumour suppressor genes: the ...

    Indian Academy of Sciences (India)

    disability, the presence of CNV including gene expressed in the brain or with specific brain function is a strong argument. In contrast, CNV affecting only genes involved in oncogen- esis are mostly ignored. However, links between some onco- genes or tumour suppressor genes and intellectual disability deserve attention.

  3. 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

  4. A STUDY OF TUMOURS OF THE CRANIAL NERVE AND PARASPINAL NERVE

    Directory of Open Access Journals (Sweden)

    Sudesh Shetty

    2016-03-01

    Full Text Available INTRODUCTION One of the frequent sites of tumour formation is the cranial nerves and paraspinal nerves. The cranial nerves perform a plethora of functions and so the signs and symptoms caused may be different. They are mainly classified into four different types. The aim of the study is: 1. To study the tumours arising from the cranial nerves in an epidemiological point of view. 2. To study the tumours histopathologically. 3. To classify the tumours according to WHO classification. Thirty-eight brain tumor cases were studied in the Department of Medicine, A. J. Shetty Institute of Medical Sciences, Mangalore. Cranial nerve tumours accounts for 4(10% among the intracranial tumours. Schwannomas makes up 3(7.39% among the Intracranial tumours. and constituted 3(75% among cranial nerve tumours. All the 3 schwannomas were located in CP angle. The geographic distribution of cases was found to be 28 cases from Mangalore and 10 cases from Kerala.

  5. Neonatal exposure to estradiol-17β modulates tumour necrosis factor alpha and cyclooxygenase-2 expression in brain and also in ovaries of adult female rats.

    Science.gov (United States)

    Shridharan, Radhika Nagamangalam; Krishnagiri, Harshini; Govindaraj, Vijayakumar; Sarangi, SitiKantha; Rao, Addicam Jagannadha

    2016-02-01

    The sexually dimorphic organization in perinatal rat brain is influenced by steroid hormones. Exposure to high levels of estrogen or endocrine-disrupting compounds during perinatal period may perturb this process, resulting in compromised reproductive physiology and behavior as observed in adult In our recent observation neonatal exposure of the female rats to estradiol-17β resulted in down-regulation of TNF-α, up-regulation of COX-2 and increase in SDN-POA size in pre-optic area in the adulthood. It is known that the control of reproductive performance in female involves a complex interplay of the hypothalamus, pituitary, and ovary. The present study was undertaken to understand the possible molecular mechanism involved in changes observed in the ovarian morphology and expression of selected genes in the ovary. Administration of estradiol-17β (100 μg) on day 2 and 3 after birth revealed up-regulation of ER-α, ER-β, COX-2 and down-regulation of TNF-α expression. Also the decrease in the ovarian weight, altered ovarian morphology and changes in the 2D protein profiles were also seen. This is apparently the first report documenting that neonatal estradiol exposure modulates TNF-α and COX-2 expression in the ovary as seen during adult stage. Our results permit us to suggest that cues originating from the modified brain structure due to neonatal exposure of estradiol-17β remodel the ovary at the molecular level in such a way that there is a disharmony in the reproductive function during adulthood and these changes are perennial and can lead to infertility and changes of reproductive behavior.

  6. Simultaneous determination of 8 neurotransmitters and their metabolite levels in rat brain using liquid chromatography in tandem with mass spectrometry: Application to the murine Nrf2 model of depression.

    Science.gov (United States)

    Wojnicz, Aneta; Avendaño Ortiz, José; Casas, Ana I; Freitas, Andiara E; G López, Manuela; Ruiz-Nuño, Ana

    2016-01-30

    Analysis of neurotransmitters and their metabolites is useful for the diagnosis of central nervous system diseases. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with protein precipitation was developed to monitor levels of adrenaline (AD), noradrenaline (NA), glutamic acid (Glu), γ-aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in rat brain tissue. Isoprenaline was used as an internal standard (IS). Neurotransmitters and metabolites were eluted with a reverse phase column under gradient conditions through a mobile phase consisting of 0.2% formic acid water solution/acetonitrile. The compounds were detected and quantified by LC-MS/MS with positive or negative electrospray ionization, which operates in multiple-reaction monitoring mode. The method was linear or polynomial (R(2)>0.99) for AD, NA, Glu, GABA, DA, 5-HT, 5-HIAA, and MHPG in the range of 0.25-200, 0.5-200, 250-20,000, 250-20,000, 0.25-200, 10-3000, 1-50, and 1-50ng/mL, respectively. The validation assays for accuracy and precision, matrix effect, extraction recovery, stability and carry-over of the samples for neurotransmitters and metabolites were consistent with the requirements of regulatory agencies. The method enables rapid quantification of neurotransmitters and their metabolites and has been applied in the nuclear factor (erythroid 2-derived)-like 2 (Nrf2) knockout mouse model of depression. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Absolute quantitative proton NMR spectroscopy based on the amplitude of the local water suppression pulse. Quantification of brain water and metabolites

    DEFF Research Database (Denmark)

    Danielsen, E R; Henriksen, O

    1994-01-01

    volunteers. Localized proton NMR spectra were obtained from a region of primarily white matter in the occipital lobe. The observable water content in the NMR spectra was 0.685 +/- 0.025. The absolute metabolite concentrations were: [total choline] = 1.25 +/- 0.21 nM, [total creatine] = 6.71 +/- 0.59 n...

  8. MR diffusion imaging of human intracranial tumours

    DEFF Research Database (Denmark)

    Krabbe, K; Gideon, P; Wagn, P

    1997-01-01

    We used MRI for in vivo measurement of brain water self-diffusion in patients with intracranial tumours. The study included 28 patients (12 with high-grade and 3 with low-grade gliomas, 7 with metastases, 5 with meningiomas and 1 with a cerebral abscess). Apparent diffusion coefficients (ADC) were...... (P meningiomas did not differ significantly from those seen with high-grade gliomas or cerebral metastases...

  9. Evaluation and metabolite studies of {sup 125}I- and {sup 123}I-labelled E-(R,R)-IQNP: potential radioligands for visualization of M{sub 1} muscarinic acetylcholine receptors in brain

    Energy Technology Data Exchange (ETDEWEB)

    Bergstroem, Kim A.; Halldin, Christer; Hiltunen, Jukka; Swahn, Carl-Gunnar; Ito, Hiroshi; Ginovart, Nathalie; Hall, Haakan; McPherson, Daniel W.; Knapp, F. F. (Russ); Larsson, Stig; Schnell, Per-Olof; Farde, Lars

    1998-04-01

    A new ligand for the M{sub 1} muscarinic receptor subtype, E-(R,R)-1-azabicyclo[2.2.2]oct-3-yl {alpha}-hydroxy-{alpha}-(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (E-IQNP), was labelled with {sup 125}I and {sup 123}I for autoradiographic studies on human whole-brain cryosections and SPET studies, respectively, in Cynomolgus monkey. Autoradiography demonstrated E-[{sup 125}I]IQNP binding in M{sub 1} receptor-rich regions such as the neocortex and the striatum. The binding was displaceable by the selective M{sub 1} antagonist biperiden. In vivo single photon emission tomography (SPET) studies with E-[{sup 123}I]IQNP demonstrated a high accumulation of radioactivity in the monkey neocortex. Rapid hydrolysis of the quinuclidinyl ester to the free acid was found to be a major biotransformation route for E-[{sup 123}I]IQNP. The free acid of E-[{sup 123}I]IQNP does not pass the blood-brain barrier, but the plasma concentration was high as compared to the total radioactivity in brain. It is thus necessary to correct for the high concentration of radioactive metabolites in parenchymal blood (CBV) to obtain accurate values for E-[{sup 123}I]IQNP binding in brain.

  10. Chiral Analysis of Methadone and its Main Metabolite, EDDP, in Postmorten Brain and Blood by Automated SPE and Liquid Chromatography-Mass Spectrometry

    DEFF Research Database (Denmark)

    Holm, Karen Marie Dollerup; Linnet, Kristian

    2012-01-01

    Vi udviklede en metode baseret på væskekromatografi med tandem-massespektrometri til kvantificering af de individuelle enantiomer af metadon og dets primære metabolit, R/S-2-ethyl-1,5-dimethyl- 3,3-diphenylpyrrolinium (EDDP), i postmortem blod og hjernevæv. Prøvebehandlingen blev udført på et Tec...

  11. Controversies in Odontogenic Tumours: Review.

    Science.gov (United States)

    Siwach, Pooja; Joy, Tabita; Tupkari, Jagdish; Thakur, Arush

    2017-08-01

    Odontogenic tumours are lesions that occur solely within the oral cavity and are so named because of their origin from the odontogenic (i.e. tooth-forming) apparatus. Odontogenic tumours comprise a variety of lesions ranging from non-neoplastic tissue proliferations to benign or malignant neoplasms. However, controversies exist regarding the pathogenesis, categorisation and clinical and histological variations of these tumours. The recent 2017 World Health Organization classification of odontogenic tumours included new entities such as primordial odontogenic tumours, sclerosing odontogenic carcinomas and odontogenic carcinosarcomas, while eliminating several previously included entities like keratocystic odontogenic tumours and calcifying cystic odonogenic tumours. The aim of the present review article was to discuss controversies and recent concepts regarding odontogenic tumours so as to increase understanding of these lesions.

  12. Warthin's tumour and smoking.

    NARCIS (Netherlands)

    Ru, J.A. de; Plantinga, R.F.; Majoor, M.H.; Benthem, P.P. van; Slootweg, P.J.; Peeters, P.H.; Hordijk, G.J.

    2005-01-01

    OBJECTIVE: In an evaluation of our patients with parotid gland neoplasms, we noticed that patients with a Warthin's tumour were heavy smokers. The aim of this study was to confirm earlier findings in the literature concerning a possible association between smoking and the development of a Warthin's

  13. Extracranial glomus faciale tumour.

    Science.gov (United States)

    Connor, S E J; Gleeson, M J; Odell, E

    2008-09-01

    To describe a unique presentation of a predominantly extracranial glomus faciale tumour. To discuss the role of imaging in the differential diagnosis and evaluation of a hypervascular parotid mass. To review the previous literature concerning the glomus faciale tumour. A 54-year-old woman presented with a six-month history of facial weakness, pain and a parotid mass. Ultrasound revealed a hypervascular parotid mass and pre-operative core biopsy suggested a paraganglioma. Computed tomography defined its deep extent and demonstrated involvement of the petrous temporal bone along the descending portion of the facial nerve canal with a pattern of permeative lucency. A tumour was surgically removed which arose from the facial nerve from the second genu to the proximal divisions within the parotid gland and histology confirmed a paraganglioma. A facial nerve glomus faciale tumour should be considered in the differential diagnosis of a hypervascular parotid mass and may present in a predominantly extracranial location. Computed tomography will prove helpful in such a case in order to limit the differential diagnosis and to define the extent of skull base involvement.

  14. Intestinal inflammatory myofibroblastic tumour

    African Journals Online (AJOL)

    Since its first description in 1937,1 the understanding of inflamma- tory myofibroblastic tumour (IMFT) has evolved from a reactive inflammatory process to a neoplasm of intermediate biological potential.2-9 Associated with nosologic, histogenetic and aetiopatho- genetic controversy, IMFTs occur in all age groups and in ...

  15. Tumour exosome integrins determine organotropic metastasis.

    Science.gov (United States)

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-11-19

    Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  16. Tumour exosome integrins determine organotropic metastasis

    Science.gov (United States)

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Mark, Milica Tesic; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E.; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M.; Dumont-Cole, Vanessa D.; Kramer, Kimberly; Wexler, Leonard H.; Narendran, Aru; Schwartz, Gary K.; Healey, John H.; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H.; Grandgenett, Paul M.; Hollingsworth, Michael A.; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K.; Jarnagin, William R.; Brady, Mary S.; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J.; Bissell, Mina J.; Garcia, Benjamin A.; Kang, Yibin; Rajasekhar, Vinagolu K.; Ghajar, Cyrus M.; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-01-01

    Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis. PMID:26524530

  17. [Central nervous system tumours in childhood: their clinical pathological aspects].

    Science.gov (United States)

    Ortega Aznar, A; Romero Vidal, F J

    Paediatric tumours affecting the central nervous system (CNS) constitute the second most frequent group of tumours at this age. Taking the WHO 2000 classification as our starting point, our intention was to describe the more important clinical and pathological features in the differential diagnosis of the different tumourous entities with the highest incidence in childhood. We highlight, above all, the characteristics that justify the need for a smooth flow of information between neurologists, neurosurgeons, neuroradiologists, neuropathologists and oncologists. We do not deal with familial tumourous syndromes, genetic aspects or clinical information derived from analyses of molecular alterations. Among CNS tumours, enough age related differences exist to be able to consider those appearing during childhood in their own right. Their topographic specificity is very characteristic and while 50% of them are infratentorial, 90% of those that occur in adults are supratentorial. Embryonic tumours are very frequent in childhood, but rare in adults, and the opposite happens with meningiomas. They are also different as regards their histological features, clinical characteristics, the early tendency to spread throughout the nervous system in the course of the disease and their biological behaviour. These data make us think that, in the pathogenesis of brain tumours in children, the molecular and epigenetic factors involved are different from those at play in the case of adults. A correct diagnosis requires a multidisciplinary approach and an understanding of the histological criteria and nomenclature by the health professionals involved in treating these patients.

  18. The positive effects of high-frequency right dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation on memory, correlated with increases in brain metabolites detected by proton magnetic resonance spectroscopy in recently detoxified alcohol-dependent patients

    Directory of Open Access Journals (Sweden)

    Qiao J

    2016-09-01

    Full Text Available Jun Qiao,1,2 Guixing Jin,1,2 Licun Lei,3 Lan Wang,1,2 Yaqiang Du,3 Xueyi Wang1,2 1Institute of Mental Health, The First Hospital of Hebei Medical University, 2Brain Ageing and Cognitive Neuroscience Laboratory, Hebei Medical University, 3Department of Radiology, The First Hospital of Hebei Medical University, Hebei, People’s Republic of China Objective: To explore the effect of right dorsolateral prefrontal cortex (DLPFC repetitive transcranial magnetic stimulation (rTMS on memory, and its correlation with levels of hippocampal brain metabolites detected by proton magnetic resonance spectroscopy (1H-MRS in recently detoxified alcohol-dependent patients. Materials and methods: In this randomized, double-blind sham-controlled trial, alcohol-dependent patients were enrolled and randomized into two groups: the experimental group (rTMS, 10 Hz, on right DLPFC, 20 sessions and the control group (sham stimulation. Memory function was assessed using Hopkins Verbal Learning Test-Revised (HVLT-R and Brief Visuospatial Memory Test-Revised (BVMT-R before and after treatment. 1H-MRS was used to detect the levels of N-acetyl aspartic acid (NAA, choline (Cho, and creatine (Cr in bilateral hippocampi before and after treatment. Results: Thirty-eight patients (18 in the experimental group and 20 in the control group were included in the analyses. The experimental group showed significantly greater changes in HVLT-R, BVMT-R, NAA/Cr, and Cho/Cr after rTMS from baseline than the control group. The percentage change in BVMT-R and HVLT-R correlated with the percentage change in NAA/Cr and Cho/Cr in the right brain. Conclusion: High-frequency right DLPFC rTMS was associated with improvement in memory dysfunction, which is correlated with levels of hippocampal brain metabolites detected by 1H-MRS in recently detoxified alcohol-dependent patients. Keywords: alcohol dependence, memory, repetitive transcranial magnetic stimulation, MR spectroscopy

  19. In vivo turnover of tau and APP metabolites in the brains of wild-type and Tg2576 mice: greater stability of sAPP in the beta-amyloid depositing mice.

    Directory of Open Access Journals (Sweden)

    Jose Morales-Corraliza

    2009-09-01

    Full Text Available The metabolism of the amyloid precursor protein (APP and tau are central to the pathobiology of Alzheimer's disease (AD. We have examined the in vivo turnover of APP, secreted APP (sAPP, Abeta and tau in the wild-type and Tg2576 mouse brain using cycloheximide to block protein synthesis. In spite of overexpression of APP in the Tg2576 mouse, APP is rapidly degraded, similar to the rapid turnover of the endogenous protein in the wild-type mouse. sAPP is cleared from the brain more slowly, particularly in the Tg2576 model where the half-life of both the endogenous murine and transgene-derived human sAPP is nearly doubled compared to wild-type mice. The important Abeta degrading enzymes neprilysin and IDE were found to be highly stable in the brain, and soluble Abeta40 and Abeta42 levels in both wild-type and Tg2576 mice rapidly declined following the depletion of APP. The cytoskeletal-associated protein tau was found to be highly stable in both wild-type and Tg2576 mice. Our findings unexpectedly show that of these various AD-relevant protein metabolites, sAPP turnover in the brain is the most different when comparing a wild-type mouse and a beta-amyloid depositing, APP overexpressing transgenic model. Given the neurotrophic roles attributed to sAPP, the enhanced stability of sAPP in the beta-amyloid depositing Tg2576 mice may represent a neuroprotective response.

  20. Diagnosing Musculoskeletal Tumours

    Directory of Open Access Journals (Sweden)

    Robert J. Grimer

    2001-01-01

    Full Text Available In 1993 we became aware of a worrying increase in apparent errors in the histopathological diagnosis of musculoskeletal tumours in our Unit. As a result all cases seen over the past 8 years were reviewed by an independent panel. Of the 1996 cases reviewed there was an error in 87. In 54 cases (2.7% this had led to some significant change in the active management of the patient. The main areas where errors arose were in those very cases where clinical and radiological features were not helpful in confirming or refuting the diagnosis. The incidence of errors rose with the passage of time, possibly related to a deterioration in the pathologist’s health. The error rate in diagnosing bone tumours in previously published series ranges from 9 to 40%. To ensure as accurate a rate of diagnosis as possible multidisciplinary working and regular audit are essential.

  1. Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma?

    NARCIS (Netherlands)

    Sie, M.; de Bont, E. S. J. M.; Scherpen, F. J. G.; Hoving, E. W.; den Dunnen, W. F. A.

    2010-01-01

    Aims: Pilocytic astrocytomas are the most frequent brain tumours in children. Because of their high vascularity, this study aimed to obtain insights into potential angiogenic related therapeutic targets in these tumours by characterization of the vasculature and the angiogenic profile. In this study

  2. 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.

  3. Accurate measurement of the essential micronutrients methionine, homocysteine, vitamins B6, B12, B9 and their metabolites in plasma, brain and maternal milk of mice using LC/MS ion trap analysis.

    Science.gov (United States)

    Oosterink, J Efraim; Naninck, Eva F G; Korosi, Aniko; Lucassen, Paul J; van Goudoever, Johannes B; Schierbeek, Henk

    2015-08-15

    Methionine, homocysteine, vitamins B6, B12, B9, and their metabolites are crucial co-factors and substrates for many basic biological pathways including one-carbon metabolism, and they are particularly important for brain function and development and epigenetic mechanisms. These are essential nutrients that cannot be synthesized endogenously and thus need to be taken in via diet. A novel method was developed that enables simultaneous assessment of the exact concentrations of these essential micronutrients in various matrices, including maternal milk, plasma, and brain of neonatal mice. The protocol for analysis of these components in the various matrices consists of a cleanup step (i.e. lipid extraction followed by protein precipitation) combined with a liquid chromatography mass spectrometry (LC/MS) ion trap method with high sensitivity and selectivity (SRM mode). This novel method enables the measurement of these essential nutrients with good recoveries (69-117%), and high intra-day (<10%) and high intra-day precision (defined as <15% for compounds with an isotopologue and <20% for compounds without an isotopologue as internal standard) in plasma, maternal milk, and brain of mice at low and high levels. In addition, lower limits of quantitation (LOQ) were determined for the various matrices in the range for methionine (700-2000nmol/L), homocysteine (280-460-nmol/L), vitamins B6 (5-230nmol/L), B12 (7-11nmol/L), B9 (20-30nmol/L). Degradation of vitamins and oxidation of homocysteine is limited to a minimum, and only small sample volumes (30μL plasma, 20mg brain and maternal milk) are needed for simultaneous measurement. This method can help to understand how these nutrients are transferred from mother to offspring via maternal milk, as well as how these nutrients are absorbed by the offspring and eventually taken up in various tissues amongst the brain in preclinical and clinical research settings. Therefore the method can help to explore critical periods in

  4. Early metabolite changes after melatonin treatment in neonatal rats with hypoxic-ischemic brain injury studied by in-vivo1H MR spectroscopy.

    Science.gov (United States)

    Berger, Hester Rijkje; Nyman, Axel K G; Morken, Tora Sund; Vettukattil, Riyas; Brubakk, Ann-Mari; Widerøe, Marius

    2017-01-01

    Melatonin is a promising neuroprotective agent after perinatal hypoxic-ischemic (HI) brain injury. We used in-vivo 1H magnetic resonance spectroscopy to investigate effects of melatonin treatment on brain metabolism after HI. Postnatal day 7 Sprague-Dawley rats with unilateral HI brain injury were treated with either melatonin 10 mg/kg dissolved in phosphate-buffered saline (PBS) with 5% dimethyl sulfoxide (DMSO) or vehicle (5% DMSO and/or PBS) directly and at 6 hours after HI. 1H MR spectra from the thalamus in the ipsilateral and contralateral hemisphere were acquired 1 day after HI. Our results showed that injured animals had a distinct metabolic profile in the ipsilateral thalamus compared to sham with low concentrations of total creatine, choline, N-acetyl aspartate (NAA), and high concentrations of lipids. A majority of the melatonin-treated animals had a metabolic profile characterized by higher total creatine, choline, NAA and lower lipid levels than other HI animals. When comparing absolute concentrations, melatonin treatment resulted in higher glutamine levels and lower lipid concentrations compared to DMSO treatment as well as higher macromolecule levels compared to PBS treatment day 1 after HI. DMSO treated animals had lower concentrations of glucose, creatine, phosphocholine and macromolecules compared to sham animals. In conclusion, the neuroprotective effects of melatonin were reflected in a more favorable metabolic profile including reduced lipid levels that likely represents reduced cell injury. Neuroprotective effects may also be related to the influence of melatonin on glutamate/glutamine metabolism. The modulatory effects of the solvent DMSO on cerebral energy metabolism might have masked additional beneficial effects of melatonin.

  5. Overexpression of Eag1 potassium channels in clinical tumours

    Directory of Open Access Journals (Sweden)

    Schliephacke Tessa

    2006-10-01

    Full Text Available Abstract Background Certain types of potassium channels (known as Eag1, KCNH1, Kv10.1 are associated with the production of tumours in patients and in animals. We have now studied the expression pattern of the Eag1 channel in a large range of normal and tumour tissues from different collections utilising molecular biological and immunohistochemical techniques. Results The use of reverse transcription real-time PCR and specifically generated monoclonal anti-Eag1 antibodies showed that expression of the channel is normally limited to specific areas of the brain and to restricted cell populations throughout the body. Tumour samples, however, showed a significant overexpression of the channel with high frequency (up to 80% depending on the tissue source regardless of the detection method (staining with either one of the antibodies, or detection of Eag1 RNA. Conclusion Inhibition of Eag1 expression in tumour cell lines reduced cell proliferation. Eag1 may therefore represent a promising target for the tailored treatment of human tumours. Furthermore, as normal cells expressing Eag1 are either protected by the blood-brain barrier or represent the terminal stage of normal differentiation, Eag1 based therapies could produce only minor side effects.

  6. Overexpression of Eag1 potassium channels in clinical tumours

    Science.gov (United States)

    Hemmerlein, Bernhard; Weseloh, Rüdiger M; Mello de Queiroz, Fernanda; Knötgen, Hendrik; Sánchez, Araceli; Rubio, María E; Martin, Sabine; Schliephacke, Tessa; Jenke, Marc; Heinz-Joachim-Radzun; Stühmer, Walter; Pardo, Luis A

    2006-01-01

    Background Certain types of potassium channels (known as Eag1, KCNH1, Kv10.1) are associated with the production of tumours in patients and in animals. We have now studied the expression pattern of the Eag1 channel in a large range of normal and tumour tissues from different collections utilising molecular biological and immunohistochemical techniques. Results The use of reverse transcription real-time PCR and specifically generated monoclonal anti-Eag1 antibodies showed that expression of the channel is normally limited to specific areas of the brain and to restricted cell populations throughout the body. Tumour samples, however, showed a significant overexpression of the channel with high frequency (up to 80% depending on the tissue source) regardless of the detection method (staining with either one of the antibodies, or detection of Eag1 RNA). Conclusion Inhibition of Eag1 expression in tumour cell lines reduced cell proliferation. Eag1 may therefore represent a promising target for the tailored treatment of human tumours. Furthermore, as normal cells expressing Eag1 are either protected by the blood-brain barrier or represent the terminal stage of normal differentiation, Eag1 based therapies could produce only minor side effects. PMID:17022810

  7. Overexpression of Eag1 potassium channels in clinical tumours.

    Science.gov (United States)

    Hemmerlein, Bernhard; Weseloh, Rüdiger M; Mello de Queiroz, Fernanda; Knötgen, Hendrik; Sánchez, Araceli; Rubio, María E; Martin, Sabine; Schliephacke, Tessa; Jenke, Marc; Heinz-Joachim-Radzun; Stühmer, Walter; Pardo, Luis A

    2006-10-05

    Certain types of potassium channels (known as Eag1, KCNH1, Kv10.1) are associated with the production of tumours in patients and in animals. We have now studied the expression pattern of the Eag1 channel in a large range of normal and tumour tissues from different collections utilising molecular biological and immunohistochemical techniques. The use of reverse transcription real-time PCR and specifically generated monoclonal anti-Eag1 antibodies showed that expression of the channel is normally limited to specific areas of the brain and to restricted cell populations throughout the body. Tumour samples, however, showed a significant overexpression of the channel with high frequency (up to 80% depending on the tissue source) regardless of the detection method (staining with either one of the antibodies, or detection of Eag1 RNA). Inhibition of Eag1 expression in tumour cell lines reduced cell proliferation. Eag1 may therefore represent a promising target for the tailored treatment of human tumours. Furthermore, as normal cells expressing Eag1 are either protected by the blood-brain barrier or represent the terminal stage of normal differentiation, Eag1 based therapies could produce only minor side effects.

  8. Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster

    Science.gov (United States)

    Jeibmann, Astrid; Eikmeier, Kristin; Linge, Anna; Kool, Marcel; Koos, Björn; Schulz, Jacqueline; Albrecht, Stefanie; Bartelheim, Kerstin; Frühwald, Michael C.; Pfister, Stefan M.; Paulus, Werner; Hasselblatt, Martin

    2014-06-01

    Atypical teratoid/rhabdoid tumours (AT/RT) are malignant brain tumours. Unlike most other human brain tumours, AT/RT are characterized by inactivation of one single gene, SMARCB1. SMARCB1 is a member of the evolutionarily conserved SWI/SNF chromatin remodelling complex, which has an important role in the control of cell differentiation and proliferation. Little is known, however, about the pathways involved in the oncogenic effects of SMARCB1 inactivation, which might also represent targets for treatment. Here we report a comprehensive genetic screen in the fruit fly that revealed several genes not yet associated with loss of snr1, the Drosophila homologue of SMARCB1. We confirm the functional role of identified genes (including merlin, kibra and expanded, known to regulate hippo signalling pathway activity) in human rhabdoid tumour cell lines and AT/RT tumour samples. These results demonstrate that fly models can be employed for the identification of clinically relevant pathways in human cancer.

  9. Stem cell research points the way to the cell of origin for intracranial germ cell tumours.

    Science.gov (United States)

    Tan, Chris; Scotting, Paul J

    2013-01-01

    Germ cell tumours found in the brain (intracranial GCTs) are a very unusual class of tumour for two reasons. First, they include a very diverse range of histological subtypes classified together due to their proposed common cell of origin. Second, this proposed cell of origin, the germ cell progenitor, would not normally be found in the tissue where these tumours arise. This is in contrast to all other primary brain tumours, in which the cell of origin is believed to be a brain cell. Indeed, no other class of primary cancer arises from a cell from a distant organ. This theory for the origins of intracranial GCTs has been in place for many decades, but recent data arising from studies of induced pluripotency for regenerative medicine raise serious questions about this dogma. Here we review the cellular origins of intracranial GCTs in the light of these new data and reanalyse the existing data on the biology of this unusual class of tumours. Together, these considerations lead us to conclude that the evidence now falls in favour of a model in which these tumours arise from the transformation of endogenous brain cells. This theory should inform future studies of the aetiology of these tumours and so lead the way to animal models in which to study their development and potential biological therapeutics. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  10. Effects of hypotension and/or hypocapnia during sevoflurane anesthesia on perfusion and metabolites in the developing brain of piglets-a blinded randomized study.

    Science.gov (United States)

    Ringer, Simone K; Ohlerth, Stefanie; Carrera, Inés; Mauch, Jacqueline; Spielmann, Nelly; Bettschart-Wolfensberger, Regula; Weiss, Markus

    2016-09-01

    Hypotension (HT) and/or hypocapnia (HC) are frequent complications occurring during pediatric anesthesia and may cause cerebral injury in the developing brain. The aim of this study is to investigate the effects of HT and/or HC on perfusion and metabolism in the developing brain. Twenty-eight piglets were randomly allocated to four groups: control (C), HT, HC, and hypotension and hyocapnia (HTC). Anesthesia was induced and maintained using sevoflurane. Fentanyl was added for instrumentation. Piglets were fully monitored and their lungs were artificially ventilated. Before treatment, conventional magnetic resonance imaging (MRI), dynamic susceptibility-contrast-enhanced T2*-weighted MRI (DSC-MRI), and single voxel proton MR spectroscopy ((1) H MRS) were performed. Hypotension (mean arterial blood pressure: 30 ± 3 mmHg) was induced by blood withdrawal and nitroprusside infusion, and hyperventilation was used to induce HC (PaCO2 : 2.7-3.3 kPa). (1) H MRS and DSC-MRI were repeated immediately once treatment goals were achieved and 120 min later. Radiologists were blinded to the groups. DSCI-MRI and (1) H MRS analyses were performed in the thalamus, occipital and parietal lobe, hippocampus, and watershed areas. In comparison to C, mean time to peak (TTP) increased with HTC in all brain areas as assessed with DSC-MRI (n = 26). Using (1) H MRS, a significant decrease in N-acetyl aspartate, choline, and myoinositol, as well as an increase in glutamine-glutamate complex (Glx) were detected independent of group. Compared to C, changes were more pronounced for Glx (due to an increase in glutamate) and myoinositol with HTC, for N-acetyl aspartate with HT, and for Glx with HC. No lactate signal was present. The combination of HT and HC during sevoflurane anesthesia resulted in alteration of cerebral perfusion with signs of neuronal dysfunction and early neuronal ischemia. HT and HC alone also resulted in signs of metabolic disturbances despite the absence of detectable

  11. 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

  12. Tumours in the Small Bowel

    Directory of Open Access Journals (Sweden)

    N. Kurniawan

    2014-01-01

    Full Text Available Small bowel tumours are rare and originate from a wide variety of benign and malignant entities. Adenocarcinomas are the most frequent primary malignant small bowel tumours. Submucosal tumours like gastrointestinal stromal tumours (GIST or neuroendocrine tumours (NET may show a central umbilication, pathologic vessels, bridging folds or an ulceration of the overlying mucosa. These signs help to differentiate them from harmless bulges caused by impression from outside, e.g. from other intestinal loops. Sarcomas of the small bowel are rare neoplasias with mesenchymal origin, sometimes presenting as protruding masses. Benign tumours like lipoma, fibrolipoma, fibroma, myoma, and heterotopias typically present as submucosal masses. They cannot be differentiated endoscopically from those with malignant potential as GIST or NET. Neuroendocrine carcinomas may present with diffuse infiltration, which may resemble other malignant tumours. The endoscopic appearance of small bowel lymphomas has a great variation from mass lesions to diffuse infiltrative changes. Melanoma metastases are the most frequent metastases to the small bowel. They may be hard to distinguish from other tumours when originating from an amelanotic melanoma.

  13. 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.

  14. Dissociated Crossed Speech Areas in a Tumour Patient

    Directory of Open Access Journals (Sweden)

    Jörg Mauler

    2017-05-01

    Full Text Available In the past, the eloquent areas could be deliberately localised by the invasive Wada test. The very rare cases of dissociated crossed speech areas were accidentally found based on the clinical symptomatology. Today functional magnetic resonance imaging (fMRI-based imaging can be employed to non-invasively localise the eloquent areas in brain tumour patients for therapy planning. A 41-year-old, left-handed man with a low-grade glioma in the left frontal operculum extending to the insular cortex, tension headaches, and anomic aphasia over 5 months underwent a pre-operative speech area localisation fMRI measurement, which revealed the evidence of the transhemispheric disposition, where the dominant Wernicke speech area is located on the left and the Broca’s area is strongly lateralised to the right hemisphere. The outcome of the Wada test and the intraoperative cortico-subcortical stimulation mapping were congruent with this finding. After tumour removal, language area function was fully preserved. Upon the occurrence of brain tumours with a risk of impaired speech function, the rare dissociate crossed speech areas disposition may gain a clinically relevant meaning by allowing for more extended tumour removal. Hence, for its identification, diagnostics which take into account both brain hemispheres, such as fMRI, are recommended.

  15. Fasting protects against the side effects of irinotecan treatment but does not affect anti-tumour activity in mice.

    Science.gov (United States)

    Huisman, Sander A; de Bruijn, Peter; Ghobadi Moghaddam-Helmantel, Inge M; IJzermans, Jan N M; Wiemer, Erik A C; Mathijssen, Ron H J; de Bruin, Ron W F

    2016-03-01

    The main limitation to the use of irinotecan in the treatment of colorectal cancer is the severity of side effects, including neutropaenia and diarrhoea. Here, we explored the effects of 3 days of fasting on irinotecan-induced toxicities, on plasma, liver and tumour pharmacokinetics and on anti-tumour activity in mice. Male BALB/c mice received C26 colon carcinoma cells subcutaneously. They were randomized 1:1 into equally sized ad libitum fed and fasted groups after which they were treated with irinotecan. Weight and adverse side effects were recorded daily. At the end of the experiment, tumours were resected and weighed, and concentrations of irinotecan and its active metabolite SN-38 were determined in plasma and tumour. Fasting prevented the diarrhoea and visible signs of discomfort induced by irinotecan. Ad libitum fed animals developed leucopenia compared with untreated controls, whereas fasted mice did not. Irinotecan suppressed tumour growth equally in both treated groups, compared with untreated controls. Levels of the active irinotecan metabolite SN-38 9 (calculated as AUC values) were significantly lower in fasted mice in both plasma and liver, but not in tumour tissue. Fasting protected against irinotecan-induced side effects without interfering with its anti-tumour efficacy. Fasting induced a lower systemic exposure to SN-38, which may explain the absence of adverse side effects, while tumour levels of SN-38 remained unchanged. These data offer important new approaches to improve treatment with irinotecan in patients. © 2015 The British Pharmacological Society.

  16. Metabolites in vertebrate Hedgehog signaling.

    Science.gov (United States)

    Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

    2014-04-11

    The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. [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.

  18. Metabolomics of Neurotransmitters and Related Metabolites in Post-Mortem Tissue from the Dorsal and Ventral Striatum of Alcoholic Human Brain.

    Science.gov (United States)

    Kashem, Mohammed Abul; Ahmed, Selina; Sultana, Nilufa; Ahmed, Eakhlas U; Pickford, Russell; Rae, Caroline; Šerý, Omar; McGregor, Iain S; Balcar, Vladimir J

    2016-02-01

    We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-β A4 precursor protein-binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L-glutamate (Glu), γ-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism.

  19. CT appearances of pleural tumours

    Energy Technology Data Exchange (ETDEWEB)

    Salahudeen, H.M. [Department of Radiology, Leeds Teaching Hospitals NHS Trust (United Kingdom)], E-mail: hmdsal@gmail.com; Hoey, E.T.D. [Department of Radiology, Leeds Teaching Hospitals NHS Trust (United Kingdom); Department of Radiology, Papworth Hospital, Cambridge (United Kingdom); Robertson, R.J.; Darby, M.J. [Department of Radiology, Leeds Teaching Hospitals NHS Trust (United Kingdom)

    2009-09-15

    Computed tomography (CT) is the imaging technique of choice for characterizing pleural masses with respect to their location, composition, and extent. CT also provides important information regarding invasion of the chest wall and surrounding structures. A spectrum of tumours can affect the pleura of which metastatic adenocarcinoma is the commonest cause of malignant pleural disease, while malignant mesothelioma is the most common primary pleural tumour. Certain CT features help differentiate benign from malignant processes. This pictorial review highlights the salient CT appearances of a range of tumours that may affect the pleura.

  20. Targeted NF1 cancer therapeutics with multiple modes of action: small molecule hormone-like agents resembling the natural anticancer metabolite, 2-methoxyoestradiol

    National Research Council Canada - National Science Library

    Shen, Yu-chi; Upadhyayula, Ravi; Cevallos, Stephanie; Messick, Ryan J; Hsia, Tammy; Leese, Mathew P; Jewett, Douglas M; Ferrer-Torres, Daysha; Roth, Therese M; Dohle, Wolfgang; Potter, Barry V L; Barald, Kate F

    2015-01-01

    ...), a naturally occurring anticancer metabolite of 17-β estradiol. Previous reports of treatment with sulfamoylated steroidal and non-steroidal derivatives of 2ME2 showed promising reductions in tumour burden in hormone-responsive cancers other than NF1...

  1. Cytochrome P450-mediated metabolism of tumour promoters modifies the inhibition of intercellular communication: a modified assay for tumour promotion

    DEFF Research Database (Denmark)

    Vang, Ole; Wallin, H.; Doehmer, J.

    1993-01-01

    The role of metabolism of tumour promoters on the inhibition of intercellular communication was investigated in a modified V79 metabolic cooperation system. V79 cells, which stably express different rat cytochrome P450 enzymes (CYP1A1, CYP1A2 or CYP2B1), were used in the metabolic cooperation assay...... B1 and 4-nitrobiphenyl, did not inhibit metabolic cooperation in either V79 cells expressing or cells not expressing cytochrome P450. We conclude that cytochrome P450-associated metabolism plays an important role in the inhibition of gap junctional intercellular communication of some tumour......-associated metabolism. 7-Octylindolactam V was as potent as TPA, whereas the related indolactam V was 100-fold less active. The carcinogenic aromatic amine 4-aminobiphenyl, but not its primary metabolite 4-hydroxyaminobiphenyl, inhibited metabolic cooperation. Other known carcinogens, ochratoxin A, aflatoxin...

  2. The Heidelberg classification of renal cell tumours

    NARCIS (Netherlands)

    Kovacs, G; Akhtar, M; Beckwith, BJ; Bugert, P; Cooper, CS; Delahunt, B; Eble, JN; Fleming, S; Ljungberg, B; Medeiros, LJ; Moch, H; Reuter, VE; Ritz, E; Roos, G; Schmidt, D; Srigley, [No Value; Storkel, S; VandenBerg, E; Zbar, B

    1997-01-01

    This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996, The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic

  3. A brief review of potent anti-CNS tumourics from marine sponges: covering the period from 1994 to 2014.

    Science.gov (United States)

    Pejin, Boris; Glumac, Miodrag

    2018-02-01

    This review covers the 1994-2014 literature data published for anti-CNS tumour natural products isolated from marine sponges. The focus was on highly potent antitumourics. It describes only eight promising bioactives (screened on even less number of the respective cell lines) suggesting that brain tumours actually represent quite a hot topic for the natural product research community worldwide.

  4. Paediatric laryngeal granular cell tumour

    Directory of Open Access Journals (Sweden)

    Dauda Ayuba

    2009-01-01

    Full Text Available Granular cell tumour (GCT affecting the larynx is not common, especially in children. Most cases are apt to be confused with respiratory papilloma and may even be mistaken for a malignant neoplasia. We present a case of laryngeal GCT in a 12-year-old child to emphasize that the tumour should be regarded in the differential of growths affecting the larynx in children.

  5. Optimal voxel size for measuring global gray and white matter proton metabolite concentrations using chemical shift imaging

    DEFF Research Database (Denmark)

    Hanson, Lars Peter Grüner; Adalsteinsson, E; Pfefferbaum, A

    2000-01-01

    Quantification of gray and white matter levels of spectroscopically visible metabolites can provide important insights into brain development and pathological conditions. Chemical shift imaging offers a gain in efficiency for estimation of global gray and white matter metabolite concentrations co...

  6. MRI characteristics of midbrain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Sun, B. [Chinese Academy of Medical Science, Beijing (China). Neurosurgical Inst.]|[Department of Neuroradiology, Beijing Tiantan Hospital (China); Wang, C.C.; Wang, J. [Chinese Academy of Medical Science, Beijing (China). Neurosurgical Inst.

    1999-03-01

    We diagnosed 60 cases of midbrain tumours by MRI between 1993 to 1997. There were 39 males and 21 females, aged 2-64 years, mean 25.6 years. We found 38 patients with true intramedullary midbrain tumours, 11 predominantly in the tectum, 20 in the tegmentum and 7 with a downward extension to the pons; there were 7 within the cerebral aqueduct. There were 22 patients with infiltrating midbrain tumours extending from adjacent structures, 11 cases each from the thalamus and pineal region. All patients received surgical treatment. Gross total resection was achieved in 42 cases, subtotal (> 75 %) resection in 18. Pathological diagnoses included 16 low-grade and 15 high-grade astrocytomas; 5 oligodendroastrocytomas; 2 ependymomas; 11 glioblastomas; and 11 pineal parenchymal or germ-cell tumours. Midbrain tumours are a heterogeneous group of neoplasms, with wide variation in clinical and MRI features, related to the site and type of tumour. MRI not only allows precise analysis of their growth pattern, but also can lead to a correct preoperative diagnosis in the majority of cases. (orig.) (orig.) With 3 figs., 3 tabs., 19 refs.

  7. Congruency of tumour volume delineated by FET PET and MRSI

    Energy Technology Data Exchange (ETDEWEB)

    Mauler, Jörg; Langen, Karl-Josef [Institute of Neuroscience and Medicine, Forschungszentrum Jülich (Germany); Maudsley, Andrew A [Miller School of Medicine, University of Miami (United States); Nikoubashman, Omid [Department of Neuroradiology, Faculty of Medicine, RWTH Aachen University (Germany); Filss, Christian; Stoffels, Gabriele; Shah, N Jon [Institute of Neuroscience and Medicine, Forschungszentrum Jülich (Germany)

    2015-05-18

    In addition to MR imaging, PET imaging of O-(2-[18F]Fluorethyl)-L-Tyrosine (FET) uptake provides information on brain tumour extent and metabolic activity. Similarly, MRS has been shown to be of value for distinguishing high- from low-grade gliomas. Based on 2D spatially resolved MRSI, an overlap between 18FET uptake and the choline/N-acetyl-aspartate (Cho/NAA) ratio of more than 75 % has been reported.

  8. Anaesthetic management for combined emergency caesarean section and craniotomy tumour removal

    Directory of Open Access Journals (Sweden)

    Dewi Y Bisri

    2017-01-01

    Full Text Available Presentation of primary intracranial tumour during pregnancy is extremely rare. Symptoms of brain tumour include nausea, vomiting, headache and seizures which mimic symptoms of pregnancy-related hyperemesis or eclampsia. In very few cases, craniotomy tumour removal is performed earlier or even simultaneously with foetal delivery. A 40-year-old woman at 32 weeks of gestation in foetal distress presented to the emergency room with decreased level of consciousness Glasgow Coma Scale 6 (E2M2V2. Computed tomographic scan revealed a mass lesion over the left temporoparietal region with midline shift and intratumoural bleeding. In view of high risk of herniation and foetal distress, she underwent emergency caesarean section followed by craniotomy tumour removal. In parturient with brain tumour, combined surgery of tumour removal and caesarean section is decided based on clinical symptoms, type of tumour and foetal viability. Successful anaesthetic management requires a comprehensive knowledge of physiology and pharmacology, individually tailored to control intracranial pressure while ensuring the safety of mother and foetus.

  9. A rare cause of infant facial paralysis: atypical teratoid rhabdoid tumour located in the cerebellopontine angle.

    Science.gov (United States)

    Öztürk, Mehmet; Siğirci, Ahmet; Karadağ, Neşe

    2015-01-01

    Atypical teratoid rhabdoid tumour (ATRT) is a rare malignant tumour of the central nervous system with embryonal roots. The majority are seen in early childhood and location is often in the posterior fossa. Surgery, radiotherapy and chemotherapy are used in treatment. Knowledge of the localisation of the mass preoperatively is necessary for direction of the chemoradiotherapy and sufficient resection in surgery. Differentiation from other brain tumours is important because of poor prognosis and differences in treatment. In this paper it was aimed to present the clinical and radiological findings of an ATRT located in the cerebellopontine angle, which occurred with facial paralysis.

  10. PTEN hamartoma tumour syndrome: early tumour development in children.

    Science.gov (United States)

    Smpokou, Patroula; Fox, Victor L; Tan, Wen-Hann

    2015-01-01

    The aim of this study was to report the earliest age of diagnosis of common clinical findings in children with PTEN hamartoma tumour syndrome (PHTS). Medical records of children with PHTS were reviewed; data included growth measurements, presence or absence of specific clinical manifestations and tumours, and documented ages of diagnosis. Children with PHTS evaluated at Boston Children's Hospital from 1996 to 2011. The cohort included 34 children diagnosed with PHTS via genetic testing, under the age of 21 years. Of these, 23 were male and 11 female. The mean age at their last documented clinical evaluation was 13.6 years. The mean follow-up time was 7.5 years. Macrocephaly and developmental/intellectual disability were consistent findings. Pigmented penile macules were noted in all males examined for this finding. Thyroid nodules, found in half the children screened with ultrasound, were diagnosed as early as at 5 years of age. Thyroid carcinoma, identified in 12% of the children in this cohort, was diagnosed as early as at 7 years of age. Other tumours included renal cell carcinoma diagnosed at 11 years of age and granulosa cell tumour of the ovary and colonic ganglioneuroma, each diagnosed at 16 years of age. Specific clinical findings and tumours are characteristic in children with PHTS. Tumour development occurs in young children with this condition, which necessitates early surveillance, especially of the thyroid. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Pitfalls in colour photography of choroidal tumours.

    Science.gov (United States)

    Schalenbourg, A; Zografos, L

    2013-02-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.

  12. Pitfalls in colour photography of choroidal tumours

    Science.gov (United States)

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  13. Preclinical impact of bevacizumab on brain and tumor distribution of irinotecan and temozolomide.

    Science.gov (United States)

    Goldwirt, Lauriane; Beccaria, Kevin; Carpentier, Alexandre; Idbaih, Ahmed; Schmitt, Charlotte; Levasseur, Camille; Labussiere, Marianne; Milane, Aline; Farinotti, Robert; Fernandez, Christine

    2015-04-01

    Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Prognosis of GBM patients is poor with median overall survival around 15 months. Temozolomide is the chemotherapeutic agent used in the standard of care of newly diagnosed GBM patients relying on radiotherapy with concurrent chemotherapy followed by chemotherapy alone. Irinotecan has shown some efficacy in recurrent malignant gliomas. Bevacizumab has been combined with irinotecan in the treatment of recurrent GBM and with temozolomide in newly diagnosed GBM. As the efficacy of GBM treatments relies on their brain distribution through the blood brain barrier, the aim of the present preclinical work was to study, in in vivo models, the impact of bevacizumab on brain and tumor distribution of temozolomide and irinotecan. Our results show that bevacizumab pre-treatment was associated with a reduced temozolomide brain distribution in tumor-free mice. In tumor bearing mice, bevacizumab increased temozolomide tumor distribution, although not statistically significant. In both tumor-free and tumor-bearing mice, bevacizumab does not modify brain distribution of irinotecan and its metabolite SN-38. Bevacizumab impacts brain distribution of some anti-tumor drugs and potentially their efficacy in GBM. Further studies are warranted to investigate other therapeutic combination.

  14. Enhanced metabolite generation

    Science.gov (United States)

    Chidambaram, Devicharan [Middle Island, NY

    2012-03-27

    The present invention relates to the enhanced production of metabolites by a process whereby a carbon source is oxidized with a fermentative microbe in a compartment having a portal. An electron acceptor is added to the compartment to assist the microbe in the removal of excess electrons. The electron acceptor accepts electrons from the microbe after oxidation of the carbon source. Other transfers of electrons can take place to enhance the production of the metabolite, such as acids, biofuels or brewed beverages.

  15. Evaluation of factors influencing 18 F-FET uptake in the brain

    OpenAIRE

    Verger, Antoine; Stegmayr, Carina; Eickhoff, Simon; Galldiks, Norbert; Van Der Gucht, Axel; Lohmann, Philipp; Stoffels, Gabriele; Shah, Nadim J.; Fink, Gereon R.; Guedj, Eric; Langen, Karl-Josef

    2018-01-01

    PET using the amino-acid O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) is gaining increasing interest for brain tumour management. Semi-quantitative analysis of tracer uptake in brain tumours is based on the standardized uptake value (SUV) and the tumour-to-brain ratio (TBR). The aim of this study was to explore physiological factors that might influence the relationship of SUV of 18F-FET uptake in various brain areas, and thus affect quantification of 18F-FET uptake in brain tumours. Negative 1...

  16. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  17. CANCER Escape from senescence boosts tumour growth

    NARCIS (Netherlands)

    Medema, Jan Paul

    2018-01-01

    Some chemotherapies block cancer growth by driving tumour cells into a state of cell-division arrest termed senescence. It emerges that such cells have a boosted capacity to drive tumour growth if they exit senescence

  18. Follicular infundibulum tumour presenting as cutaneous horn

    Directory of Open Access Journals (Sweden)

    Jayaraman M

    1996-01-01

    Full Text Available Tumour of follicular infundibulum is an organoid tumour with a plate like growth attached to the epidermis with connection from the follicular epithelium. We are reporting such a case unusually presenting as cutaneous horn.

  19. Dopamine-modified TiO2 monolith-assisted LDI MS imaging for simultaneous localization of small metabolites and lipids in mouse brain tissue with enhanced detection selectivity and sensitivity† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc00937b Click here for additional data file.

    Science.gov (United States)

    Wu, Qian; Chu, James L.; Rubakhin, Stanislav S.; Gillette, Martha U.

    2017-01-01

    Localization of metabolites using multiplexed mass spectrometry imaging (MSI) provides important chemical information for biological research. In contrast to matrix-assisted laser desorption/ionization (MALDI), TiO2-assisted laser desorption/ionization (LDI) for MSI improves detection of low molecular mass metabolites (monolithic TiO2-DA structures. The sub-micron scale and higher surface pH of the TiO2 particle sizes led to improved detection of phospholipid signals. Compared to unmodified TiO2 sub-micron particles, the DA-modified TiO2 monolith led to 10- to 30-fold increases in the signal-to-noise ratios of a number of compound peaks. The TiO2-DA monolith-assisted LDI MSI approach has higher selectivity and sensitivity for Lewis basic compounds, such as fatty acids, cholesterols, ceramides, diacylglycerols, and phosphatidylethanolamine, when analyzed in positive mode, than traditional MALDI MS. Using this new method, over 100 molecules, including amino acids, alkaloids, free fatty acids, peptides, and lipids, were localized in mouse brain sections. By comparing the presence and localization of those molecules in young and old mouse brains, the approach demonstrated good performance in the determination of aging-related neurochemical changes in the brain. PMID:28553535

  20. Tumour xenograft detection through quantitative analysis of the metabolic profile of urine in mice

    Energy Technology Data Exchange (ETDEWEB)

    Moroz, Jennifer [Department of Physics, University of Alberta, 11322-89 Avenue, Edmonton, Alberta T6G 2G7 (Canada); Turner, Joan [Department of Experimental Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Slupsky, Carolyn [Department of Nutrition, University of California, One Shields Avenue, Davis, CA 95616-8598 (United States); Fallone, Gino; Syme, Alasdair, E-mail: alasdair.syme@albertahealthservices.ca [Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada)

    2011-02-07

    The metabolic content of urine from NIH III nude mice (n = 22) was analysed before and after inoculation with human glioblastoma multiforme (GBM) cancer cells. An age- and gender-matched control population (n = 14) was also studied to identify non-tumour-related changes. Urine samples were collected daily for 6 weeks, beginning 1 week before cell injection. Metabolite concentrations were obtained via targeted profiling with Chenomx Suite 5.1, based on nuclear magnetic resonance (NMR) spectra acquired on an Oxford 800 MHz cold probe NMR spectrometer. The Wilcoxon rank sum test was used to evaluate the significance of the change in metabolite concentration between the two time points. Both the metabolite concentrations and the ratios of pairs of metabolites were studied. The complicated inter-relationships between metabolites were assessed through partial least-squares discriminant analysis (PLS-DA). Receiver operating characteristic (ROC) curves were generated for all variables and the area under the curve (AUC) calculated. The data indicate that the number of statistically significant changes in metabolite concentrations was more pronounced in the tumour-bearing population than in the control animals. This was also true of the ratios of pairs of metabolites. ROC analysis suggests that the ratios were better able to differentiate between the pre- and post-injection samples compared to the metabolite concentrations. PLS-DA models produced good separation between the populations and had the best AUC results (all models exceeded 0.937). These results demonstrate that metabolomics may be used as a screening tool for GBM cells grown in xenograft models in mice.

  1. Tumour xenograft detection through quantitative analysis of the metabolic profile of urine in mice

    Science.gov (United States)

    Moroz, Jennifer; Turner, Joan; Slupsky, Carolyn; Fallone, Gino; Syme, Alasdair

    2011-02-01

    The metabolic content of urine from NIH III nude mice (n = 22) was analysed before and after inoculation with human glioblastoma multiforme (GBM) cancer cells. An age- and gender-matched control population (n = 14) was also studied to identify non-tumour-related changes. Urine samples were collected daily for 6 weeks, beginning 1 week before cell injection. Metabolite concentrations were obtained via targeted profiling with Chenomx Suite 5.1, based on nuclear magnetic resonance (NMR) spectra acquired on an Oxford 800 MHz cold probe NMR spectrometer. The Wilcoxon rank sum test was used to evaluate the significance of the change in metabolite concentration between the two time points. Both the metabolite concentrations and the ratios of pairs of metabolites were studied. The complicated inter-relationships between metabolites were assessed through partial least-squares discriminant analysis (PLS-DA). Receiver operating characteristic (ROC) curves were generated for all variables and the area under the curve (AUC) calculated. The data indicate that the number of statistically significant changes in metabolite concentrations was more pronounced in the tumour-bearing population than in the control animals. This was also true of the ratios of pairs of metabolites. ROC analysis suggests that the ratios were better able to differentiate between the pre- and post-injection samples compared to the metabolite concentrations. PLS-DA models produced good separation between the populations and had the best AUC results (all models exceeded 0.937). These results demonstrate that metabolomics may be used as a screening tool for GBM cells grown in xenograft models in mice.

  2. Scintigraphy in benign bone tumours

    African Journals Online (AJOL)

    1989-08-05

    Aug 5, 1989 ... Ackerman LV, Spjut AJ. Tumors of Bone and Carrilage. Washington, DC: US Armed Forces Institute of Pathology, 1962: 84-89. 4. Evans RW. HislOlogical Appearances of Tumours. Edinburgh: E & S Living- stone, 1966: 187-191. 5. Lichtenstein L. Bane Tumors. 5th ed. St Louis, Mo.: CV Mosby, 1977: 30-39.

  3. The "first hit" toward alcohol reinforcement: role of ethanol metabolites.

    Science.gov (United States)

    Israel, Yedy; Quintanilla, María Elena; Karahanian, Eduardo; Rivera-Meza, Mario; Herrera-Marschitz, Mario

    2015-05-01

    This review analyzes literature that describes the behavioral effects of 2 metabolites of ethanol (EtOH): acetaldehyde and salsolinol (a condensation product of acetaldehyde and dopamine) generated in the brain. These metabolites are self-administered into specific brain areas by animals, showing strong reinforcing effects. A wealth of evidence shows that EtOH, a drug consumed to attain millimolar concentrations, generates brain metabolites that are reinforcing at micromolar and nanomolar concentrations. Salsolinol administration leads to marked increases in voluntary EtOH intake, an effect inhibited by mu-opioid receptor blockers. In animals that have ingested EtOH chronically, the maintenance of alcohol intake is no longer influenced by EtOH metabolites, as intake is taken over by other brain systems. However, after EtOH withdrawal brain acetaldehyde has a major role in promoting binge-like drinking in the condition known as the "alcohol deprivation effect"; a condition seen in animals that have ingested alcohol chronically, are deprived of EtOH for extended periods, and are allowed EtOH re-access. The review also analyzes the behavioral effects of acetate, a metabolite that enters the brain and is responsible for motor incoordination at low doses of EtOH. Also discussed are the paradoxical effects of systemic acetaldehyde. Overall, evidence strongly suggests that brain-generated EtOH metabolites play a major role in the early ("first-hit") development of alcohol reinforcement and in the generation of relapse-like drinking. Copyright © 2015 by the Research Society on Alcoholism.

  4. Melanotic neuroectodermal tumour of the pineal region

    Energy Technology Data Exchange (ETDEWEB)

    Gorhan, C.; Soto-Ares, G.; Pruvo, J.P. [Dept. of Neuroradiology, Hopital Roger Salengro, CHRU Lille, Lille (France); Ruchoux, M.M. [Dept. of Neuropathology, Hopital Roger Salengro, CHRU Lille (France); Blond, S. [Dept. of Neurosurgery, Hopital Roger Salengro, CHRU Lille (France)

    2001-11-01

    We describe CT and MR findings in a 23-month-old infant with a melanotic neuroectodermal tumour of the pineal gland. The tumour has been stereotactically biopsied and surgically resected. The pathological diagnosis was made on the resected piece. Embryology of the pineal gland and the histology of melanotic neuroectodermal tumour of infancy are discussed. (orig.)

  5. Radiofrequency for the treatment of liver tumours

    NARCIS (Netherlands)

    Ruers, TJM; de Jong, KP; Ijzermans, JNM

    2005-01-01

    Resection should still be considered the gold standard for many liver tumours. There is, however, growing interest in the use of radiofrequency (RFA) for the treatment of liver tumours. By RFA, tumour tissue can be destructed selectively without significant damage to vascular structures in the

  6. Radiofrequency for the treatment of liver tumours.

    NARCIS (Netherlands)

    Ruers, T.J.M.; Jong, K.P. de; Ijzermans, J.N.M.

    2005-01-01

    Resection should still be considered the gold standard for many liver tumours. There is, however, growing interest in the use of radiofrequency (RFA) for the treatment of liver tumours. By RFA, tumour tissue can be destructed selectively without significant damage to vascular structures in the

  7. Mohs micrographic surgery of rare cutaneous tumours

    NARCIS (Netherlands)

    Flohil, S.C.; Lee, C.B. van; Beisenherz, J.; Mureau, M.A.M.; Overbeek, L.I.H.; Nijsten, T.; Bos, R.R.

    2017-01-01

    BACKGROUND: Recurrence rates after Mohs micrographic surgery (MMS) for rare cutaneous tumours are poorly defined. OBJECTIVE: To investigate the recurrence rate after MMS for rare cutaneous tumours at a university centre. METHODS & MATERIALS: Retrospective review of all rare cutaneous tumours treated

  8. REPORT OF SEVEN CASES OF METASTATIC TUMOURS

    African Journals Online (AJOL)

    Major Adebayo

    Abstract. Background: Metastatic tumours make up approximately one per cent of all oral malignancies. Such tumours may present in the jawbones and oral soft tissues. The commonest oral site is the mandible. Nigerian reports of metastatic tumours to the jaws are very rare. Method: This is a retrospective study of six cases ...

  9. Imaging of salivary gland tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y.Y.P.; Wong, K.T.; King, A.D. [Department of Diagnostic Radiology and Organ Imaging, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin NT, Hong Kong (Hong Kong); Ahuja, A.T. [Department of Diagnostic Radiology and Organ Imaging, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin NT, Hong Kong (Hong Kong)], E-mail: aniltahuja@cuhk.edu.hk

    2008-06-15

    Salivary gland neoplasms account for <3% of all tumors. Most of them are benign and parotid gland is the commonest site. As a general rule, the smaller the involved salivary gland, the higher is the possibility of the tumor being malignant. The role of imaging in assessment of salivary gland tumour is to define intra-glandular vs. extra-glandular location, detect malignant features, assess local extension and invasion, detect nodal metastases and systemic involvement. Image guided fine needle aspiration cytology provides a safe means to obtain cytological confirmation. For lesions in the superficial parotid and submandibular gland, ultrasound is an ideal tool for initial assessment. These are superficial structures accessible by high resolution ultrasound and FNAC which provides excellent resolution and tissue characterization without a radiation hazard. Nodal involvement can also be assessed. If deep tissue extension is suspected or malignancy confirmed on cytology, an MRI or CT is mandatory to evaluate tumour extent, local invasion and perineural spread. For all tumours in the sublingual gland, MRI should be performed as the risk of malignancy is high. For lesions of the deep lobe of parotid gland and the minor salivary glands, MRI and CT are the modalities of choice. Ultrasound has limited visualization of the deep lobe of parotid gland which is obscured by the mandible. Minor salivary gland lesions in the mucosa of oral cavity, pharynx and tracheo-bronchial tree, are also not accessible by conventional ultrasound. Recent study suggests that MR spectroscopy may differentiate malignant and benign salivary gland tumours as well as distinguishing Warthin's tumor from pleomorphic adenoma. However, its role in clinical practice is not well established. Similarly, the role of nuclear medicine and PET scan, in imaging of parotid masses is limited. Sialography is used to delineate the salivary ductal system and has limited role in assessment of tumour extent.

  10. Lymphocyte migration through the blood-brain barrier (BBB) in feline immunodeficiency virus infection is significantly influenced by the pre-existence of virus and tumour necrosis factor (TNF)-alpha within the central nervous system (CNS): studies using an in vitro feline BBB model.

    Science.gov (United States)

    Fletcher, N F; Bexiga, M G; Brayden, D J; Brankin, B; Willett, B J; Hosie, M J; Jacque, J-M; Callanan, J J

    2009-12-01

    In human immunodeficiency virus infection, macrophage-tropic and lymphotropic viruses exist in the host. Central nervous system (CNS) infection is an early and ongoing event, important to understand when developing strategies to treat infection. Some knowledge exists on macrophage-tropic virus interactions with the blood-brain barrier (BBB), and the aim of this study was to investigate lymphotropic lentivirus interactions with the BBB. Interactions of the lymphotropic feline immunodeficiency virus (FIV) with an in vitro model of the feline BBB were evaluated in scenarios to mimic in vivo infections. Cell-free FIV crossed the BBB in very low quantities, and in the presence of tumour necrosis factor (TNF)-alpha, BBB integrity was unaffected. However, cell-associated FIV readily crossed the BBB, but BBB integrity was not significantly altered. Transmigration of uninfected and infected lymphocytes increased in response to TNF-alpha, accompanied by a moderate disruption of barrier integrity and an upregulation of vascular cell adhesion molecule-1 rather than intercellular adhesion molecule-1. Significant enhancement of migration and disruption of BBB tight junctions occurred when infected cells and TNF-alpha were added to the brain side of the BBB and this enhancement was not mediated through additional TNF-alpha production. Small quantities of virus in the brain together with TNF-alpha have the potential to stimulate greater cell and viral entry into the CNS and this is likely to involve important factors other than further TNF-alpha production. Lymphotropic lentivirus entry to the CNS is governed by many factors similar to macrophage-tropic strains.

  11. Characterization of the radiolabeled metabolite of tau PET tracer {sup 18}F-THK5351

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Ryuichi [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Furumoto, Shozo; Tago, Tetsuro; Iwata, Ren; Tashiro, Manabu [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Katsutoshi, Furukawa; Ishiki, Aiko; Tomita, Naoki; Arai, Hiroyuki [Tohoku University, Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Sendai (Japan); Yanai, Kazuhiko [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Kudo, Yukitsuka [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Okamura, Nobuyuki [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku Medical and Pharmaceutical University, Division of Pharmacology, Faculty of Medicine, Sendai (Japan)

    2016-11-15

    {sup 18}F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of {sup 18}F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties. Venous blood samples were collected from three human subjects after injection of {sup 18}F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples. About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of {sup 18}F-THK5351. The isolated radiometabolite of {sup 18}F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples. These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images. (orig.)

  12. Tissue distribution of rat flavanol metabolites at different doses.

    Science.gov (United States)

    Margalef, Maria; Pons, Zara; Bravo, Francisca Isabel; Muguerza, Begoña; Arola-Arnal, Anna

    2015-10-01

    Flavanols are metabolized in the small intestine and the liver to produce their glucuronidated, sulfated or methylated conjugates that can be body distributed or excreted in the urine. However, the intake of large amounts of flavanols is not directly related to their bioavailability. This study aims to investigate the administered dose dependence of flavanols' conjugation and body distribution. In this study, different doses of a grape seed proanthocyanidin extract (GSPE; 125, 250, 375 and 1000 mg/kg) were orally administered to male Wistar rats. Tissues were collected 2h after GSPE administration. Flavanols were quantified by HPLC-MS/MS. Results show that the majority of GSPE metabolites are located in the kidney, followed by the liver. Lower concentrations were found in mesenteric white adipose tissue (MWAT) and the brain. Moreover, flavanol metabolites followed a tissue-specific distribution pattern independent of dosage. In the kidney, glucuronidated metabolites were the most abundant; however, in the liver, it was mainly methyl-glucuronidated metabolites. In MWAT, free flavanols were dominant, and methylated metabolites were dominant in the brain. Concentration within a tissue was dependent on the administered dose. In conclusion, flavanol metabolites follow a tissue-specific distribution pattern and only the tissue concentration of flavanol metabolites is dependent on the administered dose. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Tumours of the fetal body: a review

    Energy Technology Data Exchange (ETDEWEB)

    Avni, Fred E.; Massez, Anne; Cassart, Marie [University Clinics of Brussels - Erasme Hospital, Department of Medical Imaging, Brussels (Belgium)

    2009-11-15

    Tumours of the fetal body are rare, but lesions have been reported in all spaces, especially in the mediastinum, the pericardial space, the adrenals, the kidney, and the liver. Lymphangioma and teratoma are the commonest histological types encountered, followed by cardiac rhabdomyoma. Adrenal neuroblastoma is the commonest malignant tumour. Imaging plays an essential role in the detection and work-up of these tumours. In addition to assisting clinicians it also helps in counselling parents. Most tumours are detected by antenatal US, but fetal MRI is increasingly used as it brings significant additional information in terms of tumour extent, composition and complications. (orig.)

  14. Comparison of contrast-enhanced modified T1-weighted 3D TSE black-blood and 3D MP-RAGE sequences for the detection of cerebral metastases and brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kammer, N.N.; Coppenrath, E.; Treitl, K.M.; Saam, T. [Ludwig-Maximilians-University Hospital Munich, Institute for Clinical Radiology, Munich (Germany); Kooijman, H. [Philips Healthcare, Hamburg (Germany); Dietrich, O. [Ludwig-Maximilians-University Hospital Munich, Josef Lissner Laboratory for Biomedical Imaging, Institute for Clinical Radiology, Munich (Germany)

    2016-06-15

    To compare a modified T1-weighted 3D TSE black-blood sequence with sub-millimetre resolution (T1-mVISTA) with a magnetization-prepared rapid gradient echo (MP-RAGE) sequence for the diagnosis of cerebral malignomas. Forty-six patients with known or suspected intracranial tumours and 15 control patients were included in this retrospective study. All patients underwent T1-mVISTA (0.75-mm isotropic resolution, 4:43 min) and MP-RAGE (0.8-mm isotropic resolution, 4:46 minutes) at 3-Tesla in random order after application of contrast agent. Two experienced radiologists determined the number of lesions. Maximum diameter, diagnostic confidence (DC), visual assessment of contrast enhancement (VCE) and CNR{sub lesion/parenchyma} were assessed for each lesion. Significantly more lesions were detected with T1-mVISTA compared to the MP-RAGE (61 vs. 36; p < 0.05). Further, DC and VCE was rated significantly higher in the T1-mVISTA (p < 0.05 and p < 0.001). Mean CNR{sub lesion/parenchyma} was twofold higher for T1-mVISTA (24.2 ± 17.5 vs. 12.7 ± 11.5, p < 0.001). The 25 lesions detected only in T1-mVISTA were significantly smaller than those detected in both sequences (4.3 ± 3.7 mm vs. 11.3 ± 10.7 mm; p < 0.01). T1-mVISTA increases the contrast of lesions significantly compared to MP-RAGE and might therefore improve detection rates of small lesions in early stages of disease. (orig.)

  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. Metastatic tumours to hypophysis: a report of three cases and review of literature

    Directory of Open Access Journals (Sweden)

    Tomaž Šmigoc

    2016-10-01

    Full Text Available Background. Metastatic tumours to pituitary are rare. The most frequent are metastases from breast and lung.Methods. In this paper, three cases of metastatic tumours to the pituitary are presented with panhypopituitarism as a common symptom: I a 60-year-old gentleman with metastasis of diffuse large B cell lymphoma, who presented with diabetes insipidus, II a 54-year-old lady with metastatic renal clear cell carcinoma and consequent disturbances in visual acuity, brain nerve paresis and III a 57-year-old lady with breast cancer metastasis, visual impairment and brain nerve paresis.Results. A transnasal endoscopic resection of the tumours was performed in all cases, followed by oncological treatment. All patients improved after the treatment.Conclusions. Despite the rarity of the disease, a metastatic tumour to the pituitary gland must be included in the differential diagnosis when symptoms such as diabetes insipidus, ophthalmoplegy due to brain nerve palsies, rapid course of the disease and headache are observed. In 20% to 30%, pituitary metastases are the first manifestation of a tumour of unknown origin. Surgical and adjuvant therapy may improve the quality of life. The survival and prognosis are generally poor.

  17. Preliminary observations and clinical value of N-acetyl resonances in ovarian tumours using in-vivo proton MR spectroscopy at 3T

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Mayumi; Matsuzaki, Kenji; Harada, Masafumi [University of Tokushima, Department of Radiology, Tokushima (Japan)

    2011-12-15

    To retrospectively evaluate the clinical significance of N-acetyl resonances at 2 ppm in in-vivo proton magnetic resonance (MR) spectroscopy for distinguishing mucinous and non-mucinous tumours in patients with ovarian masses. MR spectroscopy was performed in patients with pathologically diagnosed ovarian tumours at 3T-MR imaging. Single-voxel MR spectroscopy data were collected from a single square volume of interest that encompassed the ovarian masses. The metabolite resonance peak areas at 2 ppm were quantified relative to unsuppressed water using a software package (LCModel). A total of 32 ovarian lesions in 32 patients were evaluated in this study. High metabolite peak at 2 ppm was observed in all nine mucinous tumours (9.71 +/- 7.46 mM), whereas low peak was observed in 14 of 23 non-mucinous tumours (3.12 +/- 1.42 mM) (p < 0.001). Using a cut off value of 4.45 mM for mucinous tumours had a sensitivity of 89%, specificity of 86%, PPV of 80%, and NPV of 92%. Proton MR spectroscopy with quantitative evaluation of the metabolite at 2 ppm concentration, which may suggest the presence of mucinous material containing N-acetyl mucinous compounds, can provide helpful information in distinguishing mucinous and non-mucinous ovarian tumours. (orig.)

  18. Secondary metabolites from Ganoderma.

    Science.gov (United States)

    Baby, Sabulal; Johnson, Anil John; Govindan, Balaji

    2015-06-01

    Ganoderma is a genus of medicinal mushrooms. This review deals with secondary metabolites isolated from Ganoderma and their biological significance. Phytochemical studies over the last 40years led to the isolation of 431 secondary metabolites from various Ganoderma species. The major secondary compounds isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l) prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o) benzenoid derivatives. Ganoderma lucidum is the species extensively studied for its secondary metabolites and biological activities. Ganoderma applanatum, Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum, Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the other Ganoderma species subjected to phytochemical studies. Further phytochemical studies on Ganoderma could lead to the discovery of hitherto unknown biologically active secondary metabolites. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Tumour viruses and innate immunity.

    Science.gov (United States)

    Hopcraft, Sharon E; Damania, Blossom

    2017-10-19

    Host cells sense viral infection through pattern recognition receptors (PRRs), which detect pathogen-associated molecular patterns (PAMPs) and stimulate an innate immune response. PRRs are localized to several different cellular compartments and are stimulated by viral proteins and nucleic acids. PRR activation initiates signal transduction events that ultimately result in an inflammatory response. Human tumour viruses, which include Kaposi's sarcoma-associated herpesvirus, Epstein-Barr virus, human papillomavirus, hepatitis C virus, hepatitis B virus, human T-cell lymphotropic virus type 1 and Merkel cell polyomavirus, are detected by several different PRRs. These viruses engage in a variety of mechanisms to evade the innate immune response, including downregulating PRRs, inhibiting PRR signalling, and disrupting the activation of transcription factors critical for mediating the inflammatory response, among others. This review will describe tumour virus PAMPs and the PRRs responsible for detecting viral infection, PRR signalling pathways, and the mechanisms by which tumour viruses evade the host innate immune system.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).

  20. Understanding and classifying metabolite space and metabolite-likeness.

    Directory of Open Access Journals (Sweden)

    Julio E Peironcely

    Full Text Available While the entirety of 'Chemical Space' is huge (and assumed to contain between 10(63 and 10(200 'small molecules', distinct subsets of this space can nonetheless be defined according to certain structural parameters. An example of such a subspace is the chemical space spanned by endogenous metabolites, defined as 'naturally occurring' products of an organisms' metabolism. In order to understand this part of chemical space in more detail, we analyzed the chemical space populated by human metabolites in two ways. Firstly, in order to understand metabolite space better, we performed Principal Component Analysis (PCA, hierarchical clustering and scaffold analysis of metabolites and non-metabolites in order to analyze which chemical features are characteristic for both classes of compounds. Here we found that heteroatom (both oxygen and nitrogen content, as well as the presence of particular ring systems was able to distinguish both groups of compounds. Secondly, we established which molecular descriptors and classifiers are capable of distinguishing metabolites from non-metabolites, by assigning a 'metabolite-likeness' score. It was found that the combination of MDL Public Keys and Random Forest exhibited best overall classification performance with an AUC value of 99.13%, a specificity of 99.84% and a selectivity of 88.79%. This performance is slightly better than previous classifiers; and interestingly we found that drugs occupy two distinct areas of metabolite-likeness, the one being more 'synthetic' and the other being more 'metabolite-like'. Also, on a truly prospective dataset of 457 compounds, 95.84% correct classification was achieved. Overall, we are confident that we contributed to the tasks of classifying metabolites, as well as to understanding metabolite chemical space better. This knowledge can now be used in the development of new drugs that need to resemble metabolites, and in our work particularly for assessing the metabolite

  1. Understanding and classifying metabolite space and metabolite-likeness.

    Science.gov (United States)

    Peironcely, Julio E; Reijmers, Theo; Coulier, Leon; Bender, Andreas; Hankemeier, Thomas

    2011-01-01

    While the entirety of 'Chemical Space' is huge (and assumed to contain between 10(63) and 10(200) 'small molecules'), distinct subsets of this space can nonetheless be defined according to certain structural parameters. An example of such a subspace is the chemical space spanned by endogenous metabolites, defined as 'naturally occurring' products of an organisms' metabolism. In order to understand this part of chemical space in more detail, we analyzed the chemical space populated by human metabolites in two ways. Firstly, in order to understand metabolite space better, we performed Principal Component Analysis (PCA), hierarchical clustering and scaffold analysis of metabolites and non-metabolites in order to analyze which chemical features are characteristic for both classes of compounds. Here we found that heteroatom (both oxygen and nitrogen) content, as well as the presence of particular ring systems was able to distinguish both groups of compounds. Secondly, we established which molecular descriptors and classifiers are capable of distinguishing metabolites from non-metabolites, by assigning a 'metabolite-likeness' score. It was found that the combination of MDL Public Keys and Random Forest exhibited best overall classification performance with an AUC value of 99.13%, a specificity of 99.84% and a selectivity of 88.79%. This performance is slightly better than previous classifiers; and interestingly we found that drugs occupy two distinct areas of metabolite-likeness, the one being more 'synthetic' and the other being more 'metabolite-like'. Also, on a truly prospective dataset of 457 compounds, 95.84% correct classification was achieved. Overall, we are confident that we contributed to the tasks of classifying metabolites, as well as to understanding metabolite chemical space better. This knowledge can now be used in the development of new drugs that need to resemble metabolites, and in our work particularly for assessing the metabolite-likeness of candidate

  2. The neurotoxicity of pyridinium metabolites of haloperidol

    Directory of Open Access Journals (Sweden)

    Agnieszka Górska

    2015-10-01

    Full Text Available Haloperydol is a butyrophenone, typical neuroleptic agent characterized as a high antipsychotics effects in the treatment of schizophrenia and in palliative care to alleviation many syndromes, such as naursea, vomiting and delirium. Clinical problems occurs during and after administration of the drug are side effects, particularly extrapyrramidal symptoms (EPS. The neurotoxicity of haloperydol may be initiated by the cationic metabolites of haloperydol, HPP+, RHPP+, formed by oxidation and reduction pathways. These metabolites are transported by human organic cation transporters (hOCT to several brain structures for exapmle, in substantia nigra, striatum, caudate nucleus, hippocampus. After reaching the dopaminergic neurons inhibits mitochondrial complex I, evidence for free radical involvement, thus leading to neurodegeneration.

  3. Clinical protocols for {sup 31}P MRS of the brain and their use in evaluating optic pathway gliomas in children

    Energy Technology Data Exchange (ETDEWEB)

    Novak, Jan, E-mail: j.novak@bham.ac.uk [School of Cancer Sciences, University of Birmingham, Birmingham (United Kingdom); Birmingham Children' s Hospital, Birmingham (United Kingdom); Wilson, Martin, E-mail: martin@pipegrep.co.uk [School of Cancer Sciences, University of Birmingham, Birmingham (United Kingdom); Birmingham Children' s Hospital, Birmingham (United Kingdom); MacPherson, Lesley, E-mail: lesley.macpherson@bch.nhs.uk [Birmingham Children' s Hospital, Birmingham (United Kingdom); Arvanitis, Theodoros N., E-mail: t.arvanitis@bham.ac.uk [Birmingham Children' s Hospital, Birmingham (United Kingdom); School of Electronic, Electrical and Computer Engineering, University of Birmingham, Birmingham (United Kingdom); Davies, Nigel P., E-mail: nigel.davies@nhs.net [School of Cancer Sciences, University of Birmingham, Birmingham (United Kingdom); Birmingham Children' s Hospital, Birmingham (United Kingdom); University Hospitals Birmingham NHS Foundation Trust, Medical Physics RRPPS, Birmingham (United Kingdom); Peet, Andrew C., E-mail: a.peet@bham.ac.uk [School of Cancer Sciences, University of Birmingham, Birmingham (United Kingdom); Birmingham Children' s Hospital, Birmingham (United Kingdom)

    2014-02-15

    Introduction: In vivo {sup 31}P Magnetic Resonance Spectroscopy (MRS) measures phosphorus-containing metabolites that play an essential role in many disease processes. An advantage over {sup 1}H MRS is that total choline can be separated into phosphocholine and glycerophosphocholine which have opposite associations with tumour grade. We demonstrate {sup 31}P MRS can provide robust metabolic information on an acceptable timescale to yield information of clinical importance. Methods: All MRI examinations were carried out on a 3T whole body scanner with all {sup 31}P MRS scans conducted using a dual-tuned {sup 1}H/{sup 31}P head coil. Once optimised on phantoms, the protocol was tested in six healthy volunteers (four male and two female, mean age: 25 ± 2.7). {sup 31}P MRS was then implemented on three children with optic pathway gliomas. Results: {sup 31}P MRS on volunteers showed that a number of metabolite ratios varied significantly (p < 0.05 ANOVA) across different structures of the brain, whereas PC/GPC did not. Standard imaging showed the optic pathway gliomas were enhancing on T1-weighted imaging after contrast injection and have high tCho on {sup 1}H MRS, both of which are associated with high grade lesions. {sup 31}P MRS showed the phosphocholine/glycerophosphocholine ratio to be low (<0.6) which suggests low grade tumours in keeping with their clinical behaviour and the histology of most biopsied optic pathway gliomas. Conclusion: {sup 31}P MRS can be implemented in the brain as part of a clinical protocol to provide robust measurement of important metabolites, in particular providing a greater understanding of cases where tCho is raised on {sup 1}H MRS.

  4. Tumour risk associated with use of cellular telephones or cordless desktop telephones

    Directory of Open Access Journals (Sweden)

    Söderqvist Fredrik

    2006-10-01

    Full Text Available Abstract Background The use of cellular and cordless telephones has increased dramatically during the last decade. There is concern of health problems such as malignant diseases due to microwave exposure during the use of these devices. The brain is the main target organ. Methods Since the second part of the 1990's we have performed six case-control studies on this topic encompassing use of both cellular and cordless phones as well as other exposures. Three of the studies concerned brain tumours, one salivary gland tumours, one non-Hodgkin lymphoma (NHL and one testicular cancer. Exposure was assessed by self-administered questionnaires. Results Regarding acoustic neuroma analogue cellular phones yielded odds ratio (OR = 2.9, 95 % confidence interval (CI = 2.0–4.3, digital cellular phones OR = 1.5, 95 % CI = 1.1–2.1 and cordless phones OR = 1.5, 95 % CI = 1.04–2.0. The corresponding results were for astrocytoma grade III-IV OR = 1.7, 95 % CI = 1.3–2.3; OR = 1.5, 95 % CI = 1.2–1.9 and OR = 1.5, 95 % CI = 1.1–1.9, respectively. The ORs increased with latency period with highest estimates using > 10 years time period from first use of these phone types. Lower ORs were calculated for astrocytoma grade I-II. No association was found with salivary gland tumours, NHL or testicular cancer although an association with NHL of T-cell type could not be ruled out. Conclusion We found for all studied phone types an increased risk for brain tumours, mainly acoustic neuroma and malignant brain tumours. OR increased with latency period, especially for astrocytoma grade III-IV. No consistent pattern of an increased risk was found for salivary gland tumours, NHL, or testicular cancer.

  5. Hyperglycaemia and aberrated insulin signalling stimulate tumour progression via induction of the extracellular matrix component hyaluronan.

    Science.gov (United States)

    Twarock, Sören; Reichert, Christina; Peters, Ulrike; Gorski, Daniel J; Röck, Katharina; Fischer, Jens W

    2017-08-15

    Epidemiological studies have detected a higher incidence of various tumour entities in diabetic patients. However, the underlying mechanisms remain insufficiently understood. Glucose-derived pericellular and extracellular hyaluronan (HA) promotes tumour progression and development. In our study, we tested the hypothesis that a diabetic metabolic state, characterised by hyperglycaemia and concomitant aberrant insulin signalling, stimulates tumour progression via the induction of HA synthesis. In a streptozotocin-induced diabetic nude mouse tumour xenograft model, hyperglycaemia and lack of insulin caused an increased formation of tumour-associated HA-matrix, which in turn accelerated tumour progression and neoangiogenesis. This process was effectively attenuated by treatment with 4-methylumbelliferone, a pharmacological inhibitor of HA-synthesis. To define the mechanisms behind these in vivo observations, we investigated the impact of hyperglycaemia and insulin on the glucose metabolism in oesophageal squamous cell cancer cells (ESCC). Hyperglycaemia induced HA synthesis while insulin diminished HA production by directing glucose metabolites to glycolysis. Vice versa, inhibition of glycolysis, either by knockdown of the glycolytic key enzyme phosphofructokinase or by an experimental abrogation of insulin signalling (knockdown of the insulin receptor and long-term treatment with insulin) augmented HA synthesis. Consequently, these processes induced invasion, anchorage-independent growth and adhesion of ESCC to endothelial cells in vitro. Thus, the cellular shift in glucose usage from catabolism of glucose to anabolism of HA driven by hyperglycaemia and insulin resistance may represent an important link between diabetes and cancer progression. Hence, therapeutical inhibition of HA synthesis may represent a promising approach for tumour treatment in diabetic patients. © 2017 UICC.

  6. Metabolite Damage and Metabolite Damage Control in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  7. Fertility sparing treatment in borderline ovarian tumours

    Science.gov (United States)

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  8. An unusual presentation of a glomus tumour.

    LENUS (Irish Health Repository)

    Nugent, N

    2011-02-01

    Glomus tumours are benign, soft tissue tumours, usually of fingertips. Classically they present with severe pain, temperature sensitivity and localised tenderness. The diagnosis is often delayed due to sometimes non-specific symptoms and rarity of the disorder. While usually a clinical diagnosis, imaging may be necessary for diagnosis and localisation. We present a case of glomus tumour of the fingertip with an unusual history.

  9. Bilateral ovarian tumour in a young girl

    Directory of Open Access Journals (Sweden)

    Krishna Kumar Govindarajan

    2013-01-01

    Full Text Available Bilateral ovarian tumour in a girl presents the dilemma of conservative versus aggressive approach towards these tumours. When faced with suspicious tumour and complete replacement of the ovaries bilaterally, bilateral oophorectomy is a viable option, though the certain possibility of infertility and lifelong hormonal supplementation is unavoidable. We report a case of bilateral ovarian masses in a young girl, which on histopathological examination showed mature teratoma with aggregates of proliferating capillary and cavernous sized vessels in the tumour wall. Such associations are rare and must be differentiated from a vascular neoplasm.

  10. Tumour-targeted nanomedicines: principles and practice

    National Research Council Canada - National Science Library

    Lammers, T.G.G.M; Hennink, W.E; Storm, G

    2008-01-01

    .... Various different tumour-targeted nanomedicines have been evaluated over the years, and clear evidence is currently available for substantial improvement of the therapeutic index of anticancer agents...

  11. Elevated tumour marker: an indication for imaging?

    LENUS (Irish Health Repository)

    McMahon, Colm J

    2012-02-01

    INTRODUCTION: The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication. MATERIALS AND METHODS: Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and\\/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of \\'elevated tumour marker\\' in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated. RESULTS: Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41-91] y), were imaged to evaluate: \\'elevated tumour marker\\'. They underwent 29 imaging studies (mean [+\\/-standard deviation (SD)] per patient = 1.2 [+\\/-0.4]), and had 42 elevated tumour marker serology tests (mean [+\\/-SD] per patient = 1.7 [+\\/-0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker. CONCLUSION: The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of \\'elevated tumour marker\\'. \\'Elevated tumour marker\\

  12. Focused ultrasound for treatment of bone tumours.

    Science.gov (United States)

    Rodrigues, Dario B; Stauffer, Paul R; Vrba, David; Hurwitz, Mark D

    2015-05-01

    Focused ultrasound (FUS) is a modality with rapidly expanding applications across the field of medicine. Treatment of bone lesions with FUS including both benign and malignant tumours has been an active area of investigation. Recently, as a result of a successful phase III trial, magnetic resonance-guided FUS is now a standardised option for treatment of painful bone metastases. This report reviews the clinical applications amenable to treatment with FUS and provides background on FUS and image guidance techniques, results of clinical studies, and future directions. A comprehensive literature search and review of abstracts presented at the recently completed fourth International Focused Ultrasound Symposium was performed. Case reports and older publications revisited in more recent studies were excluded. For clinical studies that extend beyond bone tumours, only the data regarding bone tumours are presented. Fifteen studies assessing the use of focused ultrasound in treatment of primary benign bone tumours, primary malignant tumours, and metastatic tumours meeting the search criteria were identified. For these clinical studies the responders group varied within 91-100%, 85-87% and 64-94%, respectively. Major complications were reported in the ranges 0%, 0-28% and 0-4% for primary benign, malignant and metastatic tumours, respectively. Image-guided FUS is both safe and effective in the treatment of primary and secondary tumours. Additional phase III trials are warranted to more fully define the role of FUS in treatment of both benign and malignant bone tumours.

  13. N-nitroso compounds and human intracranial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Preston-Martin, S.; Henderson, B.E.

    1984-01-01

    Experimentalists have shown that various N-nitroso compounds are potent nervous system carcinogens, particularly when animals are exposed transplacentally. Information has been obtained concerning exposure to N-nitroso compounds and their precursors in three case-control studies of intracranial tumour patients in Los Angeles County, California. A study of women (185 pairs) found that level of consumption of nitrite-cured meats was related to meningioma development (p = 0.01). In a similar study of meningiomas in men (105 pairs), the association with cured meats was not clear. The most striking results were obtained in a study of young brain tumour patients (209 matched pairs). Increased risk was associated with maternal contact, during pregnancy, with N-nitrosamine-containing substances, such as burning incense, sidestream cigarette smoke and face make-up. Increased risk was also associated with maternal use of diuretics and antihistamines and with the level of maternal consumption of cured meats. Additional epidemiological studies of nervous system tumours in young people would appear to offer considerable promise for testing the hypothesis that N-nitroso compounds are etiologically related to human neurogenic neoplasms.

  14. Case Report - Bilateral synchronous testicular germ cell tumours in ...

    African Journals Online (AJOL)

    Bilateral testicular tumours are rare, and 80% of bilateral tumours are metachronous. The incidence of testicular tumours is high in cryptorchidism. Synchronous bilateral testicular tumours are rare, and bilateral synchronous testicular tumours in bilateral cryptorchidism extremely rare, probably not reported previously.

  15. Granular cell tumour of the neurohypophysis: a rare sellar tumour with specific radiological and operative features.

    LENUS (Irish Health Repository)

    Aquilina, K

    2012-02-03

    Symptomatic granular cell tumours of the neurohypophysis are rare sellar lesions. Preoperative prediction of the diagnosis on the basis of radiological appearance is useful as these tumours carry specific surgical difficulties. This is possible when the tumour arises from the pituitary stalk, rostral to a normal pituitary gland. This has not been emphasized previously.

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

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 35; Issue 2 ... Human tumour xenografts; radiation; rats; tumour bed ... Dosimetry and the corresponding methodology for radiotherapy of human non-small cell lung cancer xenograft tumours transplanted to and growing subcutaneously on the right lower limb in a nude rat ...

  17. Tumour-to-tumour metastases: prostate carcinoma metastasising to a renal oncocytoma.

    Science.gov (United States)

    Petts, Gemma; Rashid, Tina; Hrouda, David; Ngo, Nye-Thane

    2013-01-09

    This is a case report of prostate carcinoma metastasising to a renal oncocytoma. The report demonstrates the unusual presentation of metastases from a common cancer to a common benign tumour, and reviews the rare phenomenon of tumour-to-tumour metastases.

  18. Diagnostic utility of Wilms′ tumour-1 protein (WT-1 immunostaining in paediatric renal tumours

    Directory of Open Access Journals (Sweden)

    Surbhi Goyal

    2016-01-01

    Interpretation & conclusions: WT1 helps to differentiate Wilms′ tumour from other paediatric renal tumours. It may help in differentiating the two subgroups of Wilms′ tumour which have distinct molecular pathogenesis and biological behaviour, however, further prospective studies are required for validation of this hypothesis.

  19. Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment.

    Science.gov (United States)

    Yamagishi, Kazue; Onuma, Kazuo; Chiba, Yota; Yagi, Shinya; Aoki, Shigenobu; Sato, Tomoyuki; Sugawara, Yasushi; Hosoya, Noriyasu; Saeki, Yasutake; Takahashi, Minoru; Fuji, Masayoshi; Ohsaka, Takeo; Okajima, Takeyoshi; Akita, Kenji; Suzuki, Takashi; Senawongse, Pisol; Urushiyama, Akio; Kawai, Kiyoshi; Shoun, Hirofumi; Ishii, Yoshimasa; Ishikawa, Hiroya; Sugiyama, Shigeru; Nakajima, Madoka; Tsuboi, Masaru; Yamanaka, Tateo

    2012-04-01

    The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests

  20. Primary intracranial germ cell tumours: experience of a single South-East Asian institution.

    Science.gov (United States)

    Foo, Aaron S C; Lim, Cindy; Chong, Dawn Q Q; Tan, Daniel Y H; Tham, Chee Kian

    2014-10-01

    Primary intracranial germ cell tumours (ICGCT) are a rare group of brain tumours arising predominantly in the paediatric and pre-adult population, accounting for up to 9.5% of paediatric brain tumours in East Asia. The National Cancer Centre Singapore (NCCS) is a tertiary referral centre for patients from all over South-East Asia. Our study aims to describe the characteristics of ICGCT patients in South-East Asia. Data on all patients with ICGCT who were seen at the Therapeutic Radiology Department of NCCS from 2000 to 2013 were collected retrospectively. Patient demographics, disease characteristics and treatment outcomes were analysed. Characteristics and survival of our patients were similar to other centres. Pure germinomas demonstrated 5 year overall survival (OS) and disease-free survival (DFS) rates of 89.2% (95% confidence interval [CI] 60.2-97.5) and 85.2% (95%CI 60.8-95.0) respectively. Secreting germinomas, non-germinomatous germ cell tumours and mixed germ cell tumours were evaluated together and demonstrated 5 year OS of 70.6% (95%CI 41.0-87.3) and DFS of 61.4% (95%CI 31.9-81.3). Patients ⩽ 12 years had marginally better 5 year OS than their older counterparts (81.0% [95%CI 49.5-93.9] versus 77.9% [95%CI 47.3-92.0], respectively). Patients who underwent extended field radiotherapy had longer OS and DFS than those who received local field irradiation. Treatment outcomes of our ICGCT patients are comparable with those in other Asian and Western centres. Extended field radiotherapy is a pivotal component of ICGCT treatment. Adding chemotherapy confers no extra survival benefit in treating germinomas. Treatment of mixed germ cell tumours and non-germinomatous germ cell tumours involves a multidisciplinary approach that varies for each histological subtype. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. 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

  2. Steroid hormones affect binding of the sigma ligand {sup 11}C-SA4503 in tumour cells and tumour-bearing rats

    Energy Technology Data Exchange (ETDEWEB)

    Rybczynska, Anna A.; Elsinga, Philip H.; Sijbesma, Jurgen W.; Jong, Johan R. de; Vries, Erik F. de; Dierckx, Rudi A.; Waarde, Aren van [University of Groningen, Nuclear Medicine and Molecular Imaging, University of Groningen Medical Center, Groningen (Netherlands); Ishiwata, Kiichi [Tokyo Metropolitan Institute of Gerontology, Positron Medical Center, Tokyo (Japan)

    2009-07-15

    Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist {sup 11}C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels. {sup 11}C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone. Binding of {sup 11}C-SA4503 to C6 cells was increased ({proportional_to}50%) upon removal and decreased ({proportional_to}60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC{sub 50} progesterone 33 nM). Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of {sup 11}C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected. The binding of {sup 11}C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids. (orig.)

  3. Urinary glucocorticoid metabolites: biomarkers to classify adrenal incidentalomas?

    Science.gov (United States)

    Brossaud, Julie; Ducint, Dominique; Corcuff, Jean-Benoît

    2015-01-08

    Total urinary cortisol metabolites represent cortisol production and metabolism. We hypothesized that to assay metabolites could add some information to the one provided by a sole cortisol assay. We set up an inexpensive multiplex mass spectrometry assay to quantify cortisol metabolites. We investigated 43 patients with benign secreting (AT+) or silent (AT-) adrenal tumours compared to 48 lean (Nl) or 143 obese (Ob) subjects, and to 26 patients with a Cushing's disease (CD). The initial investigation included immunoreactive quantification of urinary free cortisol (UFC). Cortisol metabolites were overexcreted in CD but not in Ob subjects. Nl and Ob were thus pooled in a control population (Ctl). Cortisol, tetrahydrocortisol (THF) and tetrahydrocortisone (THE) excretions were significantly increased in AT compared to Ctl subjects, whereas immunoreactive UFC was similar. A logistic regression retaining cortisol, THF, and α- and β-cortolone as significant analytes allowed the construction of a receiver-operating characteristics (ROC) curve significantly better than the curve generated by cortisol alone (area under the curve (AUC) 0·927 vs 0·729, respectively; P < 0·0001). More importantly, although there was no significant difference between Ctl vs AT- subjects for cortisol metabolites, a logistic regression retaining cortisol, allo-THF, and α- and β-cortolone as significant analytes generated a ROC curve performing significantly better than cortisol alone (AUC 0·910 vs 0·635, respectively; P < 0·0001). Cortisol metabolite excretion is modified in AT, including AT-, patients even without modification of UFC. Clinical usefulness of these biomarkers has to be investigated in prospective studies following up patients with AT. © 2015 John Wiley & Sons Ltd.

  4. Molecular differential pathology of renal cell tumours.

    Science.gov (United States)

    Kovacs, G

    1993-01-01

    Recent application of molecular cytogenetic techniques to the evaluation of renal cell tumours revealed four subtypes, each with a characteristic combination of genetic alterations within the chromosomal and mitochondrial DNA. The most common, nonpapillary renal cell carcinomas are characterized by the loss of chromosome 3p sequences, rearrangement of the chromosome 5q region and loss of the chromosome 14q sequences. Papillary renal cell tumours can be divided into two groups. Tumours with a combined trisomy of chromosomes 7 and 17 as well as loss of the Y chromosome are papillary renal cell adenomas. Tumours with additional trisomies such as trisomy 16, 20 or 12 are papillary renal cell carcinomas. Chromophobe renal cell carcinomas show a combination of allelic losses, which do not occur in other types of renal tumours. In addition, they have a rearrangement in the mitochondrial DNA. Renal oncocytomas are benign tumours marked by normal or abnormal karyotypes with balanced or unbalanced translocations and an altered restriction pattern of the mitochondrial DNA. Although the major cytological characteristics of renal cell tumours, such as clear, granular, chromophobe and oncocytic cell phenotypes correspond to nonpapillary, papillary and chromophobe renal cell carcinomas and renal oncocytomas, there are many cases with overlapping phenotype. Therefore, a classification of renal cell tumours based on specific genetic alterations is proposed.

  5. Positron emission tomography (PET) in endocrine tumours ...

    African Journals Online (AJOL)

    endocrine pancreatic tumours is probably limited to those that are less well differentiated and metabolically active. However, a future role for PET imaging in the detection of endocrine tumours, using more specific substrates, appears very promising. Journal of Endocrinology, Metabolism and Diabetes of South Africa Vol.

  6. Tumour cell expansion in bladder epithelium

    NARCIS (Netherlands)

    J.M.J. Rebel (Annemarie)

    1995-01-01

    textabstractBladder cancer is common in western society. The major problem of patients with superficial bladder cancer is the high recurrence rate and multifocality of these tumours. In 70 % of the patients superficial bladder cancer recurs after local resection of the tumour within 15 years. The

  7. Childhood ovarian juvenile granulosa cell tumour

    African Journals Online (AJOL)

    Prof Ezechukwu

    2012-05-12

    May 12, 2012 ... exclusively localized in granulosa cell tumours. 6. Juvenile granulosa cell tumour a subtype of ovarian stro- ... organs such as endometrial hyperplasia, endometrial adenocarcinomas and increased risk of ... stem cell transplantation.5 Newer agents that block an- giogenesis are being studied; two are being ...

  8. Production of Metabolites

    DEFF Research Database (Denmark)

    2011-01-01

    A recombinant micro-organism such as Saccharomyces cerevisiae which produces and excretes into culture medium a stilbenoid metabolite product when grown under stilbenoid production conditions, which expresses in above native levels a ABC transporter which transports said stilbenoid out of said...... micro-organism cells to the culture medium. The genome of the Saccharomyces cerevisiae produces an auxotrophic phenotype which is compensated by a plasmid which also expresses one or more of said enzymes constituting said metabolic pathway producing said stilbenoid, an expression product of the plasmid...

  9. Cooperative tumour cell membrane targeted phototherapy

    Science.gov (United States)

    Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

    2017-06-01

    The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

  10. Training for planning tumour resection: augmented reality and human factors.

    Science.gov (United States)

    Abhari, Kamyar; Baxter, John S H; Chen, Elvis C S; Khan, Ali R; Peters, Terry M; de Ribaupierre, Sandrine; Eagleson, Roy

    2015-06-01

    Planning surgical interventions is a complex task, demanding a high degree of perceptual, cognitive, and sensorimotor skills to reduce intra- and post-operative complications. This process requires spatial reasoning to coordinate between the preoperatively acquired medical images and patient reference frames. In the case of neurosurgical interventions, traditional approaches to planning tend to focus on providing a means for visualizing medical images, but rarely support transformation between different spatial reference frames. Thus, surgeons often rely on their previous experience and intuition as their sole guide is to perform mental transformation. In case of junior residents, this may lead to longer operation times or increased chance of error under additional cognitive demands. In this paper, we introduce a mixed augmented-/virtual-reality system to facilitate training for planning a common neurosurgical procedure, brain tumour resection. The proposed system is designed and evaluated with human factors explicitly in mind, alleviating the difficulty of mental transformation. Our results indicate that, compared to conventional planning environments, the proposed system greatly improves the nonclinicians' performance, independent of the sensorimotor tasks performed ( ). Furthermore, the use of the proposed system by clinicians resulted in a significant reduction in time to perform clinically relevant tasks ( ). These results demonstrate the role of mixed-reality systems in assisting residents to develop necessary spatial reasoning skills needed for planning brain tumour resection, improving patient outcomes.

  11. Anti-tumour compounds illudin S and Irofulven induce DNA lesions ignored by global repair and exclusively processed by transcription- and replication-coupled repair pathways.

    NARCIS (Netherlands)

    A. Raams (Anja); M.J. Kelner (Michael); J.M.Y. Ng (Jessica); Y.M. Yamashita (Yukiko); S. Takeda (Shiunichi); T.C. McMorris (Trevor); J.H.J. Hoeijmakers (Jan); N.G.J. Jaspers (Nicolaas)

    2002-01-01

    textabstractIlludin S is a natural sesquiterpene drug with strong anti-tumour activity. Inside cells, unstable active metabolites of illudin cause the formation of as yet poorly characterised DNA lesions. In order to identify factors involved in their repair, we have performed a detailed genetic

  12. Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia

    National Research Council Canada - National Science Library

    Dewhirst, M W; Ong, E T; Braun, R D; Smith, B; Klitzman, B; Evans, S M; Wilson, D

    1999-01-01

    We previously reported that the arteriolar input in window chamber tumours is limited in number and is constrained to enter the tumour from one surface, and that the pO2 of tumour arterioles is lower...

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

    Energy Technology Data Exchange (ETDEWEB)

    Satoh, H. [Hiroshima University, School of Medicine (Japan). Dept. of Neurosurgery; Uozumi, T. [Hiroshima University, School of Medicine (Japan). Dept. of Neurosurgery; Kiya, K. [Dept. of Neurosurgery, Hiroshima Prefectural Hospital, Hiroshima (Japan); Kurisu, K. [Hiroshima University, School of Medicine (Japan). Dept. of Neurosurgery; Arita, K. [Hiroshima University, School of Medicine (Japan). Dept. of Neurosurgery; Sumida, M. [Hiroshima University, School of Medicine (Japan). Dept. of Neurosurgery; Ikawa, F. [Dept. of Neurosurgery, Hiroshima Prefectural Hospital, Hiroshima (Japan)

    1995-11-01

    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.

  14. Metabolites of Siamenoside I and Their Distributions in Rats

    Directory of Open Access Journals (Sweden)

    Xue-Rong Yang

    2016-01-01

    Full Text Available Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic pathways, a high-performance liquid chromatography-electrospray ionization-ion trap-time of flight-multistage mass spectrometry (HPLC-ESI-IT-TOF-MSn method was used to profile and identify its metabolites in rats. Altogether, 86 new metabolites were identified or tentatively identified, and 23 of them were also new metabolites of mogrosides. In rats, siamenoside I was found to undergo deglycosylation, hydroxylation, dehydrogenation, deoxygenation, isomerization, and glycosylation reactions. Among them, deoxygenation, pentahydroxylation, and didehydrogenation were novel metabolic reactions of mogrosides. The distributions of siamenoside I and its 86 metabolites in rat organs were firstly reported, and they were mainly distributed to intestine, stomach, kidney, and brain. The most widely distributed metabolite was mogroside IIIE. In addition, eight metabolites were bioactive according to literature. These findings would help to understand the metabolism and effective forms of siamenoside I and other mogrosides in vivo.

  15. Mechanisms of tumour escape from immune surveillance

    Directory of Open Access Journals (Sweden)

    Lisiecka Urszula

    2016-12-01

    Full Text Available The progressive growth and spread of tumour cells in the form of metastases requires an interaction of healthy host cells, such as endothelial cells, fibroblasts, and other cells of mesenchymal origin with immune cells taking part in innate and adaptive responses within the tumour lesion and entire body. The host cells interact with tumour cells to create a dynamic tumour microenvironment, in which healthy cells can both positively and negatively influence the growth and spread of the tumour. The balance of cellular homeostasis and the effect of substances they secrete on the tumour microenvironment determine whether the tumour has a tendency to grow or disappear, and whether the cells remain within the lesion or are capable of metastasis to other regions of the body. Intercellular interactions also determine the tumour’s susceptibility to radiation or other types of cancer treatment. They may also be a rational explanation for differences in treatment outcomes, in which some metastases regress and others progress in response to the same treatment method.

  16. MRI appearances of borderline ovarian tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bent, C.L. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)], E-mail: clare.bent@bartsandthelondon.nhs.uk; Sahdev, A.; Rockall, A.G. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Singh, N. [Department of Pathology, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Sohaib, S.A. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom); Reznek, R.H. [Cancer Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)

    2009-04-15

    This review was performed to describe the range of magnetic resonance imaging (MRI) appearances of borderline ovarian tumours. The MRI findings in 26 patients with 31 borderline ovarian tumours (mean age: 40.1 years, range: 14-85 years) were retrospectively reviewed. For each tumour, site, size, MRI characteristics, and enhancement following gadolinium administration were recorded. There were 20 serous and 11 mucinous borderline ovarian subtypes. Nine of 26 patients demonstrated bilateral disease on MRI; synchronous contralateral ovarian disease included three benign, five serous borderline, and one serous invasive tumour. A history of a metachronous mucinous borderline tumour was identified in one patient. MRI appearances were classified into four morphological categories: group 1 (6/31, 19%), unilocular cysts; group 2 (6/31, 19%), minimally septate cysts with papillary projections; group 3 (14/31, 45%), markedly septate lesions with plaque-like excrescences; and group 4 (5/31, 16%), predominantly solid with exophytic papillary projections, all of serous subtype. There was a significant difference in mean volume between serous (841.5 cm{sup 3}) and mucinous (6358.2 cm{sup 3}) subtypes (p = 0.009). All tumours demonstrated at least one MRI feature suggestive of malignancy. The present review demonstrates the variable MRI appearances of borderline ovarian tumours along with imaging features suggestive of tumour subtype. In patients in whom the clinical features are suggestive of a borderline ovarian tumour (young age and normal or minimally elevated CA125), the ability to predict a borderline disease using morphological features observed on MRI would be extremely helpful in surgical planning, with the potential to offer fertility or ovary-preserving surgery. Future studies are required to further this aim.

  17. Nitric oxide metabolites in goldfish under normoxic and hypoxic conditions

    DEFF Research Database (Denmark)

    Hansen, Marie N.; Jensen, Frank Bo

    2010-01-01

    levels was assessed from metabolic and respiratory variables. In normoxic goldfish, the concentrations of NO metabolites in plasma and tissues were comparable with values reported in mammals, indicative of similar NOS activity. Exposure to hypoxia [at PO2 (partial pressure of O2) values close......) in multiple tissues of a non-mammalian vertebrate (goldfish) under normoxic and hypoxic conditions. NO metabolites were measured in blood (plasma and red cells) and heart, brain, gill, liver, kidney and skeletal muscle, using highly sensitive reductive chemiluminescence. The severity of the chosen hypoxia...

  18. Intraoperative β{sup -} detecting probe for radio-guided surgery in tumour resection

    Energy Technology Data Exchange (ETDEWEB)

    Solfaroli Camillocci, Elena; Bellini, Fabio; Bocciy, Valerio; Collamatiyz, Francesco; Faccini, Riccardo; Paramattiy, Riccardo; Paterayz, Vincenzo; Pinciy, Davide; Recchiay, Luigi; Sciubbayz, Adalberto; Senzacqua, Martina; Voenay, Cecilia; Morgantiy, Silvio [INFN Sezione di Roma, Rome, (Italy); De Luciax, Erika; Matteixk, Ilaria; Sartizx, Alessio [Laboratori Nazionali di Frascati dell INFN, Frascati, (Italy); Russomando, Aandrea [INFN Sezione di Roma, Rome, (Italy); Center for Life Nano Science-at-Sapienza, Istituto Italiano di Tecnologia, Rome, (Italy); Marafiniy, Michela [INFN Sezione di Roma, Rome, (Italy); Museo Storico della Fisica e Centro Studi e Ricerche ' E. Fermi' , Rome, (Italy)

    2015-07-01

    The development of the β{sup -} based radio-guided surgery aims to extend the technique to those tumours where surgery is the only possible treatment and the assessment of the resection would most profit from the low background around the lesion, as for brain tumours. Feasibility studies on meningioma and gliomas already estimated the potentiality of this new treatment. To validate the technique, a prototype of the intraoperative probe detecting β{sup -} decays and specific phantoms simulating tumour remnant patterns embedded in healthy tissue have been realized. The response of the probe in this simulated environment is tested with dedicated procedures. This document discusses the innovative aspects of the method, the status of the developed intraoperative β{sup -} detecting probe and the results of the preclinical tests. (authors)

  19. Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model

    Directory of Open Access Journals (Sweden)

    Carole eGrasso

    2014-12-01

    Full Text Available Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumour environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionising radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumour, glioblastoma multiforme (GBM, is very resistant to radiation; radiosensitising GBM cells will improve survival of GBM patients. Here we demonstrate that a single fraction (6 Gy of radiation combined with a one hour exposure to ascorbate (5 mM sensitised murine glioma GL261cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy of whole brain radiation combined with daily intra-peritoneal injections of ascorbate (1 mg/kg in an intra-cranial GL261 glioma mouse model. Tumour-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain eight days after tumour implantation, a second group received daily intra-peritoneal injections of ascorbate (day 8-45 after implantation, a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumour progression, intra-peritoneal ascorbate alone had no effect on tumour progression. Tumour progression was faster in tumour-bearing mice treated with radiation and daily ascorbate than those treated with radiation alone. Histological analysis showed less necrosis in tumours treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumour micro-environment which determines whether ascorbate remains outside the cell, acting as a pro-oxidant or whether it enters the cells and acts as an anti-oxidant.

  20. Carcinoid tumour of the middle ear

    LENUS (Irish Health Repository)

    Baig, Salman

    2012-09-01

    A case of middle ear mass in a young female from Ireland is described, who presented with left ear hearing loss and intermittent bloody discharge from the same ear. Examination under microscope revealed occlusive polyp in the left ear and a biopsy had been taken under general anaesthesia. Histopathology report described an adenoma \\/ carcinoid tumour of the middle ear confirmed by positive immunohistochemical staining. CT temporal bones revealed the extension of the disease. The patient underwent left tympanotomy and excision of the tumour. In general, these tumours are regarded as benign but may be mistaken for adenocarcinomas because of their histological heterogenecity.

  1. Radiopharmaceuticals as probes to characterize tumour tissue

    Energy Technology Data Exchange (ETDEWEB)

    Alam, Israt S.; Arshad, Mubarik A.; Nguyen, Quang-De; Aboagye, Eric O. [Imperial College London, Comprehensive Cancer Imaging Centre, London (United Kingdom)

    2015-04-01

    Tumour cells exhibit several properties that allow them to grow and divide. A number of these properties are detectable by nuclear imaging methods. We discuss crucial tumour properties that can be described by current radioprobe technologies, further discuss areas of emerging radioprobe development, and finally articulate need areas that our field should aspire to develop. The review focuses largely on positron emission tomography and draws upon the seminal 'Hallmarks of Cancer' review article by Hanahan and Weinberg in 2011 placing into context the present and future roles of radiotracer imaging in characterizing tumours. (orig.)

  2. Gestational trophoblastic tumours: an update for 2014.

    Science.gov (United States)

    Froeling, Fieke E M; Seckl, Michael J

    2014-11-01

    Gestational trophoblastic disease describes a variety of pregnancy-related diseases including the premalignant conditions of a partial and complete hydatidiform mole and the malignant disorders of invasive mole, choriocarcinoma and the rare placental-site trophoblastic tumour and epithelioid trophoblastic tumour. The availability of a highly sensitive tumour marker in the form of human chorionic gonadotrophin, the chemosensitive character of the disease with effective treatment strategies and centralization of care of a rare group of diseases has resulted in excellent survival rates, which can exceed 98 %. This review gives a general overview of gestational trophoblastic disease, the most recent insights in aetiology and pathology and a summary of the different management strategies.

  3. Epithelial tumours of the lacrimal gland

    DEFF Research Database (Denmark)

    von Holstein, Sarah Linéa; Coupland, Sarah E; Briscoe, Daniel

    2013-01-01

    of the lacrimal gland, displacement of the eyeball, reduced eye motility and diplopia. Pain and symptoms of short duration before the first ophthalmic consultation are characteristic of malignant tumours. The histological diagnosis determines the subsequent treatment regimen and provides important clues regarding...... the prognosis. The purpose of this paper is to describe the various primary epithelial tumours of the lacrimal gland. In the first part of the review, the frequency, demographics, clinical presentation and diagnostic features are described. In the second part, primarily tumour-specific histological...

  4. Tumour size, tumour complexity, and surgical approach are associated with nephrectomy type in small renal cortical tumours treated electively.

    Science.gov (United States)

    Broughton, Gregory J; Clark, Peter E; Barocas, Daniel A; Cookson, Michael S; Smith, Joseph A; Herrell, S Duke; Chang, Sam S

    2012-06-01

    Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Although the benefits of nephron-sparing renal cortical tumour treatments are now widely accepted and have robust data supporting their oncological efficacy, safety, and positive effect on medium- and long-term renal function, the decision to perform partial nephrectomy (PN) remains a complex interaction between several competing factors. Various patient factors, e.g. comorbid conditions, age, body habitus, patient preference, etc. may effect this decision. Then there are the preferences of the surgeon him- or herself, including faculty with different operative techniques and surgical approaches, which may lead to one treatment decision over another. Finally, the anatomy of the tumour itself, i.e. the complexity of the tumour within the kidney and anatomical relationships within the organ, is intuitively critical to a surgeon's assessment of resectability. There is very little published data indicating which of the multitude of clinical variables have the greatest impact on the decision to perform PN. Most previous investigations into the subject have focused on either imperative or relative indications for PN (i.e. solitary kidney, bilateral renal masses, and multifocal tumours) or have used maximal tumour diameter (i.e. tumour size) alone in their assessment of the clinical variables associated with PN use. To identify preoperative variables associated with choice of partial nephrectomy (PN) vs radical nephrectomy (RN). Between January 2004 and June 2008, 203 patients were treated for clinical T1a renal cortical tumours. Of these, 154 (75.8%) had all data available and form the analytic cohort. Patients were categorized into two groups, PN and RN, based on preoperative treatment plan. Patient-, procedure-, and tumour-related variables, together with tumour complexity (based on the R.E.N.A.L Nephrometry Score [RENAL-NS]) were evaluated for their

  5. Antistaphylococcal metabolite from Aureobasidium pullulans ...

    African Journals Online (AJOL)

    Aureobasidium pullulans (NI.3) isolated from the leaves of Dracaena reflexa variegate produced intracellular antimicrobial metabolite the yield of which was 700-800 U from about 0.7-0.85 g of dry biomass. The antistaphyloccocal metabolite showed strong activity against different Staphylococcus spp. The MICs ranged from ...

  6. Liquid chromatography/tandem mass spectrometry determination of (4S,2RS)-2,5,5-trimethylthiazolidine-4-carboxylic acid, a stable adduct formed between D-(-)-penicillamine and acetaldehyde (main biological metabolite of ethanol), in plasma, liver and brain rat tissues.

    Science.gov (United States)

    Serrano, Elena; Pozo, Oscar J; Beltrán, Joaquin; Hernández, Felix; Font, Laura; Miquel, Marta; Aragon, Carlos M G

    2007-01-01

    Acetaldehyde, the main biological metabolite of ethanol, is nowadays considered to mediate some ethanol-induced effects. Previous studies on alcohol effect attenuation have shown that D-(-)-penicillamine (3-mercapto-D-valine), a thiol amino acid, acts as an effective agent for the inactivation of acetaldehyde. In the study reported here, laboratory rats were treated with ethanol and D-(-)-penicillamine at different doses looking for the interaction (in vivo) of D-(-)-penicillamine with metabolically formed acetaldehyde following a condensation reaction to form the stable adduct (4S,2RS)-2,5,5-trimethylthiazolidine-4-carboxylic acid (TMTCA). A novel and rapid procedure based on liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) was developed for quantification and reliable identification of TMTCA in different rat tissues, including plasma, liver and brain. Firstly, plasma was obtained from whole blood. Then, proteins were precipitated from plasma, brain and liver extracts with acetonitrile and the clarified extracts diluted 10-fold. A 20 microL aliquot of the final extracts was then analyzed using an Atlantis C18 5 microm, 100x2 mm column which was connected to the electrospray source of a LC/triple quadrupole mass spectrometer. The analyte was detected in positive ion mode acquiring four MS/MS transitions in selected reaction monitoring (SRM) mode. The method has been validated and it has proved to be fast, reliable and sensitive. The accuracy and precision were evaluated by means of recovery experiments from plasma, liver and brain samples fortified at two concentration levels obtaining satisfactory recoveries in all cases: 95 and 105% in plasma (at 10 and 100 ng/mL, respectively), 79 and 89% in brain (100 and 1000 ng/g), 85 and 99% in liver (100 and 1000 ng/g). Precision, expressed as repeatability, was in all tissues analyzed lower than 17% at the two concentrations tested. The estimated detection limits were 1 ng/mL in plasma, 4 ng/g in brain

  7. [Liposomal cytarabine for the treatment of leptomeningeal dissemination of central nervous system tumours in children and adolescents].

    Science.gov (United States)

    Moreno, Lucas; García Ariza, Miguel Angel; Cruz, Ofelia; Calvo, Carlota; Fuster, Jose Luis; Salinas, Jose Antonio; Moscardo, Cristina; Portugal, Raquel; Merino, Jose Manuel; Madero, Luis

    2016-11-01

    Leptomeningeal dissemination in paediatric central nervous system (CNS) tumours is associated with a poor outcome, and new therapeutic strategies are desperately needed. One of the main difficulties in the treatment of CNS tumours is blood brain barrier penetration. Intrathecal therapy has shown to be effective in several paediatric tumours. The aim of this article is to review the data available on the use of liposomal cytarabine for paediatric patients with leptomeningeal dissemination of CNS tumours, including the pharmacology, administration route, safety and efficacy data. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Decreased FOXJ1 expression and its ciliogenesis programme in aggressive ependymoma and choroid plexus tumours.

    Science.gov (United States)

    Abedalthagafi, Malak S; Wu, Michael P; Merrill, Parker H; Du, Ziming; Woo, Terri; Sheu, Shu-Hsien; Hurwitz, Shelley; Ligon, Keith L; Santagata, Sandro

    2016-03-01

    Well-differentiated human cancers share transcriptional programmes with the normal tissue counterparts from which they arise. These programmes broadly influence cell behaviour and function and are integral modulators of malignancy. Here, we show that the master regulator of motile ciliogenesis, FOXJ1, is highly expressed in cells along the ventricular surface of the human brain. Strong expression is present in cells of the ependyma and the choroid plexus as well as in a subset of cells residing in the subventricular zone. Expression of FOXJ1 and its transcriptional programme is maintained in many well-differentiated human tumours that arise along the ventricle, including low-grade ependymal tumours and choroid plexus papillomas. Anaplastic ependymomas as well as choroid plexus carcinomas show decreased FOXJ1 expression and its associated ciliogenesis programme genes. In ependymomas and choroid plexus tumours, reduced expression of FOXJ1 and its ciliogenesis programme are markers of poor outcome and are therefore useful biomarkers for assessing these tumours. Transitions in ciliogenesis define distinct differentiation states in ependymal and choroid plexus tumours with important implications for patient care. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. Malignant Renal Tumours in Adults in Nnamdi Azikiwe University ...

    African Journals Online (AJOL)

    BACKGROUND: Malignant renal tumour is the third commonest urological tumour after prostate and bladder cancer. It is however the urological tumour with the highest mortality/ incidence ratio. OBJECTIVE: To review the frequency, mode of presentation and histological pattern of patients with malignant renal tumours in ...

  10. Histo-pathological features of primary ovarian Tumours managed in ...

    African Journals Online (AJOL)

    Background: Ovarian tumours are the 2nd most common female genital tract tumour in Sokoto, northwestern, Nigeria. We determined the histo-pathological features of surgically removed ... (12.5%), malignant teratoma 2(5%) and endodermal sinus tumour (5%). There were 2 cases of metastatic tumours: one from Burkitts ...

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

    African Journals Online (AJOL)

    ... and immunohistochemical studies should help in making diagnosis. Surgical intervention with wide margin excision should reduce recurrence rate. Further characterization of these tumours is desirable in our setting. Keywords: Skin Appendage, Malignant, Eccrine Sweat gland. Sudanese Journal of Dermatology Vol.

  12. Clinicopathologic Profile Of Sweat Gland Tumours

    Directory of Open Access Journals (Sweden)

    Mohan Harsh

    2002-01-01

    Full Text Available Benign adnexal tumours of the skin, excluding pilosebaceous tumours were identified in 24 patients between the ages of 9 and 70 years with a mean age of 34 years; 17 women and 7 men. Most lesions (n = 13 occurred on the face and scalp. Apocrine hydrocystoma and eccrine acrospiroma were the commonest tumors with apocrine and eccrine differentiation respectively. Few uncommon tumors with included were chondroid syringoma, syringocystadenoma papilliferum. Excisional biopsy is the treatment of choice.

  13. Antenatally detected solid tumour of kidney

    Science.gov (United States)

    Panda, Shasanka Shekhar; Mandelia, Ankur; Gupta, Devendra Kumar; Singh, Amit

    2014-01-01

    Congenital renal tumours are rare and usually benign. Polyhydramnios is the most common mode of presentation. Although most cases have been diagnosed postnatally, with advances in imaging technology, an increasing number of cases are being detected on antenatal scans. We describe a case of solid tumour of kidney detected in the second trimester of pregnancy and managed by surgery in the postnatal period. PMID:24526198

  14. Brain-only metastases of small cell lung cancer; efficacy of whole brain radiotherapy. An EORTC phase II study

    NARCIS (Netherlands)

    Postmus, PE; Haaxma-Reiche, H; Gregor, A; Groen, HJM; Lewinski, T; Scolard, T; Kirkpatrick, A; Curran, D; Sahmoud, T; Giaccone, G

    Background and purpose: To evaluate the efficacy of WBRT as a single treatment modality in patients with brain metastases of small cell lung cancer. Patients and methods: The patients had brain metastases of small cell lung cancer without any sign of tumour outside the brain and were treated with 10

  15. Transungual surgical excision of subungual glomus tumour

    Directory of Open Access Journals (Sweden)

    Chander Grover

    2013-01-01

    Full Text Available Background: Glomus tumours are rare vascular tumours arising subungually in fingernails. Surgical excision provides histopathologic diagnosis and rapid resolution of symptoms. Objective: Present study was aimed at delineating common presentations and long-term treatment outcome of this rare subungual tumour. Patients and Methods: The clinical features and imaging results for 10 patients with subungual glomus tumours were recorded. All were treated with transungual excision. Per-operative findings and, treatment outcomes were recorded and analysed. Results: Females outnumbered males with average age being 33.3 ± 7.55 years. Presenting symptoms were severe pain (100%; nail-plate discoloration and onycholysis. X-ray was normal in 70%, though a magnetic resonance imaging done for five, helped visualise the lesion in three patients. The tumour involved nail bed in five cases and matrix in five, with an average size being 6.1 ± 2.13 mm (range 3-11 mm. An average follow-up of 16.8 months (range 8-24 months was largely uneventful with longitudinal ridging in two cases and recurrence in two (both attributed to a sister lesion. Conclusion: Subungual glomus tumours have characteristic clinical presentation. Imaging is helpful pre-operatively but has a low success rate. Transungual surgical excision is safe and effective, allowing better visualisation, easy exploration and minimal long-term complications.

  16. Transungual surgical excision of subungual glomus tumour.

    Science.gov (United States)

    Grover, Chander; Khurana, Ananta; Jain, Rajat; Rathi, Vinita

    2013-10-01

    Glomus tumours are rare vascular tumours arising subungually in fingernails. Surgical excision provides histopathologic diagnosis and rapid resolution of symptoms. Present study was aimed at delineating common presentations and long-term treatment outcome of this rare subungual tumour. The clinical features and imaging results for 10 patients with subungual glomus tumours were recorded. All were treated with transungual excision. Per-operative findings and, treatment outcomes were recorded and analysed. Females outnumbered males with average age being 33.3 ± 7.55 years. Presenting symptoms were severe pain (100%); nail-plate discoloration and onycholysis. X-ray was normal in 70%, though a magnetic resonance imaging done for five, helped visualise the lesion in three patients. The tumour involved nail bed in five cases and matrix in five, with an average size being 6.1 ± 2.13 mm (range 3-11 mm). An average follow-up of 16.8 months (range 8-24 months) was largely uneventful with longitudinal ridging in two cases and recurrence in two (both attributed to a sister lesion). Subungual glomus tumours have characteristic clinical presentation. Imaging is helpful pre-operatively but has a low success rate. Transungual surgical excision is safe and effective, allowing better visualisation, easy exploration and minimal long-term complications.

  17. 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.)

  18. Brain tumour as a rare cause of cardiac syncope.

    NARCIS (Netherlands)

    Sluijs, B.M. van der; Renier, W.O.; Kappelle, A.C.

    2004-01-01

    We report on a patient with a bradycardia followed by an asystole as expression of a complex partial seizure arising from a cerebral neoplasm in the medial part of the left temporal lobe. Previously published papers have shown that cardiac asystole and bradycardia as manifestation of epilepsy

  19. Brain tumour risk in relation to mobile telephone use

    DEFF Research Database (Denmark)

    Johansen, Christoffer

    2010-01-01

    The rapid increase in mobile telephone use has generated concern about possible health risks related to radiofrequency electromagnetic fields from this technology.......The rapid increase in mobile telephone use has generated concern about possible health risks related to radiofrequency electromagnetic fields from this technology....

  20. Oxidative metabolism of dehydroepiandrosterone (DHEA) and biologically active oxygenated metabolites of DHEA and epiandrosterone (EpiA)--recent reports.

    Science.gov (United States)

    El Kihel, Laïla

    2012-01-01

    Dehydroepiandrosterone (DHEA) is a multifunctional steroid with a broad range of biological effects in humans and animals. DHEA can be converted to multiple oxygenated metabolites in the brain and peripheral tissues. The mechanisms by which DHEA exerts its effects are not well understood. However, evidence that the effects of DHEA are mediated by its oxygenated metabolites has accumulated. This paper will review the panel of oxygenated DHEA metabolites (7, 16 and 17-hydroxylated derivatives) including a number of 5α-androstane derivatives, such as epiandrosterone (EpiA) metabolites. The most important aspects of the oxidative metabolism of DHEA in the liver, intestine and brain are described. Then, this article reviews the reported biological effects of oxygenated DHEA metabolites from recent findings with a specific focus on cancer, inflammatory and immune processes, osteoporosis, thermogenesis, adipogenesis, the cardiovascular system, the brain and the estrogen and androgen receptors. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Bignoniaceae Metabolites as Semiochemicals

    Directory of Open Access Journals (Sweden)

    Lucía Castillo

    2010-10-01

    Full Text Available Members of the family Bignoniaceae are mostly found in tropical and neo-tropical regions in America, Asia and Africa, although some of them are cultivated in other regions as ornamentals. Species belonging to this family have been extensively studied in regard to their pharmacological properties (as extracts and isolated compounds. The aim of this review is to summarize the reported scientific evidence about the chemical properties as well as that of the extracts and isolated compounds from species of this family, focusing mainly in insect-plant interactions. As it is known, this family is recognized for the presence of iridoids which are markers of oviposition and feeding preference to species which have became specialist feeders. Some herbivore species have also evolved to the point of been able to sequester iridoids and use them as defenses against their predators. However, iridoids also exhibit anti-insect properties, and therefore they may be good lead molecules to develop botanical pesticides. Other secondary metabolites, such as quinones, and whole extracts have also shown potential as anti-insect agents.

  2. Antigens in human glioblastomas and meningiomas: Search for tumour and onco-foetal antigens. Estimation of S-100 and GFA protein

    DEFF Research Database (Denmark)

    Dittmann, L; Axelsen, N H; Norgaard-Pedersen, B

    1977-01-01

    Extracts of glioblastomas and meningiomas were analysed by quantitative immunoelectrophoresis for the presence of foetal brain antigens and tumour-associated antigens, and levels of 2 normal brain-specific proteins were also determined. The following antibodies were used: monospecific anti-S-100......-alpha-foetoprotein; and monospecific anti-ferritin. Using the antibodies raised against the tumours, several antigens not present in foetal or adult normal brain were found in the glioblastomas and the meningiomas. These antigens cross-reacted with antigens present in normal liver and were therefore not tumour-associated. S-100...... was found in glioblastomas in approximately one tenth the amount in whole brain homogenate, whereas GFA was found 2-4 times enriched. The 2 proteins were absent in meningiomas. The possible use of the GFA protein as a marker for astroglial neoplasia is discussed. Five foetal antigens were found in foetal...

  3. Exophytic benign mixed epithelial stromal tumour of the kidney: case report of a rare tumour entity

    Directory of Open Access Journals (Sweden)

    Küster Jens

    2010-03-01

    Full Text Available Abstract Background Mixed epithelial and stromal tumour (MEST represents a recently described benign composite neoplasm of the kidney, which predominantly affects perimenopausal females. Most tumours are benign, although rare malignant cases have been observed. Case report A 47-year-old postmenopausal female presented to the urologist with flank pain. A CT scan of the abdomen showed a 30-mm-in-diameter uniform mass adjacent to the pelvis of the left kidney. Surgical exploration showed a tumour arising from the lower anterior hilus of the left kidney. The tumour could be excised by preserving the kidney. By intraoperative frozen section the tumour showed characteristic features of MEST with epithelial-covered cysts embedded in an "ovarian-like" stroma. Additional immunohistochemistry investigations showed expression for hormone receptors by the stromal component of the tumour. Discussion MEST typically presents in perimenopausal women as a primarily cystic mass. Commonly, the tumour arises from the renal parenchyma or pelvis. The tumour is composed of an admixture of cystic and sometimes more solid areas. The stromal cells typically demonstrate an ovarian-type stroma showing expression for the estrogen and progesterone receptors. Conclusion MEST represents a distinctive benign tumour entity of the kidney, which affects perimenopausal woman. The tumour should be distinguished from other cystic renal neoplasms. By imaging studies it is difficult to distinguish between a benign or malignant nature of the tumour. Thus, intraoperative frozen section is necessary for conservative surgery, since the overall prognosis is favourable and renal function can be preserved in most cases.

  4. NMR metabolomics of human lung tumours reveals distinct metabolic signatures for adenocarcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Rocha, Cláudia M; Barros, António S; Goodfellow, Brian J; Carreira, Isabel M; Gomes, Ana; Sousa, Vitor; Bernardo, João; Carvalho, Lina; Gil, Ana M; Duarte, Iola F

    2015-01-01

    Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through (1)H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and adjacent control tissues from 56 patients undergoing surgical excision of primary lung carcinomas. Multivariate modeling allowed tumour and control tissues to be discriminated with high accuracy (97% classification rate), mainly due to significant differences in the levels of 13 metabolites. Notably, the magnitude of those differences were clearly distinct for AdC and SqCC: major alterations in AdC were related to phospholipid metabolism (increased phosphocholine, glycerophosphocholine and phosphoethanolamine, together with decreased acetate) and protein catabolism (increased peptide moieties), whereas SqCC had stronger glycolytic and glutaminolytic profiles (negatively correlated variations in glucose and lactate and positively correlated increases in glutamate and alanine). Other tumour metabolic features were increased creatine, glutathione, taurine and uridine nucleotides, the first two being especially prominent in SqCC and the latter in AdC. Furthermore, multivariate analysis of AdC and SqCC profiles allowed their discrimination with a 94% classification rate, thus showing great potential for aiding lung tumours subtyping. Overall, this study has provided new, clear evidence of distinct metabolic signatures for lung AdC and SqCC, which can potentially impact on diagnosis and provide important leads for future research on novel therapeutic targets or imaging tracers. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Part II-specific NE tumour types

    DEFF Research Database (Denmark)

    Oberg, Kjell; Astrup, Lone Bording; Eriksson, Barbro

    2004-01-01

    Part II of the guidelines contains a description of epidemiology, histopathology, clinical presentation, diagnostic procedure, treatment, and survival for each type of neuroendocrine tumour. We are not only including gastroenteropancreatic tumours but also bronchopulmonary and thymic neuroendocrine...... tumours. These guidelines essentially cover basic knowledge in the diagnosis and management of the different forms of neuroendocrine tumour. We have, however, tried to give more updated information about the epidemiology and histopathology, which is essential for the clinical management of these tumours....

  6. Tumour-to-tumour metastasis: male breast carcinoma metastasis arising in an extrapleural solitary fibrous tumour - a case report.

    Science.gov (United States)

    Scheipl, Susanne; Moinfar, Farid; Leithner, Andreas; Sadoghi, Patrick; Jorgensen, Mette; Rinner, Beate; Liegl, Bernadette

    2014-11-25

    Tumour-to-tumour metastasis (TTM) occurs when one tumour metastasises to a separate tumour within the same individual. TTM is observed frequently in breast cancer but has not been described in male breast cancer. In addition reports describing solitary fibrous tumours (SFT) of the pleura hosting other neoplasms' metastases are limited. We report an exceptional case of male breast cancer metastasising to an extrapleural SFT, occurring in the subcutaneous tissue of the back of a 68-year old Caucasian patient. A 68-year old male was diagnosed with a metastasising ductal breast cancer. He was treated by mastectomy of the right breast and axillary lymph-adenectomy. Further staging revealed an increasing subcutaneous expansion located on the patient's back. Excision biopsy confirmed a SFT hosting a breast cancer metastasis. The patient received palliative chemotherapy but died of disease seven years after initial diagnosis. The abundance of blood vessels within these lesions might predispose SFTs for an involvement in TTM. This case describes the possibility of concurrent rare occurrences and reminds clinicians, as well as pathologists, to be open-minded and fastidious about their differential diagnoses, sampling and examination of histological specimens. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_203.

  7. Tumours and tumour-like conditions of the jaw seen in Zaria, Nigeria ...

    African Journals Online (AJOL)

    About 94% of the ameloblastomas occurred in the mandible. The malignant jaw tumours were made up of the following histological types: - 79 (75.2%) malignant lymphoma; 10 (9.5%) osteogenic sarcomas; 2 (1.9%) chondrosarcoma; 1 (1.0%) malignant ameloblastoma and 6 (5.7%) secondary tumours, 7 (6.7%) were ...

  8. Orofacial tumours and tumour-like lesions in Kano, Nigeria | Arotiba ...

    African Journals Online (AJOL)

    The most prevalent tumours were squamous cell carcinoma (46% of malignant lesions) and ameloblastoma (31% of benign lesions) the mandible (38.2%) and the maxilla (23.6%) were the most commonly affected sites. Patients usually delayed before seeking treatment and the mean duration of tumours was 30 months ...

  9. Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach

    Science.gov (United States)

    Lolas, Georgios; Bianchi, Arianna; Syrigos, Konstantinos N.

    2016-02-01

    It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination.

  10. Primary bone tumours and tumour-like lesions in children in Zaria ...

    African Journals Online (AJOL)

    osteoma 2.5%, osterochondroma 22.5%, fibroma 5%); while malignant tumours occurred in 19 (47.5%) (osteosarcoma 5%, Burkitt's lymphoma 37.5%, diffuse lympholastic lymphoma 5%). Tumour-like lesions accounted for 9 (22.5%), all Þ brous ...

  11. 18F-FDG whole body positron emission tomography (PET) in patients with unknown primary tumours (UPT)

    DEFF Research Database (Denmark)

    Lassen, U; Daugaard, G; Eigtved, A

    1999-01-01

    adenocarcinomas and 1 poorly differentiated carcinoma). The remaining patients had metastases located in bone (3), bone marrow (1), brain (1), pericardium (1), skin (1), pleura (1) and chest wall (1). All metastatic lesions were visible with PET. In 13 patients PET suggested the site for the primary tumour...

  12. Metabolite Space of Rheumatoid Arthritis

    OpenAIRE

    van Wietmarschen, Herman; van der Greef, Jan

    2012-01-01

    Metabolites play numerous roles in the healthy and diseased body, ranging from regulating physiological processes to providing building blocks for the body. Therefore, understanding the role of metabolites is important in elucidating the etiology and pathology of diseases and finding targets for new treatment options. Rheumatoid arthritis is a complex chronic disease for which new disease management strategies are needed. The aim of this review is to bring together and integrate information a...

  13. Loss of the tumour suppressor gene AIP mediates the browning of human brown fat tumours.

    Science.gov (United States)

    Magnusson, Linda; Hansen, Nils; Saba, Karim H; Nilsson, Jenny; Fioretos, Thoas; Rissler, Pehr; Nord, Karolin H

    2017-10-01

    Human brown fat tumours (hibernomas) show concomitant loss of the tumour suppressor genes MEN1 and AIP. We hypothesized that the brown fat phenotype is attributable to these mutations. Accordingly, in this study, we demonstrate that silencing of AIP in human brown preadipocytic and white fat cell lines results in the induction of the brown fat marker UCP1. In human adipocytic tumours, loss of MEN1 was found both in white (one of 51 lipomas) and in brown fat tumours. In contrast, concurrent loss of AIP was always accompanied by a brown fat morphology. We conclude that this white-to-brown phenotype switch in brown fat tumours is mediated by the loss of AIP. 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.

  14. Volume, metabolites and neuroinflammation of the hippocampus in bipolar disorder - A combined magnetic resonance imaging and positron emission tomography study

    NARCIS (Netherlands)

    Haarman, Bartholomeus C. M. ('Benno'); Burger, Huibert; Doorduin, Janine; Renken, Remco J.; Sibeijn-Kuiper, Anita J.; Marsman, Jan-Bernard C.; Vries, de Erik; de Groot, Jan Cees; Drexhage, Hemmo A.; Mendes, Richard; Nolen, Willem A.; Riemersma-Van der Lek, Rixt F.

    Background: The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in

  15. Secondary metabolites from marine microorganisms

    Directory of Open Access Journals (Sweden)

    KELECOM ALPHONSE

    2002-01-01

    Full Text Available After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  16. Naturally occurring tumours in the basal metazoan Hydra.

    Science.gov (United States)

    Domazet-Lošo, Tomislav; Klimovich, Alexander; Anokhin, Boris; Anton-Erxleben, Friederike; Hamm, Mailin J; Lange, Christina; Bosch, Thomas C G

    2014-06-24

    The molecular nature of tumours is well studied in vertebrates, although their evolutionary origin remains unknown. In particular, there is no evidence for naturally occurring tumours in pre-bilaterian animals, such as sponges and cnidarians. This is somewhat surprising given that recent computational studies have predicted that most metazoans might be prone to develop tumours. Here we provide first evidence for naturally occurring tumours in two species of Hydra. Histological, cellular and molecular data reveal that these tumours are transplantable and might originate by differentiation arrest of female gametes. Growth of tumour cells is independent from the cellular environment. Tumour-bearing polyps have significantly reduced fitness. In addition, Hydra tumours show a greatly altered transcriptome that mimics expression shifts in vertebrate cancers. Therefore, this study shows that spontaneous tumours have deep evolutionary roots and that early branching animals may be informative in revealing the fundamental mechanisms of tumorigenesis.

  17. 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.

  18. 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

  19. [Tumours of the upper cervical spine].

    Science.gov (United States)

    Hernández García, Borja Jesús; Isla Guerrero, Alberto; Castaño, Ana; Alvarez Ruiz, Fernando; Gómez de la Riva, Alvaro

    2013-01-01

    Vertebral tumours arising in the upper cervical spine are rare. We present our experience in managing these neoplasms. We retrospectively reviewed the case histories of patients treated at our institution between January 2000 and June 2011. There were 9 patients with tumours in C1-C2-C3: 2metastases, 3chordomas, 2plasmocytomas, 1chondrosarcoma and 1osteochondroma. All patients complained of neck pain at the time of diagnosis. Three patients underwent an anterior and posterior approach, 3 an exclusively posterior approach and 3 an exclusively anterior surgical approach. Tumour resection was intralesional in 7 cases. Chemo-radiotherapy was used as adjuvant therapy in patients with malignant tumours. Vertebral tumours in the upper cervical spine are usually malignant. Achieving en bloc resection is particularly challenging and is technically unfeasible in many cases. This worsens the prognosis and makes adjuvant treatment very important. Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  20. An Ectopic ACTH Secreting Metastatic Parotid Tumour

    Directory of Open Access Journals (Sweden)

    Thomas Dacruz

    2016-01-01

    Full Text Available A 60-year old woman presented with features of Cushing’s syndrome (CS secondary to an ectopic adrenocorticotropic hormone (ACTH secreting metastatic parotid tumour 3 years after excision of the original tumour. She subsequently developed fatal intestinal perforation and unfortunately died despite best possible medical measures. Ectopic ACTH secretion accounts for 5–10% of all patients presenting with ACTH dependent hypercortisolism; small cell carcinoma of lung (SCLC and neuroendocrine tumours (NET account for the majority of such cases. Although there are 4 previous case reports of ectopic ACTH secreting salivary tumours in literature, to our knowledge this is the first published case report in which the CS developed after 3 years of what was deemed as a successful surgical excision of primary salivary tumour. Our patient initially had nonspecific symptoms which may have contributed to a delay in diagnosis. Perforation of sigmoid colon is a recognised though underdiagnosed complication associated with steroid therapy and hypercortisolism. This case demonstrates the challenges faced in diagnosis as well as management of patients with CS apart from the practical difficulties faced while trying to identify source of ectopic ACTH.

  1. TUMOUR CASE IN KOI CARP (Cyprinus carpio

    Directory of Open Access Journals (Sweden)

    Lili Sholichah

    2010-12-01

    Full Text Available A case study of tumour in koi carp (Cyprinus carpio was observed in rearing periode. This tumour occurs solitary, large, pale red, fleshy masses under the lips and dental plates on the outside, and by reason of its size, may prevent closure the mouth. Moreover, this tumour goes through into the inside of the mouth. At necropsy, there were two soft, firm, small mass at inside of the mouth and the bigger mass at outside the mouth. Samples of this tumour were fixed in 10% formalin were used for histology analysis. The clinical course of the tumour is one of relatively slow but progressive growth. The proliferative stage of the neoplastic process is preceded and accompanied by a striking vascular reaction. Intensed hyperemia invariably occurs in that region of the mucosal surface which later becomes the site of neoplastic proliferation. Neoplastic cells lied around lamina propria and submucosal. These cells were joined together to make vacuolization and the other cells become pleiomorphism with hyperchromatic nucleus and N/C ratio cells are 1:1. In some area, there were many empty holes, around the holes there were debris cells, inflammation cells, and erythrocytes.

  2. Targeting the tumour microenvironment in ovarian cancer.

    Science.gov (United States)

    Hansen, Jean M; Coleman, Robert L; Sood, Anil K

    2016-03-01

    The study of cancer initiation, growth, and metastasis has traditionally been focused on cancer cells, and the view that they proliferate due to uncontrolled growth signalling owing to genetic derangements. However, uncontrolled growth in tumours cannot be explained solely by aberrations in cancer cells themselves. To fully understand the biological behaviour of tumours, it is essential to understand the microenvironment in which cancer cells exist, and how they manipulate the surrounding stroma to promote the malignant phenotype. Ovarian cancer is the leading cause of death from gynaecologic cancer worldwide. The majority of patients will have objective responses to standard tumour debulking surgery and platinum-taxane doublet chemotherapy, but most will experience disease recurrence and chemotherapy resistance. As such, a great deal of effort has been put forth to develop therapies that target the tumour microenvironment in ovarian cancer. Herein, we review the key components of the tumour microenvironment as they pertain to this disease, outline targeting opportunities and supporting evidence thus far, and discuss resistance to therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. A STUDY OF OVARIAN TUMOURS : CLINICAL AND PATHOLOGICAL CORRELATION

    Directory of Open Access Journals (Sweden)

    Uma Devi

    2015-10-01

    Full Text Available OBJECTIVE: To study incidence age distribution of benign and malignant ovarian tu mours in general population. METHODS AND MATERIAL : To study 120 patients with ovarian tumours in Govt . general hospital during June 2003 and June 2005. RESULTS: Clinical and pathological evaluation of all ovarian tumours was done and incidence, age distrib ution of various benign and malignant ovarian neoplasms were tabulated and compared with other studies. CONCLUSIONS: Most common ovarian tumours are benign tumours and serous cystadenoma is the commonest benign tumour and S erous cystadeno carcinoma is the most common malignant tumour.

  4. MRI of intracranial germ cell tumours

    Energy Technology Data Exchange (ETDEWEB)

    Sumida, M. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Uozumi, T. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Kiya, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Mukada, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Arita, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Kurisu, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Sugiyama, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Onda, J. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Satoh, H. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Ikawa, F. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Migita, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan)

    1995-01-01

    We reviewed MRI findings in proven intracranial germ cell tumours in 22 cases, 12 of whom received Gd-DTPA. On T1-weighted images, the signal intensity of the tumour parenchyma was moderately low in 19 cases and isointense in 3; on T2-weighted images, it was high in all cases. Regions of different intensity thought to be cysts were found in 17 (77 %): 7 of 12 patients with germinoma (58 %) and in all other cases. Of the 13 patients with pineal lesions T1-weighted sagittal images showed the aqueduct to be obstructed in 5, stenotic in 7 and normal in 1. Strong contrast enhancement was observed in all 12 cases. Of the 14 patients with suprasellar lesions, 5 were found to have an intrasellar extension, and in 3 of these, the normal pituitary gland, which could be distinguished from the tumour, was displaced anteriorly. Ten patients (45 %) had multiple lesions. (orig.)

  5. Angiofibroma, a rare cardiac tumour in children

    Directory of Open Access Journals (Sweden)

    G Gayen

    2013-09-01

    Full Text Available Angiofibromas, located in any other sites than nasopharynx are unusual. Cardiac angiofibromas are a very rare cardiac tumours in comparison to rhabdomyomas which are the commonest in the children. We report a right ventricular tumour in a10 year old girl which was excised under cardiopulmonary bypass successfully and diagnosed as angiofibroma on histopathology. Journal of College of Medical Sciences-Nepal, 2012, Vol-8, No-4, 51-54 DOI: http://dx.doi.org/10.3126/jcmsn.v8i4.8702  

  6. Sertoliform cystadenoma: a rare benign tumour of the rete testis.

    Science.gov (United States)

    Bremmer, Felix; Schweyer, Stefan; Behnes, Carl Ludwig; Blech, Manfred; Radzun, Heinz Joachim

    2013-02-14

    Sertoliform cystadenoma of the rete testis represents an uncommon benign tumour. They appear in patients from 26 to 62 years of age. We describe a case of a 66-year-old man with a tumour in the area of the epididymal head. The tumour markers were not increased. Under the assumption of a malignant testicular tumour an inguinal orchiectomy was performed. The cut surface of this tumour was of grey/white color and showed small cysts. The tumour consisted of two compartments. The epithelial like tumour cells showed a sertoliform growth pattern and cystic dilatations. In between the tumour cells repeatedly actin expressing sclerotic areas could be recognized as the second tumour component. Proliferative activity was not increased. Immunohistochemically the tumour cells were positiv for inhibin, S-100, and CD 99. Alpha feto protein (AFP), human chorionic gonadotropin (ß-HCG) and placental alkaline phosphatase (PLAP) as well as synaptophysin, epithelial membrane antigene (EMA), and BCL-2 were not expressed. As far as we know this is the sixth reported case of this tumour. Because of the benign nature of this tumour the correct diagnosis is important for the intra- and postoperative management. Here we present a case of this rare tumour and discuss potential differential diagnosis. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956026143857335.

  7. Effect of tetrandrine on calcium-dependent tumour necrosis factor-alpha production in glia-neurone mixed cultures.

    Science.gov (United States)

    Wang, Bin; Yang, Li; Yan, Hong-Li; Wang, Meng; Xiao, Ji-Gao

    2005-10-01

    Tumour necrosis factor-alpha is believed to have a deleterious role in the pathophysiology of brain injury. Tetrandrine has protective effect on neuronal cells, however, the mechanisms involved in its action have not been clearly established. The aim of this study was to investigate the role of tetrandrine on calcium-dependent tumour necrosis factor-alpha production in glia-neurone mixed cultures. Glia-neurone mixed cultures were treated by addition of Ca2+ regulating agents for a period of 6 hr. Tetrandrine or/and TMB-8 were added 30 min. before the stimulation. The supernatant tumour necrosis factor-alpha levels were quantified by enzyme-linked immunosorbent assay. Exposure of lipopolysaccharide 10 and 100 ng/ml caused significant increase in tumour necrosis factor-alpha production respectively, with no alteration in cultures treated with 1 ng/ml lipopolysaccharide. Glia-neurone mixed cultures exhibited a marked elevation in tumour necrosis factor-alpha production after exposure to CaCl2, KCl, thapsigargin, BHQ and norepinephrine in the presence of lipopolysaccharide at 1 ng/ml respectively. Tetrandrine 0.3, 1, and 3 microM concentration-dependently reduced tumour necrosis factor-alpha production evoked by CaCl2 or KCl. Tetrandrine preincubation had no significant effect on the response to Ca2+-ATPase inhibitor thapsigargin or BHQ. Norepinephrine-induced tumour necrosis factor-alpha production was significantly reduced by tetrandrine and almost abolished by combination of tetrandrine and intracellular Ca2+ release inhibitor TMB-8. These results suggested that tetrandrine at a concentration of 0.3, 1, or 3 microM inhibited tumour necrosis factor-alpha production induced by Ca2+ entry in glia-neurone mixed cultures.

  8. In vivo imaging of tumour xenografts with an antibody targeting the potassium channel Kv10.1.

    Science.gov (United States)

    Napp, Joanna; Pardo, Luis A; Hartung, Franziska; Tietze, Lutz F; Stühmer, Walter; Alves, Frauke

    2016-10-01

    The Kv10.1 (Eag1) voltage-gated potassium channel represents a promising molecular target for novel cancer therapies or diagnostic purposes. Physiologically, it is only expressed in the brain, but it was found overexpressed in more than 70 % of tumours of diverse origin. Furthermore, as a plasma membrane protein, it is easily accessible to extracellular interventions. In this study we analysed the feasibility of the anti-Kv10.1 monoclonal antibody mAb62 to target tumour cells in vitro and in vivo and to deliver therapeutics to the tumour. Using time-domain near infrared fluorescence (NIRF) imaging in a subcutaneous MDA-MB-435S tumour model in nude mice, we showed that mAb62-Cy5.5 specifically accumulates at the tumour for at least 1 week in vivo with a maximum intensity at 48 h. Blocking experiments with an excess of unlabelled mAb62 and application of the free Cy5.5 fluorophore demonstrate specific binding to the tumour. Ex vivo NIRF imaging of whole tumours as well as NIRF imaging and microscopy of tumour slices confirmed the accumulation of the mAb62-Cy5.5 in tumours but not in brain tissue. Moreover, mAb62 was conjugated to the prodrug-activating enzyme β-D-galactosidase (β-gal; mAb62-β-gal). The β-gal activity of the mAb62-β-gal conjugate was analysed in vitro on Kv10.1-expressing MDA-MB-435S cells in comparison to control AsPC-1 cells. We show that the mAb62-β-gal conjugate possesses high β-gal activity when bound to Kv10.1-expressing MDA-MB-435S cells. Moreover, using the β-gal activatable NIRF probe DDAOG, we detected mAb62-β-gal activity in vivo over the tumour area. In summary, we could show that the anti-Kv10.1 antibody is a promising tool for the development of novel concepts of targeted cancer therapy.

  9. Mu receptor binding of some commonly used opioids and their metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhaorong; Irvine, R.J. (Univ. of Adelaide (Australia)); Somogyi, A.A.; Bochner, F. (Univ. of Adelaide (Australia) Royal Adelaide Hospital (Australia))

    1991-01-01

    The binding affinity to the {mu} receptor of some opioids chemically related to morphine and some of their metabolites was examined in rat brain homogenates with {sup 3}H-DAMGO. The chemical group at position 6 of the molecule had little effect on binding. Decreasing the length of the alkyl group at position 3 decreased the K{sub i} values (morphine < codeine < ethylmorphine < pholcodine). Analgesics with high clinical potency containing a methoxyl group at position 3 had relatively weak receptor binding, while their O-demethylated metabolites had much stronger binding. Many opioids may exert their pharmacological actions predominantly through metabolites.

  10. Study on the radiation-induced biological responses based on the analysis of metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sungkee; Jung, Uhee; Park, Haeran; Roh, Changhyun; Shin, Heejune; Ryu, Dongkyoung

    2013-01-15

    1. Objectives □ Establishment of basis of biological radiation response study by metabolite analysis 2. Project results □ Establishment of analytical basis of radiation-responsive metabolites in biological samples - Large scale collection of tissue samples from irradiated animal for radiation metabolomics research - Establishment of mass spectromety (GC MS, LC MS-MS) analysis methods of biological samples - 3 Standard Operation Protocols (SOP) for ultra high resolution mass spectrometry (FT-ICR MS, Q-TOF MS) analysis of metabolites from biological samples - Establishment of database for radiation metabolites □ Basic research on radiation-responsive metabolites and the interpretation of their functions - Validation of spermidine as a candidate biomarker of acute radiation response in mouse blood - Verification of 5 radiation-responsive steroid hormones and alteration of their metabolic enzyme activities in mouse blood - Verification of 13 radiation-responsive amino acids (related to oxidative stress, neurotransmission, energy metabolism) in regional mouse brain -Verification of 10 radiation-responsive amino acids (related to oxidative stress, neurotransmission, energy metabolism) in regional mouse brain - Verification of 74 radiation-responsive metabolites in whole rat brain by ultra high resolution FT-ICR MS and Q-TOF MS analysis 3. Expected benefits and plan of application □ Establishment of research basis of radiation metabolomics in Korea □ Provision of core technology in radiation bioscience and safety field by application of radiation metabolomics results to the technology development in radiation biodosimetry, and radiation response evaluation and modulation.

  11. Ovarian hilus-cell tumour: a case report.

    Science.gov (United States)

    Georgiev, T N; Valkov, I M; Dokumov, S I

    1980-01-01

    A case of hilus-cell tumour of the ovary, associated with polycystic ovarian disease is reported. The authors discuss the data from hormonal investigations, the morphological picture and the genesis of the tumour.

  12. Sexual function in patients with metastatic midgut carcinoid tumours

    NARCIS (Netherlands)

    van der Horst-Schrivers, Anouk N. A.; van Ieperen, Ellen; Wymenga, A. N. Machteld; Boezen, H. Marike; Weijmar-Schultz, Willibrord C. M.; Kema, Ido P.; Meijer, Wim G.; de Herder, Wouter W.; Willemse, Pax H. B.; Links, Thera P.; de Vries, Elisabeth G. E.

    2009-01-01

    Background: Sexual dysfunction is a poorly studied aspect of quality of life in patients with midgut carcinoid tumours. We investigated whether carcinoid patients experience sexual problems. Methods: Patients with metastatic midgut carcinoid tumours filled in a validated questionnaire for sexual

  13. Laryngeal tumours: clinical features and management challenges as ...

    African Journals Online (AJOL)

    Laryngeal tumours: clinical features and management challenges as seen in two centres in Port Harcourt, Nigeria. ... The commonest mode of presentation was hoarseness (100%). Twenty ... Keywords: Challenges, Management, Laryngeal tumours, Squamous cell carcinoma, Papillomas, Total laryngectomy, Port Harcourt ...

  14. Prospective therapies for high-grade glial tumours: A literature review

    Directory of Open Access Journals (Sweden)

    Sayed Samed Talibi

    2014-09-01

    Full Text Available After three decades of intensive research, cytoreductive surgery remains the gold standard of treatment of malignant gliomas. Survivorship at both 1-year and 5-years has not drastically changed in the UK. Concomitant chemo- and radiotherapy has enhanced the efficiency of surgery, enabling more aggressive tumour resection whilst also preserving the surrounding healthy brain parenchyma. More accurate imaging techniques have also played a role in tumour identification, key to this has been pre- and intra-operative contrast enhancement and compounds that have a high affinity in binding to glioma cells. Intra-operative imaging has heralded the ability to give the operating surgeon continuous feedback to assess the completeness of resection. Research is shifting into investigating the complex cellular and molecular glial tumour-genesis, and has led to the development of efficacious chemotherapy agents and trial novel therapies. Oncolytic virotherapy has shown promise in clinical trials and gene therapy in-vitro studies. Surgery however remains the primary therapeutic option for the management of malignant gliomas removing the mass of proliferating malignant tumour cells and decompression of the space-occupying lesion.

  15. Secondary metabolites from Eremostachys laciniata

    DEFF Research Database (Denmark)

    Calis, Ihsan; Güvenc, Aysegül; Armagan, Metin

    2008-01-01

    ), and forsythoside B (18), and five flavone derivatives, luteolin (19), luteolin 7-O-β-D-glucopyranoside (20), luteolin 7-O-(6''-O-β-D-apiofuranosyl)-β-D-glucopyranoside (21), apigenin 7-O-β-D-glucopyranoside (22), and apigenin 7-O-(6''-O-p-coumaroyl)-β-D-glucopyranoside (23). The structures of the metabolites were...... elucidated from spectroscopic (UV, IR, 1D- and 2D-NMR) and ESI-MS evidence, as well as from their specific optical rotation. The presence of these metabolites of three different classes strongly supports the close relationship of the genera Eremostachys and Phlomis....

  16. Functional brain imaging: an evidence-based analysis.

    Science.gov (United States)

    2006-01-01

    The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer's disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson's disease (PD). TARGET POPULATION AND CONDITION Alzheimer's disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006. In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging. Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci. Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including

  17. Brain Basics

    Medline Plus

    Full Text Available ... About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain Brain ... called the hypothalamic-pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life— ...

  18. Platinum compounds with anti-tumour activity

    NARCIS (Netherlands)

    Plooy, A.C.M.; Lohman, P.H.M.

    1980-01-01

    Ten platinum (Pt) coordination complexes with different ligands, comprising both Pt(II) and Pt(IV) complexes of which the cis-compounds all possessed at least some anti-tumour activity and the trans-compounds were inactive, were tested as to their effect on cell survival and the induction and repair

  19. Spermatogenesis and testicular tumours in ageing dogs

    NARCIS (Netherlands)

    Peters, M. A.; de rooij, D. G.; Teerds, K. J.; van de Gaag, I.; van Sluijs, F. J.

    2001-01-01

    The aims of this investigation were to quantify the changes in canine spermatogenesis that occur during ageing and to study the prevalence of testicular tumours and their effects on spermatogenesis in dogs. Testes from 74 dogs of various breeds without clinically detected testicular disease and from

  20. Granular cell tumour of the urinary bladder

    Directory of Open Access Journals (Sweden)

    Christoph von Klot

    2012-04-01

    Full Text Available With only 16 cases reported in the literature, the mostly benign granular cell tumour of the urinary bladder is exceptionally rare. We present the case of a 68-year old patient with one of these lesions demonstrating our histological findings including several immunohistochemical stainings used to differentiate between other more common entities.

  1. Melanotic neuroectodermal tumour of infancy (progonoma) treated ...

    African Journals Online (AJOL)

    The two infants both presented within three months of each other and though clinically Burkitt's lymphoma was stated as a possible diagnosis, the correct diagnosis was made on biopsy specimens. Radical surgery consisting of wide resection of the tumour with margins of healthy tissue via hemi-maxillectomy was performed ...

  2. Unique Juxtaposition of Onchocerca Nodule and Tumoural ...

    African Journals Online (AJOL)

    A 45-year-old Igbo man presented with a subcutaneous nodule in the lateral aspect of his left thigh. Following its excision, the lesion turned out on microscopy to be due to the unique juxtaposition of onchocerca nodule and tumoural calcinosis. Such selectivity in disease localization is deemed to be worthy of documentation ...

  3. Maxillary brown tumour: unusual presentation of parathyroid ...

    African Journals Online (AJOL)

    This is a report of a maxillary brown tumour caused by primary hyperparathyroidism (HPT) secondary to parathyroid carcinoma. A 62-year-old man presented with a large swelling in the right maxilla, which caused right-sided nasal obstruction, intermittent bleeding and diplopia. A computed tomography scan demonstrated ...

  4. POSTERIOR CRANIAL FOSSA TUMOURS IN CHILDREN AT ...

    African Journals Online (AJOL)

    hi-tech

    2004-05-05

    May 5, 2004 ... symptoms were the most common mode of presentation (30%) followed by headaches and vomiting. Twenty percent of our patients ... paediatric posterior fossa tumours are medulloblastoma. (20%) astrocytoma (15%) ... cranial nerve palsies, headaches, vomiting and blindness due to raised intracranial ...

  5. Gastrointestinal stromal tumour presenting as gastroduodenal intussusception.

    LENUS (Irish Health Repository)

    Wilson, Mark H

    2012-08-01

    Gastroduodenal intussusception secondary to gastrointestinal stromal tumour is a very rare cause for intestinal obstruction. The diagnosis of this condition can be challenging, as symptoms are often non-specific and intermittent. This article reports a case where the diagnosis was made preoperatively with abdominal imaging and was treated by a combination of endoscopic reduction and laparoscopic resection.

  6. The role of methylation in urological tumours

    NARCIS (Netherlands)

    Heijden, A.G. van der

    2013-01-01

    Alterations in DNA methylation have been described in human cancer for more than thirty years now. Since the last decade DNA methylation gets more and more important in cancer research. In this review the different alterations of DNA methylation are discussed in testicular germ cell tumours,

  7. Cystic lesions accompanying extra-axial tumours

    NARCIS (Netherlands)

    Lohle, PNM; Wurzer, HAL; Seelen, PJ; Kingma, LM; Go, KG

    We examined the mechanism of cyst formation in extra-axial tumours in the central nervous system (CNS). Cyst fluid, cerebrospinal fluid (CSF) and blood plasma were analysed in eight patients with nine peritumoral cysts: four with meningiomas, two with intracranial and two spinal intradural

  8. Minor salivary gland tumours in Kaduna, Nigeria

    African Journals Online (AJOL)

    were 6 metastatic lesions (5 loco—regiona1 and l pulmonary). Duration of symptoms ranged from 2 weeks to 192 months (mean. 22.3 months). Treatment protocol (Table. 2) for malignant tumours was surgery. (n=l9), radiotherapy (n=l l), chemotherapy. 102 andiradiotherapy (nil). Suprahyoid neck dissection was undertaken ...

  9. Tumour and tumour-like lesions of the patella - a multicentre experience

    Energy Technology Data Exchange (ETDEWEB)

    Singh, J.; James, S.L.; Davies, A.M. [The Royal Orthopaedic Hospital, Department of Radiology, Birmingham (United Kingdom); Kroon, H.M. [Leiden University Medical Centre, Department of Radiology, C-2-S, P. O Box 9600, Leiden (Netherlands); Woertler, K. [Technische Universitaet Muenchen, Department of Radiology, Munich (Germany); Anderson, S.E. [Knochentumor- Referenzzentrum der Schweizerischen Gesellschaft fuer Pathologie, Basel (Switzerland)

    2009-03-15

    Fifty-nine cases of lesions presenting in the patella were identified after review of the databases of four European bone tumour registries. Of the 59 cases, 46% were non neoplastic, 39% were benign and 15% were malignant. The commonest benign neoplasm was giant cell tumour (GCT) (11 cases). Younger patients were more likely to have a benign neoplasm. Lesions in patients less than 40 years of age included giant cell tumour, chondroblastoma, aneurysmal bone cyst (ABC), osteomyelitis, osteoid osteoma and solitary bone cyst. In patients older than 40 years, the following were common lesions: intra-osseous gout, metastasis and intra-osseous ganglion. Expansion of the patella with thinning of cortex was seen more commonly in GCT and brown tumour in hyperparathyroidism. There was associated soft tissue extension in gout and malignant lesions. (orig.)

  10. Primitive neuroectodermal tumour of the kidney with vena caval and atrial tumour thrombus: a case report.

    Science.gov (United States)

    Ong, Poh Ho; Manikandan, Ramaswamy; Philip, Joe; Hope, Kirsten; Williamson, Michael

    2008-08-11

    Renal primitive neuroectodermal tumour is an extremely rare malignancy. A 21-year-old woman presented with microscopic haematuria, a palpable right loin mass, dyspnoea, dizziness and fatigue. Initial ultrasound scan of the kidneys revealed an 11 cm right renal mass with venous extension into the inferior vena cava. Computed tomography of the thorax and abdomen revealed an extension of the large renal mass into the right renal vein, inferior vena cava and up to the right atrium. A small paracaval lymph node was noted and three small metastatic nodules were identified within the lung parenchyma. The patient underwent a radical nephrectomy and inferior vena caval tumour (level IV) thrombectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest. Immunohistochemical staining of the specimen showed a highly specific cluster of differentiation (CD) 99, thus confirming the diagnosis of a primitive neuroectodermal tumour. It is important that a renal primitive neuroectodermal tumour be considered, particularly in young patients with a renal mass and extensive thrombus.

  11. Fas Ligand Expression in Lynch Syndrome-Associated Colorectal Tumours

    NARCIS (Netherlands)

    Koornstra, Jan J.; de Jong, Steven; Boersma-van Eck, Wietske; Zwart, Nynke; Hollema, Harry; de Vries, Elisabeth G. E.; Kleibeuker, Jan H.

    Fas Ligand (FasL) expression by cancer cells may contribute to tumour immune escape via the Fas counterattack against tumour-infiltrating lymphocytes (TILs). Whether this plays a role in colorectal carcinogenesis in Lynch syndrome was examined studying FasL expression, tumour cell apoptosis and

  12. Odontogenic tumours in Children and Adilescents: A Review od ...

    African Journals Online (AJOL)

    Ameloblastoma was the commonest odontogenic tumours with 14 (29.1%) solid ameloblastoma and 9 (18.8%) cystic ameloblastoma cases followed by fibromyxoma with 8 (16.7%) cases. calcifying epithelial odontogenic tumour , calcifying cystic odontogenic tumour and odontogenic fibroma were occasionally seen.

  13. GRANULAR CELL TUMOUR OF THE LARYNX – A CASE REPORT

    African Journals Online (AJOL)

    2015-12-01

    Dec 1, 2015 ... neuroectodermal origin as demonstrated by immunophenotypic and ultrastructural evidence.1. These tumours occur commonly in the tongue though they can occur in any part of the body. Granular cell tumours (GCTs) may be benign or malignant though the latter versions are rare (2% of all such tumours).

  14. Clinico-pathological analysis of malignant salivary gland tumours in ...

    African Journals Online (AJOL)

    BACKGROUND Salivary gland tumours are common head and neck tumours. Malignant salivary gland tumours generally occur less frequently than benign ones and account for greater morbidity and mortality. Patients in our environment are seen to present at late stages and Mucoepidermoid carcinoma is the commonest ...

  15. Calcifying epithelial odontogenic tumour-case series from five ...

    African Journals Online (AJOL)

    Background: Calcifying epithelial odontogenic tumour (CEOT) also known as Pindborg's tumour is a relatively rare odontogenic neoplasm of epithelial derivation that constitutes about 0.4-3% of all intraosseous odontogenic tumours. Objectives: To document all cases of CEOT encountered in five tertiary centres in Nigeria ...

  16. Multicentre study of Wilm's tumours treated by different therapeutic ...

    African Journals Online (AJOL)

    Both National Wilm's Tumour Study (NWTS) group and the International Society of Paediatric Oncology (SIOP) have helped to improve the clinical management and outcome of patients with Wilm's tumours. In this study, we compared three groups of patients with Wilm's tumours from different racial backgrounds and ...

  17. tumours and cancers in graeco-roman times 1. introduction

    African Journals Online (AJOL)

    benign (in modern terms), whilst oidêmata were soft, painless tumours and even includ- .... Oidêma.6 A soft, usually non-tender tumour, sometimes pitting on ..... Tumours and cancers in Graeco-Roman times. 1923. Prognostic. Regimen in acute diseases. The sacred disease. The art. Breaths. Law. Decorum. Physician.

  18. Carcinoid heart disease secondary to ovarian tumour: a logical ...

    African Journals Online (AJOL)

    2013-03-13

    Mar 13, 2013 ... Carcinoid heart disease secondary to ovarian tumours is uncommon. The ovarian carcinoids do not have metastasis in the liver unlike gastrointestinal tumours. Hence the management priorities need to be different. We present a case in which removal of the primary tumour before heart surgery resulted in a ...

  19. Mesenchymal tumours of the mediastinum—part II

    NARCIS (Netherlands)

    M.A. den Bakker (Michael); A. Marx (Alexander); K. Mukai (Kiyoshi); P. Ströbel (Philipp)

    2015-01-01

    textabstractThis is the second part of a two-part review on soft tissue tumours which may be encountered in the mediastinum. This review is based on the 2013 WHO classification of soft tissue tumours and the 2015 WHO classification of tumours of the lung, pleura, thymus and heart and provides an

  20. Central nervous system tumours in children in Ibadan, Nigeria: a ...

    African Journals Online (AJOL)

    CNS) tumours are uncommon in black children, these neoplasms are the fourth most common paediatric tumours in Ibadan. Our centre is the major referral centre for CNS tumours in Nigeria. The last major study of paediatric CNS neoplasms from ...

  1. Tumour suppressor genes in sporadic epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Liu, Ying; Ganesan, Trivadi S

    2002-01-01

    of the evolution of tumour progression. A major focus of research has been to identify tumour suppressor genes implicated in sporadic ovarian cancer over the past decade. Several tumour suppressor genes have been identified by strategies such as positional cloning and differential expression display. Further...

  2. Neonatal testicular tumour presenting as an acute scrotum

    African Journals Online (AJOL)

    Ann Pediatr Surg 8:19–21 c. 2012 Annals of Pediatric Surgery. Annals of Pediatric Surgery 2012, 8:19–21. Keywords: acute scrotum, granulosa cell tumour, neonatal, testicular tumour .... that trisomy 12 may be widespread (75%) in paediatric granulosa stromal cell tumours and can be identified by fluorescence in-situ ...

  3. Management of Giant Cell Tumour: A Nigerian Experience | Eyesan ...

    African Journals Online (AJOL)

    Giant cell tumours (GCT) are the commonest bone tumours worldwide. It is rarely malignant but when it does it progresses to fibrosarcoma with high mortality. Otherwise it causes poor cosmesis, disability and pathological fractures. A total of 19 cases of histologically established Giant cell tumour of the bone were reviewed ...

  4. Regional tumour glutamine supply affects chromatin and cell identity

    DEFF Research Database (Denmark)

    Højfeldt, Jonas W; Helin, Kristian

    2016-01-01

    Limited perfusion of solid tumours produces a nutrient-deprived tumour core microenvironment. Low glutamine levels in the tumour core are now shown to lead to reduced levels of α-ketoglutarate and decreased histone demethylase activity, thereby promoting a less differentiated and more therapy...

  5. Largest recorded non-invasive true intrathoracic desmoid tumour ...

    African Journals Online (AJOL)

    Intrathoracic desmoid tumours are rare soft-tissue neoplasms arising from fascial or musculo-aponeurotic structures, accounting for less than 0.03% of all neoplasms. Most cases in fact represent intrathoracic extension of chest wall tumours. This case report describes the largest recorded true intrathoracic desmoid tumour ...

  6. Urological Tumours in Jos University Teaching Hospital, Jos, Nigeria

    African Journals Online (AJOL)

    This is a hospital based retrospective histopathological study of urological tumours in 10 years. Specimens consisted of all surgical excisions, trucut and fine needle biopsies of kidney, prostate, urinary bladder, testis and penis. Urological tumours accounted for 11.45% of all malignant tumours during the period of study.

  7. Spinal cord compression due to tumours at Kenyatta Nationa ...

    African Journals Online (AJOL)

    The commonest spinal cord tumour was meningioma (23.7%) followed by neurofibroma (15.8%). Most of the patients (70%) did not show any clinical improvement after surgery. Conclusion: Spinal cord tumours accounted for about 15% of all CNS tumours treated at the Kenyatta National Hospital. Most of the patients had ...

  8. Primary Central Nervous System Tumours in Children and ...

    African Journals Online (AJOL)

    Primary CNS tumours are the commonest childhood solid tumours in most developed countries, accounting for 25-30% of cases. In our environment they occur less frequently. These tumours are nonetheless the cause of significant morbidity and mortality in the paediatric age group worldwide. However paediatric CNS ...

  9. Hypophosphataemia-inducing mesenchymal tumour in the foot.

    Science.gov (United States)

    Bauer, Christa; Brücker, Rolf; Bützberger, Stefan; Schmid, Christoph

    2010-10-06

    Tumour-induced (or oncogenic) osteomalacia is a paraneoplastic syndrome characterised by progressive fatigue, muscle weakness, bone pain, non-healing and recurrent fractures caused by mesenchymal tumours that secrete proteins that inhibit renal phosphate transport and 1α-hydroxylation of 25-OH-vitamin D. The potentially curative treatment of choice is complete surgical excision of the tumour.

  10. Orbito-Ocular Tumours In Nigerian Children | Onwasigwe ...

    African Journals Online (AJOL)

    Conclusion: This study has brought to light the many aspect of orbito-ocular tumours in Nigerian children and also highlighted the many problems caused by inadequate facilities for diagnosis and management. Key words: Orbito-ocular tumours, children, retinoblastoma, tumour sites. [Jnl College of Medicine Vol.7(2) 2002: ...

  11. Malignant tumours of childhood in Zaria | Samaila | African Journal ...

    African Journals Online (AJOL)

    The fi ve commonest tumours over-all were rhabdomyosarcoma, Burkitt lymphoma, retinoblastoma, non-Hodgkin's lymphoma and nephroblastoma. Germ cell tumours affected the ovary predominantly and two of the endodermal sinus tumour cases were seen in the testis of an eighteen month child and sacrococcygeum of a ...

  12. A Retroperitoneal Extra-Renal Wilms' Tumour: A Case Report

    African Journals Online (AJOL)

    2017-03-06

    Mar 6, 2017 ... Abdominal ultrasound and CT scans revealed an extra-renal mass. Intravenous urogram (IVU) showed prompt excretion bilaterally. Post excision histology of the tumour confirmed a Wilms' tumour. A Retroperitoneal Extra-Renal Wilms' Tumour: A Case Report. Address for correspondence: Dr. Samuel ...

  13. Congenital granula cell tumour: report of a case | Olojede | Nigerian ...

    African Journals Online (AJOL)

    Congenital granular cell tumour of the newborn is an uncommon benign tumour of uncertain origin. Mostly, it occurs as a single tumour but rarely as multiple. The lesion arises from the mucosa of the gingiva either from maxillary or mandibular alveolar ridge. This paper reports a three-day old female patient who presented at ...

  14. Orbital tumours and tumour-like lesions: exploring the armamentarium of multiparametric imaging.

    Science.gov (United States)

    Purohit, Bela S; Vargas, Maria Isabel; Ailianou, Angeliki; Merlini, Laura; Poletti, Pierre-Alexandre; Platon, Alexandra; Delattre, Bénédicte M; Rager, Olivier; Burkhardt, Karim; Becker, Minerva

    2016-02-01

    Although the orbit is a small anatomical space, the wide range of structures present within it are often the site of origin of various tumours and tumour-like conditions, both in adults and children. Cross-sectional imaging is mandatory for the detection, characterization, and mapping of these lesions. This review focuses on multiparametric imaging of orbital tumours. Each tumour is reviewed in relation to its clinical presentation, compartmental location, imaging characteristics, and its histological features. We herein describe orbital tumours as lesions of the globe (retinoblastoma, uveal melanoma), optic nerve sheath complex (meningioma, optic nerve glioma), conal-intraconal compartment (hemangioma), extraconal compartment (dermoid/epidermoid, lacrimal gland tumours, lymphoma, rhabdomysarcoma), and bone and sinus compartment (fibrous dysplasia). Lesions without any typical compartmental localization and those with multi-compartment involvement (veno-lymphatic malformation, plexiform neurofibroma, idiopathic orbital pseudotumour, IgG4 related disease, metastases) are also reviewed. We discuss the role of advanced imaging techniques, such as MR diffusion-weighted imaging (DWI), diffusion tensor imaging, fluoro-2-deoxy-D-glucose positron emission tomography CT (FDG-PET CT), and positron emission tomography MRI (MRI PET) as problem-solving tools in the evaluation of those orbital masses that present with non-specific morphologic imaging findings. Main messages/Teaching points • A compartment-based approach is essential for the diagnosis of orbital tumours. • CT and MRI play a key role in the work-up of orbital tumours. • DWI, PET CT, and MRI PET are complementary tools to solve diagnostic dilemmas. • Awareness of salient imaging pearls and diagnostic pitfalls avoids interpretation errors.

  15. 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.

  16. Unbiased Metabolite Profiling of Schizophrenia Fibroblasts under Stressful Perturbations Reveals Dysregulation of Plasmalogens and Phosphatidylcholines.

    Science.gov (United States)

    Huang, Joanne H; Park, Hyoungjun; Iaconelli, Jonathan; Berkovitch, Shaunna S; Watmuff, Bradley; McPhie, Donna; Öngür, Dost; Cohen, Bruce M; Clish, Clary B; Karmacharya, Rakesh

    2017-02-03

    We undertook an unbiased metabolite profiling of fibroblasts from schizophrenia patients and healthy controls to identify metabolites and pathways that are dysregulated in disease, seeking to gain new insights into the disease biology of schizophrenia and to discover potential disease-related biomarkers. We measured polar and nonpolar metabolites in the fibroblasts under normal conditions and under two stressful physiological perturbations: growth in low-glucose media and exposure to the steroid hormone dexamethasone. We found that metabolites that were significantly different between schizophrenia and control subjects showed separation of the two groups by partial least-squares discriminant analysis methods. This separation between schizophrenia and healthy controls was more robust with metabolites identified under the perturbation conditions. The most significant individual metabolite differences were also found in the perturbation experiments. Metabolites that were significantly different between schizophrenia and healthy controls included a number of plasmalogens and phosphatidylcholines. We present these results in the context of previous reports of metabolic profiling of brain tissue and plasma in schizophrenia. These results show the applicability of metabolite profiling under stressful perturbations to reveal cellular pathways that may be involved in disease biology.

  17. Infective complications following tumour endoprosthesis surgery for bone and soft tissue tumours.

    Science.gov (United States)

    Peel, T; May, D; Buising, K; Thursky, K; Slavin, M; Choong, P

    2014-09-01

    This study aims to describe the incidence of infective complications, including tumour endoprosthesis infection, in a cohort of patients undergoing tumour endoprosthesis surgery in Victoria, Australia. This retrospective cohort study was performed over 15 years (January 1996-December 2010). 121 patients underwent tumour endoprosthesis surgery during the study period. Patients were followed for a median of 34 months (interquartile range [IQR] 17, 80). Overall, 34 patients (28%) experienced infective complications including: bacteraemia in 19 patients (16%) and tumour endoprosthesis infection in 17 (14%). The majority of patients with early and late acute infections (haematogenous) were managed with debridement and retention of the prosthesis in addition to biofilm-active antibiotics. Late chronic infections were predominantly managed by exchange of the prosthesis. The overall success rate of treatment was 71%. The success rate for debridement and retention was 75% compared with 67% for exchange procedures. There is a significant rate of infective complications following tumour endoprosthesis surgery including 14% of patients experiencing infection involving the tumour endoprosthesis. This study is the first to report on outcomes from debridement and retention of the prosthesis; which had comparable success rates to other treatment modalities. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  18. Immunohistochemical detection of tumour cell proliferation and intratumoural microvessel density in canine malignant mammary tumours

    Directory of Open Access Journals (Sweden)

    Sennazli Gulbin

    2015-06-01

    Full Text Available The objective of this study was to investigate the correlation between different histological types and grades of canine malignant mammary tumours, tumour cell proliferation and their angiogenic activity using immunohistochemical markers. Mammary tissue samples from 47 bitches with mammary cancer were evaluated. The expression of cellular proliferation marker Ki-67 and endothelial marker Von Willebrand’s factor (vWF were immunohistochemically demonstrated. The tumours with the highest Ki-67 and vWF expressions were found to share similar histomorphological features. Simple solid carcinoma had the highest levels of Ki-67, vWF, and higher histological grade while complex carcinomas, osteosarcomas, and carcinosarcomas had the lowest ones. The differences between the expressions of Ki-67 and vWF in different tumour types were considered to be of great importance in determination of biological behaviour and prognosis of these tumours. This study is one of the few studies that evaluate these differences among the subtypes of malignant canine mammary tumours

  19. Primary liver tumour of intermediate (hepatocyte-bile duct cell) phenotype: a progenitor cell tumour?

    Science.gov (United States)

    Robrechts, C; De Vos, R; Van den Heuvel, M; Van Cutsem, E; Van Damme, B; Desmet, V; Roskams, T

    1998-08-01

    A 57-year-old female patient presented with painless obstructive jaundice and mild mesogastric pain; she was in good general condition on admission. Abdominal ultrasonography revealed diffuse tumoral invasion of the liver, suggesting diffuse metastases. A liver biopsy showed a tumour with a trabecular growth pattern, composed of uniform relatively small cells, very suggestive of an endocrine carcinoma. Additional immunohistochemical stains, however, did not show any endocrine differentiation, but showed positivity for both hepatocyte-type cytokeratins (cytokeratin 8 and 18) and bile duct-type cytokeratins (cytokeratin 7 and 19). In addition, parathyroid hormone-related peptide, shown to be a good marker for cholangiocarcinoma, was immunoreactive. Electron microscopy revealed tumour cells with an intermediate phenotype: the cells clearly showed hepatocyte features on one hand and bile duct cell features on the other hand. Nine days after admission, the patient died due to liver failure and hepatic encephalopathy. Autopsy excluded another primary tumour site. Overall, this tumour was a primary liver tumour with an intermediate phenotype and with a very rapid clinical course. The intermediate (between hepatocyte and bile duct cell) phenotype suggests an immature progenitor cell origin, which is concordant with a rapid clinical course. This type of tumour has not been described previously and provides additional evidence for the existence of progenitor cells in human liver.

  20. [Tumour of the corpus callosum: the association between interhemispheric disconnection and an anterograde amnesia syndrome].

    Science.gov (United States)

    Bustamante, J; Lopera, F

    Sperry, or interhemispheric disconnection, syndrome was reported in patients who had undergone surgical section of the corpus callosum carried out in an attempt to control medication-resistant epilepsy. It has occasionally been linked to tumours of the corpus callosum and, although even more rarely, it has also been associated to an amnesic syndrome. In this paper we report the anatomical and neuropsychological findings in a patient with interhemispheric disconnection syndrome associated to a hippocampal-type amnesic syndrome, caused by a tumour in the splenius of the corpus callosum that extended into the fornix. A 52-year-old white male who visited because of loss of memory; on admission to hospital the physical examination revealed a certain degree of asomatognosia with regard to the left-hand side of the body. An axial tomography brain scan showed a dense central lesion in the brain that extended laterally and occluded the body of both lateral ventricles. A biopsy study revealed an undifferentiated astrocytoma that affected the corpus callosum and the fornix. Sperry, or interhemispheric disconnection, syndrome produced by a tumour in the splenius of the corpus callosum is very likely to course with an amnesic syndrome due to disconnection caused by destruction of the fornix. This association, which characterised our patient's clinical picture, has only previously been described in three cases.

  1. Lesser-known myelin-related disorders: focal tumour-like demyelinating lesions.

    Science.gov (United States)

    Jiménez Arango, J A; Uribe Uribe, C S; Toro González, G

    2015-03-01

    Focal tumour-like demyelinating lesions are defined as solitary demyelinating lesions with a diameter greater than 2 cm. In imaging studies, these lesions may mimic a neoplasm or brain abscess; as a result, invasive diagnostic and therapeutic measures may be performed that will in some cases increase morbidity. Our aim was to analyse and characterise these lesions according to their clinical, radiological, and pathological characteristics, and this data in addition to our literature review will contribute to a better understanding of these lesions. This descriptive study includes 5 cases with pathological diagnoses. We provide subject characteristics gathered through reviewing their clinical, radiology, and pathology reports. Patients' ages ranged from 12 to 60 years; 3 patients were female. The time delay between symptom onset and hospital admission was 3 to 120 days. Clinical manifestations were diverse and dependent on the location of the lesion, pyramidal signs were found in 80% of patients, there were no clinical or radiological signs of spinal cord involvement, and follow-up times ranged from 1 to 15 years. Brain biopsy is the gold standard for the diagnosis of demyelinating tumour-like lesions; however, their clinical features, along with several magnetic resonance imaging features such as open ring enhancement, venular enhancement, the presence of glutamate in spectroscopy, and others, may be sufficient to differentiate neoplastic lesions from focal tumour-like demyelinating lesions. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  2. Metabolomics technologies and metabolite identification

    NARCIS (Netherlands)

    Moco, S.I.A.; Bino, R.J.; Vos, de C.H.; Vervoort, J.J.M.

    2007-01-01

    Metabolomics studies rely on the analysis of the multitude of small molecules (metabolites) present in a biological system. Most commonly, metabolomics is heavily supported by mass spectrometry (MS) and nuclear magnetic resonance (NMR) as parallel technologies that provide an overview of the

  3. BIOACTIVE METABOLITES FROM TRICHODERMA HARZIANUM ...

    African Journals Online (AJOL)

    a

    biocontrol agents against plant pathogens and could be a possible source of fungicides against. A. mellea fungus. It is therefore essential to identify and bioassay the secondary metabolites from Trichoderma isolates against A. mellea. Some Trichoderma species are antagonistic to many soil borne phytopathogenic fungi ...

  4. Childhood tumours with a high probability of being part of a tumour predisposition syndrome; reason for referral for genetic consultation

    NARCIS (Netherlands)

    Postema, Floor A M; Hopman, Saskia M J; Aalfs, Cora M; Berger, Lieke P V; Bleeker, Fonnet E; Dommering, Charlotte J; Jongmans, Marjolijn C J|info:eu-repo/dai/nl/314344349; Letteboer, Tom G W|info:eu-repo/dai/nl/304815837; Olderode-Berends, Maran J W; Wagner, Anja; Hennekam, Raoul C; Merks, Johannes H M

    2017-01-01

    INTRODUCTION: Recognising a tumour predisposition syndrome (TPS) in childhood cancer patients is of major clinical relevance. The presence of a TPS may be suggested by the type of tumour in the child. We present an overview of 23 childhood tumours that in themselves should be a reason to refer a

  5. Childhood tumours with a high probability of being part of a tumour predisposition syndrome; reason for referral for genetic consultation

    NARCIS (Netherlands)

    Postema, Floor A. M.; Hopman, Saskia M. J.; Aalfs, Cora M.; Berger, Lieke P. V.; Bleeker, Fonnet E.; Dommering, Charlotte J.; Jongmans, Marjolijn C. J.; Letteboer, Tom G. W.; Olderode-Berends, Maran J. W.; Wagner, Anja; Hennekam, Raoul C.; Merks, Johannes H. M.

    2017-01-01

    Recognising a tumour predisposition syndrome (TPS) in childhood cancer patients is of major clinical relevance. The presence of a TPS may be suggested by the type of tumour in the child. We present an overview of 23 childhood tumours that in themselves should be a reason to refer a child for genetic

  6. Childhood tumours with a high probability of being part of a tumour predisposition syndrome; reason for referral for genetic consultation

    NARCIS (Netherlands)

    Postema, Floor A. M.; Hopman, Saskia M. J.; Aalfs, Cora M.; Berger, Lieke P. V.; Bleeker, Fonnet E.; Dommering, Charlotte J.; Jongmans, Marjolijn C. J.; Letteboer, Tom G. W.; Olderode - Berends, Maran J.W.; Wagner, Anja; Hennekam, Raoul C.; Merks, Johannes H. M.

    Introduction: Recognising a tumour predisposition syndrome (TPS) in childhood cancer patients is of major clinical relevance. The presence of a TPS may be suggested by the type of tumour in the child. We present an overview of 23 childhood tumours that in themselves should be a reason to refer a

  7. Brain metastasization of breast cancer.

    Science.gov (United States)

    Custódio-Santos, Tânia; Videira, Mafalda; Brito, Maria Alexandra

    2017-08-01

    Central nervous system metastases have been reported in 15-25% of breast cancer patients, and the incidence is increasing. Moreover, the survival of these patients is generally poor, with reports of a 1-year survival rate of 20%. Therefore, a better knowledge about the determinants of brain metastasization is essential for the improvement of the clinical outcomes. Here, we summarize the current data about the metastatic cascade, ranging from the output of cancer cells from the primary tumour to their colonization in the brain, which involves the epithelial-mesenchymal transition, invasion of mammary tissue, intravasation into circulation, and homing into and extravasation towards the brain. The phenotypic change in malignant cells, and the importance of the microenvironment in the formation of brain metastases are also inspected. Finally, the importance of genetic and epigenetic changes, and the recently disclosed effects of microRNAs in brain metastasization of breast cancer are highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Analysis of losses of heterozygosity of the candidate tumour suppressor gene DMBT1 in melanoma resection specimens

    DEFF Research Database (Denmark)

    Deichmann, M; Mollenhauer, J; Helmke, B

    2002-01-01

    Deleted in malignant brain tumours 1 (DMBT1), a candidate tumour suppressor gene located on chromosome 10q25.3-q26.1, has recently been identified and found to be deleted in several different types of human tumours. In melanomas, the chromosomal region 10q22-qter is commonly affected by losses......, hence we screened primary melanoma samples for losses of heterozygosity (LOH), and acquired melanocytic naevi and melanomas for transcription of DMBT1 and protein expression. Of 38 informative melanomas, 1 nodular melanoma and 2 subcutaneous metastases showed LOH of both microsatellites flanking...... the gene, suggesting loss of 1 DMBT1 allele. Three further melanomas showed LOH at 1 informative locus but were heterozygous for the second marker. Applying reverse-transcription polymerase chain reaction (RT-PCR), DMBT1 transcription was not found in melanomas. However, DMBT1 transcription was also absent...

  9. Cognitive outcome after awake surgery for left and right hemisphere tumours

    Directory of Open Access Journals (Sweden)

    Elke De Witte

    2015-04-01

    Full Text Available INTRODUCTION: Awake surgery in eloquent brain regions is performed to preserve language and other cognitive functions. Although in general, no major permanent cognitive deficits are found after awake brain surgery, clinically relevant impairments are detected and cognitive recovery takes longer than generally assumed (3 months (Santini et al., 2012; Satoer et al., 2014; Talacchi et al., 2012. However, as there is a lack of extensive cognitive follow-up data it is unknown when recovery takes place. In addition, the influence of critical language sites identified by direct electrical stimulation (DES and tumour variables (e.g. left/right tumour location, tumour grade on long-term cognitive findings remains unclear. METHODS: In this longitudinal study the short-term and long-term effects of awake surgery on cognition were investigated in 40 patients (29 patients with left and 11 with right hemisphere tumours. Language, memory, attentional, executive and visuospatial functions were assessed in the preoperative phase, at short-term follow-up (6 weeks postsurgery and at long-term follow-up (6 months postsurgery with a neuropsychological protocol. In addition, the effect of intraoperative critical language sites, left/right tumour location, hemispheric language dominance, extent of resection and adjuvant treatment on cognitive change was studied. RESULTS: Both pre- and postoperatively, the mean performance of the patients was worse (impairment = z-score below -2 than the performance of the normal population in the language domain, the memory domain, the attentional and executive domain (p .05. Awake surgery negatively affected language, attentional and executive functions but not memory and visuospatial functions. At 6 weeks postsurgery, performance on all language, attentional and executive tasks deteriorated (object/action naming, semantic/phonological fluency from DuLIP, Token test; Trail Making Test A & B, Stroop I, II, & III. At 6 months

  10. Anti-tumour compounds illudin S and Irofulven induce DNA lesions ignored by global repair and exclusively processed by transcription- and replication-coupled repair pathways.

    OpenAIRE

    Raams, Anja; Kelner, Michael; Ng, Jessica; Yamashita, Yukiko; Takeda, Shiunichi; McMorris, Trevor; Hoeijmakers, Jan; Jaspers, Nicolaas

    2002-01-01

    textabstractIlludin S is a natural sesquiterpene drug with strong anti-tumour activity. Inside cells, unstable active metabolites of illudin cause the formation of as yet poorly characterised DNA lesions. In order to identify factors involved in their repair, we have performed a detailed genetic survey of repair-defective mutants for responses to the drug. We show that 90% of illudin's lethal effects in human fibroblasts can be prevented by an active nucleotide excision repair (NER) system. C...

  11. INTRACRANIAL AND INTRASPINAL TUMOURS: REVIEW OF MRI FINDINGS IN A RARE NF - 2 CASE

    Directory of Open Access Journals (Sweden)

    Sahoo

    2015-02-01

    Full Text Available Neurofibromatosis type 2 is a rare autosomal dominant syndrome, characterized by multiple intracranial and intraspinal tumours associated with ocular abnormalities. The most common tumor associated with the disease is the vestibule cochlear schwannoma, and as many as 10% of patients with this tumor have neurofibromatosis type 2. Based on clinical and imaging findings the diagnostic of neurofibromatosis type 2 can be made. In this report we aim to report a 24 - year - old male who was evaluated for progressive h earing loss, vertigo, ataxic gait and right lower limb weakness. During the workup, cranial CT, Brain and whole s pine MRI was done which showed all the findings in one patient including bilateral vestibulocochlear schwannoma, multiple meningiomas, and intr amedullary and extramedullary tumours in spinal cord.

  12. 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

  13. Molecular characterisation of soft tissue tumours: a gene expression study.

    Science.gov (United States)

    Nielsen, Torsten O; West, Rob B; Linn, Sabine C; Alter, Orly; Knowling, Margaret A; O'Connell, John X; Zhu, Shirley; Fero, Mike; Sherlock, Gavin; Pollack, Jonathan R; Brown, Patrick O; Botstein, David; van de Rijn, Matt

    2002-04-13

    Soft-tissue tumours are derived from mesenchymal cells such as fibroblasts, muscle cells, or adipocytes, but for many such tumours the histogenesis is controversial. We aimed to start molecular characterisation of these rare neoplasms and to do a genome-wide search for new diagnostic markers. We analysed gene-expression patterns of 41 soft-tissue tumours with spotted cDNA microarrays. After removal of errors introduced by use of different microarray batches, the expression patterns of 5520 genes that were well defined were used to separate tumours into discrete groups by hierarchical clustering and singular value decomposition. Synovial sarcomas, gastrointestinal stromal tumours, neural tumours, and a subset of the leiomyosarcomas, showed strikingly distinct gene-expression patterns. Other tumour categories--malignant fibrous histiocytoma, liposarcoma, and the remaining leiomyosarcomas--shared molecular profiles that were not predicted by histological features or immunohistochemistry. Strong expression of known genes, such as KIT in gastrointestinal stromal tumours, was noted within gene sets that distinguished the different sarcomas. However, many uncharacterised genes also contributed to the distinction between tumour types. These results suggest a new method for classification of soft-tissue tumours, which could improve on the method based on histological findings. Large numbers of uncharacterised genes contributed to distinctions between the tumours, and some of these could be useful markers for diagnosis, have prognostic significance, or prove possible targets for treatment.

  14. Primary bone tumours of the hand. Report of 21 cases

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Azouz, E.M.; Campbell, J.; Marton, D.; Morris, L.; Padovani, J.; Sprague, P.; Beluffi, G.; Berzero, G.F.; Cherubino, P.

    1988-02-01

    Twenty-one primary bone tumours of the hand in children from 8 paediatric hospitals are reported. Osteochondromas and enchondromas were not included. Our material consisted of 16 patients with common tumours (3 Ewing's sarcoma, 5 aneurysmal bone cyst, 6 osteoid osteoma and 2 epithelioma) and 5 patients with uncommon tumours (osteoma, simple bone cyst, haemangiopericytoma, capillary angiomatous tumour and benign ossifying fibroma or osteoblastoma). The X-ray diagnosis of the common tumours should have high concordance with histology, whereas that of uncommon tumours in much more difficult and uncertain. The characteristic features of Ewing's sarcoma are stressed as all our children with this tumour had a delayed diagnosis and a fatal outcome. Differential diagnosis with other short tubular bone lesions of the hand - specifically osteomyelitis - is discussed and the posibilities of microscopic diagnosis are stressed.

  15. Aniridia-Wilms′ tumour syndrome-A case report

    Directory of Open Access Journals (Sweden)

    Vidyasagar M

    1992-01-01

    Full Text Available Wilms′ tumour is rarely associated with sporadic non-familial congenital aniridia. A child with sporadic aniridia has a 25% chance of subsequently developing Wilms′ tumour. Unawareness of this association can lead to a delayed diagnosis of Wilms′ tumour. One such case in a 2 year old is reported. Wilms′ tumour, one of the common childhood malignancies, is associated with other congenital anomalies in about 15% of cases. These include hemihypertrophy, genitourinary abnormalities, mental retardation, aniridia etc. Sporadic non-familial aniridia was noted in only 1.1% of 547 children with Wilms′ tumours evaluated by the National Wilms′ Tumour study group. Unawareness on the part of a clinician about these associated anomalies can lead to an avoidable delay in diagnosing Wilms′ tumour. One such case in a two year old girl is being reported.

  16. [Signal symptoms in tumours of the petrous bone (author's transl)].

    Science.gov (United States)

    Charachon, R

    1981-01-01

    Supra-labyrinthic tumours usually produce lesions of the Vth and VIth cranial nerves, whereas infra-labyrinthic tumours affect the sensory-motor nerves. Both types of tumour may reveal themselves by cochleo-vestibular disorders and/or middle ear symptoms. The author has treated a series of patients with such tumours and describes the most frequent types of intrapetrosal growth: cholesteatoma (12 cases), glomic tumours (11 cases), facial nerve tumours (3 cases), metastases (2 cases). Meningiomas can also be encountered, as well as rarer tumours (4 cases), such as embryonic sarcoma, chordoma, chondroma and chondrosarcoma, cavernous angioma, eosinophilic granuloma, solitary plasmocytoma and fibrous dysplasia of the petrous bone. Some signal symptoms (sudden deafness, mucous otitis media, paralysis of vocal cords) can be particularly misleading.

  17. Primary Malignant Neuroendocrine Tumour of Pleura: First Case Report

    Directory of Open Access Journals (Sweden)

    Anirban Das

    2016-01-01

    Full Text Available Metastatic tumours of pleura are the most common malignant tumours causing malignant pleural effusion. Lungs are the most common primary sites. Primary pleural tumours are rarely seen and diffuse malignant mesothelioma is the most common malignant tumour of pleura. Primary malignant neuroendocrine tumour of pleura is not reported in the literature. Here, we report a rare case of primary malignant neuroendocrine tumour of pleura in a fifty-two-year-old, nonsmoker female who presented with right-sided pleural effusion and ipsilateral, dull aching chest pain. Clinical presentations of inflammatory lesions like tuberculous pleuritis and benign and malignant neoplasms of pleura are indistinguishable; hence, fluid cytology, pleural biopsy, and immunohistochemistry are necessary for exact tissue diagnosis of the tumours, which is mandatory for correct treatment and prognostic assessment.

  18. Radiobiological hypoxia, histological parameters of tumour microenvironment and local tumour control after fractionated irradiation.

    Science.gov (United States)

    Yaromina, Ala; Thames, Howard; Zhou, Xuanjing; Hering, Sandra; Eicheler, Wolfgang; Dörfler, Annegret; Leichtner, Thomas; Zips, Daniel; Baumann, Michael

    2010-07-01

    To investigate the relationships between radiobiological hypoxic fraction (rHF), pimonidazole hypoxic fraction (pHF) as well as other histological parameters of the tumour microenvironment, and local tumour control after fractionated irradiation in human squamous cell carcinomas (hSCCs). Ten different hSCC cell lines were transplanted into nude mice and rHF was calculated from local tumour control rates after single dose irradiation under normal or clamped blood flow conditions. In parallel, tumours were irradiated with 30 fractions within 6 weeks. Radiation response was quantified as dose required to cure 50% of tumours (TCD(50)). Unirradiated tumours were excised for histological evaluation including relative hypoxic area (pHF), relative vascular area (RVA), and fraction of perfused vessels (PF). A weak but significant positive correlation between rHF (R(2)=0.6, p=0.014) and TCD(50) after fractionated irradiation was found. The pHF did not correlate with rHF but was significantly associated with the TCD(50) after single dose clamp (R(2)=0.8, p=0.003) and showed a trend for an association with TCD(50) after fractionated irradiation (R(2)=0.4, p=0.067). Relative vascular area and fraction of perfused vessels did not show an association with rHF or TCD(50) after fractionated irradiation. Our data suggest that radiobiological hypoxia contributes to the response after fractionated irradiation but that also other radiobiological mechanisms are involved. In the present study, pimonidazole labelling does not reflect rHF and has a limited value to predict local tumour control after fractionated irradiation. The association between pHF and TCD(50) after single dose clamp warrants further investigation. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  19. COX-2, VEGF and tumour angiogenesis.

    LENUS (Irish Health Repository)

    Toomey, D P

    2009-06-01

    Epidemiological evidence suggests a protective effective of regular NSAID use against developing cancer. Cyclooxygenase-2, a target of NSAIDs, is upregulated in many cancers and has been associated with increased VEGF production and angiogenesis. Angiogenesis is the formation of new vessels from existing vasculature and as an essential process for tumour development represents an important therapeutic target. Following an extensive review of the literature this article details the current knowledge on the role of COX-2 in tumorigenesis focusing on its relationship to angiogenesis and VEGF production by tumour cells. While COX-2 is clearly detrimental to prognosis and NSAIDs have a beneficial effect, the possibility of COX-2 independent effects being partly or wholly responsible for this benefit cannot be excluded.

  20. [Surgical treatment of children with hepatic tumours

    DEFF Research Database (Denmark)

    Rasmussen, A.; Kvist, N.; Kirkegaard, P.

    2008-01-01

    %). There was no difference in survival dependent on the type of resection, and there was no impact of the extension of tumour growth at the time of diagnosis. CONCLUSION: The combination of neoadjuvant chemotherapy followed by liver resection or liver transplantation is the treatment of choice in all children...... with hepatoblastoma. The results have improved dramatically over the last decades. The results in Denmark compare well with international results. Since 2000, very effective chemotherapy has downstaged all referred patients, so subsequent liver resection have been possible Udgivelsesdato: 2008/4/14......INTRODUCTION: In this paper we review the results of surgical treatment of children with hepatic tumours. MATERIALS AND METHODS: The study comprises 33 children who have undergone lever resection or liver transplantation since 1990. 26 patients had hepatoblastoma, 3 had hepatocellular carcinoma, 2...