WorldWideScience

Sample records for brain tumour model

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

    Directory of Open Access Journals (Sweden)

    Li Xingang

    2009-12-01

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

  2. 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),

  3. 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.

  4. 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.

  5. 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.

  6. Neuropathological diagnosis of brain tumours.

    Science.gov (United States)

    Pollo, Bianca

    2011-11-01

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

  7. 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.

  8. 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....

  9. 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...

  10. 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.

  11. 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....

  12. 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...

  13. 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.)

  14. 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

  15. 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...

  16. 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.

  17. 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 ...

  18. 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 ...

  19. 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

  20. 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...

  1. 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

  2. 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.

  3. 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.

  4. 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 ...

  5. 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.

  6. 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...

  7. 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.

  8. 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.

  9. 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....

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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...

  16. 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.

  17. 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.

  18. 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 ...

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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 ...

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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....

  14. 3D Multiscale Modelling of Angiogenesis and Vascular Tumour Growth

    KAUST Repository

    Perfahl, H.

    2012-11-01

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

  15. Mathematical modelling of the development of a cylindrical tumour

    Directory of Open Access Journals (Sweden)

    Algis Kavaliauskas

    2014-08-01

    Full Text Available The article deals with interaction of tumour cells and leucocytes in the cylindrical cavities. This type of interaction is typical in the cases of development of a tumour in the intestine, blood vessel or in a bone cavity. Two cases are separated: the case of soft and hard tumour. In the case of a solid tumour, leucocytes can interact only with the surface cells of the tumour. This type of interaction is described by the system of two nonlinear first degree differential equations. The expressions of stationary points are obtained and analysis of their stability is performed. In the case of a soft tumour the system of two partial differential equations with first order derivatives and initial and boundary conditions is proposed. An algorithm for computing the numeric solution of the mathematical model is applied. In this case the diffusion of leucocytes and their ability to reach the tumour cells in the whole volume of the tumour is included. The algorithm is constructed and the system is solved numerically. Bifurcation curve is obtained. It separates two qualitatively different areas on the two parameter plane. Under the same initial parameters in the first area development of the tumour cells cannot be stopped, whereas in the second area leukocytes defeat the tumour cells.DOI: http://dx.doi.org/10.15181/csat.v2i1.183

  16. 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.

  17. 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

  18. {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.

  19. 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.

  20. 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.

  1. 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

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

    KAUST Repository

    Hubbard, M.E.

    2013-01-01

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

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. Modelling breast cancer tumour growth for a stable disease population.

    Science.gov (United States)

    Isheden, Gabriel; Humphreys, Keith

    2017-01-01

    Statistical models of breast cancer tumour progression have been used to further our knowledge of the natural history of breast cancer, to evaluate mammography screening in terms of mortality, to estimate overdiagnosis, and to estimate the impact of lead-time bias when comparing survival times between screen detected cancers and cancers found outside of screening programs. Multi-state Markov models have been widely used, but several research groups have proposed other modelling frameworks based on specifying an underlying biological continuous tumour growth process. These continuous models offer some advantages over multi-state models and have been used, for example, to quantify screening sensitivity in terms of mammographic density, and to quantify the effect of body size covariates on tumour growth and time to symptomatic detection. As of yet, however, the continuous tumour growth models are not sufficiently developed and require extensive computing to obtain parameter estimates. In this article, we provide a detailed description of the underlying assumptions of the continuous tumour growth model, derive new theoretical results for the model, and show how these results may help the development of this modelling framework. In illustrating the approach, we develop a model for mammography screening sensitivity, using a sample of 1901 post-menopausal women diagnosed with invasive breast cancer.

  8. 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....

  9. 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...

  10. Towards a more realistic biomechanical modelling of breast malignant tumours

    Science.gov (United States)

    Wessel, Carolina; Schnabel, Julia A.; Brady, Michael

    2012-02-01

    We develop a biomechanical model of an isolated stellate breast tumour under mammographic compression forces for a range of reported mechanical properties, both linear elastic and hyperelastic. We also introduce different volumes of increased density/stiffness around the tumour as well as a solid pressure effect. We show that each of these issues—well known to clinicians but ignored to date in models—has a non-negligible effect on stresses and strains/deformations.

  11. 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.

  12. 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 ...

  13. 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.

  14. 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

  15. (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

  16. 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

  17. {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.

  18. 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.

  19. 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.

  20. 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.)

  1. 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.)

  2. Numerical resolution of a model of tumour growth.

    Science.gov (United States)

    Muñoz, Ana I

    2016-03-01

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

  3. 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.

  4. Blood vessel hyperpermeability and pathophysiology in human tumour xenograft models of breast cancer: a comparison of ectopic and orthotopic tumours

    Directory of Open Access Journals (Sweden)

    Ho Karyn S

    2012-12-01

    Full Text Available Abstract Background Human tumour xenografts in immune compromised mice are widely used as cancer models because they are easy to reproduce and simple to use in a variety of pre-clinical assessments. Developments in nanomedicine have led to the use of tumour xenografts in testing nanoscale delivery devices, such as nanoparticles and polymer-drug conjugates, for targeting and efficacy via the enhanced permeability and retention (EPR effect. For these results to be meaningful, the hyperpermeable vasculature and reduced lymphatic drainage associated with tumour pathophysiology must be replicated in the model. In pre-clinical breast cancer xenograft models, cells are commonly introduced via injection either orthotopically (mammary fat pad, MFP or ectopically (subcutaneous, SC, and the organ environment experienced by the tumour cells has been shown to influence their behaviour. Methods To evaluate xenograft models of breast cancer in the context of EPR, both orthotopic MFP and ectopic SC injections of MDA-MB-231-H2N cells were given to NOD scid gamma (NSG mice. Animals with matched tumours in two size categories were tested by injection of a high molecular weight dextran as a model nanocarrier. Tumours were collected and sectioned to assess dextran accumulation compared to liver tissue as a positive control. To understand the cellular basis of these observations, tumour sections were also immunostained for endothelial cells, basement membranes, pericytes, and lymphatic vessels. Results SC tumours required longer development times to become size matched to MFP tumours, and also presented wide size variability and ulcerated skin lesions 6 weeks after cell injection. The 3 week MFP tumour model demonstrated greater dextran accumulation than the size matched 5 week SC tumour model (for P  Conclusions Dextran accumulation and immunostaining results suggest that small MFP tumours best replicate the vascular permeability required to observe the EPR effect

  5. 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.)

  6. 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.

  7. 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.

  8. 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...

  9. 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...

  10. 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.

  11. 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...

  12. 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...

  13. 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...

  14. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  16. 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....

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

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

    Indian Academy of Sciences (India)

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

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

    Indian Academy of Sciences (India)

    Srinivas

    new insights into both vascular collapse and tumour growth dynamics. A particular ... a vascular tumour. The model also highlights the roles of various tissue properties in inducing vascular collapse. Jackson et al (1999) proposed a promising two-step approach that is ... In order to access the tumour's response to the.

  4. 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.

  5. 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...

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Brain Network Modelling

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther

    Three main topics are presented in this thesis. The first and largest topic concerns network modelling of functional Magnetic Resonance Imaging (fMRI) and Diffusion Weighted Imaging (DWI). In particular nonparametric Bayesian methods are used to model brain networks derived from resting state f...... for their ability to reproduce node clustering and predict unseen data. Comparing the models on whole brain networks, BCD and IRM showed better reproducibility and predictability than IDM, suggesting that resting state networks exhibit community structure. This also points to the importance of using models, which...... allow for complex interactions between all pairs of clusters. In addition, it is demonstrated how the IRM can be used for segmenting brain structures into functionally coherent clusters. A new nonparametric Bayesian network model is presented. The model builds upon the IRM and can be used to infer...

  14. 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.

  15. 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.

  16. 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.

  17. 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).

  18. 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

  19. 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.

  20. [A tumour-mimic pig liver model for guiding focused ultrasound thermal ablation].

    Science.gov (United States)

    Melodelima, D; N'djin, Wa; Parmentier, H; Chesnais, S; Rivoire, M; Chapelon, J-Y

    2007-11-01

    There is no established liver tumour model in pigs to study the efficacy of ablative treatment options available for the treatment of liver tumours by physical agents. A tumour-mimic model visible with high contrast on sonograms and on gross pathology has been studied at mid-term on 20 pigs. The aim was to determine if these tumour-mimics are well tolerated and can be used to validate the use of thermal therapies at a preclinical stage. The dimensions of the tumour-mimics measured on sonograms were reproducible (diameter: 9.6 +/- 1.9 mm) and correlated with those performed in gross pathology (R(2)=0.73). The accuracy of focused ultrasound thermal therapy can be evaluated preclinically using these tumour-mimics.

  1. 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.

  2. 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

  3. Characterising the tumour morphological response to therapeutic intervention: an ex vivo model

    Directory of Open Access Journals (Sweden)

    Anne Savage

    2013-01-01

    In cancer, morphological assessment of histological tissue samples is a fundamental part of both diagnosis and prognosis. Image analysis offers opportunities to support that assessment through quantitative metrics of morphology. Generally, morphometric analysis is carried out on two-dimensional tissue section data and so only represents a small fraction of any tumour. We present a novel application of three-dimensional (3D morphometrics for 3D imaging data obtained from tumours grown in a culture model. Minkowski functionals, a set of measures that characterise geometry and topology in n-dimensional space, are used to quantify tumour topology in the absence of and in response to therapeutic intervention. These measures are used to stratify the morphological response of tumours to therapeutic intervention. Breast tumours are characterised by estrogen receptor (ER status, human epidermal growth factor receptor (HER2 status and tumour grade. Previously, we have shown that ER status is associated with tumour volume in response to tamoxifen treatment ex vivo. Here, HER2 status is found to predict the changes in morphology other than volume as a result of tamoxifen treatment ex vivo. Finally, we show the extent to which Minkowski functionals might be used to predict tumour grade. Minkowski functionals are generalisable to any 3D data set, including in vivo and cellular systems. This quantitative topological analysis can provide a valuable link among biomarkers, drug intervention and tumour morphology that is complementary to existing, non-morphological measures of tumour response to intervention and could ultimately inform patient treatment.

  4. Predictive model for functional consequences of oral cavity tumour resections

    NARCIS (Netherlands)

    van Alphen, M.J.A.; Hageman, T.A.G.; Hageman, Tijmen Antoon Geert; Smeele, L.E.; Balm, Alfonsus Jacobus Maria; Balm, A.J.M.; van der Heijden, Ferdinand; Lemke, H.U.

    2013-01-01

    The prediction of functional consequences after treatment of large oral cavity tumours is mainly based on the size and location of the tumour. However, patient specific factors play an important role in the functional outcome, making the current predictions unreliable and subjective. An objective

  5. 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....

  6. The impact of hypoxia on the activity of lactate dehydrogenase in two different pre-clinical tumour models

    DEFF Research Database (Denmark)

    Lukacova, Slavka; Sørensen, Brita; Alsner, Jan

    2008-01-01

    squamous cell carcinoma, respectively. Low oxygen breathing for 1-72 h was used to increase tumour hypoxia. Ldh activity was measured in the serum and tumour cytosole with a colorimetric method. Tumour Ldha mRNA levels were assessed with RT-PCR. Results. The serum Ldh in non-tumour bearing CDF1 mice and C3...... carcinoma bearing mice. Reoxygenation for 4 or 24 hours had no additional effect on Ldh activity in any of the models. Discussion. Serum Ldh activity can be a marker for tumour burden in certain types of cancer. The relationship between serum and tumour Ldh and tumour hypoxia has not been confirmed. However...

  7. Nonlinear modelling of cancer: bridging the gap between cells and tumours

    Science.gov (United States)

    Lowengrub, J. S.; Frieboes, H. B.; Jin, F.; Chuang, Y.-L.; Li, X.; Macklin, P.; Wise, S. M.; Cristini, V.

    2010-01-01

    Despite major scientific, medical and technological advances over the last few decades, a cure for cancer remains elusive. The disease initiation is complex, and including initiation and avascular growth, onset of hypoxia and acidosis due to accumulation of cells beyond normal physiological conditions, inducement of angiogenesis from the surrounding vasculature, tumour vascularization and further growth, and invasion of surrounding tissue and metastasis. Although the focus historically has been to study these events through experimental and clinical observations, mathematical modelling and simulation that enable analysis at multiple time and spatial scales have also complemented these efforts. Here, we provide an overview of this multiscale modelling focusing on the growth phase of tumours and bypassing the initial stage of tumourigenesis. While we briefly review discrete modelling, our focus is on the continuum approach. We limit the scope further by considering models of tumour progression that do not distinguish tumour cells by their age. We also do not consider immune system interactions nor do we describe models of therapy. We do discuss hybrid-modelling frameworks, where the tumour tissue is modelled using both discrete (cell-scale) and continuum (tumour-scale) elements, thus connecting the micrometre to the centimetre tumour scale. We review recent examples that incorporate experimental data into model parameters. We show that recent mathematical modelling predicts that transport limitations of cell nutrients, oxygen and growth factors may result in cell death that leads to morphological instability, providing a mechanism for invasion via tumour fingering and fragmentation. These conditions induce selection pressure for cell survivability, and may lead to additional genetic mutations. Mathematical modelling further shows that parameters that control the tumour mass shape also control its ability to invade. Thus, tumour morphology may serve as a predictor of

  8. 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.

  9. The influence of mitoses rate on growth dynamics of a cellular automata model of tumour growth

    NARCIS (Netherlands)

    Naumov, L.; Hoekstra, A.; Sloot, P.

    2010-01-01

    Mitosis inside a tumour can be prohibited for different reasons, such as overcrowding or physical pressure. At the same time, the rate of successful mitoses inside a tumour can hardly be measured in vivo or vitro, but is easily modeled in silico. In this paper we present a study of the influence of

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

    Directory of Open Access Journals (Sweden)

    O. G. Isaeva

    2009-01-01

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

  11. 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.

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

    Indian Academy of Sciences (India)

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

  13. 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.

  14. 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...

  15. 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.

  16. 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).

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Maini PK

    2010-04-01

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

  19. 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 ...

  20. 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.

  1. Cell adhesion heterogeneity reinforces tumour cell dissemination: novel insights from a mathematical model.

    Science.gov (United States)

    Reher, David; Klink, Barbara; Deutsch, Andreas; Voss-Böhme, Anja

    2017-08-11

    Cancer cell invasion, dissemination, and metastasis have been linked to an epithelial-mesenchymal transition (EMT) of individual tumour cells. During EMT, adhesion molecules like E-cadherin are downregulated and the decrease of cell-cell adhesion allows tumour cells to dissociate from the primary tumour mass. This complex process depends on intracellular cues that are subject to genetic and epigenetic variability, as well as extrinsic cues from the local environment resulting in a spatial heterogeneity in the adhesive phenotype of individual tumour cells. Here, we use a novel mathematical model to study how adhesion heterogeneity, influenced by intrinsic and extrinsic factors, affects the dissemination of tumour cells from an epithelial cell population. The model is a multiscale cellular automaton that couples intracellular adhesion receptor regulation with cell-cell adhesion. Simulations of our mathematical model indicate profound effects of adhesion heterogeneity on tumour cell dissemination. In particular, we show that a large variation of intracellular adhesion receptor concentrations in a cell population reinforces cell dissemination, regardless of extrinsic cues mediated through the local cell density. However, additional control of adhesion receptor concentration through the local cell density, which can be assumed in healthy cells, weakens the effect. Furthermore, we provide evidence that adhesion heterogeneity can explain the remarkable differences in adhesion receptor concentrations of epithelial and mesenchymal phenotypes observed during EMT and might drive early dissemination of tumour cells. Our results suggest that adhesion heterogeneity may be a universal trigger to reinforce cell dissemination in epithelial cell populations. This effect can be at least partially compensated by a control of adhesion receptor regulation through neighbouring cells. Accordingly, our findings explain how both an increase in intra-tumour adhesion heterogeneity and the

  2. 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.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Zagozdzon Agnieszka M

    2012-05-01

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

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

    LENUS (Irish Health Repository)

    Zagozdzon, Agnieszka M

    2012-05-30

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

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

    Science.gov (United States)

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

    2010-11-01

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

  8. Modelling circulating tumour cells for personalised survival prediction in metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Gianluca Ascolani

    2015-05-01

    Full Text Available Ductal carcinoma is one of the most common cancers among women, and the main cause of death is the formation of metastases. The development of metastases is caused by cancer cells that migrate from the primary tumour site (the mammary duct through the blood vessels and extravasating they initiate metastasis. Here, we propose a multi-compartment model which mimics the dynamics of tumoural cells in the mammary duct, in the circulatory system and in the bone. Through a branching process model, we describe the relation between the survival times and the four markers mainly involved in metastatic breast cancer (EPCAM, CD47, CD44 and MET. In particular, the model takes into account the gene expression profile of circulating tumour cells to predict personalised survival probability. We also include the administration of drugs as bisphosphonates, which reduce the formation of circulating tumour cells and their survival in the blood vessels, in order to analyse the dynamic changes induced by the therapy. We analyse the effects of circulating tumour cells on the progression of the disease providing a quantitative measure of the cell driver mutations needed for invading the bone tissue. Our model allows to design intervention scenarios that alter the patient-specific survival probability by modifying the populations of circulating tumour cells and it could be extended to other cancer metastasis dynamics.

  9. A combination of cisplatin-eluting gelatin microspheres and flavopiridol enhances anti-tumour effects in a rabbit VX2 liver tumour model.

    Science.gov (United States)

    Nitta, N; Sonoda, A; Seko, A; Ohta, S; Nagatani, Y; Tsuchiya, K; Otani, H; Tanaka, T; Kanasaki, S; Takahashi, M; Murata, K

    2010-05-01

    The aim of this study was to investigate whether the combination of cisplatin-eluting gelatin microspheres (GMSs) and flavopiridol enhances anti-tumour effects in a rabbit VX2 liver tumour model. Tumour-bearing rabbits (n = 21) were divided into five groups and infused from the proper hepatic artery. Group 1 (n = 5) received cisplatin-eluting GMSs (1 mg kg(-1)) and flavopiridol (3 mg kg(-1)), group 2 (n = 5) cisplatin-eluting GMSs alone (1 mg kg(-1)), Group 3 (n = 5) flavopiridol (3 mg kg(-1)), Group 4 (n = 3) GMSs alone (1 mg kg(-1)), and Group 5 (n = 3) was the control group receiving physiological saline (1 ml kg(-1)). On days 0 and 7 after procedures the liver tumour volume was measured using a horizontal open MRI system and the relative tumour volume growth rates for 7 days after treatment were calculated. On T(1) weighted images, the tumours were visualised as circular, low-intensity areas just below the liver surface. After treatment, the signals remained similar. The relative tumour volume growth rate for 7 days after treatment was 54.2+/-22.4% in Group 1, 134.1+/-40.1% in Group 2,166.7+/-48.1% in Group 3, 341.8+/-8.6% in Group 4 and 583.1+/-46.9% in Group 5; the growth rate was significantly lower in Group 1 than the other groups (pflavopiridol was effective.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-02-15

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

  11. The Klein–Gordon equation in mixture models of tumour growth

    Energy Technology Data Exchange (ETDEWEB)

    Caviglia, G. [DIMA, University of Genoa, Via Dodecaneso 35, 16146 Genoa (Italy); Morro, A. [DIBRIS, University of Genoa, Via Opera Pia 13, 16145 Genoa (Italy); Pinamonti, N., E-mail: pinamont@dima.unige.it [DIMA, University of Genoa, Via Dodecaneso 35, 16146 Genoa (Italy); INFN, Sezione di Genova, Via Dodecaneso 33, 16146 Genoa (Italy)

    2014-11-14

    A mixture model of tumour microenvironment is considered, which consists of a solid phase for the tumour cells, a liquid phase for the interstitial fluid, and a nutrient phase. The balance equations for the three phases take into account exchange of mass between tumour and nutrients, and exchange of drag forces between the constituents. Under rather natural assumptions, the determination of the nutrient density is reduced to the solution of a Klein–Gordon equation, with source term depending on mass injection from outside. A chain of decoupled equations for the remaining unknowns is then determined in terms of the nutrient density. Finally, the growth of tumour volume is investigated under the assumption of spherical symmetry.

  12. 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

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

    Science.gov (United States)

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

    2017-07-13

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

  14. 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.

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

    Science.gov (United States)

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

    2017-04-01

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

  16. 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

  17. 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

  18. 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.)

  19. Oxygen-Driven Tumour Growth Model: A Pathology-Relevant Mathematical Approach.

    Directory of Open Access Journals (Sweden)

    Juan A Delgado-SanMartin

    2015-10-01

    Full Text Available Xenografts--as simplified animal models of cancer-differ substantially in vasculature and stromal architecture when compared to clinical tumours. This makes mathematical model-based predictions of clinical outcome challenging. Our objective is to further understand differences in tumour progression and physiology between animal models and the clinic. To achieve that, we propose a mathematical model based upon tumour pathophysiology, where oxygen--as a surrogate for endocrine delivery--is our main focus. The Oxygen-Driven Model (ODM, using oxygen diffusion equations, describes tumour growth, hypoxia and necrosis. The ODM describes two key physiological parameters. Apparent oxygen uptake rate (k'R represents the amount of oxygen cells seem to need to proliferate. The more oxygen they appear to need, the more the oxygen transport. k'R gathers variability from the vasculature, stroma and tumour morphology. Proliferating rate (kp deals with cell line specific factors to promote growth. The KH,KN describe the switch of hypoxia and necrosis. Retrospectively, using archived data, we looked at longitudinal tumour volume datasets for 38 xenografted cell lines and 5 patient-derived xenograft-like models. Exploration of the parameter space allows us to distinguish 2 groups of parameters. Group 1 of cell lines shows a spread in values of k'R and lower kp, indicating that tumours are poorly perfused and slow growing. Group 2 share the value of the oxygen uptake rate (k'R and vary greatly in kp, which we interpret as having similar oxygen transport, but more tumour intrinsic variability in growth. However, the ODM has some limitations when tested in explant-like animal models, whose complex tumour-stromal morphology may not be captured in the current version of the model. Incorporation of stroma in the ODM will help explain these discrepancies. We have provided an example. The ODM is a very simple -and versatile- model suitable for the design of preclinical

  20. 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...

  1. In Silico Modelling of Tumour Margin Diffusion and Infiltration: Review of Current Status

    Directory of Open Access Journals (Sweden)

    Fatemeh Leyla Moghaddasi

    2012-01-01

    Full Text Available As a result of advanced treatment techniques, requiring precise target definitions, a need for more accurate delineation of the Clinical Target Volume (CTV has arisen. Mathematical modelling is found to be a powerful tool to provide fairly accurate predictions for the Microscopic Extension (ME of a tumour to be incorporated in a CTV. In general terms, biomathematical models based on a sequence of observations or development of a hypothesis assume some links between biological mechanisms involved in cancer development and progression to provide quantitative or qualitative measures of tumour behaviour as well as tumour response to treatment. Generally, two approaches are taken: deterministic and stochastic modelling. In this paper, recent mathematical models, including deterministic and stochastic methods, are reviewed and critically compared. It is concluded that stochastic models are more promising to provide a realistic description of cancer tumour behaviour due to being intrinsically probabilistic as well as discrete, which enables incorporation of patient-specific biomedical data such as tumour heterogeneity and anatomical boundaries.

  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. 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...

  4. 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.

  5. Modeling Structural Brain Connectivity

    DEFF Research Database (Denmark)

    Ambrosen, Karen Marie Sandø

    The human brain consists of a gigantic complex network of interconnected neurons. Together all these connections determine who we are, how we react and how we interpret the world. Knowledge about how the brain is connected can further our understanding of the brain’s structural organization, help...... improve diagnosis, and potentially allow better treatment of a wide range of neurological disorders. Tractography based on diffusion magnetic resonance imaging is a unique tool to estimate this “structural connectivity” of the brain non-invasively and in vivo. During the last decade, brain connectivity...... has increasingly been analyzed using graph theoretic measures adopted from network science and this characterization of the brain’s structural connectivity has been shown to be useful for the classification of populations, such as healthy and diseased subjects. The structural connectivity of the brain...

  6. 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...

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Sergey V. Tokalov

    2010-01-01

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

  9. 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.

  10. 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 ...

  11. 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.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-09-15

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

  13. 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.)

  14. 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.

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

    Indian Academy of Sciences (India)

    Abstract. We investigate an initial value problem which is closely related to the. Williams±Bjerknes tumour model for a cancer which spreads through an epithelial basal layer modeled on I & Z2. The solution of this problem is a family p ˆ … pi…t††, where each pi…t† could be considered as an approximation to the ...

  16. 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...

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

    Science.gov (United States)

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

    2018-01-01

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

  18. Bayesian Calibration, Validation and Uncertainty Quantification for Predictive Modelling of Tumour Growth: A Tutorial.

    Science.gov (United States)

    Collis, Joe; Connor, Anthony J; Paczkowski, Marcin; Kannan, Pavitra; Pitt-Francis, Joe; Byrne, Helen M; Hubbard, Matthew E

    2017-04-01

    In this work, we present a pedagogical tumour growth example, in which we apply calibration and validation techniques to an uncertain, Gompertzian model of tumour spheroid growth. The key contribution of this article is the discussion and application of these methods (that are not commonly employed in the field of cancer modelling) in the context of a simple model, whose deterministic analogue is widely known within the community. In the course of the example, we calibrate the model against experimental data that are subject to measurement errors, and then validate the resulting uncertain model predictions. We then analyse the sensitivity of the model predictions to the underlying measurement model. Finally, we propose an elementary learning approach for tuning a threshold parameter in the validation procedure in order to maximize predictive accuracy of our validated model.

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

    Science.gov (United States)

    Sharifi, N; Ozgoli, S; Ramezani, A

    2017-06-01

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

  20. 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...

  1. 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.)

  2. Cisplatin plus paclitaxel and maintenance of bevacizumab on tumour progression, dissemination, and survival of ovarian carcinoma xenograft models.

    Science.gov (United States)

    Oliva, P; Decio, A; Castiglioni, V; Bassi, A; Pesenti, E; Cesca, M; Scanziani, E; Belotti, D; Giavazzi, R

    2012-07-10

    Bevacizumab is being incorporated as first-line therapy with standard-of-care chemotherapy on epithelial ovarian carcinoma (EOC). We investigated bevacizumab combined with chemotherapy on tumour progression and mouse survival in EOC xenograft models. Bevacizumab was administered concomitantly with cisplatin plus paclitaxel (DDP+PTX), continued after induction (maintenance) or started after chemotherapy. The effect on tumour progression was monitored by bioluminescence imaging (BLI) (1A9-luc xenograft). Tumour dissemination into the peritoneal organs and ascites formation (HOC22 xenograft) was evaluated by histological analysis at the end of treatment (interim) and at euthanasia (survival). The effects on overall survival (OS) were investigated in both EOC models. Bevacizumab with PTX+DDP delayed tumour progression in mice bearing EOC xenografts. OS was significantly extended, with complete responses, by bevacizumab continued after stopping chemotherapy in the HOC22 xenograft. Bevacizumab alone inhibited ascites formation, with only limited effect on tumour burden, but combined with PTX+DDP reduced ascites and metastases. Bevacizumab started after induction with PTX+DDP and maintained was equally effective on tumour progression and survival on 1A9-luc xenograft. Bevacizumab combined with chemotherapy not only affected tumour progression, but when administered as maintenance regimen significantly prolonged survival, reducing ascites, and tumour dissemination. We believe our findings are consistent with the clinical results and shed light on the potential effects of this kind of treatment on tumour progression.

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

    Science.gov (United States)

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

    2017-03-01

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

  4. A heterogeneous in vitro three dimensional model of tumour-stroma interactions regulating sprouting angiogenesis.

    Science.gov (United States)

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

    2012-01-01

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

  5. A heterogeneous in vitro three dimensional model of tumour-stroma interactions regulating sprouting angiogenesis.

    Directory of Open Access Journals (Sweden)

    Pedro Correa de Sampaio

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

  6. 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.

  7. A preliminary study on a new model system to evaluate tumour-detection and tumour-purging protocols in ovarian cortex tissue intended for fertility preservation.

    Science.gov (United States)

    Peek, R; Bastings, L; Westphal, J R; Massuger, L F A G; Braat, D D M; Beerendonk, C C M

    2015-04-01

    Is it possible to create a model system that mimics ovarian metastatic disease in order to devise new strategies to detect cancer cells and prevent cancer cell transmission via ovarian tissue autotransplantation in cancer survivors? Injection of bovine or human ovarian cortex fragments with cells from different cancer types led to the formation of proliferating tumour masses and newly formed small metastatic lesions. Autotransplantation of ovarian tissue comes with the major concern of cancer cells possibly being present in the tissue. A model system to develop strategies aimed at enhancing the safety of ovarian tissue autotransplantation is currently lacking. The ability of injected human leukaemia, lymphoma, Ewing's sarcoma or breast cancer cells to proliferate and form tumour-like structures in bovine and human ovarian cortex tissue in vitro was assessed. The injected cells were from human cancer cell lines. After 4 days of culture, some tissue fragments were harvested for standard histological staining and immunohistochemical staining of tumour cell specific antigens and the Ki67 proliferation marker, while the remaining fragments were incubated for an additional 6 days (bovine tissue) or 3 days (human tissue) before analysis. Experiments were performed with ovarian tissue from women after prophylactic salpingo-oophorectomy. Bovine ovarian tissue was obtained at an abattoir. Glucose uptake during in vitro culture was monitored to quantify the viability of tissue. Tumour formation was assessed at Day 4 and Day 10 in bovine ovarian tissue and at Day 4 and Day 7 in human ovarian tissue, using histology and immunohistochemistry. We found that bovine and human ovarian cortex tissue could be cultured for up to 10 and 7 days, respectively, without any loss of viability. Our preliminary results show that all cell lines tested were capable of forming proliferating tumours in ovarian cortex tissue in vitro. Lymphoma and breast cancer cells produced small metastases near

  8. 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

  9. Combination of radiotherapy with the immunocytokine L19-IL2: Additive effect in a NK cell dependent tumour model.

    Science.gov (United States)

    Rekers, Nicolle H; Zegers, Catharina M L; Yaromina, Ala; Lieuwes, Natasja G; Biemans, Rianne; Senden-Gijsbers, Birgit L M G; Losen, Mario; Van Limbergen, Evert J; Germeraad, Wilfred T V; Neri, Dario; Dubois, Ludwig; Lambin, Philippe

    2015-09-01

    Recently, we have shown that radiotherapy (RT) combined with the immunocytokine L19-IL2 can induce long-lasting antitumour effects, dependent on ED-B expression and infiltration of cytotoxic T cells. On the other hand, in certain tumours, IL2 treatment can trigger a natural killer cell (NK) immune response. The aim of this study is to investigate the therapeutic effect of our combination therapy in the ED-B positive F9 teratocarcinoma model, lacking MHCI expression and known to be dependent on NK immune responses. In syngeneic F9 tumour bearing 129/FvHsd mice tumour growth delay was evaluated after local tumour irradiation (10Gy) combined with systemic administration of L19-IL2. Immunological responses were investigated using flow cytometry. Tumour growth delay of L19-IL2 can be further improved by a single dose of RT administered before immunotherapy, but not during immunotherapy. Furthermore, treatment of L19-IL2 favours a NK response and lacks cytotoxic T cell tumour infiltrating immune cells, which may be explained by the absence of MHCI expression. An additive effect can be detected when the NK dependent F9 tumour model is treated with radiotherapy and L19-IL2 and therefore this combination could be useful in the absence of tumoural MHCI expression. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  10. 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

  11. Analysis of tumour infiltrating leukocytes in colon cancer carcinoma in a syngeneic rat model

    OpenAIRE

    Borgström, Annelie

    2010-01-01

    Tumour immunity is a balance between immune mediators that promote tumor progression versus mediators that promote tumor rejection. Infiltrating lymphocytes in human colorectal cancer tissues are independent prognostic factors for a better survival and a high number of cytotoxic CD8+ T-cells have been associated with a better prognosis in terms of a longer and disease free survival for the patient. In our syngeneic rat model we induce colon carcinoma subperitoneally by injecting...

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

    Science.gov (United States)

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

    2016-07-07

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

  13. Thermal therapy of pancreatic tumours using endoluminal ultrasound: Parametric and patient-specific modelling.

    Science.gov (United States)

    Adams, Matthew S; Scott, Serena J; Salgaonkar, Vasant A; Sommer, Graham; Diederich, Chris J

    2016-01-01

    The aim of this study is to investigate endoluminal ultrasound applicator configurations for volumetric thermal ablation and hyperthermia of pancreatic tumours using 3D acoustic and biothermal finite element models. Parametric studies compared endoluminal heating performance for varying applicator transducer configurations (planar, curvilinear-focused, or radial-diverging), frequencies (1-5 MHz), and anatomical conditions. Patient-specific pancreatic head and body tumour models were used to evaluate feasibility of generating hyperthermia and thermal ablation using an applicator positioned in the duodenal or stomach lumen. Temperature and thermal dose were calculated to define ablation (> 240 EM(43 °C)) and moderate hyperthermia (40-45 °C) boundaries, and to assess sparing of sensitive tissues. Proportional-integral control was incorporated to regulate maximum temperature to 70-80 °C for ablation and 45 °C for hyperthermia in target regions. Parametric studies indicated that 1-3 MHz planar transducers are the most suitable for volumetric ablation, producing 5-8 cm(3) lesion volumes for a stationary 5-min sonication. Curvilinear-focused geometries produce more localised ablation to 20-45 mm depth from the GI tract and enhance thermal sparing (T(max) Modelling studies indicate the feasibility of endoluminal ultrasound for volumetric thermal ablation or hyperthermia treatment of pancreatic tumour tissue.

  14. 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.

  15. Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression.

    Science.gov (United States)

    Estrada, Marta F; Rebelo, Sofia P; Davies, Emma J; Pinto, Marta T; Pereira, Hugo; Santo, Vítor E; Smalley, Matthew J; Barry, Simon T; Gualda, Emilio J; Alves, Paula M; Anderson, Elizabeth; Brito, Catarina

    2016-02-01

    3D cell tumour models are generated mainly in non-scalable culture systems, using bioactive scaffolds. Many of these models fail to reflect the complex tumour microenvironment and do not allow long-term monitoring of tumour progression. To overcome these limitations, we have combined alginate microencapsulation with agitation-based culture systems, to recapitulate and monitor key aspects of the tumour microenvironment and disease progression. Aggregates of MCF-7 breast cancer cells were microencapsulated in alginate, either alone or in combination with human fibroblasts, then cultured for 15 days. In co-cultures, the fibroblasts arranged themselves around the tumour aggregates creating distinct epithelial and stromal compartments. The presence of fibroblasts resulted in secretion of pro-inflammatory cytokines and deposition of collagen in the stromal compartment. Tumour cells established cell-cell contacts and polarised around small lumina in the interior of the aggregates. Over the culture period, there was a reduction in oestrogen receptor and membranous E-cadherin alongside loss of cell polarity, increased collective cell migration and enhanced angiogenic potential in co-cultures. These phenotypic alterations, typical of advanced stages of cancer, were not observed in the mono-cultures of MCF-7 cells. The proposed model system constitutes a new tool to study tumour-stroma crosstalk, disease progression and drug resistance mechanisms. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    as control. Ten tumours were imaged 48 hours post-treatment and five tumours were imaged for up to five times after treatment. All tumours were harvested for histological analysis and comparison with elasticity measurements. Elastic (Young's) modulus prior to treatment was correlated with tumour volume (r...

  17. Live Cell Imaging of Viscosity in 3D Tumour Cell Models.

    Science.gov (United States)

    Shirmanova, Marina V; Shimolina, Lubov' E; Lukina, Maria M; Zagaynova, Elena V; Kuimova, Marina K

    2017-01-01

    Abnormal levels of viscosity in tissues and cells are known to be associated with disease and malfunction. While methods to measure bulk macroscopic viscosity of bio-tissues are well developed, imaging viscosity at the microscopic scale remains a challenge, especially in vivo. Molecular rotors are small synthetic viscosity-sensitive fluorophores in which fluorescence parameters are strongly correlated to the microviscosity of their immediate environment. Hence, molecular rotors represent a promising instrument for mapping of viscosity in living cells and tissues at the microscopic level. Quantitative measurements of viscosity can be achieved by recording time-resolved fluorescence decays of molecular rotor using fluorescence lifetime imaging microscopy (FLIM), which is also suitable for dynamic viscosity mapping, both in cellulo and in vivo. Among tools of experimental oncology, 3D tumour cultures, or spheroids, are considered a more adequate in vitro model compared to a cellular monolayer, and represent a less labour-intensive and more unified approach compared to animal tumour models. This chapter describes a methodology for microviscosity imaging in tumour spheroids using BODIPY-based molecular rotors and two photon-excited FLIM.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    O. Yu. Mukhomorova

    2015-01-01

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

  20. 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.

  1. 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.

  2. Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes.

    Science.gov (United States)

    Paul-Gilloteaux, Perrine; Potiron, Vincent; Delpon, Grégory; Supiot, Stéphane; Chiavassa, Sophie; Paris, François; Costes, Sylvain V

    2017-05-23

    The concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimization of various radiotherapy protocols with respect to tumour resistance and the microenvironment heterogeneity. This model combines automata approaches with image processing algorithms to simulate the cellular response of tumours exposed to ionizing radiation, modelling the alteration of oxygen permeabilization in blood vessels against repeated doses, and introducing mitotic catastrophe (as opposed to arbitrary delayed cell-death) as a means of modelling radiation-induced cell death. Published data describing cell death in vitro as well as tumour oxygenation in vivo are used to inform parameters. Our model is validated by comparing simulations to in vivo data obtained from the radiation treatment of mice transplanted with human prostate tumours. We then predict the efficacy of untested hypofractionation protocols, hypothesizing that tumour control can be optimized by adjusting daily radiation dosage as a function of the degree of hypoxia in the tumour environment. Further biological refinement of this tool will permit the rapid development of more sophisticated strategies for radiotherapy.

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

    OpenAIRE

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

    2016-01-01

    C L Campbell acknowledges financial support from an UK EPSRC PhD studentship (EP/K503162/1) and the Alfred Stewart Trust. We explore the effects of three dimensional (3D) tumour structures on depth dependent fluence rates, photodynamic doses (PDD) and fluorescence images through Monte Carlo radiation transfer modelling of photodynamic therapy. The aim with this work was to compare the commonly used uniform tumour densities with non-uniform densities to determine the importance of including...

  4. Hierarchical models in the brain.

    Directory of Open Access Journals (Sweden)

    Karl Friston

    2008-11-01

    Full Text Available This paper describes a general model that subsumes many parametric models for continuous data. The model comprises hidden layers of state-space or dynamic causal models, arranged so that the output of one provides input to another. The ensuing hierarchy furnishes a model for many types of data, of arbitrary complexity. Special cases range from the general linear model for static data to generalised convolution models, with system noise, for nonlinear time-series analysis. Crucially, all of these models can be inverted using exactly the same scheme, namely, dynamic expectation maximization. This means that a single model and optimisation scheme can be used to invert a wide range of models. We present the model and a brief review of its inversion to disclose the relationships among, apparently, diverse generative models of empirical data. We then show that this inversion can be formulated as a simple neural network and may provide a useful metaphor for inference and learning in the brain.

  5. 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

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

    Science.gov (United States)

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

    2007-02-01

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

  7. Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model

    Science.gov (United States)

    Conde, João; Oliva, Nuria; Zhang, Yi; Artzi, Natalie

    2016-10-01

    Conventional cancer therapies involve the systemic delivery of anticancer agents that neither discriminate between cancer and normal cells nor eliminate the risk of cancer recurrence. Here, we demonstrate that the combination of gene, drug and phototherapy delivered through a prophylactic hydrogel patch leads, in a colon cancer mouse model, to complete tumour remission when applied to non-resected tumours and to the absence of tumour recurrence when applied following tumour resection. The adhesive hydrogel patch enhanced the stability and provided local delivery of embedded nanoparticles. Spherical gold nanoparticles were used as a first wave of treatment to deliver siRNAs against Kras, a key oncogene driver, and rod-shaped gold nanoparticles mediated the conversion of near-infrared radiation into heat, causing the release of a chemotherapeutic as well as thermally induced cell damage. This local, triple-combination therapy can be adapted to other cancer cell types and to molecular targets associated with disease progression.

  8. 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.)

  9. A G-quadruplex-binding compound showing anti-tumour activity in an in vivo model for pancreatic cancer

    Science.gov (United States)

    Ohnmacht, Stephan A; Marchetti, Chiara; Gunaratnam, Mekala; Besser, Rachael J; Haider, Shozeb M; Di Vita, Gloria; Lowe, Helen L; Mellinas-Gomez, Maria; Diocou, Seckou; Robson, Mathew; Šponer, Jiri; Islam, Barira; Barbara Pedley, R; Hartley, John A; Neidle, Stephen

    2015-01-01

    We report here that a tetra-substituted naphthalene-diimide derivative (MM41) has significant in vivo anti-tumour activity against the MIA PaCa-2 pancreatic cancer xenograft model. IV administration with a twice-weekly 15 mg/kg dose produces ca 80% tumour growth decrease in a group of tumour-bearing animals. Two animals survived tumour-free after 279 days. High levels of MM41 are rapidly transported into cell nuclei and were found to accumulate in the tumour. MM41 is a quadruplex-interactive compound which binds strongly to the quadruplexes encoded in the promoter sequences of the BCL-2 and k-RAS genes, both of which are dis-regulated in many human pancreatic cancers. Levels of BCL-2 were reduced by ca 40% in tumours from MM41-treated animals relative to controls, consistent with BCL-2 being a target for MM41. Molecular modelling suggests that MM41 binds to a BCL-2 quadruplex in a manner resembling that previously observed in co-crystal structures with human telomeric quadruplexes. This supports the concept that MM41 (and by implication other quadruplex-targeting small molecules) can bind to quadruplex-forming promoter regions in a number of genes and down-regulate their transcription. We suggest that quadruplexes within those master genes that are up-regulated drivers for particular cancers, may be selective targets for compounds such as MM41. PMID:26077929

  10. 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.

  11. Tracer kinetic modelling of tumour angiogenesis based on dynamic contrast-enhanced CT and MRI measurements

    Energy Technology Data Exchange (ETDEWEB)

    Brix, Gunnar [Federal Office for Radiation Protection, Department of Medical and Occupational Radiation Protection, Oberschleissheim (Germany); Bundesamt fuer Strahlenschutz (BfS), Abteilung fuer medizinischen und beruflichen Strahlenschutz, Oberschleissheim (Germany); Griebel, Juergen [Federal Office for Radiation Protection, Department of Medical and Occupational Radiation Protection, Oberschleissheim (Germany); Kiessling, Fabian [RWTH-Aachen University, Department of Experimental Molecular Imaging, Aachen (Germany); Wenz, Frederik [University Medical Center Mannheim, University of Heidelberg, Department of Radiation Oncology, Mannheim (Germany)

    2010-08-15

    Technical developments in both magnetic resonance imaging (MRI) and computed tomography (CT) have helped to reduce scan times and expedited the development of dynamic contrast-enhanced (DCE) imaging techniques. Since the temporal change of the image signal following the administration of a diffusible, extracellular contrast agent (CA) is related to the local blood supply and the extravasation of the CA into the interstitial space, DCE imaging can be used to assess tissue microvasculature and microcirculation. It is the aim of this review to summarize the biophysical and tracer kinetic principles underlying this emerging imaging technique offering great potential for non-invasive characterization of tumour angiogenesis. In the first part, the relevant contrast mechanisms are presented that form the basis to relate signal variations measured by serial CT and MRI to local tissue concentrations of the administered CA. In the second part, the concepts most widely used for tracer kinetic modelling of concentration-time courses derived from measured DCE image data sets are described in a consistent and unified manner to highlight their particular structure and assumptions as well as the relationships among them. Finally, the concepts presented are exemplified by the analysis of representative DCE data as well as discussed with respect to present and future applications in cancer diagnosis and therapy. Depending on the specific protocol used for the acquisition of DCE image data and the particular model applied for tracer kinetic analysis of the derived concentration-time courses, different aspects of tumour angiogenesis can be quantified in terms of well-defined physiological tissue parameters. DCE imaging offers promising prospects for improved tumour diagnosis, individualization of cancer treatment as well as the evaluation of novel therapeutic concepts in preclinical and early-stage clinical trials. (orig.)

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

    Science.gov (United States)

    Borges, Ana; Sousa, Inês; Castro, Luis

    2017-06-01

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

  13. New Ideas for Brain Modelling

    Directory of Open Access Journals (Sweden)

    Kieran Greer

    2016-01-01

    Full Text Available This paper describes some biologically-inspired processes that could be used to build the sort of networks that we associate with the human brain. New to this paper, a ‘refined’ neuron will be proposed. This is a group of neurons that by joining together can produce a more analogue system, but with the same level of control and reliability that a binary neuron would have. With this new structure, it will be possible to think of an essentially binary system in terms of a more variable set of values. The paper also shows how recent research can be combined with established theories, to produce a more complete picture.The propositions are largely in line with conventional thinking, but possibly with one or two more radical suggestions. An earlier cognitive model can be filled in with more specific details, based on the new research results, where the components appear to fit together almost seamlessly. The intention of the research has been to describe plausible ‘mechanical’ processes that can produce the appropriate brain structures and mechanisms, but that could be used without the magical ‘intelligence’ part that is still not fully understood.There are also some important updates from an earlier version of this paper.Keywords: neuron, neural network, cognitive model, self-organise, analogue, resonance.

  14. Kinetic analysis of experimental rabbit tumour and inflammation model with {sup 18}F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Liu, P. [Dept. of Nuclear Medicine, Ninth People' s Hospital, Medical School of Jiaotong Univ., SH (China); Huang, G.; Dong, S.; Wan, L. [Dept. of Nuclear Medicine, Renji Hospital, Medical School of Jiaotong Univ., SH (China)

    2009-07-01

    Non-specific accumulation of {sup 18}F-FDG by both tumour and inflammatory lesions can make diagnostic analysis difficult. Our aim was to explore the difference in {sup 18}F-FDG uptake kinetics between tumour and inflammatory cells. To this end, we investigated VX2 tumour lesions and inflammatory lesions in rabbits. Methods: Six rabbits with VX2 tumour cells transplanted into one forelimb muscle and inflammatory lesions induced by turpentine oil in the contralateral forelimb were scanned for 60 minutes post {sup 18}F-FDG injection. Imaging data was analyzed with the standard 2-tissue-compartment model. Parameters, VB, Ki, K1, k2, k3, k4, were compared between tumour and inflammatory lesions. SUV and dual time scan methods were also compared in the experiment. Results: Time activity curves of VX2 tumour lesions showed a characteristic pattern of gradually increasing {sup 18}F-FDG uptake up to 60 min, whereas, {sup 18}F-FDG uptake in inflammatory lesions increased more slowly than in tumours. Parameters estimated from the uptake process showed that forward transport constant, K1, and influx constant, Ki, values in VX2 tumour lesions (0.186 {+-} 0.053 and 0.048 {+-} 0.014, respectively) was significantly higher than that in inflammatory lesions (0.129 {+-} 0.024 and 0.022 {+-} 0.007, respectively) (p < 0.05). In contrast, mean values of VB, k2, k3 and k4 derived from VX2 tumours were not significantly different from that of inflammatory lesions. SUVs at 60 minutes post {sup 18}F-FDG injection were also significantly higher in the VX2 tumor lesions than in the inflammatory lesions. Retention index (RI) was not significantly different between VX2 tumours and inflammatory lesions (1.134 {+-} 0.076 vs. 1.060 {+-} 0.058, p > 0.05). Conclusion: Different kinetic parameters (Ki, K1, k3) exist between inflammatory and tumour lesions. (orig.)

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Samantha Brownhill

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

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

    Science.gov (United States)

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

    2015-10-01

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

  18. Use of 5-[{sup 76}Br]bromo-2'-fluoro-2'-deoxyuridine as a ligand for tumour proliferation: validation in an animal tumour model

    Energy Technology Data Exchange (ETDEWEB)

    Borbath, I.; Pauwels, S. [Dept. of Nuclear Medicine, Catholic Univ. of Louvain, Brussels (Belgium); Gregoire, V. [Dept. of Radiation Oncology, Catholic Univ. of Louvain, Brussels (Belgium); Bergstroem, M.; Laryea, D.; Laangstroem, B. [Uppsala University PET Center, Uppsala (Sweden)

    2002-01-01

    Uncontrolled cell proliferation is one of the prominent features in cancer development. Precise tools are needed for determination of the proliferation rate before, during and after treatment, thereby permitting assessment of treatment efficacy. The purpose of this study was to validate the use of 5-[{sup 76}Br]bromo-2'-fluoro-2'-deoxyuridine ({sup 76}Br-BFU) as a proliferation marker in an animal tumour model. Comparison was made with 2-[{sup 14}C]thymidine ({sup 14}C-TdR) incorporation and the labelling index assessed by bromodeoxyuridine (BrdUrd-LI). Fibrosarcoma (NFSA)-bearing mice were used for all experiments. Gemcitabine (dFdC), a potent inhibitor of DNA synthesis, was used to modulate cell proliferation. dFdC was injected intraperitoneally at a dose of 0.5 mg/kg or 40 mg/kg to induce partial ({approx}50%) or complete inhibition of DNA synthesis, respectively. {sup 76}Br-BFU (0.5-3 MBq per animal), {sup 14}C-TdR (37-74 kBq per animal) and cold BrdUrd (60 mg/kg) were injected intraperitoneally in combination or alone. Animals were sacrificed at various times after tracer administration, and tumour and small intestine were removed for determination of radioactivity in whole tissue and the DNA fraction, as well as for LI assessment by flow cytometry. Cimetidine (6 mg/kg) was used to decrease {sup 76}Br-BFU elimination and increase its bioavailability. The fraction of radioactivity associated with DNA increased with the time interval between tracer injection and tissue removal. At 6 h after injection, for both tracers, more than 95% of the radioactivity in the tumours was associated with the DNA fraction and an excellent correlation was observed with the LI. Similar findings were observed in the small intestine. Under all experimental conditions, {sup 76}Br-BFU uptake was 4-10 times lower than {sup 14}C-TdR uptake. Co-injection of cimetidine resulted in a three- to fourfold increase in {sup 76}Br-BFU incorporation without affecting the effect of d

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

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

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

  20. Effect of lung flooding and high-intensity focused ultrasound on lung tumours: an experimental study in an ex vivo human cancer model and simulated in vivo tumours in pigs.

    Science.gov (United States)

    Wolfram, Frank; Boltze, Carsten; Schubert, Harald; Bischoff, Sabine; Lesser, Thomas Günther

    2014-01-07

    High-intensity focused ultrasound is a valuable tool for minimally invasive tumour ablation. However, due to the air content in ventilated lungs, lung tumours have never been treated with high-intensity focused ultrasound. Lung flooding enables efficient lung sonography and tumour imaging in ex vivo human and in vivo porcine lung cancer models. The current study evaluates the effectiveness of lung flooding and sonography-guided high-intensity focused ultrasound for lung tumour ablation in ex vivo human and in vivo animal models. Lung flooding was performed in four human lung lobes which were resected from non-small cell lung cancers. B-mode imaging and temperature measurements were simultaneously obtained during high-intensity focused ultrasonography of centrally located lung cancers. The tumour was removed immediately following insonation and processed for nicotinamide adenine dinucleotide phosphate-diaphorase and H&E staining. In addition, the left lungs of three pigs were flooded. Purified BSA in glutaraldehyde was injected centrally into the left lower lung lobe to simulate a lung tumour. The ultrasound was focused transthoracically through the flooded lung into the simulated tumour with the guidance of sonography. The temperature of the tumour was simultaneously measured. The vital signs of the animal were monitored during the procedure. A well-demarcated lesion of coagulation necrosis was produced in four of four human lung tumours. There did not appear to be any damage to the surrounding lung parenchyma. After high-intensity focused ultrasound insonation, the mean temperature increase was 7.5-fold higher in the ex vivo human tumour than in the flooded lung tissue (52.1 K ± 8.77 K versus 7.1 K ± 2.5 K). The transthoracic high-intensity focused ultrasound of simulated tumours in the in vivo model resulted in a mean peak temperature increase up to 53.7°C (±4.5). All of the animals survived the procedure without haemodynamic complications. High

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

    Directory of Open Access Journals (Sweden)

    Araceli Tobío

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

  2. In vivo imaging of pancreatic tumours and liver metastases using 7 Tesla MRI in a murine orthotopic pancreatic cancer model and a liver metastases model

    Directory of Open Access Journals (Sweden)

    Hadlich Stefan

    2011-01-01

    Full Text Available Abstract Background Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 Tesla MRI and evaluate its clinical relevance and applicability. Methods 6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA. Results MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p 3+/-243 mm3 with MRI (mean 918 mm3+/-193 mm3 with MRI being more precise. Histology (n = 5 confirmed MRI tumour measurements (mean size MRI 38.5 mm2+/-22.8 mm2 versus 32.6 mm2+/-22.6 mm2 (histology, p 3+/-56.7 mm3 after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p Conclusions This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.

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

    Science.gov (United States)

    Casares-Magaz, Oscar; van der Heide, Uulke A; Rørvik, Jarle; Steenbergen, Peter; Muren, Ludvig Paul

    2016-04-01

    Standard tumour control probability (TCP) models assume uniform tumour cell density across the tumour. The aim of this study was to develop an individualised TCP model by including index-tumour regions extracted form multi-parametric magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) maps-based cell density distributions. ADC maps in a series of 20 prostate cancer patients were applied to estimate the initial number of cells within each voxel, using three different approaches for the relation between ADC values and cell density: a linear, a binary and a sigmoid relation. All TCP models were based on linear-quadratic cell survival curves assuming α/β=1.93Gy (consistent with a recent meta-analysis) and α set to obtain a 70% of TCP when 77Gy was delivered to the entire prostate in 35 fractions (α=0.18Gy(-1)). Overall, TCP curves based on ADC maps showed larger differences between individuals than those assuming uniform cell densities. The range of the dose required to reach 50% TCP across the patient cohort was 20.1Gy, 18.7Gy and 13.2Gy using an MRI-based voxel density (linear, binary and sigmoid approach, respectively), compared to 4.1Gy using a constant density. Inclusion of tumour-index information together with ADC maps-based cell density increases inter-patient tumour response differentiation for use in prostate cancer RT, resulting in TCP curves with a larger range in D50% across the cohort compared with those based on uniform cell densities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. 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...

  5. Beyond anaemia management: evolving role of erythropoietin therapy in neurological disorders, multiple myeloma and tumour hypoxia models.

    Science.gov (United States)

    Boogaerts, Marc; Mittelman, Moshe; Vaupel, Peter

    2005-01-01

    Recombinant human erythropoietin (epoetin) has become the standard of care in the treatment of anaemia resulting from cancer and its treatment, and chronic kidney disease. The discovery that erythropoietin and its receptor are located in regions outside the erythropoietic system has led to interest in the potential role of epoetin in other tissues, such as the central nervous system. Animal studies have shown that systemically applied epoetin can cross the blood-brain barrier, where it reduces tissue injury associated with stroke, blunt trauma and experimental autoimmune encephalomyelitis. Pilot studies in humans have shown that epoetin treatment given within 8 h of stroke reduces infarct size and results in a significantly better outcome when compared with placebo treatment. Studies also suggest that epoetin has the potential to improve cognitive impairment associated with adjuvant chemotherapy in patients with cancer. Anaemia is a major factor causing tumour hypoxia, a condition that can promote changes within neoplastic cells that further tumour survival and malignant progression and also reduces the effectiveness of several anticancer therapies including radiotherapy and oxygen-dependent cytotoxic agents. Use of epoetin to prevent or correct anaemia has the potential to reduce tumour hypoxia and improve treatment outcome. Several therapeutic studies in anaemic animals with experimental tumours have shown a beneficial effect of epoetin on delaying tumour growth. Furthermore, clinical observations in patients with multiple myeloma and animal studies have suggested that epoetin has an antimyeloma effect, mediated via the immune system through activation of CD8+ T cells. Therefore, the role of epoetin may go well beyond that of increasing haemoglobin levels in anaemic patients, although additional studies are required to confirm these promising results. Copyright 2005 S. Karger AG, Basel.

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

    Directory of Open Access Journals (Sweden)

    Kazuyuki Yusa

    2017-06-01

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

  7. 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...

  8. Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact.

    Science.gov (United States)

    Pareja, Jennifer C Munoz; Keeley, Kristen; Duhaime, Ann-Christine; Dodge, Carter P

    2016-01-01

    The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma.

  9. 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

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

    Science.gov (United States)

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

    2012-03-27

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

  11. Derivation of the Tumour Control Probability (TCP from a Cell Cycle Model

    Directory of Open Access Journals (Sweden)

    A. Dawson

    2006-01-01

    Full Text Available In this paper, a model for the radiation treatment of cancer which includes the effects of the cell cycle is derived from first principles. A malignant cell population is divided into two compartments based on radiation sensitivities. The active compartment includes the four phases of the cell cycle, while the quiescent compartment consists of the G0 state. Analysis of this active-quiescent radiation model confirms the classical interpretation of the linear quadratic (LQ model, which is that a larger α/β ratio corresponds to a fast cell cycle, while a smaller ratio corresponds to a slow cell cycle. Additionally, we find that a large α/β ratio indicates the existence of a significant quiescent phase. The active-quiescent model is extended as a nonlinear birth–death process in order to derive an explicit time dependent expression for the tumour control probability (TCP. This work extends the TCP formula from Zaider and Minerbo and it enables the TCP to be calculated for general time dependent treatment schedules.

  12. Modeling premature brain injury and recovery

    Science.gov (United States)

    Scafidi, Joey; Fagel, Devon M.; Ment, Laura R.; Vaccarino, Flora M.

    2009-01-01

    Premature birth is a growing and significant public health problem because of the large number of infants that survive with neurodevelopmental sequelae from brain injury. Recent advances in neuroimaging have shown that although some neuroanatomical structures are altered, others improve over time. This review outlines recent insights into brain structure and function in these preterm infants at school age and relevant animal models. These animal models have provided scientists with an opportunity to explore in depth the molecular and cellular mechanisms of injury as well as the potential of the brain for recovery. The endogenous potential that the brain has for neurogenesis and gliogenesis, and how environment contributes to recovery, are also outlined. These preclinical models will provide important insights into the genetic and epigenetic mechanisms responsible for variable degrees of injury and recovery, permitting the exploration of targeted therapies to facilitate recovery in the developing preterm brain. PMID:19482072

  13. 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.

  14. 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.

  15. Development of immune memory to glial brain tumours after tumour regression induced by immunotherapeutic Toll-like receptor 7/8 activation

    NARCIS (Netherlands)

    Stathopoulos, A.; Pretto, C.; Devilliers, L.; Hofman, F.M.; Kruse, C.A.; Jadus, M.; Chen, T.C.; Schijns, V.E.J.C.

    2012-01-01

    The efficacy of immunotherapeutic TLR7/8 activation by resiquimod (R848) was evaluated in vivo, in the CNS-1 rat glioma model syngeneic to Lewis rats. The immune treatment was compared with cytotoxic cyclophosphamide chemotherapy, and as well, was compared with the combination cytotoxic and

  16. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

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

    NARCIS (Netherlands)

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

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

  18. A mathematical model of tumour angiogenesis incorporating cellular traction and viscoelastic effects.

    Science.gov (United States)

    Holmes, M J; Sleeman, B D

    2000-01-21

    Angiogenesis is defined as the outgrowth and formation of new vessels from a pre-existing vascular network (Rakusan, In: Cardiac Growth and Regeneration. Annals of the New York Academy of Sciences, 1995), and is of fundamental importance in understanding the processes by which a tumour achieves vascularization. Diffusible substances, collectively called tumour angiogenesis factors are released from the tumour to elicit a variety of responses from the surrounding tissues, most importantly the migration of endothelial cells (lining neighbouring vessels) towards the tumour. To facilitate locomotion, the cells exert appreciable traction forces upon the interstitial extracellular matrix which, in turn, influences the resulting direction of their migration. In this paper, we examine the role played by cellular traction during cell migration and the corresponding viscoelastic effects of the extracellular matrix. Copyright 2000 Academic Press.

  19. Combination of Fospeg-IPDT and a natural antioxidant compound prevents photosensitivity in a murine prostate cancer tumour model.

    Science.gov (United States)

    Petri, Aspasia; Alexandratou, Eleni; Kyriazi, Maria; Rallis, Michail; Roussis, Vassilios; Yova, Dido

    2012-06-01

    The aim of the present research was to investigate the potential use of a natural compound rich in antioxidant agents, derived from Pinus halepensis (P. halepensis), to prevent PDT induced photosensitivity. The present research progressed in two levels. The first one evolved the optimization of Fospeg-interstitial photodynamic therapy (IPDT) in a prostate cancer animal model. In the second one, P. halepensis bark extract, was evaluated for its potential use to prevent photosensitivity. Two sets of experiments were performed, IPDT only and IPDT in the presence of antioxidant. For both of them, Fospeg was administrated intravenously to SCID mice bearing prostate cancer, followed by IPDT after 6 h. For the IPDT+antioxidant experiments, P. halepensis was injected intratumourously 1 h prior the tumour illumination. Treatment outcome was monitored twice a week by an imaging system and by measuring tumour dimensions using a caliper. Photosensitivity was assessed by monitoring erythema of the tail using the imaging system. IPDT with Fospeg and 15 J total light energy is a therapeutic scheme that can eliminate tumours in the murine model of prostate cancer. Two months after complete tumour remission no tumour recurrence was observed. Also, the cosmetic outcome of the research was excellent. The major drawback of this treatment scheme was that 90% of the animals developed photosensitivity. The addition of P. halepensis bark extract resulted in prevention of the photosensitivity, leaving PDT outcome unaffected. The combined use of PDT and the used antioxidant agent could broaden the implementation of photodynamic therapy, by eliminating photosensitivity. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    2014-01-01

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

  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. Bayesian Modelling of Functional Whole Brain Connectivity

    DEFF Research Database (Denmark)

    Røge, Rasmus

    the prevalent strategy of standardizing of fMRI time series and model data using directional statistics or we model the variability in the signal across the brain and across multiple subjects. In either case, we use Bayesian nonparametric modeling to automatically learn from the fMRI data the number......This thesis deals with parcellation of whole-brain functional magnetic resonance imaging (fMRI) using Bayesian inference with mixture models tailored to the fMRI data. In the three included papers and manuscripts, we analyze two different approaches to modeling fMRI signal; either we accept...... of funcional units, i.e. parcels. We benchmark the proposed mixture models against state of the art methods of brain parcellation, both probabilistic and non-probabilistic. The time series of each voxel are most often standardized using z-scoring which projects the time series data onto a hypersphere...

  3. Deletion of the amino acid transporter Slc6a14 suppresses tumour growth in spontaneous mouse models of breast cancer.

    Science.gov (United States)

    Babu, Ellappan; Bhutia, Yangzom D; Ramachandran, Sabarish; Gnanaprakasam, Jaya P; Prasad, Puttur D; Thangaraju, Muthusamy; Ganapathy, Vadivel

    2015-07-01

    SLC6A14 mediates Na(+)/Cl(-)-coupled concentrative uptake of a broad-spectrum of amino acids. It is expressed at low levels in many tissues but up-regulated in certain cancers. Pharmacological blockade of SLC6A14 causes amino acid starvation in estrogen receptor positive (ER+) breast cancer cells and suppresses their proliferation in vitro and in vivo. In the present study, we interrogated the role of this transporter in breast cancer by deleting Slc6a14 in mice and monitoring the consequences of this deletion in models of spontaneous breast cancer (Polyoma middle T oncogene-transgenic mouse and mouse mammary tumour virus promoter-Neu-transgenic mouse). Slc6a14-knockout mice are viable, fertile and phenotypically normal. The plasma amino acids were similar in wild-type and knockout mice and there were no major compensatory changes in the expression of other amino acid transporter mRNAs. There was also no change in mammary gland development in the knockout mouse. However, when crossed with PyMT-Tg mice or MMTV/Neu (mouse mammary tumour virus promoter-Neu)-Tg mice, the development and progression of breast cancer were markedly decreased on Slc6a14(-/-) background. Analysis of transcriptomes in tumour tissues from wild-type mice and Slc6a14-null mice indicated no compensatory changes in the expression of any other amino acid transporter mRNA. However, the tumours from the null mice showed evidence of amino acid starvation, decreased mTOR signalling and decreased cell proliferation. These studies demonstrate that SLC6A14 is critical for the maintenance of amino acid nutrition and optimal mammalian target of rapamycin (mTOR) signalling in ER+ breast cancer and that the transporter is a potential target for development of a novel class of anti-cancer drugs targeting amino acid nutrition in tumour cells. © 2015 Authors; published by Portland Press Limited.

  4. 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...

  5. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

    Science.gov (United States)

    Kircher, David A.; Silvis, Mark R.; Cho, Joseph H.; Holmen, Sheri L.

    2016-01-01

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

  6. 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.

  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)

    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

  8. 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.

  9. D-galactose-induced brain ageing model

    DEFF Research Database (Denmark)

    Sadigh-Eteghad, Saeed; Majdi, Alireza; McCann, Sarah K.

    2017-01-01

    Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent...

  10. RF tumour ablation: computer simulation and mathematical modelling of the effects of electrical and thermal conductivity.

    Science.gov (United States)

    Lobo, S M; Liu, Z-J; Yu, N C; Humphries, S; Ahmed, M; Cosman, E R; Lenkinski, R E; Goldberg, W; Goldberg, S N

    2005-05-01

    This study determined the effects of thermal conductivity on RF ablation tissue heating using mathematical modelling and computer simulations of RF heating coupled to thermal transport. Computer simulation of the Bio-Heat equation coupled with temperature-dependent solutions for RF electric fields (ETherm) was used to generate temperature profiles 2 cm away from a 3 cm internally-cooled electrode. Multiple conditions of clinically relevant electrical conductivities (0.07-12 S m-1) and 'tumour' radius (5-30 mm) at a given background electrical conductivity (0.12 S m-1) were studied. Temperature response surfaces were plotted for six thermal conductivities, ranging from 0.3-2 W m-1 degrees C (the range of anticipated clinical and experimental systems). A temperature response surface was obtained for each thermal conductivity at 25 electrical conductivities and 17 radii (n=425 temperature data points). The simulated temperature response was fit to a mathematical model derived from prior phantom data. This mathematical model is of the form (T=a+bRc exp(dR) s(f) exp(g)(s)) for RF generator-energy dependent situations and (T=h+k exp(mR)+n?exp(p)(s)) for RF generator-current limited situations, where T is the temperature (degrees C) 2 cm from the electrode and a, b, c, d, f, g, h, k, m, n and p are fitting parameters. For each of the thermal conductivity temperature profiles generated, the mathematical model fit the response surface to an r2 of 0.97-0.99. Parameters a, b, c, d, f, k and m were highly correlated to thermal conductivity (r2=0.96-0.99). The monotonic progression of fitting parameters permitted their mathematical expression using simple functions. Additionally, the effect of thermal conductivity simplified the above equation to the extent that g, h, n and p were found to be invariant. Thus, representation of the temperature response surface could be accurately expressed as a function of electrical conductivity, radius and thermal conductivity. As a result

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

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

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

  12. Modeling high dimensional multichannel brain signals

    KAUST Repository

    Hu, Lechuan

    2017-03-27

    In this paper, our goal is to model functional and effective (directional) connectivity in network of multichannel brain physiological signals (e.g., electroencephalograms, local field potentials). The primary challenges here are twofold: first, there are major statistical and computational difficulties for modeling and analyzing high dimensional multichannel brain signals; second, there is no set of universally-agreed measures for characterizing connectivity. To model multichannel brain signals, our approach is to fit a vector autoregressive (VAR) model with sufficiently high order so that complex lead-lag temporal dynamics between the channels can be accurately characterized. However, such a model contains a large number of parameters. Thus, we will estimate the high dimensional VAR parameter space by our proposed hybrid LASSLE method (LASSO+LSE) which is imposes regularization on the first step (to control for sparsity) and constrained least squares estimation on the second step (to improve bias and mean-squared error of the estimator). Then to characterize connectivity between channels in a brain network, we will use various measures but put an emphasis on partial directed coherence (PDC) in order to capture directional connectivity between channels. PDC is a directed frequency-specific measure that explains the extent to which the present oscillatory activity in a sender channel influences the future oscillatory activity in a specific receiver channel relative all possible receivers in the network. Using the proposed modeling approach, we have achieved some insights on learning in a rat engaged in a non-spatial memory task.

  13. Cyclopentenyl cytosine has biological and anti-tumour activity, but does not enhance the efficacy of gemcitabine and radiation in two animal tumour models

    NARCIS (Netherlands)

    van Bree, Chris; Barten-van Rijbroek, Angeliqué D.; Leen, René; Rodermond, Hans M.; van Kuilenburg, André B. P.; Kal, Henk B.

    2009-01-01

    Cyclopentenyl cytosine (CPEC), targetting the de novo biosynthesis of cytidine triphosphate (CTP), increases the cytotoxicity of gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) alone and in combination with irradiation in several human tumour cells in vitro. We investigated whether OPEC enhances

  14. Computational modeling of neurostimulation in brain diseases.

    Science.gov (United States)

    Wang, Yujiang; Hutchings, Frances; Kaiser, Marcus

    2015-01-01

    Neurostimulation as a therapeutic tool has been developed and used for a range of different diseases such as Parkinson's disease, epilepsy, and migraine. However, it is not known why the efficacy of the stimulation varies dramatically across patients or why some patients suffer from severe side effects. This is largely due to the lack of mechanistic understanding of neurostimulation. Hence, theoretical computational approaches to address this issue are in demand. This chapter provides a review of mechanistic computational modeling of brain stimulation. In particular, we will focus on brain diseases, where mechanistic models (e.g., neural population models or detailed neuronal models) have been used to bridge the gap between cellular-level processes of affected neural circuits and the symptomatic expression of disease dynamics. We show how such models have been, and can be, used to investigate the effects of neurostimulation in the diseased brain. We argue that these models are crucial for the mechanistic understanding of the effect of stimulation, allowing for a rational design of stimulation protocols. Based on mechanistic models, we argue that the development of closed-loop stimulation is essential in order to avoid inference with healthy ongoing brain activity. Furthermore, patient-specific data, such as neuroanatomic information and connectivity profiles obtainable from neuroimaging, can be readily incorporated to address the clinical issue of variability in efficacy between subjects. We conclude that mechanistic computational models can and should play a key role in the rational design of effective, fully integrated, patient-specific therapeutic brain stimulation. © 2015 Elsevier B.V. All rights reserved.

  15. Targeting of histone deacetylases to reactivate tumour suppressor genes and its therapeutic potential in a human cervical cancer xenograft model.

    Directory of Open Access Journals (Sweden)

    Dingqing Feng

    Full Text Available Aberrant histone acetylation plays an essential role in the neoplastic process via the epigenetic silencing of tumour suppressor genes (TSGs; therefore, the inhibition of histone deacetylases (HDAC has become a promising target in cancer therapeutics. To investigate the correlation of histone acetylation with clinicopathological features and TSG expression, we examined the expression of acetylated H3 (AcH3, RARβ2, E-cadherin, and β-catenin by immunohistochemistry in 65 cervical squamous cell carcinoma patients. The results revealed that the absence of AcH3 was directly associated with poor histological differentiation and nodal metastasis as well as reduced/negative expression of RARβ2, E-cadherin, and β-catenin in clinical tumour samples. We further demonstrated that the clinically available HDAC inhibitors valproic acid (VPA and suberoylanilide hydroxamic acid (SAHA, in combination with all-trans retinoic acid (ATRA, can overcome the epigenetic barriers to transcription of RARβ2 in human cervical cancer cells. Chromatin immunoprecipitation analysis showed that the combination treatment increased the enrichment of acetylated histone in the RARβ2-RARE promoter region. In view of these findings, we evaluated the antitumor effects induced by combined VPA and ATRA treatment in a xenograft model implanted with poorly differentiated human squamous cell carcinoma. Notably, VPA restored RARβ2 expression via epigenetic modulation. Additive antitumour effects were produced in tumour xenografts by combining VPA with ATRA treatment. Mechanistically, the combination treatment reactivated the expression of TSGs RARβ2, E-cadherin, P21 (CIP1 , and P53 and reduced the level of p-Stat3. Sequentially, upregulation of involucrin and loricrin, which indicate terminal differentiation, strongly contributed to tumour growth inhibition along with partial apoptosis. In conclusion, targeted therapy with HDAC inhibitors and RARβ2 agonists may represent a novel

  16. A LQ-based kinetic model formulation for exploring dynamics of treatment response of tumours in patients.

    Science.gov (United States)

    Scheidegger, Stephan; Lutters, Gerd; Bodis, Stephan

    2011-09-01

    A kinetic bio-mathematical, linear-quadratic (LQ) based model description for clonogenic survival is presented. In contrast to widely used formulations of models, a dynamic approach based on ordinary differential equations for coupling a repair model with a tumour growth model is used to allow analysis of intercellular process dynamics and submodel interference. The purpose of the model formulation is to find a quantitative framework for investigation of tumour response to radiotherapy in vivo. It is not the intention of the proposed model formulation to give a mechanistic explanation for cellular repair processes. This article addresses bio-mathematical aspects of the simplistic kinetic approach used for description of repair. The model formulation includes processes for cellular death, repopulation and cellular repair. The explicit use of the population size in the model facilitates the coupling of the sub-models including aspects of tissue dynamics (competition, oxygenation). The cellular repair is summarized by using a kinetic model for a dose equivalent Γ describing production and elimination of sublethal lesions. This dose equivalent replaces the absorbed dose used in the common LQ- model. Therefore, this approach is called the Γ- LQ- formulation. A comparison with two kinetic radiobiological models (the LPL model of Curtis and the compartmental model of Carlone) is carried out. The resulting differential equations are solved by numerical integration using a Runge-Kutta algorithm. The comparison reveals a good agreement between the Γ- LQ- formulation and the models of Curtis and Carlone under certain, defined conditions: The proposed formulation leads to results which are identical to the model of Carlone over a wide range of investigated biological parameters and different fractionation schemes when using first order repair kinetics. The comparison with experimental data and the LPL- model of Curtis shows a good agreement of the Γ- LQ- formulation using

  17. Treatment with a vascular disrupting agent does not increase recruitment of indium labelled human endothelial outgrowth cells in an experimental tumour model.

    Science.gov (United States)

    Bertelsen, Lotte B; Bohn, Anja B; Shen, Yuan Yuan; Falborg, Lise; Stødkilde-Jørgensen, Hans; Horsman, Michael R

    2014-12-02

    The effect of vascular disrupting agents in tumour therapy depends on both the immediate vascular shutdown, and on the following re-vascularization of the tumour. The aim of this study was to use a tumour model to investigate whether endothelial outgrowth cells (EOCs) influenced the short term treatment efficiency of combretastatin A-4 disodium phosphate (CA4P) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by increasing EOC tumour recruitment. In order to visualize the recruitment of EOCs to the tumours, umbilical cord blood derived human EOCs were labelled with 111Indium-tropolone in a dose of 0.37 MBq pr 3×106 cells and were injected intravenously into mice carrying a C3H mammary carcinoma on their right rear foot. DMXAA and CA4P in different concentrations and at different exposure times were used to create a hypoxic environment in the C3H mammary carcinoma in the mice. Three different mice strains with various degrees of functional immune system were used to study the homing capability of EOCs. Our data showed that approximately 4% of the total injected radioactive dose per gram of tissue was found in the tumour after treatment with CA4P and DMXAA. Regardless of the concentration and the treatment duration, CA4P did not increase EOC recruitment to the tumour in comparison to EOC recruitment in control tumours in any of the 3 mice strains studied. Our data showed that regardless of the grade of the immune system, ranging from a fully working to a fully compromised immune system, treatment with CA4P did not increase recruitment of xenotransplanted EOCs to tumour tissue.

  18. Simulating Radiotherapy Effect in High-Grade Glioma by Using Diffusive Modeling and Brain Atlases

    Directory of Open Access Journals (Sweden)

    Alexandros Roniotis

    2012-01-01

    Full Text Available Applying diffusive models for simulating the spatiotemporal change of concentration of tumour cells is a modern application of predictive oncology. Diffusive models are used for modelling glioblastoma, the most aggressive type of glioma. This paper presents the results of applying a linear quadratic model for simulating the effects of radiotherapy on an advanced diffusive glioma model. This diffusive model takes into consideration the heterogeneous velocity of glioma in gray and white matter and the anisotropic migration of tumor cells, which is facilitated along white fibers. This work uses normal brain atlases for extracting the proportions of white and gray matter and the diffusion tensors used for anisotropy. The paper also presents the results of applying this glioma model on real clinical datasets.

  19. 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.

  20. 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.

  1. 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

  2. Quantification of antiangiogenic treatment effects on tissue heterogeneity in glioma tumour xenograft model using a combination of DCE-MRI and 3D-ultramicroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Dominietto, Marco [University and ETH Zurich, Institute for Biomedical Engineering, Zurich (Switzerland); University of Basel, Biomaterials Science Center, Allschwil (Switzerland); Dobosz, Michael; Renner, Anja; Scheuer, Werner [Roche Innovation Center Penzberg, Discovery Oncology, Pharmaceutical Research and Early Development (pRED), Penzberg (Germany); Buergi, Sandra; Rudin, Markus [University and ETH Zurich, Institute for Biomedical Engineering, Zurich (Switzerland); Zahlmann, Gudrun [pRED, Oncology DTA, Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel (Switzerland)

    2017-07-15

    This study aimed at assessing the effects of an anti-angiogenic treatment, which neutralises vascular endothelial growth factor (VEGF), on tumour heterogeneity. Murine glioma cells have been inoculated into the right brain frontal lobe of 16 mice. Anti-VEGF antibody was administered to a first group (n = 8), while a second group (n = 8) received a placebo. Magnetic resonance acquisitions, performed at days 10, 12, 15 and 23 following the implantation, allowed the derivation of a three-dimensional features dataset characterising tumour heterogeneity. Three-dimensional ultramicroscopy and standard histochemistry analysis have been performed to verify in vivo results. Placebo-treated mice displayed a highly-vascularised area at the tumour periphery, a monolithic necrotic core and a chaotic dense vasculature across the entire tumour. In contrast, the B20-treated group did not show any highly vascularised regions and presents a fragmented necrotic core. A significant reduction of the number of vessel segments smaller than 17 μm has been observed. There was no difference in overall tumour volume and growth rate between the two groups. Region-specific analysis revealed that VEGF inhibition affects only: (1) highly angiogenic compartments expressing high levels of VEGF and characterised by small capillaries, and also (2) the formation and structure of necrotic regions. These effects appear to be transient and limited in time. (orig.)

  3. Modeling High-Dimensional Multichannel Brain Signals

    KAUST Repository

    Hu, Lechuan

    2017-12-12

    Our goal is to model and measure functional and effective (directional) connectivity in multichannel brain physiological signals (e.g., electroencephalograms, local field potentials). The difficulties from analyzing these data mainly come from two aspects: first, there are major statistical and computational challenges for modeling and analyzing high-dimensional multichannel brain signals; second, there is no set of universally agreed measures for characterizing connectivity. To model multichannel brain signals, our approach is to fit a vector autoregressive (VAR) model with potentially high lag order so that complex lead-lag temporal dynamics between the channels can be captured. Estimates of the VAR model will be obtained by our proposed hybrid LASSLE (LASSO + LSE) method which combines regularization (to control for sparsity) and least squares estimation (to improve bias and mean-squared error). Then we employ some measures of connectivity but put an emphasis on partial directed coherence (PDC) which can capture the directional connectivity between channels. PDC is a frequency-specific measure that explains the extent to which the present oscillatory activity in a sender channel influences the future oscillatory activity in a specific receiver channel relative to all possible receivers in the network. The proposed modeling approach provided key insights into potential functional relationships among simultaneously recorded sites during performance of a complex memory task. Specifically, this novel method was successful in quantifying patterns of effective connectivity across electrode locations, and in capturing how these patterns varied across trial epochs and trial types.

  4. Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy.

    Science.gov (United States)

    Valiulienė, Giedrė; Treigytė, Gražina; Savickienė, Jūratė; Matuzevičius, Dalius; Alksnė, Milda; Jarašienė-Burinskaja, Rasa; Bukelskienė, Virginija; Navakauskas, Dalius; Navakauskienė, Rūta

    2016-04-01

    Xenograft models are suitable for in vivo study of leukemia's pathogenesis and the preclinical development of anti-leukemia agents but understanding of epigenetic regulatory mechanisms linking to adult cell functions in pathological conditions during different in vivo treatments is yet unknown. In this study, for the first time epigenetic chromatin modifications were characterized in tissues and tumours from murine xenograft model generated using the human acute promyelocytic leukemia (APL) NB4 cells engrafted in immunodeficient NOG mice. Xenografts were subjected to combined epigenetic treatment by histone deacetylase inhibitor Belinostat, histone methyltransferase inhibitor 3-DZNeaplanocin A and all-trans-retinoic acid based on in vitro model, where such combination inhibited NB4 cell growth and enhanced retinoic acid-induced differentiation to granulocytes. Xenotransplantation was assessed by peripheral blood cells counts, the analysis of cell surface markers (CD15, CD33, CD45) and the expression of certain genes (PML-RAR alpha, CSF3, G-CSFR, WT1). The combined treatment prolonged APL xenograft mice survival and prevented tumour formation. The analysis of the expression of histone marks such as acetylation of H4, trimethylation of H3K4, H3K9 and H3K27 in APL xenograft mice tumours and tissues demonstrated tissue-specific changes in the level of histone modifications and the APL prognostic mark, WT1 protein. In summary, the effects of epigenetic agents used in this study were positive for leukemia prevention and linked to a modulation of the chromatin epigenetic environment in adult tissues of malignant organism. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Brain-inspired Stochastic Models and Implementations

    KAUST Repository

    Al-Shedivat, Maruan

    2015-05-12

    One of the approaches to building artificial intelligence (AI) is to decipher the princi- ples of the brain function and to employ similar mechanisms for solving cognitive tasks, such as visual perception or natural language understanding, using machines. The recent breakthrough, named deep learning, demonstrated that large multi-layer networks of arti- ficial neural-like computing units attain remarkable performance on some of these tasks. Nevertheless, such artificial networks remain to be very loosely inspired by the brain, which rich structures and mechanisms may further suggest new algorithms or even new paradigms of computation. In this thesis, we explore brain-inspired probabilistic mechanisms, such as neural and synaptic stochasticity, in the context of generative models. The two questions we ask here are: (i) what kind of models can describe a neural learning system built of stochastic components? and (ii) how can we implement such systems e ̆ciently? To give specific answers, we consider two well known models and the corresponding neural architectures: the Naive Bayes model implemented with a winner-take-all spiking neural network and the Boltzmann machine implemented in a spiking or non-spiking fashion. We propose and analyze an e ̆cient neuromorphic implementation of the stochastic neu- ral firing mechanism and study the e ̄ects of synaptic unreliability on learning generative energy-based models implemented with neural networks.

  6. Selection of appropriate tumour data sets for Benchmark Dose Modelling (BMD) and derivation of a Margin of Exposure (MoE) for substances that are genotoxic and carcinogenic: considerations of biological relevance of tumour type, data quality and uncertainty assessment.

    Science.gov (United States)

    Edler, Lutz; Hart, Andy; Greaves, Peter; Carthew, Philip; Coulet, Myriam; Boobis, Alan; Williams, Gary M; Smith, Benjamin

    2014-08-01

    This article addresses a number of concepts related to the selection and modelling of carcinogenicity data for the calculation of a Margin of Exposure. It follows up on the recommendations put forward by the International Life Sciences Institute - European branch in 2010 on the application of the Margin of Exposure (MoE) approach to substances in food that are genotoxic and carcinogenic. The aims are to provide practical guidance on the relevance of animal tumour data for human carcinogenic hazard assessment, appropriate selection of tumour data for Benchmark Dose Modelling, and approaches for dealing with the uncertainty associated with the selection of data for modelling and, consequently, the derived Point of Departure (PoD) used to calculate the MoE. Although the concepts outlined in this article are interrelated, the background expertise needed to address each topic varies. For instance, the expertise needed to make a judgement on biological relevance of a specific tumour type is clearly different to that needed to determine the statistical uncertainty around the data used for modelling a benchmark dose. As such, each topic is dealt with separately to allow those with specialised knowledge to target key areas of guidance and provide a more in-depth discussion on each subject for those new to the concept of the Margin of Exposure approach. Copyright © 2013 ILSI Europe. Published by Elsevier Ltd.. All rights reserved.

  7. Therapeutic efficacy of the combination of doxorubicin-loaded liposomes with inertial cavitation generated by confocal ultrasound in AT2 Dunning rat tumour model.

    Science.gov (United States)

    Mestas, Jean-Louis; Fowler, R Andrew; Evjen, Tove J; Somaglino, Lucie; Moussatov, Alexei; Ngo, Jacqueline; Chesnais, Sabrina; Røgnvaldsson, Sibylla; Fossheim, Sigrid L; Nilssen, Esben A; Lafon, Cyril

    2014-09-01

    The combination of liposomal doxorubicin (DXR) and confocal ultrasound (US) was investigated for the enhancement of drug delivery in a rat tumour model. The liposomes, based on the unsaturated phospholipid dierucoylphosphocholine, were designed to be stable during blood circulation in order to maximize accumulation in tumour tissue and to release drug content upon US stimulation. A confocal US setup was developed for delivering inertial cavitation to tumours in a well-controlled and reproducible manner. In vitro studies confirm drug release from liposomes as a function of inertial cavitation dose, while in vivo pharmacokinetic studies show long blood circulation times and peak tumour accumulation at 24-48 h post intravenous administration. Animals injected 6 mg kg(-1) liposomal DXR exposed to US treatment 48 h after administration show significant tumour growth delay compared to control groups. A liposomal DXR dose of 3 mg kg(-1), however, did not induce any significant therapeutic response. This study demonstrates that inertial cavitation can be generated in such a fashion as to disrupt drug carrying liposomes which have accumulated in the tumour, and thereby increase therapeutic effect with a minimum direct effect on the tissue. Such an approach is an important step towards a therapeutic application of cavitation-induced drug delivery and reduced chemotherapy toxicity.

  8. Multicellular Tumour Spheroid as a model for evaluation of [18F]FDG as biomarker for breast cancer treatment monitoring

    Directory of Open Access Journals (Sweden)

    Josephsson Raymond

    2006-03-01

    Full Text Available Abstract Background In order to explore a pre-clinical method to evaluate if [18F]FDG is valid for monitoring early response, we investigated the uptake of FDG in Multicellular tumour spheroids (MTS without and with treatment with five routinely used chemotherapy agents in breast cancer. Methods The response to each anticancer treatment was evaluated by measurement of the [18F]FDG uptake and viable volume of the MTSs after 2 and 3 days of treatment. Results The effect of Paclitaxel and Docetaxel on [18F]FDG uptake per viable volume was more evident in BT474 (up to 55% decrease than in MCF-7 (up to 25% decrease. Doxorubicin reduced the [18F]FDG uptake per viable volume more noticeable in MCF-7 (25% than in BT474 MTSs. Tamoxifen reduced the [18F]FDG uptake per viable volume only in MCF-7 at the highest dose of 1 μM. No effect of Imatinib was observed. Conclusion MTS was shown to be appropriate to investigate the potential of FDG-PET for early breast cancer treatment monitoring; the treatment effect can be observed before any tumour size changes occur. The combination of PET radiotracers and image analysis in MTS provides a good model to evaluate the relationship between tumour volume and the uptake of metabolic tracer before and after chemotherapy. This feature could be used for screening and selecting PET-tracers for early assessment of treatment response. In addition, this new method gives a possibility to assess quickly, and in vitro, a good preclinical profile of existing and newly developed anti-cancer drugs.

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

    Directory of Open Access Journals (Sweden)

    Mohamed A Alfaleh

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

  10. 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.

  11. Occurrence studies of intracranial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Larjavaara, S.

    2011-07-01

    approximately two-thirds (64%; 95% CI, 50 - 78). The underreporting was more pronounced among the elderly and in those with no histological confirmation of the meningioma diagnosis. An increasing trend of VS incidence was observed, but with considerable differences between countries. The overall annual increase of VS incidence was 2.8% per year (95% CI, 2.3 - 3.2) in 1987 - 2007, when all the four countries and both sexes were combined. However, no statistically significant increase was seen in the rates of VS incidence in Finnish men or Swedish women, and the incidence even showed some decrease in Finnish women (-0.4%, 95% CI, -1.8 to +1.1) during the study period. The overall increase in rates stabilized in the late 1990s, with relatively constant incidence rates and even some decline after 2000. Gliomas were distributed unevenly in the brain, with substantial variation between the cerebral lobes showing an excess of gliomas in the frontal and temporal lobes (over four-fold relative to occipital lobe, even after accounting for tissue volume). In the detailed spatial 3D-analysis, statistically significant heterogeneity was found with most gliomas in the anterior subcortical part of the brain. There was no excess of gliomas in the parts of the brain nearest to the typical location where mobile phones are held. Gliomas among never-regular mobile phone users and contralateral users (phone held on the opposite side of the head than the side of tumour) were closer to the source of electromagnetic field (EMF) than among regular and ipsilateral (exposure at the same side as the tumour location) users. In the case-specular analysis, the distance from the glioma cases to the mobile phone was shorter than for the speculars (hypothetical controls assigned for each glioma case). However, no such association was found in analyses by amount of phone use. In both models, glioma cases were closer to the source of exposure in long-term users (over ten years of use), but the differences

  12. Mouse Genetic Models of Human Brain Disorders

    Directory of Open Access Journals (Sweden)

    Celeste eLeung

    2016-03-01

    Full Text Available Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioural phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases.

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

    Directory of Open Access Journals (Sweden)

    Jakob H Lagerlöf

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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Cameron N. Johnstone

    2015-03-01

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

  19. Mannitol Improves Brain Tissue Oxygenation in a Model of Diffuse Traumatic Brain Injury.

    Science.gov (United States)

    Schilte, Clotilde; Bouzat, Pierre; Millet, Anne; Boucheix, Perrine; Pernet-Gallay, Karin; Lemasson, Benjamin; Barbier, Emmanuel L; Payen, Jean-François

    2015-10-01

    Based on evidence supporting a potential relation between posttraumatic brain hypoxia and microcirculatory derangements with cell edema, we investigated the effects of the antiedematous agent mannitol on brain tissue oxygenation in a model of diffuse traumatic brain injury. Experimental study. Neurosciences and physiology laboratories. Adult male Wistar rats. Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were IV administered with either a saline solution (traumatic brain injury-saline group) or 20% mannitol (1 g/kg) (traumatic brain injury-mannitol group). Sham-saline and sham-mannitol groups received no insult. Two series of experiments were conducted 2 hours after traumatic brain injury (or equivalent) to investigate 1) the effect of mannitol on brain edema and oxygenation, using a multiparametric magnetic resonance-based approach (n = 10 rats per group) to measure the apparent diffusion coefficient, tissue oxygen saturation, mean transit time, and blood volume fraction in the cortex and caudoputamen; 2) the effect of mannitol on brain tissue PO2 and on venous oxygen saturation of the superior sagittal sinus (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 per group, taken from the first experiment). Compared with the sham-saline group, the traumatic brain injury-saline group had significantly lower tissue oxygen saturation, brain tissue PO2, and venous oxygen saturation of the superior sagittal sinus values concomitant with diffuse brain edema. These effects were associated with microcirculatory collapse due to astrocyte swelling. Treatment with mannitol after traumatic brain injury reversed all these effects. In the absence of traumatic brain injury, mannitol had no effect on brain oxygenation. Mean transit time and blood volume fraction were comparable between the four groups of rats. The development of posttraumatic brain edema can limit the oxygen utilization by brain tissue

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-28

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

  1. Endothelial progenitor cells physiology and metabolic plasticity in brain angiogenesis and blood-brain barrier modeling

    Directory of Open Access Journals (Sweden)

    Natalia Malinovskaya

    2016-12-01

    Full Text Available Currently, there is a considerable interest to the assessment of blood-brain barrier (BBB development as a part of cerebral angiogenesis developmental program. Embryonic and adult angiogenesis in the brain is governed by the coordinated activity of endothelial progenitor cells, brain microvascular endothelial cells, and non-endothelial cells contributing to the establishment of the BBB (pericytes, astrocytes, neurons. Metabolic and functional plasticity of endothelial progenitor cells controls their timely recruitment, precise homing to the brain microvessels, and efficient support of brain angiogenesis. Deciphering endothelial progenitor cells physiology would provide novel engineering approaches to establish adequate microfluidically-supported BBB models and brain microphysiological systems for translational studies.

  2. 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.

  3. Palbociclib (PD-0332991), a selective CDK4/6 inhibitor, restricts tumour growth in preclinical models of hepatocellular carcinoma.

    Science.gov (United States)

    Bollard, Julien; Miguela, Verónica; Ruiz de Galarreta, Marina; Venkatesh, Anu; Bian, C Billie; Roberto, Mark P; Tovar, Victoria; Sia, Daniela; Molina-Sánchez, Pedro; Nguyen, Christie B; Nakagawa, Shigeki; Llovet, Josep M; Hoshida, Yujin; Lujambio, Amaia

    2017-07-01

    Advanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Palbociclib, a well-tolerated and selective CDK4/6 inhibitor, has shown promising results in the treatment of retinoblastoma (RB1)-positive breast cancer. RB1 is rarely mutated in HCC, suggesting that palbociclib could potentially be used for HCC therapy. Here, we provide a comprehensive characterisation of the efficacy of palbociclib in multiple preclinical models of HCC. The effects of palbociclib on cell proliferation, cellular senescence and cell death were investigated in a panel of human liver cancer cell lines, in ex vivo human HCC samples, in a genetically engineered mouse model of liver cancer, and in human HCC xenografts in vivo. The mechanisms of intrinsic and acquired resistance to palbociclib were assessed in human liver cancer cell lines and human HCC samples by protein and gene expression analyses. Palbociclib suppressed cell proliferation in human liver cancer cell lines by promoting a reversible cell cycle arrest. Intrinsic and acquired resistance to palbociclib was determined by loss of RB1. A signature of 'RB1 loss of function' was found in Palbociclib, alone or combined with sorafenib, the standard of care for HCC, impaired tumour growth in vivo and significantly increased survival. Palbociclib shows encouraging results in preclinical models of HCC and represents a novel therapeutic strategy for HCC treatment, alone or particularly in combination with sorafenib. Palbociclib could potentially benefit patients with RB1-proficient tumours, which account for 70% of all patients with HCC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-27

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

  5. Interplay between pro-inflammatory cytokines and brain oxidative stress biomarkers: evidence of parallels between butyl paraben intoxication and the valproic acid brain physiopathology in autism rat model.

    Science.gov (United States)

    Hegazy, Hoda G; Ali, Elham H A; Elgoly, Amany H Mahmoud

    2015-02-01

    Butyl paraben is a preservative used in food, drugs and cosmetics. Neurotoxic effect was reported recently beside the potential estrogenic activity of parabens. There is controversy as to the potential harmful effects of butyl parabens, which are suspected to contribute to autism and learning disabilities. The purpose of this study was to examine the similarities between paraben intoxication signs in the rat brain and brain markers in an autistic like rat model. This study provides evidence of many parallels between the two, including (1) oxidative stress, (2) decreased reduced glutathione levels and elevated oxidised glutathione, (3) mitochondrial dysfunction, and (4) neuroinflammation and increased pro-inflammatory cytokine levels in the brain (tumour necrosis factor-alpha, interleukin-1-beta, and interleukin-6). (5) Increased protein oxidation reported by a significant increase in 3-nitrotyrosine (3-NT)/tyrosine ratio. (6) A marked disturbance was found in the production of energy carriers (AMP, ATP and AMP/ATP ratio) in comparison with the control. The evidence suggests that paraben may, to some extent, either cause or contribute to the brain physiopathology in ASDs or pathogens that produce the brain pathology observed in the diagnosed rat model of ASD. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-12-01

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

  7. 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)

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  9. 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

  10. 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.

  11. 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.

  12. Deciphering PDT-induced inflammatory responses using real-time FDG-PET in a mouse tumour model.

    Science.gov (United States)

    Cauchon, Nicole; Hasséssian, Haroutioun M; Turcotte, Eric; Lecomte, Roger; van Lier, Johan E

    2014-10-01

    Dynamic positron emission tomography (PET), combined with constant infusion of 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG), enables real-time monitoring of transient metabolic changes in vivo, which can serve to understand the underlying physiology. Here we investigated characteristic changes in the tumour FDG-uptake profiles in relation to acute localized inflammatory responses induced by photodynamic therapy (PDT). Dynamic PET imaging with constant FDG infusion was used with EMT-6 tumour bearing mice. FDG time-activity uptake curves were measured simultaneously, in treated and reference tumours, for 3 hours, before, during and after PDT light treatment. Inflammation was studied when evoked, either by PDT using a trisulfonated porphyrazine photosensitizer, or lipopolysaccharide (LPS), and inhibited using indomethacin. The distinct transient patterns, characterized by drops and subsequent recovery of tumour FDG uptake rates, were also analysed using immunohistochemical markers for apoptosis, necrosis, and inflammation. Typical profiles for tumour FDG-uptake, consisted of a drop during PDT, followed by a gradual recovery period. Tumours treated with LPS, but not with light, showed a continuous increase in FDG-uptake during the 3 h experimental period. Treatment with indomethacin, inhibited the rise in FDG-uptake observed with either LPS or PDT. Tumour FDG-uptake profiles correlated with necrosis markers during PDT, and inflammatory response markers post-PDT, but not with an apoptosis marker at any time during or after PDT. Dynamic FDG-PET imaging combined with indomethacin reveals that, the drop in the tumour FDG-uptake rate during the PDT illumination phase reflects vascular collapse and necrosis, while the increased tumour FDG-uptake rate immediately post-illumination involves an acute localized inflammatory response. Dynamic FDG infusion and PET imaging, combined with the use of selective inhibitors, provides unique insight for deciphering the complex underlying

  13. A Culture-Behavior-Brain Loop Model of Human Development.

    Science.gov (United States)

    Han, Shihui; Ma, Yina

    2015-11-01

    Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Rodent brain extraction using B-spline based deformable model.

    Science.gov (United States)

    Weimin Huang; Chen Ling; Su Huang; Zhongkang Lu; Zhiping Lin

    2017-07-01

    Accurate rodent brain extraction is one of the basic steps for many translational study using Magnetic Resonance Imaging (MRI). In this paper, we present a new approach to model the rodent brain variation using non-rigid B-spline image registration for the brain extraction in MRI images. We model the shape and appearance with the B-spline parameters together with a mean brain image. Followed by a method using multi-expert, we refine the brain extraction region. Compared with the image-based template model using cross-correlation, the performance for rodent brain extraction has shown much improvement on one data set while maintaining the similar yet more consistent performance for another. Both template based methods however outperform the voxel based method (3D PCNN) and a modified BET version for rodent brain extraction.

  15. Modeling brain resonance phenomena using a neural mass model.

    Directory of Open Access Journals (Sweden)

    Andreas Spiegler

    2011-12-01

    Full Text Available Stimulation with rhythmic light flicker (photic driving plays an important role in the diagnosis of schizophrenia, mood disorder, migraine, and epilepsy. In particular, the adjustment of spontaneous brain rhythms to the stimulus frequency (entrainment is used to assess the functional flexibility of the brain. We aim to gain deeper understanding of the mechanisms underlying this technique and to predict the effects of stimulus frequency and intensity. For this purpose, a modified Jansen and Rit neural mass model (NMM of a cortical circuit is used. This mean field model has been designed to strike a balance between mathematical simplicity and biological plausibility. We reproduced the entrainment phenomenon observed in EEG during a photic driving experiment. More generally, we demonstrate that such a single area model can already yield very complex dynamics, including chaos, for biologically plausible parameter ranges. We chart the entire parameter space by means of characteristic Lyapunov spectra and Kaplan-Yorke dimension as well as time series and power spectra. Rhythmic and chaotic brain states were found virtually next to each other, such that small parameter changes can give rise to switching from one to another. Strikingly, this characteristic pattern of unpredictability generated by the model was matched to the experimental data with reasonable accuracy. These findings confirm that the NMM is a useful model of brain dynamics during photic driving. In this context, it can be used to study the mechanisms of, for example, perception and epileptic seizure generation. In particular, it enabled us to make predictions regarding the stimulus amplitude in further experiments for improving the entrainment effect.

  16. 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

  17. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    OpenAIRE

    Qiao, Guanqun; Li, Qingquan; Peng, Gang; Ma, Jun; Fan, Hongwei; Li, Yingbin

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain t...

  18. Tumour necrosis factor-mediated homeostatic synaptic plasticity in behavioural models: testing a role in maternal immune activation.

    Science.gov (United States)

    Konefal, Sarah C; Stellwagen, David

    2017-03-05

    The proinflammatory cytokine tumour necrosis factor-alpha (TNFα) has long been characterized for its role in the innate immune system, but more recently has been found to have a distinct role in the nervous system that does not overlap with other proinflammatory cytokines. Through regulation of neuronal glutamate and GABA receptor trafficking, TNF mediates a homeostatic form of synaptic plasticity, but plays no direct role in Hebbian forms of plasticity. As yet, there is no evidence to suggest that this adaptive plasticity plays a significant role in normal development, but it does maintain neuronal circuit function in the face of several types of disruption. This includes developmental plasticity in primary sensory cortices, as well as modulating the response to antidepressants, chronic antipsychotics and drugs of abuse. TNF is also a prominent component of the neuroinflammation occurring in most neuropathologies, but the role of TNF-mediated synaptic plasticity in this context remains to be determined. We tested this in a maternal immune activation (MIA) model of neurodevelopmental disorders. Using TNF -/- mice, we observed that TNF is not required for the expression of abnormal social or anxious behaviour in this model. This indicates that TNF does not uniquely contribute to the development of neuronal dysfunction in this model, and suggests that during neuroinflammatory events, compensation between the various proinflammatory cytokines is the norm.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'. © 2017 The Author(s).

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

    Science.gov (United States)

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

    2017-01-01

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

  20. Experimental deep brain stimulation in animal models.

    Science.gov (United States)

    Tan, Sonny Kh; Vlamings, Rinske; Lim, Leewei; Sesia, Thibault; Janssen, Marcus Lf; Steinbusch, Harry Wm; Visser-Vandewalle, Veerle; Temel, Yasin

    2010-10-01

    DEEP BRAIN STIMULATION (DBS) as a therapy in neurological and psychiatric disorders is widely applied in the field of functional and stereotactic neurosurgery. In this respect, experimental DBS in animal models is performed to evaluate new indications and new technology. In this article, we review our experience with the concept of experimental DBS, including its development and validation. An electrode construction was developed using clinical principles to perform DBS unilaterally or bilaterally in freely moving rats. The stimulation parameters were adjusted for the rat using current density calculations. We performed validation studies in 2 animal models: a rat model of Parkinson's disease (bilateral 6-hydroxydopamine infusion in the striatum) and a rat model of Huntington's disease (transgenic rats). The effects of DBS were evaluated in different behavioral tasks measuring motor and cognitive functions. The electrode construction developed allows experimental DBS to be performed in freely moving rats. With the current setup, electrodes are placed in the target in 70% to 95% of the cases. Using a rat model, we showed that bilateral DBS of the subthalamic nucleus improves parkinsonian motor disability, but can induce behavioral side effects, similar to the clinical situation. In addition, we showed that DBS of the globus pallidus can improve motor and cognitive symptoms in a rat model of Huntington's disease. Nevertheless, during the process of the development and validation of experimental DBS, we encountered specific problems. These are discussed in detail. Experimental DBS in freely moving animals is an adequate tool to explore new indications for DBS and to refine DBS technology.

  1. 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.

  2. 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)

  3. Comparing Structural Brain Connectivity by the Infinite Relational Model

    DEFF Research Database (Denmark)

    Ambrosen, Karen Marie Sandø; Herlau, Tue; Dyrby, Tim

    2013-01-01

    The growing focus in neuroimaging on analyzing brain connectivity calls for powerful and reliable statistical modeling tools. We examine the Infinite Relational Model (IRM) as a tool to identify and compare structure in brain connectivity graphs by contrasting its performance on graphs from...

  4. Individual brain structure and modelling predict seizure propagation.

    Science.gov (United States)

    Proix, Timothée; Bartolomei, Fabrice; Guye, Maxime; Jirsa, Viktor K

    2017-03-01

    See Lytton (doi:10.1093/awx018) for a scientific commentary on this article.Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate with the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffusion magnetic resonance imaging have sufficient predictive power to improve diagnosis and surgery outcome. In partial epilepsy, seizures originate in a local network, the so-called epileptogenic zone, before recruiting other close or distant brain regions. We create personalized large-scale brain networks for 15 patients and simulate the individual seizure propagation patterns. Model validation is performed against the presurgical stereotactic electroencephalography data and the standard-of-care clinical evaluation. We demonstrate that the individual brain models account for the patient seizure propagation patterns, explain the variability in postsurgical success, but do not reliably augment with the use of patient-specific connectivity. Our results show that connectome-based brain network models have the capacity to explain changes in the organization of brain activity as observed in some brain disorders, thus opening up avenues towards discovery of novel clinical interventions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  5. Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

    Science.gov (United States)

    Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

    2009-01-01

    This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

  6. Modelling DW-MRI data from primary and metastatic ovarian tumours

    Energy Technology Data Exchange (ETDEWEB)

    Winfield, Jessica M. [Institute of Cancer Research, CRUK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, Surrey (United Kingdom); Royal Marsden NHS Foundation Trust, Surrey (United Kingdom); Institute of Cancer Research and Royal Marsden Hospital, MRI Unit, Surrey (United Kingdom); DeSouza, Nandita M.; Collins, David J. [Institute of Cancer Research, CRUK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, Surrey (United Kingdom); Royal Marsden NHS Foundation Trust, Surrey (United Kingdom); Priest, Andrew N.; Hodgkin, Charlotte; Freeman, Susan [University of Cambridge, Department of Radiology, Addenbrooke' s Hospital, Cambridge (United Kingdom); Wakefield, Jennifer C.; Orton, Matthew R. [Institute of Cancer Research, CRUK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, Surrey (United Kingdom)

    2015-07-15

    To assess goodness-of-fit and repeatability of mono-exponential, stretched exponential and bi-exponential models of diffusion-weighted MRI (DW-MRI) data in primary and metastatic ovarian cancer. Thirty-nine primary and metastatic lesions from thirty-one patients with stage III or IV ovarian cancer were examined before and after chemotherapy using DW-MRI with ten diffusion-weightings. The data were fitted with (a) a mono-exponential model to give the apparent diffusion coefficient (ADC), (b) a stretched exponential model to give the distributed diffusion coefficient (DDC) and stretching parameter (α), and (c) a bi-exponential model to give the diffusion coefficient (D), perfusion fraction (f) and pseudodiffusion coefficient (D*). Coefficients of variation, established from repeated baseline measurements, were: ADC 3.1 %, DDC 4.3 %, α 7.0 %, D 13.2 %, f 44.0 %, D* 165.1 %. The bi-exponential model was unsuitable in these data owing to poor repeatability. After excluding the bi-exponential model, analysis using Akaike Information Criteria showed that the stretched exponential model provided the better fit to the majority of pixels in 64 % of lesions. The stretched exponential model provides the optimal fit to DW-MRI data from ovarian, omental and peritoneal lesions and lymph nodes in pre-treatment and post-treatment measurements with good repeatability. (orig.)

  7. Prognostic value of blood-biomarkers related to hypoxia, inflammation, immune response and tumour load in non-small cell lung cancer - A survival model with external validation.

    Science.gov (United States)

    Carvalho, Sara; Troost, Esther G C; Bons, Judith; Menheere, Paul; Lambin, Philippe; Oberije, Cary

    2016-06-01

    Improve the prognostic prediction of clinical variables for non-small cell lung cancer (NSCLC), by selecting from blood-biomarkers, non-invasively describing hypoxia, inflammation and tumour load. Model development and validation included 182 and 181 inoperable stage I-IIIB NSCLC patients treated radically with radiotherapy (55.2%) or chemo-radiotherapy (44.8%). Least absolute shrinkage and selection operator (LASSO), selected from blood-biomarkers related to hypoxia [osteopontin (OPN) and carbonic anhydrase IX (CA-IX)], inflammation [interleukin-6 (IL-6), IL-8, and C-reactive protein (CRP)], and tumour load [carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1 (Cyfra 21-1)]. Sequent model extension selected from alpha-2-macroglobulin (α2M), serum interleukin-2 receptor (sIL2r), toll-like receptor 4 (TLR4), and vascular endothelial growth factor (VEGF). Discrimination was reported by concordance-index. OPN and Cyfra 21-1 (hazard ratios of 3.3 and 1.7) significantly improved a clinical model comprising gender, World Health Organization performance-status, forced expiratory volume in 1s, number of positive lymph node stations, and gross tumour volume, from a concordance-index of 0.66 to 0.70 (validation=0.62 and 0.66). Extension of the validated model yielded a concordance-index of 0.67, including α2M, sIL2r and VEGF (hazard ratios of 4.6, 3.1, and 1.4). Improvement of a clinical model including hypoxia and tumour load blood-biomarkers was validated. New immunological markers were associated with overall survival. Data and models can be found at www.cancerdata.org (http://dx.doi.org/10.17195/candat.2016.04.1) and www.predictcancer.org. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Carrageenan-induced acute inflammation in the mouse air pouch synovial model. Role of tumour necrosis factor

    Directory of Open Access Journals (Sweden)

    M. Romano

    1997-01-01

    Full Text Available We used the mouse air pouch model of inflammation to study the interaction between cytokines, prostaglandin E2 (PGE2 and cell migration during the various phases of acute local inflammation induced by carrageenan. In serum, the levels of interleukin 1 (IL-1, interleukin 6 (IL-6, tumour necrosis factor (TNF, serum amiloid-A (SAA and Fe++ were never different from controls, indicating that no systemic inflammatory changes were induced. Locally the exudate volume and the number of leukocytes recruited into the pouch increased progressively until 7 days after carrageenan. The same was true for PGE2 production. We could not measure IL-1 but the production of IL-6 and TNF reached a maximum after 5-24 h then quickly decreased. Anti-TNF antibodies inhibited cell migration by 50% 24 h after treatment. Pretreatment with interleukin 10 (IL-10 inhibited TNF production almost completely and cell migration by 60%. Carrageenan-induced inflammation was modulated by anti-inflammatory drugs. Pretreatment with dexamethasone (DEX or indomethacin (INDO inhibited cell migration and reduced the concentration of TNF in the exudate. Production of PGE2 or vascular permeability did not correlate with the number of cells in the pouch. Local TNF seems to play an important role in this model, particularly for leukocyte migration in the first phase of the inflammatory process. In conclusion, the air pouch seems to be a good model for studying the regulation of the early events of local inflammation, particularly the role of cytokines and cell migration.

  9. A monograph proposing the use of canine mammary tumours as a model for the study of hereditary breast cancer susceptibility genes in humans.

    Science.gov (United States)

    Goebel, Katie; Merner, Nancy D

    2017-05-01

    Canines are excellent models for cancer studies due to their similar physiology and genomic sequence to humans, companion status and limited intra-breed heterogeneity. Due to their affliction to mammary cancers, canines can serve as powerful genetic models of hereditary breast cancers. Variants within known human breast cancer susceptibility genes only explain a fraction of familial cases. Thus, further discovery is necessary but such efforts have been thwarted by genetic heterogeneity. Reducing heterogeneity is key, and studying isolated human populations have helped in the endeavour. An alternative is to study dog pedigrees, since artificial selection has resulted in extreme homogeneity. Identifying the genetic predisposition to canine mammary tumours can translate to human discoveries - a strategy currently underutilized. To explore this potential, we reviewed published canine mammary tumour genetic studies and proposed benefits of next generation sequencing canine cohorts to facilitate moving beyond incremental advances.

  10. 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

  11. Volumetric Intraoperative Brain Deformation Compensation: Model Development and Phantom Validation

    Science.gov (United States)

    DeLorenzo, Christine; Papademetris, Xenophon; Staib, Lawrence H.; Vives, Kenneth P.; Spencer, Dennis D.; Duncan, James S.

    2012-01-01

    During neurosurgery, nonrigid brain deformation may affect the reliability of tissue localization based on preoperative images. To provide accurate surgical guidance in these cases, preoperative images must be updated to reflect the intraoperative brain. This can be accomplished by warping these preoperative images using a biomechanical model. Due to the possible complexity of this deformation, intraoperative information is often required to guide the model solution. In this paper, a linear elastic model of the brain is developed to infer volumetric brain deformation associated with measured intraoperative cortical surface displacement. The developed model relies on known material properties of brain tissue, and does not require further knowledge about intraoperative conditions. To provide an initial estimation of volumetric model accuracy, as well as determine the model’s sensitivity to the specified material parameters and surface displacements, a realistic brain phantom was developed. Phantom results indicate that the linear elastic model significantly reduced localization error due to brain shift, from >16 mm to under 5 mm, on average. In addition, though in vivo quantitative validation is necessary, preliminary application of this approach to images acquired during neocortical epilepsy cases confirms the feasibility of applying the developed model to in vivo data. PMID:22562728

  12. Statistical Challenges in Modeling Big Brain Signals

    KAUST Repository

    Yu, Zhaoxia

    2017-11-01

    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible solutions, and highlight future research directions.

  13. Statistical Challenges in Modeling Big Brain Signals

    OpenAIRE

    Yu, Zhaoxia; Pluta, Dustin; Shen, Tong; Chen, Chuansheng; Xue, Gui; Ombao, Hernando

    2017-01-01

    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible solutions, and highlight future research directions.

  14. Animal models of brain dysfunction in phenylketonuria

    NARCIS (Netherlands)

    Martynyuk, A. E.; van Spronsen, F. J.; Van der Zee, E. A.

    2010-01-01

    Phenylketonuria (PKU) is a metabolic disorder that results in significant brain dysfunction if untreated. Although phenylalanine restricted diets instituted at birth have clearly improved PKU outcomes, neuropsychological deficits and neurological changes still represent substantial problems. The

  15. Catastrophic shifts and lethal thresholds in a propagating front model of unstable tumour progression

    CERN Document Server

    Amor, Daniel R

    2014-01-01

    Unstable dynamics characterizes the evolution of most solid tumors. Because of an increased failure of maintaining genome integrity, a cumulative increase in the levels of gene mutation and loss is observed. Previous work suggests that instability thresholds to cancer progression exist, defining phase transition phenomena separating tumor-winning scenarios from tumor extinction or coexistence phases. Here we present an integral equation approach to the quasispecies dynamics of unstable cancer. The model exhibits two main phases, characterized by either the success or failure of cancer tissue. Moreover, the model predicts that tumor failure can be due to either a reduced selective advantage over healthy cells or excessive instability. We also derive an approximate, analytical solution that predicts the front speed of aggressive tumor populations on the instability space.

  16. Large Scale Computing for the Modelling of Whole Brain Connectivity

    DEFF Research Database (Denmark)

    Albers, Kristoffer Jon

    of nodes with a shared connectivity pattern. Modelling the brain in great detail on a whole-brain scale is essential to fully understand the underlying organization of the brain and reveal the relations between structure and function, that allows sophisticated cognitive behaviour to emerge from ensembles...... of neurons. Relying on Markov Chain Monte Carlo (MCMC) simulations as the workhorse in Bayesian inference however poses significant computational challenges, especially when modelling networks at the scale and complexity supported by high-resolution whole-brain MRI. In this thesis, we present how to overcome...... these computational limitations and apply Bayesian stochastic block models for un-supervised data-driven clustering of whole-brain connectivity in full image resolution. We implement high-performance software that allows us to efficiently apply stochastic blockmodelling with MCMC sampling on large complex networks...

  17. A hidden Markov model-based algorithm for identifying tumour subtype using array CGH data

    Directory of Open Access Journals (Sweden)

    Zhang Ke

    2011-12-01

    Full Text Available Abstract Background The recent advancement in array CGH (aCGH research has significantly improved tumor identification using DNA copy number data. A number of unsupervised learning methods have been proposed for clustering aCGH samples. Two of the major challenges for developing aCGH sample clustering are the high spatial correlation between aCGH markers and the low computing efficiency. A mixture hidden Markov model based algorithm was developed to address these two challenges. Results The hidden Markov model (HMM was used to model the spatial correlation between aCGH markers. A fast clustering algorithm was implemented and real data analysis on glioma aCGH data has shown that it converges to the optimal cluster rapidly and the computation time is proportional to the sample size. Simulation results showed that this HMM based clustering (HMMC method has a substantially lower error rate than NMF clustering. The HMMC results for glioma data were significantly associated with clinical outcomes. Conclusions We have developed a fast clustering algorithm to identify tumor subtypes based on DNA copy number aberrations. The performance of the proposed HMMC method has been evaluated using both simulated and real aCGH data. The software for HMMC in both R and C++ is available in ND INBRE website http://ndinbre.org/programs/bioinformatics.php.

  18. The use of pigs in neuroscience: Modeling brains disorders

    DEFF Research Database (Denmark)

    Lind, Nanna Marie; Moustgaard, Anette; Jelsing, Jacob

    2007-01-01

    The use of pigs in neuroscience research has increased in the past decade, which has seen broader recognition of the potential of pigs as an animal for experimental modeling of human brain disorders. The volume of available background data concerning pig brain anatomy and neurochemistry has...

  19. Reptiles: a new model for brain evo-devo research.

    Science.gov (United States)

    Nomura, Tadashi; Kawaguchi, Masahumi; Ono, Katsuhiko; Murakami, Yasunori

    2013-03-01

    Vertebrate brains exhibit vast amounts of anatomical diversity. In particular, the elaborate and complex nervous system of amniotes is correlated with the size of their behavioral repertoire. However, the evolutionary mechanisms underlying species-specific brain morphogenesis remain elusive. In this review we introduce reptiles as a new model organism for understanding brain evolution. These animal groups inherited ancestral traits of brain architectures. We will describe several unique aspects of the reptilian nervous system with a special focus on the telencephalon, and discuss the genetic mechanisms underlying reptile-specific brain morphology. The establishment of experimental evo-devo approaches to studying reptiles will help to shed light on the origin of the amniote brains. Copyright © 2013 Wiley Periodicals, Inc.

  20. Quantification of the effect of electrical and thermal parameters on radiofrequency ablation for concentric tumour model of different sizes.

    Science.gov (United States)

    Jamil, Muhammad; Ng, E Y K

    2015-07-01

    Radiofrequency ablation (RFA) has been increasingly used in treating cancer for multitude of situations in various tissue types. To perform the therapy safely and reliably, the effect of critical parameters needs to be known beforehand. Temperature plays an important role in the outcome of the therapy and any uncertainties in temperature assessment can be lethal. This study presents the RFA case of fixed tip temperature where we've analysed the effect of electrical conductivity, thermal conductivity and blood perfusion rate of the tumour and surrounding normal tissue on the radiofrequency ablation. Ablation volume was chosen as the characteristic to be optimised and temperature control was achieved via PID controller. The effect of all 6 parameters each having 3 levels was quantified with minimum number of experiments harnessing the fractional factorial characteristic of Taguchi's orthogonal arrays. It was observed that as the blood perfusion increases the ablation volume decreases. Increasing electrical conductivity of the tumour results in increase of ablation volume whereas increase in normal tissue conductivity tends to decrease the ablation volume and vice versa. Likewise, increasing thermal conductivity of the tumour results in enhanced ablation volume whereas an increase in thermal conductivity of the surrounding normal tissue has a debilitating effect on the ablation volume and vice versa. With increase in the size of the tumour (i.e., 2-3cm) the effect of each parameter is not linear. The parameter effect varies with change in size of the tumour that is manifested by the different gradient observed in ablation volume. Most important is the relative insensitivity of ablation volume to blood perfusion rate for smaller tumour size (2cm) that is also in accordance with the previous results presented in literature. These findings will provide initial insight for safe, reliable and improved treatment planning perceptively. Copyright © 2015 Elsevier Ltd. All

  1. 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.)

  2. Tumours with elevated levels of the Notch and Wnt pathways exhibit efficacy to PF-03084014, a γ-secretase inhibitor, in a preclinical colorectal explant model.

    Science.gov (United States)

    Arcaroli, J J; Quackenbush, K S; Purkey, A; Powell, R W; Pitts, T M; Bagby, S; Tan, A C; Cross, B; McPhillips, K; Song, E-K; Tai, W M; Winn, R A; Bikkavilli, K; Vanscoyk, M; Eckhardt, S G; Messersmith, W A

    2013-08-06

    Dysregulation of the Notch pathway has been identified to play an important role in the development and progression of colorectal cancer (CRC). In this study, we used a patient-derived CRC explant model to investigate the efficacy of the clinical γ-secretase inhibitor (GSI) PF-03084014. A total of 16 CRC explants were treated with PF-03084014. Knockdown of RBPjκ gene was used to determine the specificity of PF-03084014. Evaluation of the Notch and Wnt pathways in CRC explant tumours was performed by gene array and immunoblotting. We identified a subset of CRC tumours that exhibited elevations of the Notch and Wnt pathways sensitive to PF-03084014. Treatment with the GSI resulted in a significant reduction in cleaved Notch, Axin2 (Wnt-dependent gene) and active β-catenin. In addition, knockdown of the RBPjκ gene showed that PF-03084014 has specificity for the Notch pathway in an HCT116 cell line xenograft model. Finally, an increase in apoptosis was observed in CRC001- and CRC021-sensitive tumours. This study provides evidence that inhibition of γ-secretase may be beneficial in a subset of patients with elevated levels of the Wnt and Notch pathways.

  3. A novel three-phase model of brain tissue microstructure.

    Directory of Open Access Journals (Sweden)

    Jana L Gevertz

    Full Text Available We propose a novel biologically constrained three-phase model of the brain microstructure. Designing a realistic model is tantamount to a packing problem, and for this reason, a number of techniques from the theory of random heterogeneous materials can be brought to bear on this problem. Our analysis strongly suggests that previously developed two-phase models in which cells are packed in the extracellular space are insufficient representations of the brain microstructure. These models either do not preserve realistic geometric and topological features of brain tissue or preserve these properties while overestimating the brain's effective diffusivity, an average measure of the underlying microstructure. In light of the highly connected nature of three-dimensional space, which limits the minimum diffusivity of biologically constrained two-phase models, we explore the previously proposed hypothesis that the extracellular matrix is an important factor that contributes to the diffusivity of brain tissue. Using accurate first-passage-time techniques, we support this hypothesis by showing that the incorporation of the extracellular matrix as the third phase of a biologically constrained model gives the reduction in the diffusion coefficient necessary for the three-phase model to be a valid representation of the brain microstructure.

  4. Pharmacokinetic-pharmacodynamic modeling of the inhibitory effect of erythromycin on tumour necrosis factor-alpha and interleukin-6 production

    NARCIS (Netherlands)

    Guchelaar, H. J.; Schultz, M. J.; van der Poll, T.; Koopmans, R. P.

    2001-01-01

    Erythromycin inhibits the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL6) induced by heat-killed Streptococcus pneumoniae in human whole blood ex-vivo. The objective of the present study was to determine and characterize the concentration-effect relationship of this

  5. Development of a model for whole brain learning of physiology.

    Science.gov (United States)

    Eagleton, Saramarie; Muller, Anton

    2011-12-01

    In this report, a model was developed for whole brain learning based on Curry's onion model. Curry described the effect of personality traits as the inner layer of learning, information-processing styles as the middle layer of learning, and environmental and instructional preferences as the outer layer of learning. The model that was developed elaborates on these layers by relating the personality traits central to learning to the different quadrants of brain preference, as described by Neethling's brain profile, as the inner layer of the onion. This layer is encircled by the learning styles that describe different information-processing preferences for each brain quadrant. For the middle layer, the different stages of Kolb's learning cycle are classified into the four brain quadrants associated with the different brain processing strategies within the information processing circle. Each of the stages of Kolb's learning cycle is also associated with a specific cognitive learning strategy. These two inner circles are enclosed by the circle representing the role of the environment and instruction on learning. It relates environmental factors that affect learning and distinguishes between face-to-face and technology-assisted learning. This model informs on the design of instructional interventions for physiology to encourage whole brain learning.

  6. A porcine model of haematogenous brain infectionwith staphylococcus aureus

    DEFF Research Database (Denmark)

    Astrup, Lærke Boye; Agerholm, Jørgen Steen; Nielsen, Ole Lerberg

    2012-01-01

    A PORCINE MODEL OF HAEMATOGENOUS BRAIN INFECTION WITH STAPHYLOCOCCUS AUREUS Astrup Lærke1, Agerholm Jørgen1, Nielsen Ole1, Jensen Henrik1, Leifsson Páll1, Iburg Tine2. 1: Faculty of Health and Medical Sciences, University of Copenhagen, Denmark boye@life.ku.dk 2: National Veterinary Institute......, Uppsala, Sweden Introduction Staphylococcus aureus (S.aureus) is a common cause of sepsis and brain abscesses in man and a frequent cause of porcine pyaemia. Here we present a porcine model of haematogenous S. aureus-induced brain infection. Materials and Methods Four pigs had two intravenous catheters...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-04-01

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

  9. Modelling Brain Tissue using Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Dyrby, Tim Bjørn

    2008-01-01

    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking...

  10. Fuzzy object models for newborn brain MR image segmentation

    Science.gov (United States)

    Kobashi, Syoji; Udupa, Jayaram K.

    2013-03-01

    Newborn brain MR image segmentation is a challenging problem because of variety of size, shape and MR signal although it is the fundamental study for quantitative radiology in brain MR images. Because of the large difference between the adult brain and the newborn brain, it is difficult to directly apply the conventional methods for the newborn brain. Inspired by the original fuzzy object model introduced by Udupa et al. at SPIE Medical Imaging 2011, called fuzzy shape object model (FSOM) here, this paper introduces fuzzy intensity object model (FIOM), and proposes a new image segmentation method which combines the FSOM and FIOM into fuzzy connected (FC) image segmentation. The fuzzy object models are built from training datasets in which the cerebral parenchyma is delineated by experts. After registering FSOM with the evaluating image, the proposed method roughly recognizes the cerebral parenchyma region based on a prior knowledge of location, shape, and the MR signal given by the registered FSOM and FIOM. Then, FC image segmentation delineates the cerebral parenchyma using the fuzzy object models. The proposed method has been evaluated using 9 newborn brain MR images using the leave-one-out strategy. The revised age was between -1 and 2 months. Quantitative evaluation using false positive volume fraction (FPVF) and false negative volume fraction (FNVF) has been conducted. Using the evaluation data, a FPVF of 0.75% and FNVF of 3.75% were achieved. More data collection and testing are underway.

  11. Development of a Model for Whole Brain Learning of Physiology

    Science.gov (United States)

    Eagleton, Saramarie; Muller, Anton

    2011-01-01

    In this report, a model was developed for whole brain learning based on Curry's onion model. Curry described the effect of personality traits as the inner layer of learning, information-processing styles as the middle layer of learning, and environmental and instructional preferences as the outer layer of learning. The model that was developed…

  12. 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

  13. Image guided constitutive modeling of the silicone brain phantom

    Science.gov (United States)

    Puzrin, Alexander; Skrinjar, Oskar; Ozan, Cem; Kim, Sihyun; Mukundan, Srinivasan

    2005-04-01

    The goal of this work is to develop reliable constitutive models of the mechanical behavior of the in-vivo human brain tissue for applications in neurosurgery. We propose to define the mechanical properties of the brain tissue in-vivo, by taking the global MR or CT images of a brain response to ventriculostomy - the relief of the elevated intracranial pressure. 3D image analysis translates these images into displacement fields, which by using inverse analysis allow for the constitutive models of the brain tissue to be developed. We term this approach Image Guided Constitutive Modeling (IGCM). The presented paper demonstrates performance of the IGCM in the controlled environment: on the silicone brain phantoms closely simulating the in-vivo brain geometry, mechanical properties and boundary conditions. The phantom of the left hemisphere of human brain was cast using silicon gel. An inflatable rubber membrane was placed inside the phantom to model the lateral ventricle. The experiments were carried out in a specially designed setup in a CT scanner with submillimeter isotropic voxels. The non-communicative hydrocephalus and ventriculostomy were simulated by consequently inflating and deflating the internal rubber membrane. The obtained images were analyzed to derive displacement fields, meshed, and incorporated into ABAQUS. The subsequent Inverse Finite Element Analysis (based on Levenberg-Marquardt algorithm) allowed for optimization of the parameters of the Mooney-Rivlin non-linear elastic model for the phantom material. The calculated mechanical properties were consistent with those obtained from the element tests, providing justification for the future application of the IGCM to in-vivo brain tissue.

  14. 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.

  15. 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.)

  16. Establishment of a tumour-stroma airway model (OncoCilAir) to accelerate the development of human therapies against lung cancer.

    Science.gov (United States)

    Mas, Christophe; Boda, Bernadett; Caul Futy, Mireille; Huang, Song; Wisniewski, Ludovic; Constant, Samuel

    2016-10-01

    This paper highlights the work for which OncoTheis, a Swiss biotechnology company, engaged in the development of innovative bioengineered tissues and organoids for cancer research, was co-awarded the 2015 Lush Science Prize. Noting that the use of animal models failed to lead to the design of effective treatments for cancer, OncoTheis has opted to develop in vitro models based exclusively on human cells. The company currently focuses on lung cancer, which is the leading cause of cancer-related deaths worldwide, with more than one million deaths per year. To address this public health concern, we developed OncoCilAir™, a new 3-D model that mimics in vitro the progression of the disease as it happens in patients. In this system, bronchial and lung tumour cells obtained from discarded surgical tissue are cocultured in a Petri dish to reconstitute a fragment of the human lung. After appropriate differentiation, the culture closely reproduces malignant pulmonary nodules invading a small piece of functional airway tissue. As OncoCilAir includes both healthy and cancerous tissues, it can be used to test tumour-killing activity and the adverse effects of chemotherapies and other anti-cancer drugs. Moreover, a single culture can be maintained for up to three months, which permits studies of longer-term effects, including the assessment of drug resistance and tumour recurrence. OncoCilAir heralds a new generation of integrated in vitro models, which is expected to increase the quality of preclinical research while replacing animal testing. 2016 FRAME.

  17. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  18. Modeling and analysis of extracellular field potentials in the brain

    OpenAIRE

    Lindén, Henrik

    2010-01-01

    In order to model processes occuring in the brain it is necessary to have reliable measures of neural activity, with a clear intepretation rooted in the biophysics of the neural tissue. One of the most important probes of neural activity is the measurement of extracellular field potentials. The potential picked up by an electrode placed inside the brain is typically filtered in to two distinct frequency bands: the high-frequency part (>500 Hz) captures the spiking output of nearby cells (term...

  19. Multi-Scale Computational Models for Electrical Brain Stimulation

    Science.gov (United States)

    Seo, Hyeon; Jun, Sung C.

    2017-01-01

    Electrical brain stimulation (EBS) is an appealing method to treat neurological disorders. To achieve optimal stimulation effects and a better understanding of the underlying brain mechanisms, neuroscientists have proposed computational modeling studies for a decade. Recently, multi-scale models that combine a volume conductor head model and multi-compartmental models of cortical neurons have been developed to predict stimulation effects on the macroscopic and microscopic levels more precisely. As the need for better computational models continues to increase, we overview here recent multi-scale modeling studies; we focused on approaches that coupled a simplified or high-resolution volume conductor head model and multi-compartmental models of cortical neurons, and constructed realistic fiber models using diffusion tensor imaging (DTI). Further implications for achieving better precision in estimating cellular responses are discussed. PMID:29123476

  20. 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.

  1. Model of brain activation predicts the neural collective influence map of the brain.

    Science.gov (United States)

    Morone, Flaviano; Roth, Kevin; Min, Byungjoon; Stanley, H Eugene; Makse, Hernán A

    2017-04-11

    Efficient complex systems have a modular structure, but modularity does not guarantee robustness, because efficiency also requires an ingenious interplay of the interacting modular components. The human brain is the elemental paradigm of an efficient robust modular system interconnected as a network of networks (NoN). Understanding the emergence of robustness in such modular architectures from the interconnections of its parts is a longstanding challenge that has concerned many scientists. Current models of dependencies in NoN inspired by the power grid express interactions among modules with fragile couplings that amplify even small shocks, thus preventing functionality. Therefore, we introduce a model of NoN to shape the pattern of brain activations to form a modular environment that is robust. The model predicts the map of neural collective influencers (NCIs) in the brain, through the optimization of the influence of the minimal set of essential nodes responsible for broadcasting information to the whole-brain NoN. Our results suggest intervention protocols to control brain activity by targeting influential neural nodes predicted by network theory.

  2. Dynamic causal modelling of brain-behaviour relationships.

    Science.gov (United States)

    Rigoux, L; Daunizeau, J

    2015-08-15

    In this work, we expose a mathematical treatment of brain-behaviour relationships, which we coin behavioural Dynamic Causal Modelling or bDCM. This approach aims at decomposing the brain's transformation of stimuli into behavioural outcomes, in terms of the relative contribution of brain regions and their connections. In brief, bDCM places the brain at the interplay between stimulus and behaviour: behavioural outcomes arise from coordinated activity in (hidden) neural networks, whose dynamics are driven by experimental inputs. Estimating neural parameters that control network connectivity and plasticity effectively performs a neurobiologically-constrained approximation to the brain's input-outcome transform. In other words, neuroimaging data essentially serves to enforce the realism of bDCM's decomposition of input-output relationships. In addition, post-hoc artificial lesions analyses allow us to predict induced behavioural deficits and quantify the importance of network features for funnelling input-output relationships. This is important, because this enables one to bridge the gap with neuropsychological studies of brain-damaged patients. We demonstrate the face validity of the approach using Monte-Carlo simulations, and its predictive validity using empirical fMRI/behavioural data from an inhibitory control task. Lastly, we discuss promising applications of this work, including the assessment of functional degeneracy (in the healthy brain) and the prediction of functional recovery after lesions (in neurological patients). Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Regional mechanical properties of human brain tissue for computational models of traumatic brain injury.

    Science.gov (United States)

    Finan, John D; Sundaresh, Sowmya N; Elkin, Benjamin S; McKhann, Guy M; Morrison, Barclay

    2017-06-01

    To determine viscoelastic shear moduli, stress relaxation indentation tests were performed on samples of human brain tissue resected in the course of epilepsy surgery. Through the use of a 500µm diameter indenter, regional mechanical properties were measured in cortical grey and white matter and subregions of the hippocampus. All regions were highly viscoelastic. Cortical grey matter was significantly more compliant than the white matter or hippocampus which were similar in modulus. Although shear modulus was not correlated with the age of the donor, cortex from male donors was significantly stiffer than from female donors. The presented material properties will help to populate finite element models of the brain as they become more anatomically detailed. We present the first mechanical characterization of fresh, post-operative human brain tissue using an indentation loading mode. Indentation generates highly localized data, allowing structure-specific mechanical properties to be determined from small tissue samples resected during surgery. It also avoids pitfalls of cadaveric tissue and allows data to be collected before degenerative processes alter mechanical properties. To correctly predict traumatic brain injury, finite element models must calculate intracranial deformation during head impact. The functional consequences of injury depend on the anatomical structures injured. Therefore, morbidity depends on the distribution of deformation across structures. Accurate prediction of structure-specific deformation requires structure-specific mechanical properties. This data will facilitate deeper understanding of the physical mechanisms that lead to traumatic brain injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. 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.

  5. Evaluation of cat brain infarction model using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. J.; Lee, D. S.; Kim, J. H.; Hwang, D. W.; Jung, J. G.; Lee, M. C [College of Medicine, Seoul National University, Seoul (Korea, Republic of); Lim, S. M [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-07-01

    PET has some disadvantage in the imaging of small animal due to poor resolution. With the advance of microPET scanner, it is possible to image small animals. However, the image quality was not so much satisfactory as human image. As cats have relatively large sized brain, cat brain imaging was superior to mice or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCl. A burr hole was made at 1cm right lateral to the bregma. Collagenase type IV 10 ul was injected using 30G needle for 5 minutes to establish the infarction model. F-18 FDG microPET (Concorde Microsystems Inc., Knoxville. TN) scans were performed 1. 11 and 32 days after the infarction. In addition. 18F-FDG PET scans were performed using Gemini PET scanner (Philips medical systems. CA, USA) 13 and 47 days after the infarction. Two cat brain infarction models were established. The glucose metabolism of an infraction lesion improved with time. An infarction lesion was also distinguishable in the Gemini PET scan. We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using F-18 FDG microPET scanner.

  6. Evaluation of cat brain infarction model using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Jin; Lee, Dong Soo; Kim, Yun Hui; Hwang, Do Won; Kim, Jin Su; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of); Lim, Sang Moo [Korea Institite of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-12-01

    PET has some disadvantage in the imaging of small animal due to poor resolution. With the advent of microPET scanner, it is possible to image small animals. However, the image quality was not good enough as human image. Due to larger brain, cat brain imaging was superior to mouse or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCI. A burr hole was made at 1 cm right lateral to the bregma. Collagenase type IV 10 {mu}l was injected using 30 G needle for 5 minutes to establish the infarction model. {sup 18}F-FDG microPET (Concorde Microsystems Inc., Knoxville, TN) scans were performed 1, 11 and 32 days after the infarction. In addition, {sup 18}F-FDG PET scans were performed using human PET scanner (Gemini, Philips medical systems, CA, USA) 13 and 47 days after the infarction. Two cat brain infarction models were established. The glucose metabolism of an infarction lesion improved with time. An infarction lesion was also distinguishable in the human PET scan. We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using {sup 18}F-FDG microPET scanner.

  7. An adaptive complex network model for brain functional networks.

    Directory of Open Access Journals (Sweden)

    Ignacio J Gomez Portillo

    Full Text Available Brain functional networks are graph representations of activity in the brain, where the vertices represent anatomical regions and the edges their functional connectivity. These networks present a robust small world topological structure, characterized by highly integrated modules connected sparsely by long range links. Recent studies showed that other topological properties such as the degree distribution and the presence (or absence of a hierarchical structure are not robust, and show different intriguing behaviors. In order to understand the basic ingredients necessary for the emergence of these complex network structures we present an adaptive complex network model for human brain functional networks. The microscopic units of the model are dynamical nodes that represent active regions of the brain, whose interaction gives rise to complex network structures. The links between the nodes are chosen following an adaptive algorithm that establishes connections between dynamical elements with similar internal states. We show that the model is able to describe topological characteristics of human brain networks obtained from functional magnetic resonance imaging studies. In particular, when the dynamical rules of the model allow for integrated processing over the entire network scale-free non-hierarchical networks with well defined communities emerge. On the other hand, when the dynamical rules restrict the information to a local neighborhood, communities cluster together into larger ones, giving rise to a hierarchical structure, with a truncated power law degree distribution.

  8. Data-driven forward model inference for EEG brain imaging

    DEFF Research Database (Denmark)

    Hansen, Sofie Therese; Hauberg, Søren; Hansen, Lars Kai

    2016-01-01

    Electroencephalography (EEG) is a flexible and accessible tool with excellent temporal resolution but with a spatial resolution hampered by volume conduction. Reconstruction of the cortical sources of measured EEG activity partly alleviates this problem and effectively turns EEG into a brain......-of-concept study, we show that, even when anatomical knowledge is unavailable, a suitable forward model can be estimated directly from the EEG. We propose a data-driven approach that provides a low-dimensional parametrization of head geometry and compartment conductivities, built using a corpus of forward models....... Combined with only a recorded EEG signal, we are able to estimate both the brain sources and a person-specific forward model by optimizing this parametrization. We thus not only solve an inverse problem, but also optimize over its specification. Our work demonstrates that personalized EEG brain imaging...

  9. Joint Modelling of Structural and Functional Brain Networks

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther; Herlau, Tue; Mørup, Morten

    Functional and structural magnetic resonance imaging have become the most important noninvasive windows to the human brain. A major challenge in the analysis of brain networks is to establish the similarities and dissimilarities between functional and structural connectivity. We formulate a non......-parametric Bayesian network model which allows for joint modelling and integration of multiple networks. We demonstrate the model’s ability to detect vertices that share structure across networks jointly in functional MRI (fMRI) and diffusion MRI (dMRI) data. Using two fMRI and dMRI scans per subject, we establish...... significant structures that are consistently shared across subjects and data splits. This provides an unsupervised approach for modeling of structure-function relations in the brain and provides a general framework for multimodal integration....

  10. 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

  11. 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.

  12. Tracer kinetic modelling for DCE-MRI quantification of subtle blood-brain barrier permeability.

    Science.gov (United States)

    Heye, Anna K; Thrippleton, Michael J; Armitage, Paul A; Valdés Hernández, Maria Del C; Makin, Stephen D; Glatz, Andreas; Sakka, Eleni; Wardlaw, Joanna M

    2016-01-15

    There is evidence that subtle breakdown of the blood-brain barrier (BBB) is a pathophysiological component of several diseases, including cerebral small vessel disease and some dementias. Dynamic contrast-enhanced MRI (DCE-MRI) combined with tracer kinetic modelling is widely used for assessing permeability and perfusion in brain tumours and body tissues where contrast agents readily accumulate in the extracellular space. However, in diseases where leakage is subtle, the optimal approach for measuring BBB integrity is likely to differ since the magnitude and rate of enhancement caused by leakage are extremely low; several methods have been reported in the literature, yielding a wide range of parameters even in healthy subjects. We hypothesised that the Patlak model is a suitable approach for measuring low-level BBB permeability with low temporal resolution and high spatial resolution and brain coverage, and that normal levels of scanner instability would influence permeability measurements. DCE-MRI was performed in a cohort of mild stroke patients (n=201) with a range of cerebral small vessel disease severity. We fitted these data to a set of nested tracer kinetic models, ranking their performance according to the Akaike information criterion. To assess the influence of scanner drift, we scanned 15 healthy volunteers that underwent a "sham" DCE-MRI procedure without administration of contrast agent. Numerical simulations were performed to investigate model validity and the effect of scanner drift. The Patlak model was found to be most appropriate for fitting low-permeability data, and the simulations showed vp and K(Trans) estimates to be reasonably robust to the model assumptions. However, signal drift (measured at approximately 0.1% per minute and comparable to literature reports in other settings) led to systematic errors in calculated tracer kinetic parameters, particularly at low permeabilities. Our findings justify the growing use of the Patlak model in low

  13. Causation model of autism: Audiovisual brain specialization in infancy competes with social brain networks.

    Science.gov (United States)

    Heffler, Karen Frankel; Oestreicher, Leonard M

    2016-06-01

    Earliest identifiable findings in autism indicate that the autistic brain develops differently from the typical brain in the first year of life, after a period of typical development. Twin studies suggest that autism has an environmental component contributing to causation. Increased availability of audiovisual (AV) materials and viewing practices of infants parallel the time frame of the rise in prevalence of autism spectrum disorder (ASD). Studies have shown an association between ASD and increased TV/cable screen exposure in infancy, suggesting AV exposure in infancy as a possible contributing cause of ASD. Infants are attracted to the saliency of AV materials, yet do not have the experience to recognize these stimuli as socially relevant. The authors present a developmental model of autism in which exposure to screen-based AV input in genetically susceptible infants stimulates specialization of non-social sensory processing in the brain. Through a process of neuroplasticity, the autistic infant develops the skills that are driven by the AV viewing. The AV developed neuronal pathways compete with preference for social processing, negatively affecting development of social brain pathways and causing global developmental delay. This model explains atypical face and speech processing, as well as preference for AV synchrony over biological motion in ASD. Neural hyper-connectivity, enlarged brain size and special abilities in visual, auditory and motion processing in ASD are also explained by the model. Positive effects of early intervention are predicted by the model. Researchers studying causation of autism have largely overlooked AV exposure in infancy as a potential contributing factor. The authors call for increased public awareness of the association between early screen viewing and ASD, and a concerted research effort to determine the extent of causal relationship. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. 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.

  15. Improved brain tumor segmentation by utilizing tumor growth model in longitudinal brain MRI

    Science.gov (United States)

    Pei, Linmin; Reza, Syed M. S.; Li, Wei; Davatzikos, Christos; Iftekharuddin, Khan M.

    2017-03-01

    In this work, we propose a novel method to improve texture based tumor segmentation by fusing cell density patterns that are generated from tumor growth modeling. To model tumor growth, we solve the reaction-diffusion equation by using Lattice-Boltzmann method (LBM). Computational tumor growth modeling obtains the cell density distribution that potentially indicates the predicted tissue locations in the brain over time. The density patterns is then considered as novel features along with other texture (such as fractal, and multifractal Brownian motion (mBm)), and intensity features in MRI for improved brain tumor segmentation. We evaluate the proposed method with about one hundred longitudinal MRI scans from five patients obtained from public BRATS 2015 data set, validated by the ground truth. The result shows significant improvement of complete tumor segmentation using ANOVA analysis for five patients in longitudinal MR images.

  16. The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth and metastases in vasopressin type 2 receptor-expressing breast cancer models

    Science.gov (United States)

    GARONA, JUAN; PIFANO, MARINA; ORLANDO, ULISES D.; PASTRIAN, MARIA B.; IANNUCCI, NANCY B.; ORTEGA, HUGO H.; PODESTA, ERNESTO J.; GOMEZ, DANIEL E.; RIPOLL, GISELLE V.; ALONSO, DANIEL F.

    2015-01-01

    Desmopressin (dDAVP) is a safe haemostatic agent with previously reported antitumour activity. It acts as a selective agonist for the V2 vasopressin membrane receptor (V2r) present on tumour cells and microvasculature. The purpose of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r-expressing preclinical mouse models of breast cancer. We assessed antitumour effects of [V4Q5]dDAVP using human MCF-7 and MDA-MB-231 breast carcinoma cells, as well as the highly metastatic mouse F3II cell line. Effect on in vitro cancer cell growth was evaluated by cell proliferation and clonogenic assays. Cell cycle distribution was analysed by flow cytometry. In order to study the effect of intravenously administered [V4Q5]dDAVP on tumour growth and angiogenesis, breast cancer xenografts were generated in athymic mice. F3II cells were injected into syngeneic mice to evaluate the effect of [V4Q5]dDAVP on spontaneous and experimental metastatic spread. In vitro cytostatic effects of [V4Q5]dDAVP against breast cancer cells were greater than those of dDAVP, and associated with V2r-activated signal transduction and partial cell cycle arrest. In MDA-MB-231 xenografts, [V4Q5]dDAVP (0.3 μg/kg, thrice a week) reduced tumour growth and angiogenesis. Treatment of F3II mammary tumour-bearing immunocompetent mice resulted in complete inhibition of metastatic progression. [V4Q5]dDAVP also displayed greater antimetastatic efficacy than dDAVP on experimental lung colonisation by F3II cells. The novel analogue was well tolerated in preliminary acute toxicology studies, at doses ≥300-fold above that required for anti-angiogenic/antimetastatic effects. Our data establish the preclinical activity of [V4Q5]dDAVP in aggressive breast cancer, providing the rationale for further clinical trials. PMID:25846632

  17. The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth and metastases in vasopressin type 2 receptor-expressing breast cancer models.

    Science.gov (United States)

    Garona, Juan; Pifano, Marina; Orlando, Ulises D; Pastrian, Maria B; Iannucci, Nancy B; Ortega, Hugo H; Podesta, Ernesto J; Gomez, Daniel E; Ripoll, Giselle V; Alonso, Daniel F

    2015-01-01

    Desmopressin (dDAVP) is a safe haemostatic agent with previously reported antitumour activity. It acts as a selective agonist for the V2 vasopressin membrane receptor (V2r) present on tumour cells and microvasculature. The purpose of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r-expressing preclinical mouse models of breast cancer. We assessed antitumour effects of [V4Q5]dDAVP using human MCF-7 and MDA-MB-231 breast carcinoma cells, as well as the highly metastatic mouse F3II cell line. Effect on in vitro cancer cell growth was evaluated by cell proliferation and clonogenic assays. Cell cycle distribution was analysed by flow cytometry. In order to study the effect of intravenously administered [V4Q5]dDAVP on tumour growth and angiogenesis, breast cancer xenografts were generated in athymic mice. F3II cells were injected into syngeneic mice to evaluate the effect of [V4Q5]dDAVP on spontaneous and experimental metastatic spread. In vitro cytostatic effects of [V4Q5]dDAVP against breast cancer cells were greater than those of dDAVP, and associated with V2r-activated signal transduction and partial cell cycle arrest. In MDA-MB-231 xenografts, [V4Q5]dDAVP (0.3 µg/kg, thrice a week) reduced tumour growth and angiogenesis. Treatment of F3II mammary tumour-bearing immunocompetent mice resulted in complete inhibition of metastatic progression. [V4Q5]dDAVP also displayed greater antimetastatic efficacy than dDAVP on experimental lung colonisation by F3II cells. The novel analogue was well tolerated in preliminary acute toxicology studies, at doses ≥ 300-fold above that required for anti-angiogenic/antimetastatic effects. Our data establish the preclinical activity of [V4Q5]dDAVP in aggressive breast cancer, providing the rationale for further clinical trials.

  18. Nano-Modeling and Computation in Bio and Brain Dynamics

    Directory of Open Access Journals (Sweden)

    Paolo Di Sia

    2016-04-01

    Full Text Available The study of brain dynamics currently utilizes the new features of nanobiotechnology and bioengineering. New geometric and analytical approaches appear very promising in all scientific areas, particularly in the study of brain processes. Efforts to engage in deep comprehension lead to a change in the inner brain parameters, in order to mimic the external transformation by the proper use of sensors and effectors. This paper highlights some crossing research areas of natural computing, nanotechnology, and brain modeling and considers two interesting theoretical approaches related to brain dynamics: (a the memory in neural network, not as a passive element for storing information, but integrated in the neural parameters as synaptic conductances; and (b a new transport model based on analytical expressions of the most important transport parameters, which works from sub-pico-level to macro-level, able both to understand existing data and to give new predictions. Complex biological systems are highly dependent on the context, which suggests a “more nature-oriented” computational philosophy.

  19. An Evolutionary Game Theory Model of Spontaneous Brain Functioning.

    Science.gov (United States)

    Madeo, Dario; Talarico, Agostino; Pascual-Leone, Alvaro; Mocenni, Chiara; Santarnecchi, Emiliano

    2017-11-22

    Our brain is a complex system of interconnected regions spontaneously organized into distinct networks. The integration of information between and within these networks is a continuous process that can be observed even when the brain is at rest, i.e. not engaged in any particular task. Moreover, such spontaneous dynamics show predictive value over individual cognitive profile and constitute a potential marker in neurological and psychiatric conditions, making its understanding of fundamental importance in modern neuroscience. Here we present a theoretical and mathematical model based on an extension of evolutionary game theory on networks (EGN), able to capture brain's interregional dynamics by balancing emulative and non-emulative attitudes among brain regions. This results in the net behavior of nodes composing resting-state networks identified using functional magnetic resonance imaging (fMRI), determining their moment-to-moment level of activation and inhibition as expressed by positive and negative shifts in BOLD fMRI signal. By spontaneously generating low-frequency oscillatory behaviors, the EGN model is able to mimic functional connectivity dynamics, approximate fMRI time series on the basis of initial subset of available data, as well as simulate the impact of network lesions and provide evidence of compensation mechanisms across networks. Results suggest evolutionary game theory on networks as a new potential framework for the understanding of human brain network dynamics.

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

    Directory of Open Access Journals (Sweden)

    Georgios S. Stamatakos

    2009-10-01

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

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

    Science.gov (United States)

    Stamatakos, Georgios S; Dionysiou, Dimitra D

    2009-10-21

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

  2. Directions for Mind, Brain, and Education: Methods, Models, and Morality

    Science.gov (United States)

    Stein, Zachary; Fischer, Kurt W.

    2011-01-01

    In this article we frame a set of important issues in the emerging field of Mind, Brain, and Education in terms of three broad headings: methods, models, and morality. Under the heading of methods we suggest that the need for synthesis across scientific and practical disciplines entails the pursuit of usable knowledge via a catalytic symbiosis…

  3. Human cadaver brain infusion skull model for neurosurgical training.

    Science.gov (United States)

    Olabe, Jon; Olabe, Javier; Roda, Jose Maria; Sancho, Vidal

    2011-01-01

    Microsurgical technique and anatomical knowledge require extensive laboratory training. Human cadaver models are especially valuable as they supply a good microsurgical training environment simultaneously providing authentic brain anatomy. We developed the "skull infusion model" as an extension of our previous "brain infusion model" taking it a step further maintaining simplicity but enhancing realism. Four human cadaveric brains donated for educational purposes were explanted at autopsy. The specimens were prepared cannulating carotid and vertebral arteries with plastic tubings, flushed with abundant water and fixed for 1 month in formaldehyde. They were then enclosed with white silk clothing (emulating the dura mater) and inserted into human skulls cut previously into two pieces. Tap water at a flow rate of 10 L/h was infused through the arterial tubings. Diverse microsurgical procedures were performed by two trainees, including craniotomies with microsurgical approaches and techniques such as sylvian fissure exposure, extra-intracranial and intra-intracranial bypass, approaches to the ventricles and choroidal fissure opening. The water infusion fills the arterial system, leaking into the interstitial and cisternal space and finally moistening the whole specimen. This makes vascular microsurgical techniques become extremely realistic, increasing its compliance making manipulations easier and more authentic. Standard microsurgical laboratories frequently have difficulties to work with decapitated human cadaver heads but could have human brains readily available. Using the infusion model and inserting it in a human skull makes the environment much more realistic. Its simplicity and inexpensiveness make it a good alternative for developing microsurgical techniques.

  4. Stochastic model of Tsc1 lesions in mouse brain.

    Directory of Open Access Journals (Sweden)

    Shilpa Prabhakar

    Full Text Available Tuberous sclerosis complex (TSC is an autosomal dominant disorder due to mutations in either TSC1 or TSC2 that affects many organs with hamartomas and tumors. TSC-associated brain lesions include subependymal nodules, subependymal giant cell astrocytomas and tubers. Neurologic manifestations in TSC comprise a high frequency of mental retardation and developmental disorders including autism, as well as epilepsy. Here, we describe a new mouse model of TSC brain lesions in which complete loss of Tsc1 is achieved in multiple brain cell types in a stochastic pattern. Injection of an adeno-associated virus vector encoding Cre recombinase into the cerebral ventricles of mice homozygous for a Tsc1 conditional allele on the day of birth led to reduced survival, and pathologic findings of enlarged neurons, cortical heterotopias, subependymal nodules, and hydrocephalus. The severity of clinical and pathologic findings as well as survival was shown to be dependent upon the dose and serotype of Cre virus injected. Although several other models of TSC brain disease exist, this model is unique in that the pathology reflects a variety of TSC-associated lesions involving different numbers and types of cells. This model provides a valuable and unique addition for therapeutic assessment.

  5. Using Data-Driven Model-Brain Mappings to Constrain Formal Models of Cognition

    OpenAIRE

    Borst, Jelmer P; Menno Nijboer; Taatgen, Niels A.; Hedderik van Rijn; John R Anderson

    2015-01-01

    In this paper we propose a method to create data-driven mappings from components of cognitive models to brain regions. Cognitive models are notoriously hard to evaluate, especially based on behavioral measures alone. Neuroimaging data can provide additional constraints, but this requires a mapping from model components to brain regions. Although such mappings can be based on the experience of the modeler or on a reading of the literature, a formal method is preferred to prevent researcher-bas...

  6. Quantification of Brain Access of Exendin-4 in the C57BL Mouse Model by SPIM Fluorescence Imaging and the Allen Mouse Brain Reference Model

    DEFF Research Database (Denmark)

    Jensen, Casper Bo; Secher, Anna; Hecksher-Sørensen, Jacob

    2015-01-01

    construct a SPIM brain atlas based on the Allen mouse brain 3D reference model and use it to analyze the access of peripherally injected Exendin-4 into the brain compared to a negative control group. The constructed atlas consists of an average SPIM volume obtained from eight C57BL mouse brains using group......-wise registration. A cross-modality registration is performed between the constructed average volume and the Allen mouse brain reference model to allow propagation of annotations to the SPIM average brain. Finally, manual corrections of the annotations are performed and validated by visual inspection. The study...

  7. CSF transthyretin neuroprotection in a mouse model of brain ischemia

    DEFF Research Database (Denmark)

    Santos, Sofia Duque; Lambertsen, Kate Lykke; Clausen, Bettina Hjelm

    2010-01-01

    Brain injury caused by ischemia is a major cause of human mortality and physical/cognitive disability worldwide. Experimentally, brain ischemia can be induced surgically by permanent middle cerebral artery occlusion. Using this model, we studied the influence of transthyretin in ischemic stroke....... However, TTR null mice, heterozygous for the heat-shock transcription factor 1 (TTR(-/-) HSF1(+/-) mice), which compromised the stress response, showed a significant increase in cortical infarction, cerebral edema and the microglial-leukocyte response compared with TTR(+/+) HSF1(+/-) mice. Unexpectedly...

  8. Modelling the correlation between EGFr expression and tumour cell radiosensitivity, and combined treatments of radiation and monoclonal antibody EGFr inhibitors

    Directory of Open Access Journals (Sweden)

    Pedicini Piernicola

    2012-06-01

    Full Text Available Abstract Purpose To estimate the effects of heterogeneity on tumour cell sensitivity to radiotherapy combined with radiosensitizing agents attributable to differences in expression levels of Epidermal Growth Factor Receptor (EGFr. Materials and methods Differences in radiosensitivity are not limited to cells of different cancer histotypes but also occur within the same cancer, or appear during radiotherapy if radiosensitizing drugs are combined with ionizing radiation. A modified biologically effective dose (MBED, has been introduced to account for changes in radiosensitivity parameters (α and α/β rather than changes in dose/fraction or total dose as normally done with standard biologically effective dose (BED. The MBED approach was applied to cases of EGFr over-expression and cases where EGFr inhibitors were combined with radiation. Representative examples in clinical practice were considered. Results Assuming membrane EGFr over-expression corresponds to reduced radiosensitivity (αH = 0.15 Gy-1 and αH/βH = 7.5 Gy relative to normal radiosensitivity (α = 0.2 Gy-1 and α/β = 10 Gy, an increased dose per fraction of 2.42 Gy was obtained through the application of MBED, which is equivalent to the effect of a reference schedule with 30 fractions of 2 Gy. An equivalent hypo-fractionated regime with a dose per fraction of 2.80 Gy is obtained if 25 fractions are set. Dose fractionations modulated according to drug pharmacokinetics are estimated for combined treatments with biological drugs. Soft and strong modulated equivalent hypo-fractionations result from subtraction of 5 or 10 fractions, respectively. Conclusions During this computational study, a new radiobiological tool has been introduced. The MBED allows the required dose per fraction to be estimated when tumour radiosensitivity is reduced because EGFr is over-expressed. If radiotherapy treatment is combined with EGFr inhibitors, MBED suggests new treatment strategies

  9. Modeling and Targeting MYC Genes in Childhood Brain Tumors.

    Science.gov (United States)

    Hutter, Sonja; Bolin, Sara; Weishaupt, Holger; Swartling, Fredrik J

    2017-03-23

    Brain tumors are the second most common group of childhood cancers, accounting for about 20%-25% of all pediatric tumors. Deregulated expression of the MYC family of transcription factors, particularly c-MYC and MYCN genes, has been found in many of these neoplasms, and their expression levels are often correlated with poor prognosis. Elevated c-MYC/MYCN initiates and drives tumorigenesis in many in vivo model systems of pediatric brain tumors. Therefore, inhibition of their oncogenic function is an attractive therapeutic target. In this review, we explore the roles of MYC oncoproteins and their molecular targets during the formation, maintenance, and recurrence of childhood brain tumors. We also briefly summarize recent progress in the development of therapeutic approaches for pharmacological inhibition of MYC activity in these tumors.

  10. A Mixed Approach for Modeling Blood Flow in Brain Microcirculation

    Science.gov (United States)

    Lorthois, Sylvie; Peyrounette, Myriam; Davit, Yohan; Quintard, Michel; Groupe d'Etude sur les Milieux Poreux Team

    2015-11-01

    Consistent with its distribution and exchange functions, the vascular system of the human brain cortex is a superposition of two components. At small-scale, a homogeneous and space-filling mesh-like capillary network. At large scale, quasi-fractal branched veins and arteries. From a modeling perspective, this is the superposition of: (a) a continuum model resulting from the homogenization of slow transport in the small-scale capillary network; and (b) a discrete network approach describing fast transport in the arteries and veins, which cannot be homogenized because of their fractal nature. This problematic is analogous to fast conducting wells embedded in a reservoir rock in petroleum engineering. An efficient method to reduce the computational cost is to use relatively large grid blocks for the continuum model. This makes it difficult to accurately couple both components. We solve this issue by adapting the ``well model'' concept used in petroleum engineering to brain specific 3D situations. We obtain a unique linear system describing the discrete network, the continuum and the well model. Results are presented for realistic arterial and venous geometries. The mixed approach is compared with full network models including various idealized capillary networks of known permeability. ERC BrainMicroFlow GA615102.

  11. Inheritance of fibrosarcomatous liver tumours in White Leghorn chicks inoculated vu the chorioallantoic membrane with subgroup A Rous sarcoma virus: A four-allele genetic model.

    Science.gov (United States)

    Pani, P K; Naithani, S

    1990-10-01

    An investigation was made using White Leghorn fowl to study the genetic control of subgroup A Rous sarcoma virus-induced fibrosarcomatous liver tumours (LT) in chicks inoculated via the chorioallantoic membrane (CAM). A total of 723 CAM-inoculated embryos were hatched in three experiments. In Expt 1, CAM-susceptibility and LT-mortality were examined on a within sire family basis to ascertain the inter-relationship between the two parameters. In Expt 2, sires that had records of high or low LT(+) deaths in the families were selected to produce progeny within high and low incidence lines in the next generation to ascertain the amenability of the trait (LT death) to selection pressure. Survivors of LT-assay (Expt 1) were mated inter se in Expt 3 to study the inheritance of the two traits according to known or proposed genetic models. It was shown that LT mortality is a genetic trait because of its amenability to selection, with a high realised heritability (h(2)(R)= 1.16). In the three experiments, most CAM-susceptibles (S) died of LT(+), and most CAM-resistants(R) survived, but there were some conversely associated phenotypes i.e. S(LT-) and R(LT+). The conventional 2-allele model of the tva (tumour virus a) locus with pleiotropic effect, or a 2-locus model with linkage, were considered inadequate to explain the occurrence of conversely associated phenotypes on a within family basis. However, a 4-allele model of the tva locus showed a good fit to the results of this study.

  12. Dosha brain-types: A neural model of individual differences

    Directory of Open Access Journals (Sweden)

    Frederick T Travis

    2015-01-01

    Full Text Available This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations.

  13. Dosha brain-types: A neural model of individual differences.

    Science.gov (United States)

    Travis, Frederick T; Wallace, Robert Keith

    2015-01-01

    This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations.

  14. A spatio-temporal reference model of the aging brain.

    Science.gov (United States)

    Huizinga, W; Poot, D H J; Vernooij, M W; Roshchupkin, G V; Bron, E E; Ikram, M A; Rueckert, D; Niessen, W J; Klein, S

    2017-12-05

    Both normal aging and neurodegenerative disorders such as Alzheimer's disease (AD) cause morphological changes of the brain. It is generally difficult to distinguish these two causes of morphological change by visual inspection of magnetic resonance (MR) images. To facilitate making this distinction and thus aid the diagnosis of neurodegenerative disorders, we propose a method for developing a spatio-temporal model of morphological differences in the brain due to normal aging. The method utilizes groupwise image registration to characterize morphological variation across brain scans of people with different ages. To extract the deformations that are due to normal aging we use partial least squares regression, which yields modes of deformations highly correlated with age, and corresponding scores for each input subject. Subsequently, we determine a distribution of morphologies as a function of age by fitting smooth percentile curves to these scores. This distribution is used as a reference to which a person's morphology score can be compared. We validate our method on two different datasets, using images from both cognitively normal subjects and patients with Alzheimer disease (AD). Results show that the proposed framework extracts the expected atrophy patterns. Moreover, the morphology scores of cognitively normal subjects are on average lower than the scores of AD subjects, indicating that morphology differences between AD subjects and healthy subjects can be partly explained by accelerated aging. With our methods we are able to assess accelerated brain aging on both population and individual level. A spatio-temporal aging brain model derived from 988 T1-weighted MR brain scans from a large population imaging study (age range 45.9-91.7y, mean age 68.3y) is made publicly available at www.agingbrain.nl. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. General solutions to poroviscoelastic model of hydrocephalic human brain tissue.

    Science.gov (United States)

    Mehrabian, Amin; Abousleiman, Younane

    2011-12-21

    Hydrocephalus is a well-known disorder of brain fluidic system. It is commonly associated with complexities in cerebrospinal fluid (CSF) circulation in brain. In this paper, hydrocephalus and shunting surgery which is used in its treatment are modeled. Brain tissues are considered to follow a poroviscoelastic constitutive model in order to address the effects of time dependence of mechanical properties of soft tissues and fluid flow hydraulics. Our solution draws from Biot's theory of poroelasticity, generalized to account for viscoelastic effects through the correspondence principle. Geometrically, the brain is conceived to be spherically symmetric, where the ventricles are assumed to be a hollow concentric space filled with cerebrospinal fluid. A generalized Kelvin model is considered for the rheological properties of brain tissues. The solution presented is useful in the analysis of the disorder of hydrocephalus as well as the treatment associated with it, namely, ventriclostomy surgery. The sensitivity of the solution to various factors such as aqueduct blockage level and trabeculae stiffness is thoroughly analyzed using numerical examples. Results indicate that partial aqueduct stenosis may be a cause of hydrocephalus. However, only severe occlusion of the aqueduct can cause a significant increase in the ventricle and brain's extracellular fluid pressure. Ventriculostomy shunts are commonly used as a remedy to hydrocephalus. They serve to reduce the ventricular pressure to the normal level. However, sensitivity analysis on the shunt's fluid deliverability parameter has shown that inappropriate design or selection of design shunt may cause under-drainage or over-drainage of the ventricles. Excessive drainage of CSF may increase the normal tensile stress on trabeculae. It can cause rupture of superior cerebral veins or damage to trabeculae or even brain tissues which in turn may lead to subdural hematoma, a common side-effect of the surgery. These Post

  16. 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.

  17. 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)

  18. 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.

  19. MR Vascular Fingerprinting in Stroke and Brain Tumors Models

    Science.gov (United States)

    Lemasson, B.; Pannetier, N.; Coquery, N.; Boisserand, Ligia S. B.; Collomb, Nora; Schuff, N.; Moseley, M.; Zaharchuk, G.; Barbier, E. L.; Christen, T.

    2016-11-01

    In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.

  20. 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.

  1. 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.

  2. Lateral fluid percussion: model of traumatic brain injury in mice.

    Science.gov (United States)

    Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P; Thakker-Varia, Smita

    2011-08-22

    Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific

  3. 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.

  4. 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.

  5. Avoiding Boltzmann Brain domination in holographic dark energy models

    Science.gov (United States)

    Horvat, R.

    2015-11-01

    In a spatially infinite and eternal universe approaching ultimately a de Sitter (or quasi-de Sitter) regime, structure can form by thermal fluctuations as such a space is thermal. The models of Dark Energy invoking holographic principle fit naturally into such a category, and spontaneous formation of isolated brains in otherwise empty space seems the most perplexing, creating the paradox of Boltzmann Brains (BB). It is thus appropriate to ask if such models can be made free from domination by Boltzmann Brains. Here we consider only the simplest model, but adopt both the local and the global viewpoint in the description of the Universe. In the former case, we find that if a dimensionless model parameter c, which modulates the Dark Energy density, lies outside the exponentially narrow strip around the most natural c = 1 line, the theory is rendered BB-safe. In the latter case, the bound on c is exponentially stronger, and seemingly at odds with those bounds on c obtained from various observational tests.

  6. Avoiding Boltzmann Brain domination in holographic dark energy models

    Directory of Open Access Journals (Sweden)

    R. Horvat

    2015-11-01

    Full Text Available In a spatially infinite and eternal universe approaching ultimately a de Sitter (or quasi-de Sitter regime, structure can form by thermal fluctuations as such a space is thermal. The models of Dark Energy invoking holographic principle fit naturally into such a category, and spontaneous formation of isolated brains in otherwise empty space seems the most perplexing, creating the paradox of Boltzmann Brains (BB. It is thus appropriate to ask if such models can be made free from domination by Boltzmann Brains. Here we consider only the simplest model, but adopt both the local and the global viewpoint in the description of the Universe. In the former case, we find that if a dimensionless model parameter c, which modulates the Dark Energy density, lies outside the exponentially narrow strip around the most natural c=1 line, the theory is rendered BB-safe. In the latter case, the bound on c is exponentially stronger, and seemingly at odds with those bounds on c obtained from various observational tests.

  7. Liver cancer arterial perfusion modelling and CFD boundary conditions methodology: a case study of the haemodynamics of a patient-specific hepatic artery in literature-based healthy and tumour-bearing liver scenarios.

    Science.gov (United States)

    Aramburu, Jorge; Antón, Raúl; Rivas, Alejandro; Ramos, Juan Carlos; Sangro, Bruno; Bilbao, José Ignacio

    2016-11-01

    Some of the latest treatments for unresectable liver malignancies (primary or metastatic tumours), which include bland embolisation, chemoembolisation, and radioembolisation, among others, take advantage of the increased arterial blood supply to the tumours to locally attack them. A better understanding of the factors that influence this transport may help improve the therapeutic procedures by taking advantage of flow patterns or by designing catheters and infusion systems that result in the injected beads having increased access to the tumour vasculature. Computational analyses may help understand the haemodynamic patterns and embolic-microsphere transport through the hepatic arteries. In addition, physiological inflow and outflow boundary conditions are essential in order to reliably represent the blood flow through arteries. This study presents a liver cancer arterial perfusion model based on a literature review and derives boundary conditions for tumour-bearing liver-feeding hepatic arteries based on the arterial perfusion characteristics of normal and tumorous liver segment tissue masses and the hepatic artery branching configuration. Literature-based healthy and tumour-bearing realistic scenarios are created and haemodynamically analysed for the same patient-specific hepatic artery. As a result, this study provides boundary conditions for computational fluid dynamics simulations that will allow researchers to numerically study, for example, various intravascular devices used for liver disease intra-arterial treatments with different cancer scenarios. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Genetic mouse models of brain ageing and Alzheimer's disease.

    Science.gov (United States)

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. 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...

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

    Directory of Open Access Journals (Sweden)

    Terry L Pinfold

    2014-05-01

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

  11. Human cadaver brain infusion model for neurosurgical training.

    Science.gov (United States)

    Olabe, Jon; Olabe, Javier; Sancho, Vidal

    2009-12-01

    Microneurosurgical technique and anatomical knowledge require extensive laboratory training before mastering these skills. There are diverse training models based on synthetic materials, anesthetized animals, cadaver animals, or human cadaver. Human cadaver models are especially beneficial because they are the closest to live surgery with the greatest disadvantage of lacking hemodynamic factors. We developed the "brain infusion model" to provide a simple but realistic training method minimizing animal use or needs for special facilities. Four human cadaveric brains donated for educational purposes were explanted at autopsy. Carotids and vertebral arteries were cannulated with plastic tubes and fixed with suture. Water was flushed through the tubings until the whole arterial vasculature was observed as clean. The cannulated specimens were fixed with formaldehyde. Tap water infusion at a flow rate of 10 L/h was infused through the arterial tubings controlled with a drip regulator filling the arterial tree and leaking into the interstitial and cisternal space. Multiple microneurosurgical procedures were performed by 4 trainees. Cisternal and vascular dissection was executed in a very realistic fashion. Bypass anastomosis was created as well as aneurysm simulation with venous pouches. Vessel and aneurysm clipping and rupture situations were emulated and solution techniques were trained. Standard microsurgical laboratories regularly have scarce opportunities for working with decapitated human cadaver heads but could have human brains readily available. The human brain infusion model presents a realistic microneurosurgical training method. It is inexpensive and easy to set up. Such simplicity provides the adequate environment for developing microsurgical techniques. Copyright 2009 Elsevier Inc. All rights reserved.

  12. Multivariate Modeling and Inference for Brain Networks: ERGMs and Mixed Models

    OpenAIRE

    Simpson, Sean L.

    2017-01-01

    Talk given during the "How To Be a Skeptical Neuroimager: Functional Connectivity & Causal Modelling" Half-Day Educational Course at the 2017 Organisation for Human Brain Mapping meeting, Monday 25 June.

  13. Variation, "evolution", immortality and genetic instabilities in tumour cells.

    Science.gov (United States)

    Bignold, L P

    2007-08-18

    The pathological characteristics of tumour cells often include variation of their histopathological features (i.e. "degrees of de-differentiation") between cases of the same tumour type and between different foci within individual tumours. Usually, only a few cell lines from tumours are immortal. Currently, somatic mutation, replicative infidelity of DNA and aneuploidy are suggested as alternative mechanisms of genomic disturbance underlying tumours. Nevertheless, apart from Hansemann's ideas of "anaplasia" and "de-differentiation" (proposed in the 1890s), and supposed "evolutionary themes" in cancer cell biology, little has been published concerning how histopathologic variation and immortality in tumour cells might arise. This paper reviews applications of the concepts of "variation" to tumours, including concepts of "evolution" and "cellular Darwinism". It is proposed that combinations of somatic mutation, DNA replicative infidelity and aneuploidy may explain the variabilities in tumours, and provide immortality in occasional tumour cells. A possible model involves (i) an initial somatic mutation causing reduced replicative fidelity of DNA, which could be variable in intensity, and thus give rise to variations between cases; (ii) a phase of replicative infidelity of DNA causing daughter cells lines to develop various abnormalities to different degrees, and hence provide for variation between areas of the same tumour. As a last event (iii) occasional asymmetric chromosomal distributions (aneuploidy) might "refresh" the ability of a daughter cell to replicate DNA faithfully causing them to become immortal. Thus extensively mutant and variable, hyperploid, and occasionally immortal cells might arise.

  14. Site-specific volumetric analysis of lung tumour motion

    Energy Technology Data Exchange (ETDEWEB)

    Pepin, Eric W [School of Health Sciences, Purdue University, West Lafayette, IN 47907 (United States); Wu Huanmei [Purdue School of Engineering and Technology, IUPUI, Indianapolis, IN 46202 (United States); Sandison, George A [Department of Radiation Oncology, University of Washington, Seattle, WA 98195 (United States); Langer, Mark [Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Shirato, Hiroki, E-mail: epepin@purdue.ed [Hokkaido University School of Medicine, Sapporo (Japan)

    2010-06-21

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

  15. In vitro models of the blood–brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use

    Science.gov (United States)

    Helms, Hans C; Abbott, N Joan; Burek, Malgorzata; Cecchelli, Romeo; Couraud, Pierre-Olivier; Deli, Maria A; Förster, Carola; Galla, Hans J; Romero, Ignacio A; Shusta, Eric V; Stebbins, Matthew J; Vandenhaute, Elodie; Weksler, Babette

    2016-01-01

    The endothelial cells lining the brain capillaries separate the blood from the brain parenchyma. The endothelial monolayer of the brain capillaries serves both as a crucial interface for exchange of nutrients, gases, and metabolites between blood and brain, and as a barrier for neurotoxic components of plasma and xenobiotics. This “blood-brain barrier” function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized brain endothelial cell lines, have been developed, in order to facilitate in vitro studies of drug transport to the brain and studies of endothelial cell biology and pathophysiology. In this review, we aim to give an overview of established in vitro blood–brain barrier models with a focus on their validation regarding a set of well-established blood–brain barrier characteristics. As an ideal cell culture model of the blood–brain barrier is yet to be developed, we also aim to give an overview of the advantages and drawbacks of the different models described. PMID:26868179

  16. Drosophila melanogaster as a Model Organism of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Werner Paulus

    2009-02-01

    Full Text Available Drosophila melanogaster has been utilized to model human brain diseases. In most of these invertebrate transgenic models, some aspects of human disease are reproduced. Although investigation of rodent models has been of significant impact, invertebrate models offer a wide variety of experimental tools that can potentially address some of the outstanding questions underlying neurological disease. This review considers what has been gleaned from invertebrate models of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, metabolic diseases such as Leigh disease, Niemann-Pick disease and ceroid lipofuscinoses, tumor syndromes such as neurofibromatosis and tuberous sclerosis, epilepsy as well as CNS injury. It is to be expected that genetic tools in Drosophila will reveal new pathways and interactions, which hopefully will result in molecular based therapy approaches.

  17. Biothermal Model of Patient for Brain Hypothermia Treatment

    Science.gov (United States)

    Wakamatsu, Hidetoshi; Gaohua, Lu

    A biothermal model of patient is proposed and verified for the brain hypothermia treatment, since the conventionally applied biothermal models are inappropriate for their unprecedented application. The model is constructed on the basis of the clinical practice of the pertinent therapy and characterized by the mathematical relation with variable ambient temperatures, in consideration of the clinical treatments such as the vital cardiopulmonary regulation. It has geometrically clear representation of multi-segmental core-shell structure, database of physiological and physical parameters with a systemic state equation setting the initial temperature of each compartment. Its step response gives the time constant about 3 hours in agreement with clinical knowledge. As for the essential property of the model, the dynamic temperature of its face-core compartment is realized, which corresponds to the tympanic membrane temperature measured under the practical anesthesia. From the various simulations consistent with the phenomena of clinical practice, it is concluded that the proposed model is appropriate for the theoretical analysis and clinical application to the brain hypothermia treatment.

  18. Tumour heterogeneity promotes collective invasion and cancer metastatic dissemination.

    Science.gov (United States)

    Hallou, Adrien; Jennings, Joel; Kabla, Alexandre J

    2017-08-01

    Heterogeneity within tumour cell populations is commonly observed in most cancers. However, its impact on metastatic dissemination, one of the primary determinants of the disease prognosis, remains poorly understood. Working with a simplified numerical model of tumour spheroids, we investigated the impact of mechanical heterogeneity on the onset of tumour invasion into surrounding tissues. Our work establishes a positive link between tumour heterogeneity and metastatic dissemination, and recapitulates a number of invasion patterns identified in vivo, such as multicellular finger-like protrusions. Two complementary mechanisms are at play in heterogeneous tumours. A small proportion of stronger cells are able to initiate and lead the escape of cells, while collective effects in the bulk of the tumour provide the coordination required to sustain the invasive process through multicellular streaming. This suggests that the multicellular dynamics observed during metastasis is a generic feature of mechanically heterogeneous cell populations and might rely on a limited and generic set of attributes.

  19. Internet and Social Media Use After Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

    Science.gov (United States)

    Baker-Sparr, Christina; Hart, Tessa; Bergquist, Thomas; Bogner, Jennifer; Dreer, Laura; Juengst, Shannon; Mellick, David; OʼNeil-Pirozzi, Therese M; Sander, Angelle M; Whiteneck, Gale G

    To characterize Internet and social media use among adults with moderate to severe traumatic brain injury (TBI) and to compare demographic and socioeconomic factors associated with Internet use between those with and without TBI. Ten Traumatic Brain Injury Model Systems centers. Persons with moderate to severe TBI (N = 337) enrolled in the TBI Model Systems National Database and eligible for follow-up from April 1, 2014, to March 31, 2015. Prospective cross-sectional observational cohort study. Internet usage survey. The proportion of Internet users with TBI was high (74%) but significantly lower than those in the general population (84%). Smartphones were the most prevalent means of Internet access for persons with TBI. The majority of Internet users with TBI had a profile account on a social networking site (79%), with more than half of the sample reporting multiplatform use of 2 or more social networking sites. Despite the prevalence of Internet use among persons with TBI, technological disparities remain in comparison with the general population. The extent of social media use among persons with TBI demonstrates the potential of these platforms for social engagement and other purposes. However, further research examining the quality of online activities and identifying potential risk factors of problematic use is recommended.

  20. Longitudinal Examination of Resilience After Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

    Science.gov (United States)

    Marwitz, Jennifer H; Sima, Adam P; Kreutzer, Jeffrey S; Dreer, Laura E; Bergquist, Thomas F; Zafonte, Ross; Johnson-Greene, Douglas; Felix, Elizabeth R

    2018-02-01

    To evaluate (1) the trajectory of resilience during the first year after a moderate-severe traumatic brain injury (TBI); (2) factors associated with resilience at 3, 6, and 12 months postinjury; and (3) changing relationships over time between resilience and other factors. Longitudinal analysis of an observational cohort. Five inpatient rehabilitation centers. Patients with TBI (N=195) enrolled in the resilience module of the TBI Model Systems study with data collected at 3-, 6-, and 12-month follow-up. Not applicable. Connor-Davidson Resilience Scale. Initially, resilience levels appeared to be stable during the first year postinjury. Individual growth curve models were used to examine resilience over time in relation to demographic, psychosocial, and injury characteristics. After adjusting for these characteristics, resilience actually declined over time. Higher levels of resilience were related to nonminority status, absence of preinjury substance abuse, lower anxiety and disability level, and greater life satisfaction. Resilience is a construct that is relevant to understanding brain injury outcomes and has potential value in planning clinical interventions. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  1. 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.

  2. Longitudinal MRI contrast enhanced monitoring of early tumour development with manganese chloride (MnCl2 and superparamagnetic iron oxide nanoparticles (SPIOs in a CT1258 based in vivo model of prostate cancer

    Directory of Open Access Journals (Sweden)

    Sterenczak Katharina A

    2012-07-01

    Full Text Available Abstract Background Cell lines represent a key tool in cancer research allowing the generation of neoplasias which resemble initial tumours in in-vivo animal models. The characterisation of early tumour development is of major interest in order to evaluate the efficacy of therapeutic agents. Magnetic resonance imaging (MRI based in-vivo characterisation allows visualisation and characterisation of tumour development in early stages prior to manual palpation. Contrast agents for MRI such as superparamagnetic iron oxide nanoparticles (SPIOs and manganese chloride (MnCl2 represent powerful tools for the in-vivo characterisation of early stage tumours. In this experimental study, we labelled prostate cancer cells with MnCl2 or SPIOs in vitro and used 1 T MRI for tracing labelled cells in-vitro and 7 T MRI for tracking in an in-vivo animal model. Methods Labelling of prostate cancer cells CT1258 was established in-vitro with MnCl2 and SPIOs. In-vitro detection of labelled cells in an agar phantom was carried out through 1 T MRI while in-vivo detection was performed using 7 T MRI after subcutaneous (s.c. injection of labelled cells into NOD-Scid mice (n = 20. The animals were scanned in regular intervals until euthanization. The respective tumour volumes were analysed and corresponding tumour masses were subjected to histologic examination. Results MnCl2in-vitro labelling resulted in no significant metabolic effects on proliferation and cell vitality. In-vitro detection-limit accounted 105 cells for MnCl2 as well as for SPIOs labelling. In-vivo 7 T MRI scans allowed detection of 103 and 104 cells. In-vivo MnCl2 labelled cells were detectable from days 4–16 while SPIO labelling allowed detection until 4 days after s.c. injection. MnCl2 labelled cells were highly tumourigenic in NOD-Scid mice and the tumour volume development was characterised in a time dependent manner. The amount of injected cells correlated with tumour size

  3. Longitudinal MRI contrast enhanced monitoring of early tumour development with manganese chloride (MnCl2) and superparamagnetic iron oxide nanoparticles (SPIOs) in a CT1258 based in vivo model of prostate cancer.

    Science.gov (United States)

    Sterenczak, Katharina A; Meier, Martin; Glage, Silke; Meyer, Matthias; Willenbrock, Saskia; Wefstaedt, Patrick; Dorsch, Martina; Bullerdiek, Jörn; Murua Escobar, Hugo; Hedrich, Hans; Nolte, Ingo

    2012-07-11

    Cell lines represent a key tool in cancer research allowing the generation of neoplasias which resemble initial tumours in in-vivo animal models. The characterisation of early tumour development is of major interest in order to evaluate the efficacy of therapeutic agents. Magnetic resonance imaging (MRI) based in-vivo characterisation allows visualisation and characterisation of tumour development in early stages prior to manual palpation. Contrast agents for MRI such as superparamagnetic iron oxide nanoparticles (SPIOs) and manganese chloride (MnCl2) represent powerful tools for the in-vivo characterisation of early stage tumours. In this experimental study, we labelled prostate cancer cells with MnCl2 or SPIOs in vitro and used 1 T MRI for tracing labelled cells in-vitro and 7 T MRI for tracking in an in-vivo animal model. Labelling of prostate cancer cells CT1258 was established in-vitro with MnCl2 and SPIOs. In-vitro detection of labelled cells in an agar phantom was carried out through 1 T MRI while in-vivo detection was performed using 7 T MRI after subcutaneous (s.c.) injection of labelled cells into NOD-Scid mice (n = 20). The animals were scanned in regular intervals until euthanization. The respective tumour volumes were analysed and corresponding tumour masses were subjected to histologic examination. MnCl2in-vitro labelling resulted in no significant metabolic effects on proliferation and cell vitality. In-vitro detection-limit accounted 105 cells for MnCl2 as well as for SPIOs labelling. In-vivo 7 T MRI scans allowed detection of 103 and 104 cells. In-vivo MnCl2 labelled cells were detectable from days 4-16 while SPIO labelling allowed detection until 4 days after s.c. injection. MnCl2 labelled cells were highly tumourigenic in NOD-Scid mice and the tumour volume development was characterised in a time dependent manner. The amount of injected cells correlated with tumour size development and disease progression. Histological analysis of

  4. Cyclosporin safety in a simplified rat brain tumor implantation model

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

    Full Text Available Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate. This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

  5. Multiscale modeling and simulation of brain blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Perdikaris, Paris, E-mail: parisp@mit.edu [Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Grinberg, Leopold, E-mail: leopoldgrinberg@us.ibm.com [IBM T.J Watson Research Center, 1 Rogers St, Cambridge, Massachusetts 02142 (United States); Karniadakis, George Em, E-mail: george-karniadakis@brown.edu [Division of Applied Mathematics, Brown University, Providence, Rhode Island 02912 (United States)

    2016-02-15

    The aim of this work is to present an overview of recent advances in multi-scale modeling of brain blood flow. In particular, we present some approaches that enable the in silico study of multi-scale and multi-physics phenomena in the cerebral vasculature. We discuss the formulation of continuum and atomistic modeling approaches, present a consistent framework for their concurrent coupling, and list some of the challenges that one needs to overcome in achieving a seamless and scalable integration of heterogeneous numerical solvers. The effectiveness of the proposed framework is demonstrated in a realistic case involving modeling the thrombus formation process taking place on the wall of a patient-specific cerebral aneurysm. This highlights the ability of multi-scale algorithms to resolve important biophysical processes that span several spatial and temporal scales, potentially yielding new insight into the key aspects of brain blood flow in health and disease. Finally, we discuss open questions in multi-scale modeling and emerging topics of future research.

  6. Resilience Following Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

    Science.gov (United States)

    Kreutzer, Jeffrey S; Marwitz, Jennifer H; Sima, Adam P; Bergquist, Thomas F; Johnson-Greene, Douglas; Felix, Elizabeth R; Whiteneck, Gale G; Dreer, Laura E

    2016-05-01

    To examine resilience at 3 months after traumatic brain injury (TBI). Cross-sectional analysis of an ongoing observational cohort. Five inpatient rehabilitation centers, with 3-month follow-up conducted primarily by telephone. Persons with TBI (N=160) enrolled in the resilience module of the TBI Model System study with 3-month follow-up completed. Not applicable. Connor-Davidson Resilience Scale. Resilience scores were lower than those of the general population. A multivariable regression model, adjusting for other predictors, showed that higher education, absence of preinjury substance abuse, and less anxiety at follow-up were significantly related to greater resilience. Analysis suggests that lack of resilience may be an issue for some individuals after moderate to severe TBI. Identifying persons most likely at risk for low resilience may be useful in planning clinical interventions. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  7. Inhibition of miR-9 de-represses HuR and DICER1 and impairs Hodgkin lymphoma tumour outgrowth in vivo

    DEFF Research Database (Denmark)

    Leucci, E; Zriwil, A; Gregersen, L H

    2012-01-01

    MicroRNAs are important regulators of gene expression in normal development and disease. miR-9 is overexpressed in several cancer forms, including brain tumours, hepatocellular carcinomas, breast cancer and Hodgkin lymphoma (HL). Here we demonstrated a relevance for miR-9 in HL pathogenesis...... of miR-9 by a systemically delivered antimiR-9 in a xenograft model of HL increases the protein levels of HuR and DICER1 and results in decreased tumour outgrowth, confirming that miR-9 actively participates in HL pathogenesis and points to miR-9 as a potential therapeutic target.Oncogene advance online...

  8. 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

  9. 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.

  10. 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 ...

  11. Performance modeling of a wearable brain PET (BET) camera

    Science.gov (United States)

    Schmidtlein, C. R.; Turner, J. N.; Thompson, M. O.; Mandal, K. C.; Häggström, I.; Zhang, J.; Humm, J. L.; Feiglin, D. H.; Krol, A.

    2016-03-01

    Purpose: To explore, by means of analytical and Monte Carlo modeling, performance of a novel lightweight and low-cost wearable helmet-shaped Brain PET (BET) camera based on thin-film digital Geiger Avalanche Photo Diode (dGAPD) with LSO and LaBr3 scintillators for imaging in vivo human brain processes for freely moving and acting subjects responding to various stimuli in any environment. Methods: We performed analytical and Monte Carlo modeling PET performance of a spherical cap BET device and cylindrical brain PET (CYL) device, both with 25 cm diameter and the same total mass of LSO scintillator. Total mass of LSO in both the BET and CYL systems is about 32 kg for a 25 mm thick scintillator, and 13 kg for 10 mm thick scintillator (assuming an LSO density of 7.3 g/ml). We also investigated a similar system using an LaBr3 scintillator corresponding to 22 kg and 9 kg for the 25 mm and 10 mm thick systems (assuming an LaBr3 density of 5.08 g/ml). In addition, we considered a clinical whole body (WB) LSO PET/CT scanner with 82 cm ring diameter and 15.8 cm axial length to represent a reference system. BET consisted of distributed Autonomous Detector Arrays (ADAs) integrated into Intelligent Autonomous Detector Blocks (IADBs). The ADA comprised of an array of small LYSO scintillator volumes (voxels with base a×a: 1.0 50% better noise equivalent count (NEC) performance relative to the CYL geometry, and >1100% better performance than a WB geometry for 25 mm thick LSO and LaBr3. For 10 mm thick LaBr3 equivalent mass systems LSO (7 mm thick) performed ~40% higher NEC than LaBr3. Analytic and Monte Carlo simulations also showed that 1×1×3 mm scintillator crystals can achieve ~1.2 mm FWHM spatial resolution. Conclusions: This study shows that a spherical cap brain PET system can provide improved NEC while preserving spatial resolution when compared to an equivalent dedicated cylindrical PET brain camera and shows greatly improved PET performance relative to a conventional

  12. Deleted in malignant brain tumour 1 (DMBT1) is secreted in the oviduct and involved in the mechanism of fertilization in equine and porcine species

    DEFF Research Database (Denmark)

    Ambruosi, Barbara; Accogli, Gianluca; Douet, Cecile

    2013-01-01

    fertilization (IVF) in porcine and equine species that represent divergent IVF models. We first performed IVF after pre-incubation of oocytes with or without oviductal fluid supplemented or not with antibodies directed against DMBT1. We showed that oviductal fluid induces an increase of the monospermic...... fertilization rate, and that this effect is cancelled by the addition of antibodies, in both porcine and equine species. Moreover, pre-incubation of oocytes with recombinant DMBT1 induces an increase of the monospermic fertilization rate in the pig, confirming an involvement of DMBT1 in the fertilization...... in the zona pellucida and cytoplasm of equine and porcine oocytes was observed using immunofluorescence analysis and confocal microscopy. Moreover, we showed an interaction between DMBT1 and porcine spermatozoa using surface plasmon resonance studies. Finally, a bioinformatics and phylogenetic analysis...

  13. A simulation model for analysing brain structure deformations

    Science.gov (United States)

    Di Bona, Sergio; Lutzemberger, Ludovico; Salvetti, Ovidio

    2003-12-01

    Recent developments of medical software applications—from the simulation to the planning of surgical operations—have revealed the need for modelling human tissues and organs, not only from a geometric point of view but also from a physical one, i.e. soft tissues, rigid body, viscoelasticity, etc. This has given rise to the term 'deformable objects', which refers to objects with a morphology, a physical and a mechanical behaviour of their own and that reflects their natural properties. In this paper, we propose a model, based upon physical laws, suitable for the realistic manipulation of geometric reconstructions of volumetric data taken from MR and CT scans. In particular, a physically based model of the brain is presented that is able to simulate the evolution of different nature pathological intra-cranial phenomena such as haemorrhages, neoplasm, haematoma, etc and to describe the consequences that are caused by their volume expansions and the influences they have on the anatomical and neuro-functional structures of the brain.

  14. A simulation model for analysing brain structure deformations

    Energy Technology Data Exchange (ETDEWEB)

    Bona, Sergio Di [Institute for Information Science and Technologies, Italian National Research Council (ISTI-8211-CNR), Via G Moruzzi, 1-56124 Pisa (Italy); Lutzemberger, Ludovico [Department of Neuroscience, Institute of Neurosurgery, University of Pisa, Via Roma, 67-56100 Pisa (Italy); Salvetti, Ovidio [Institute for Information Science and Technologies, Italian National Research Council (ISTI-8211-CNR), Via G Moruzzi, 1-56124 Pisa (Italy)

    2003-12-21

    Recent developments of medical software applications from the simulation to the planning of surgical operations have revealed the need for modelling human tissues and organs, not only from a geometric point of view but also from a physical one, i.e. soft tissues, rigid body, viscoelasticity, etc. This has given rise to the term 'deformable objects', which refers to objects with a morphology, a physical and a mechanical behaviour of their own and that reflects their natural properties. In this paper, we propose a model, based upon physical laws, suitable for the realistic manipulation of geometric reconstructions of volumetric data taken from MR and CT scans. In particular, a physically based model of the brain is presented that is able to simulate the evolution of different nature pathological intra-cranial phenomena such as haemorrhages, neoplasm, haematoma, etc and to describe the consequences that are caused by their volume expansions and the influences they have on the anatomical and neuro-functional structures of the brain.

  15. A murine model for virotherapy of malignant brain tumors

    Directory of Open Access Journals (Sweden)

    E. Gambini

    2011-01-01

    Full Text Available Glioblastomas (GBMs are very aggressive and almost incurable brain tumors. The development of new therapeutical approaches capable of selectively killing cancer cells could represent a step forward to fight cancer. With this aim we tested the efficacy of a novel oncolytic therapy based on recombinant herpes simplex viruses (HSVs infecting exclusively cells expressing the human receptor HER-2 [1, 2], overexpressed in about 15% of GBM model based on PDGF-B embryonic transduction [4, 5]. We engineered cell cultures derived from this model to express HER-2 and we injected intracranically such cultures in NOD/SCID mice. We evaluated the efficacy of R-LM113, a recombinant HSV directed to HER-2, in this glioma model expressing HER-2. We demostrated that mice injected with engineered glioma cells infected with R-LM113 developed glioma with a statistically significant delay compared to mice injected with non-infected engineered glioma cells.

  16. Brain Dynamics An Introduction to Models and Simualtions

    CERN Document Server

    Haken, Hermann

    2008-01-01

    Brain Dynamics serves to introduce graduate students and nonspecialists from various backgrounds to the field of mathematical and computational neurosciences. Some of the advanced chapters will also be of interest to the specialists. The book approaches the subject through pulse-coupled neural networks, with at their core the lighthouse and integrate-and-fire models, which allow for the highly flexible modelling of realistic synaptic activity, synchronization and spatio-temporal pattern formation. Topics also include pulse-averaged equations and their application to movement coordination. The book closes with a short analysis of models versus the real neurophysiological system. The second edition has been thoroughly updated and augmented by two extensive chapters that discuss the interplay between pattern recognition and synchronization. Further, to enhance the usefulness as textbook and for self-study, the detailed solutions for all 34 exercises throughout the text have been added.

  17. MR diffusion-weighted imaging-based subcutaneous tumour volumetry in a xenografted nude mouse model using 3D Slicer: an accurate and repeatable method.

    Science.gov (United States)

    Ma, Zelan; Chen, Xin; Huang, Yanqi; He, Lan; Liang, Cuishan; Liang, Changhong; Liu, Zaiyi

    2015-10-22

    Accurate and repeatable measurement of the gross tumour volume(GTV) of subcutaneous xenografts is crucial in the evaluation of anti-tumour therapy. Formula and image-based manual segmentation methods are commonly used for GTV measurement but are hindered by low accuracy and reproducibility. 3D Slicer is open-source software that provides semiautomatic segmentation for GTV measurements. In our study, subcutaneous GTVs from nude mouse xenografts were measured by semiautomatic segmentation with 3D Slicer based on morphological magnetic resonance imaging(mMRI) or diffusion-weighted imaging(DWI)(b = 0,20,800 s/mm(2)) . These GTVs were then compared with those obtained via the formula and image-based manual segmentation methods with ITK software using the true tumour volume as the standard reference. The effects of tumour size and shape on GTVs measurements were also investigated. Our results showed that, when compared with the true tumour volume, segmentation for DWI(P = 0.060-0.671) resulted in better accuracy than that mMRI(P method(P methods. Therefore, DWI-based semiautomatic segmentation, which is accurate and reproducible and also provides biological information, is the optimal GTV measurement method in the assessment of anti-tumour treatments.

  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. [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.

  20. Enhanced brain distribution of carboplatin in a primate model after blood-brain barrier disruption using an implantable ultrasound device.

    Science.gov (United States)

    Goldwirt, Lauriane; Canney, Michael; Horodyckid, Catherine; Poupon, Joel; Mourah, Samia; Vignot, Alexandre; Chapelon, Jean-Yves; Carpentier, Alexandre

    2016-01-01

    Glioblastoma is both the most common and aggressive primary brain tumor in adults. Carboplatin chemotherapy has shown only modest efficacy in progressive high-grade gliomas. The limited clinical efficacy of carboplatin may be due to its low concentration in tissue when the drug is delivered intravenously. The aim of this study was to assess whether the tissue concentration of intravenously administered carboplatin could be enhanced by ultrasound-induced blood-brain disruption in a primate model. Carboplatin was administered intravenously for 60 min to a single primate following blood-brain barrier opening induced by an implantable ultrasound device. Blood and brain samples were collected after animal killing, which occurred 60 min after the end of carboplatin administration. Platinum quantification in ultrafiltrate plasma and brain samples was performed using inductively coupled plasma mass spectrometry. The brain concentration of platinum was highly enhanced (5.2×) in the 3.9 cm(3) region sonicated by the US beam, with a higher concentration in more vascularized anatomical structures. At 5 and 10 mm from the US beam axis, platinum concentrations were slightly enhanced (2.2× and 1.3× respectively). This study demonstrates that BBB opening using an implantable ultrasound transducer enhances the brain distribution of carboplatin in a loco-regional manner. Such a treatment approach is of significant interest for the treatment of primary brain tumors and is under current evaluation in a phase 1 clinical trial (NCT02253212).

  1. Modeling the brain-pituitary-gonad axis in salmon

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jonghan; Hayton, William L.; Schultz, Irv R.

    2006-08-24

    To better understand the complexity of the brain-pituitary-gonad axis (BPG) in fish, we developed a biologically based pharmacodynamic model capable of accurately predicting the normal functioning of the BPG axis in salmon. This first-generation model consisted of a set of 13 equations whose formulation was guided by published values for plasma concentrations of pituitary- (FSH, LH) and ovary- (estradiol, 17a,20b-dihydroxy-4-pregnene-3-one) derived hormones measured in Coho salmon over an annual spawning period. In addition, the model incorporated pertinent features of previously published mammalian models and indirect response pharmacodynamic models. Model-based equations include a description of gonadotropin releasing hormone (GnRH) synthesis and release from the hypothalamus, which is controlled by environmental variables such as photoperiod and water temperature. GnRH stimulated the biosynthesis of mRNA for FSH and LH, which were also influenced by estradiol concentration in plasma. The level of estradiol in the plasma was regulated by the oocytes, which moved along a maturation progression. Estradiol was synthesized at a basal rate and as oocytes matured, stimulation of its biosynthesis occurred. The BPG model can be integrated with toxico-genomic, -proteomic data, allowing linkage between molecular based biomarkers and reproduction in fish.

  2. Modeling Brain Responses in an Arithmetic Working Memory Task

    Science.gov (United States)

    Hamid, Aini Ismafairus Abd; Yusoff, Ahmad Nazlim; Mukari, Siti Zamratol-Mai Sarah; Mohamad, Mazlyfarina; Manan, Hanani Abdul; Hamid, Khairiah Abdul

    2010-07-01

    Functional magnetic resonance imaging (fMRI) was used to investigate brain responses due to arithmetic working memory. Nine healthy young male subjects were given simple addition and subtraction instructions in noise and in quiet. The general linear model (GLM) and random field theory (RFT) were implemented in modelling the activation. The results showed that addition and subtraction evoked bilateral activation in Heschl's gyrus (HG), superior temporal gyrus (STG), inferior frontal gyrus (IFG), supramarginal gyrus (SG) and precentral gyrus (PCG). The HG, STG, SG and PCG activate higher number of voxels in noise as compared to in quiet for addition and subtraction except for IFG that showed otherwise. The percentage of signal change (PSC) in all areas is higher in quiet as compared to in noise. Surprisingly addition (not subtraction) exhibits stronger activation.

  3. Planarian brain regeneration as a model system for developmental neurotoxicology

    Science.gov (United States)

    Hagstrom, Danielle; Cochet‐Escartin, Olivier

    2016-01-01

    Abstract Freshwater planarians, famous for their regenerative prowess, have long been recognized as a valuable in vivo animal model to study the effects of chemical exposure. In this review, we summarize the current techniques and tools used in the literature to assess toxicity in the planarian system. We focus on the planarian's particular amenability for neurotoxicology and neuroregeneration studies, owing to the planarian's unique ability to regenerate a centralized nervous system. Zooming in from the organismal to the molecular level, we show that planarians offer a repertoire of morphological and behavioral readouts while also being amenable to mechanistic studies of compound toxicity. Finally, we discuss the open challenges and opportunities for planarian brain regeneration to become an important model system for modern toxicology. PMID:27499880

  4. 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.

  5. Language Model Applications to Spelling with Brain-Computer Interfaces

    Science.gov (United States)

    Mora-Cortes, Anderson; Manyakov, Nikolay V.; Chumerin, Nikolay; Van Hulle, Marc M.

    2014-01-01

    Within the Ambient Assisted Living (AAL) community, Brain-Computer Interfaces (BCIs) have raised great hopes as they provide alternative communication means for persons with disabilities bypassing the need for speech and other motor activities. Although significant advancements have been realized in the last decade, applications of language models (e.g., word prediction, completion) have only recently started to appear in BCI systems. The main goal of this article is to review the language model applications that supplement non-invasive BCI-based communication systems by discussing their potential and limitations, and to discern future trends. First, a brief overview of the most prominent BCI spelling systems is given, followed by an in-depth discussion of the language models applied to them. These language models are classified according to their functionality in the context of BCI-based spelling: the static/dynamic nature of the user interface, the use of error correction and predictive spelling, and the potential to improve their classification performance by using language models. To conclude, the review offers an overview of the advantages and challenges when implementing language models in BCI-based communication systems when implemented in conjunction with other AAL technologies. PMID:24675760

  6. Language Model Applications to Spelling with Brain-Computer Interfaces

    Directory of Open Access Journals (Sweden)

    Anderson Mora-Cortes

    2014-03-01

    Full Text Available Within the Ambient Assisted Living (AAL community, Brain-Computer Interfaces (BCIs have raised great hopes as they provide alternative communication means for persons with disabilities bypassing the need for speech and other motor activities. Although significant advancements have been realized in the last decade, applications of language models (e.g., word prediction, completion have only recently started to appear in BCI systems. The main goal of this article is to review the language model applications that supplement non-invasive BCI-based communication systems by discussing their potential and limitations, and to discern future trends. First, a brief overview of the most prominent BCI spelling systems is given, followed by an in-depth discussion of the language models applied to them. These language models are classified according to their functionality in the context of BCI-based spelling: the static/dynamic nature of the user interface, the use of error correction and predictive spelling, and the potential to improve their classification performance by using language models. To conclude, the review offers an overview of the advantages and challenges when implementing language models in BCI-based communication systems when implemented in conjunction with other AAL technologies.

  7. Language model applications to spelling with Brain-Computer Interfaces.

    Science.gov (United States)

    Mora-Cortes, Anderson; Manyakov, Nikolay V; Chumerin, Nikolay; Van Hulle, Marc M

    2014-03-26

    Within the Ambient Assisted Living (AAL) community, Brain-Computer Interfaces (BCIs) have raised great hopes as they provide alternative communication means for persons with disabilities bypassing the need for speech and other motor activities. Although significant advancements have been realized in the last decade, applications of language models (e.g., word prediction, completion) have only recently started to appear in BCI systems. The main goal of this article is to review the language model applications that supplement non-invasive BCI-based communication systems by discussing their potential and limitations, and to discern future trends. First, a brief overview of the most prominent BCI spelling systems is given, followed by an in-depth discussion of the language models applied to them. These language models are classified according to their functionality in the context of BCI-based spelling: the static/dynamic nature of the user interface, the use of error correction and predictive spelling, and the potential to improve their classification performance by using language models. To conclude, the review offers an overview of the advantages and challenges when implementing language models in BCI-based communication systems when implemented in conjunction with other AAL technologies.

  8. Anti-Tumor Action, Clinical Biochemistry Profile and Phytochemical Constituents of a Pharmacologically Active Fraction of S. crispus in NMU-Induced Rat Mammary Tumour Model.

    Directory of Open Access Journals (Sweden)

    Nik Soriani Yaacob

    Full Text Available Cancer patients seek alternative remedies such as traditional medicinal plants for safe and effective treatment and help overcome the side effects of conventional therapy. Current knowledge indicates that extracts of Strobilanthes crispus of the Acanthaceae family exhibit potent anticancer properties in vitro and are non-toxic in vivo. S. crispus was also reported to be protective against chemical hepatocarcinogenesis. We previously showed that a bioactive fraction of S. crispus leaves also synergized with tamoxifen to cause apoptosis of human breast cancer cell lines without damaging non-malignant epithelial cells. The present study aimed to evaluate the antitumor effect of S. crispus dichloromethane fraction (F3 using N-methyl-N-Nitrosourea (NMU-induced rat mammary tumor model. Tumor regression was observed in 75% of the rats following 8-week oral administration of F3 with no secondary tumour formation and no signs of anemia or infection. However, no improvement in the liver and renal function profiles was observed. Major constituents of F3 were identified as lutein, 131-hydroxy-132-oxo-pheophytin a, campesterol, stigmasterol, β-sitosterol, pheophytin a and 132-hydroxy-pheophytin a. These compounds however, may not significantly contribute to the antitumor effect of F3.

  9. Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders.

    Science.gov (United States)

    Gabriel, Elke; Gopalakrishnan, Jay

    2017-04-14

    The restricted availability of suitable in vitro models that can reliably represent complex human brain development is a significant bottleneck that limits the translation of basic brain research into clinical application. While induced pluripotent stem cells (iPSCs) have replaced the ethically questionable human embryonic stem cells, iPSC-based neuronal differentiation studies remain descriptive at the cellular level but fail to adequately provide the details that could be derived from a complex, 3D human brain tissue. This gap is now filled through the application of iPSC-derived, 3D brain organoids, "Brains in a dish," that model many features of complex human brain development. Here, a method for generating iPSC-derived, 3D brain organoids is described. The organoids can help with modeling autosomal recessive primary microcephaly (MCPH), a rare human neurodevelopmental disorder. A widely accepted explanation for the brain malformation in MCPH is a depletion of the neural stem cell pool during the early stages of human brain development, a developmental defect that is difficult to recreate or prove in vitro. To study MCPH, we generated iPSCs from patient-derived fibroblasts carrying a mutation in the centrosomal protein CPAP. By analyzing the ventricular zone of microcephaly 3D brain organoids, we showed the premature differentiation of neural progenitors. These 3D brain organoids are a powerful in vitro system that will be instrumental in modeling congenital brain disorders induced by neurotoxic chemicals, neurotrophic viral infections, or inherited genetic mutations.

  10. In vitro models of the blood-brain barrier

    DEFF Research Database (Denmark)

    Helms, Hans Christian Cederberg; Abbott, N Joan; Burek, Malgorzata

    2016-01-01

    components of plasma and xenobiotics. This "blood-brain barrier" function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized brain endothelial cell lines, have been developed, in order to facilitate in vitro studies of drug...

  11. Cluster imaging of multi-brain networks (CIMBN: a general framework for hyperscanning and modeling a group of interacting brains

    Directory of Open Access Journals (Sweden)

    Lian eDuan

    2015-07-01

    Full Text Available Studying the neural basis of human social interactions is a key topic in the field of social neuroscience. Brain imaging studies in this field usually focus on the neural correlates of the social interactions between two participants. However, as the participant number further increases, even by a small amount, great difficulties raise. One challenge is how to concurrently scan all the interacting brains with high ecological validity, especially for a large number of participants. The other challenge is how to effectively model the complex group interaction behaviors emerging from the intricate neural information exchange among a group of socially organized people. Confronting these challenges, we propose a new approach called Cluster Imaging of Multi-brain Networks (CIMBN. CIMBN consists of two parts. The first part is a cluster imaging technique with high ecological validity based on multiple functional near-infrared spectroscopy (fNIRS systems. Using this technique, we can easily extend the simultaneous imaging capacity of social neuroscience studies up to dozens of participants. The second part of CIMBN is a multi-brain network (MBN modeling method based on graph theory. By taking each brain as a network node and the relationship between any two brains as a network edge, one can construct a network model for a group of interacting brains. The emergent group social behaviors can then be studied using the network’s properties, such as its topological structure and information exchange efficiency. Although there is still much work to do, as a general framework for hyperscanning and modeling a group of interacting brains, CIMBN can provide new insights into the neural correlates of group social interactions, and advance social neuroscience and social psychology.

  12. 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

  13. Clostridium butyricum exerts a neuroprotective effect in a mouse model of traumatic brain injury via the gut-brain axis.

    Science.gov (United States)

    Li, H; Sun, J; Du, J; Wang, F; Fang, R; Yu, C; Xiong, J; Chen, W; Lu, Z; Liu, J

    2017-11-27

    Traumatic brain injury (TBI) is a common occurrence following gastrointestinal dysfunction. Recently, more and more attentions are being focused on gut microbiota in brain and behavior. Glucagon-like peptide-1 (GLP-1) is considered as a mediator that links the gut-brain axis. The aim of this study was to explore the neuroprotective effects of Clostridium butyricum (Cb) on brain damage in a mouse model of TBI. Male C57BL/6 mice were subjected to a model of TBI-induced by weight-drop impact head injury and were treated intragastrically with Cb. The cognitive deficits, brain water content, neuronal death, and blood-brain barrier (BBB) permeability were evaluated. The expression of tight junction (TJ) proteins, Bcl-2, Bax, GLP-1 receptor (GLP-1R), and phosphorylation of Akt (p-Akt) in the brain were also measured. Moreover, the intestinal barrier permeability, the expression of TJ protein and GLP-1, and IL-6 level in the intestine were detected. Cb treatment significantly improved neurological dysfunction, brain edema, neurodegeneration, and BBB impairment. Meanwhile, Cb treatment also significantly increased the expression of TJ proteins (occludin and zonula occluden-1), p-Akt and Bcl-2, but decreased expression of Bax. Moreover, Cb treatment exhibited more prominent effects on decreasing the levels of plasma d-lactate and colonic IL-6, upregulating expression of Occludin, and protecting intestinal barrier integrity. Furthermore, Cb-treated mice showed increased the secretion of intestinal GLP-1 and upregulated expression of cerebral GLP-1R. Our findings demonstrated the neuroprotective effect of Cb in TBI mice and the involved mechanisms were partially attributed to the elevating GLP-1 secretion through the gut-brain axis. © 2017 John Wiley & Sons Ltd.

  14. Modeling Brain Circuitry over a Wide Range of Scales

    Directory of Open Access Journals (Sweden)

    Pascal eFua

    2015-04-01

    Full Text Available If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM can now provide the nanometer resolution that is needed to image synapses, and therefore connections, while Light Microscopes (LM see at the micrometer resolution required to model the 3D structure of the dendritic network. Since both the topology and the connection strength are integral parts of the brain's wiring diagram, being able to combine these two modalities is critically important.In fact, these microscopes now routinely produce high-resolution imagery in such large quantities that the bottleneck becomes automated processing and interpretation, which is needed for such data to be exploited to its full potential. In this paper, we briefly review the Computer Vision techniques we have developed at EPFL to address this need. They include delineating dendritic arbors from LM imagery, segmenting organelles from EM, and combining the two into a consistent representation.

  15. Modeling of a segmented electrode for desynchronizing deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Julia eBuhlmann

    2011-12-01

    Full Text Available Deep brain stimulation (DBS is an effective therapy for medically refrac- tory movement disorders like Parkinson’s disease. The electrodes, implanted in the target area within the human brain, generate an electric field which activates nerve fibers and cell bodies in the proximate vicinity. Even though the different target nuclei display considerable differences in their anatomical structure, only few types of electrodes are currently commercially available. It is desirable to adjust the electric field and in particular the volume of tissue activated around the electrode with respect to the corresponding target nucleus in a such way that side effects can be reduced. Furthermore, a more selective and partial activation of the target structure is desirable for an optimal application of novel stimulation strate- gies, e.g. coordinated reset neuromodulation. Hence we designed a DBS electrode with a segmented design allowing a more selective activation of the target struc- ture. We created a finite element model (FEM of the electrode and analyzed the volume of tissue activated for this electrode design. The segmented electrode ac- tivated an area in a targeted manner, of which the dimension and position relative to the electrode could be controlled by adjusting the stimulation parameters for each contact. According to our computational analysis, this directed stimulation might be superior with respect to the occurrence of side effects and it enables the application of coordinated reset neuromodulation under optimal conditions.

  16. Knowledge Modeling for the Outcome of Brain Stereotactic Radiosurgery

    Science.gov (United States)

    Hauck, Jillian E.

    Purpose: To build a model that will predict the survival time for patients that were treated with stereotactic radiosurgery for brain metastases using support vector machine (SVM) regression. Methods and Materials: This study utilized data from 481 patients, which were equally divided into training and validation datasets randomly. The SVM model used a Gaussian RBF function, along with various parameters, such as the size of the epsilon insensitive region and the cost parameter (C) that are used to control the amount of error tolerated by the model. The predictor variables for the SVM model consisted of the actual survival time of the patient, the number of brain metastases, the graded prognostic assessment (GPA) and Karnofsky Performance Scale (KPS) scores, prescription dose, and the largest planning target volume (PTV). The response of the model is the survival time of the patient. The resulting survival time predictions were analyzed against the actual survival times by single parameter classification and two-parameter classification. The predicted mean survival times within each classification were compared with the actual values to obtain the confidence interval associated with the model's predictions. In addition to visualizing the data on plots using the means and error bars, the correlation coefficients between the actual and predicted means of the survival times were calculated during each step of the classification. Results: The number of metastases and KPS scores, were consistently shown to be the strongest predictors in the single parameter classification, and were subsequently used as first classifiers in the two-parameter classification. When the survival times were analyzed with the number of metastases as the first classifier, the best correlation was obtained for patients with 3 metastases, while patients with 4 or 5 metastases had significantly worse results. When the KPS score was used as the first classifier, patients with a KPS score of 60 and

  17. A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

    Science.gov (United States)

    Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

    2016-11-01

    The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes-permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.

  18. Resuscitation speed affects brain injury in a large animal model of traumatic brain injury and shock

    DEFF Research Database (Denmark)

    Sillesen, Martin; Jin, Guang; Johansson, Pär I

    2014-01-01

    infusion speed increment NS (n¿=¿7). Hemodynamic variables over a 6-hour observation phase were recorded. Following euthanasia, brains were harvested and lesion size as well as brain swelling was measured.ResultsBolus FFP resuscitation resulted in greater brain swelling (22.36¿±¿1.03% vs. 15.58¿±¿2.52%, p...

  19. Modeling the dynamics of human brain activity with recurrent neural networks

    NARCIS (Netherlands)

    Güçlü, U.; Gerven, M.A.J. van

    2017-01-01

    Encoding models are used for predicting brain activity in response to sensory stimuli with the objective of elucidating how sensory information is represented in the brain. Encoding models typically comprise a nonlinear transformation of stimuli to features (feature model) and a linear convolution

  20. Informing pedagogy through the brain-targeted teaching model.

    Science.gov (United States)

    Hardiman, Mariale

    2012-01-01

    Improving teaching to foster creative thinking and problem-solving for students of all ages will require two essential changes in current educational practice. First, to allow more time for deeper engagement with material, it is critical to reduce the vast number of topics often required in many courses. Second, and perhaps more challenging, is the alignment of pedagogy with recent research on cognition and learning. With a growing focus on the use of research to inform teaching practices, educators need a pedagogical framework that helps them interpret and apply research findings. This article describes the Brain-Targeted Teaching Model, a scheme that relates six distinct aspects of instruction to research from the neuro- and cognitive sciences.

  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. 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. A propositional representation model of anatomical and functional brain data.

    Science.gov (United States)

    Maturana, Pablo; Batrancourt, Bénédicte

    2011-01-01

    Networks can represent a large number of systems. Recent advances in the domain of networks have been transferred to the field of neuroscience. For example, the graph model has been used in neuroscience research as a methodological tool to examine brain networks organization, topology and complex dynamics, as well as a framework to test the structure-function hypothesis using neuroimaging data. In the current work we propose a graph-theoretical framework to represent anatomical, functional and neuropsychological assessment instruments information. On the one hand, interrelationships between anatomic elements constitute an anatomical graph. On the other hand, a functional graph contains several cognitive functions and their more elementary cognitive processes. Finally, the neuropsychological assessment instruments graph includes several neuropsychological tests and scales linked with their different sub-tests and variables. The two last graphs are connected by relations of type "explore" linking a particular instrument with the cognitive function it explores. We applied this framework to a sample of patients with focal brain damage. Each patient was related to: (i) the cerebral entities injured (assessed with structural neuroimaging data) and (ii) the neusopsychological assessment tests carried out (weight by performance). Our model offers a suitable platform to visualize patients' relevant information, facilitating the representation, standardization and sharing of clinical data. At the same time, the integration of a large number of patients in this framework will make possible to explore relations between anatomy (injured entities) and function (performance in different tests assessing different cognitive functions) and the use of neurocomputational tools for graph analysis may help diagnostic and contribute to the comprehension of neural bases of cognitive functions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Increased Stability and Breakdown of Brain Effective Connectivity During Slow-Wave Sleep: Mechanistic Insights from Whole-Brain Computational Modelling

    OpenAIRE

    Jobst, Beatrice M; Hindriks, Rikkert; Laufs, Helmut; Tagliazucchi, E; Hahn, Gerald; Ponce-Alvarez, Adrián; Stevner, Angus B. A.; Kringelbach, Morten L.; Deco, Gustavo

    2017-01-01

    Recent research has found that the human sleep cycle is characterised by changes in spatiotemporal patterns of brain activity. Yet, we are still missing a mechanistic explanation of the local neuronal dynamics underlying these changes. We used whole-brain computational modelling to study the differences in global brain functional connectivity and synchrony of fMRI activity in healthy humans during wakefulness and slow-wave sleep. We applied a whole-brain model based on the normal form of a su...

  5. Early response assessment in prostate carcinoma by {sup 18}F-fluorothymidine following anticancer therapy with docetaxel using preclinical tumour models

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Nobuyuki; Hasegawa, Yoko; Yokoyama, Osamu [University of Fukui, Department of Urology, Faculty of Medical Sciences, Fukui (Japan); Kiyono, Yasushi; Kobayashi, Masato; Fujibayashi, Yasuhisa [University of Fukui, Biomedical Imaging Research Center, Fukui (Japan); Ponde, Datta E.; Dence, Carmen [Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, MO (United States); Welch, Michael J. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, MO (United States); Washington University School of Medicine, Siteman Cancer Center, St. Louis, MO (United States)

    2011-01-15

    The aim of the study was to assess the potential usefulness of 3-deoxy-3-{sup 18}F-fluorothymidine (FLT) as a radiopharmaceutical for imaging the early therapeutic effects of docetaxel (DTX) on tumour proliferation in hormone-refractory prostate cancer (HRPC). Cells of the androgen-independent human prostate tumour cell line, 22Rv1, were implanted in athymic male mice. Approximately 3 weeks after cell implantation, the mice were treated with DTX or vehicle. Before and after the treatment, the mice were imaged with a microPET-Focus-F120 scanner (Concorde Microsystems, Knoxville, TN, USA) using FLT and {sup 18}F-fluorodeoxyglucose (FDG). Tracer accumulations in the tumours were then analysed and compared with the proliferation activity and apoptotic index of the tumours. In a separate cell study, 22Rv1 cells were treated with DTX, then incubated with FLT or FDG and examined for their tracer uptake. The microPET imaging showed a significant decrease of FLT uptake in tumours after administration of DTX, while the changes of FDG uptake were minimal. Immunohistochemical analysis of the tumours revealed that the changes of FLT uptake were well correlated with those of proliferation activity but not with the apoptotic index. In vitro studies demonstrated that the significant decrease of FLT uptake in the cells after incubation with DTX correlated with the % S-phase cell fraction, while there were only minimal changes in the prostate-specific antigen concentration of the cell medium and FDG uptake in the cells. These results indicate that FLT is a promising tracer for monitoring the early effects of anticancer therapy with DTX in patients with HRPC. (orig.)

  6. Influence of honey bee products on transplantable murine tumours.

    Science.gov (United States)

    Orsolić, N; Knezević, A; Sver, L; Terzić, S; Hackenberger, B K; Basić, I

    2003-12-01

    The effect of propolis [it is a water-soluble derivative (WSDP)] and related polyphenolic compounds of propolis (caffeic acid, caffeic acid phenethyl ester and quercetin), honey, royal jelly and bee venom on tumour growth, metastasizing ability and induction of apoptosis and necrosis in murine tumour models (mammary carcinoma and colon carcinoma) was investigated. WSDP and related polyphenolic compounds showed significant anti-metastatic effect (P Honey also exerted pronounced anti-metastatic effect (P bee venom injection, the number of tumour nodules in the lung was significantly lower (P bee venom subcutaneously. Local presence of bee venom in the tissue caused significant delay in subcutaneous tumour formation. These findings clearly demonstrate that anti-tumour and anti-metastatic effects of bee venom are highly dependent on the route of injection and on close contact between components of the bee venom and tumour cells. These data show that honey bee products given orally or systemically may have an important role in the control of tumour growth and tumour metastasizing ability.

  7. Training in Brain Retraction Using a Self-Made Three-Dimensional Model.

    Science.gov (United States)

    Mashiko, Toshihiro; Konno, Takehiko; Kaneko, Naoki; Watanabe, Eiju

    2015-08-01

    A hollow brain model was created using soft urethane. A tube passing through the hollow was attached for use as a water inlet and manometer. Water sufficient in quantity to realize the intended initial pressure was infused through the tube. The brain model was retracted with a brain spatula and the surgical corridor was opened. By measuring local force with a sensor set on the brain spatula, the model could be used for training in brain retraction. At the same time, the water column of the manometer was measured and the relationship with the force of the brain spatula was investigated. A positive correlation between the water column and local force was confirmed. This indicated that it was possible to use this model without a force sensor for the same training using water column measurements. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC.

    Science.gov (United States)

    Herz, Corinna; Hertrampf, Anke; Zimmermann, Stefan; Stetter, Nadine; Wagner, Meike; Kleinhans, Claudia; Erlacher, Miriam; Schüler, Julia; Platz, Stefanie; Rohn, Sascha; Mersch-Sundermann, Volker; Lamy, Evelyn

    2014-12-01

    In contrast to cancer cells, most normal human cells have no or low telomerase levels which makes it an attractive target for anti-cancer drugs. The small molecule sulforaphane from broccoli is known for its cancer therapeutic potential in vitro and in vivo. In animals and humans it was found to be quickly metabolized into 4-methylthiobutyl isothiocyanate (MTBITC, erucin) which we recently identified as strong selective apoptosis inducer in hepatocellular carcinoma (HCC) cells. Here, we investigated the relevance of telomerase abrogation for cytotoxic efficacy of MTBITC against HCC. The drug was effective against telomerase, independent from TP53 and MTBITC also blocked telomerase in chemoresistant subpopulations. By using an orthotopic human liver cancer xenograft model, we give first evidence that MTBITC at 50 mg/KG b.w./d significantly decreased telomerase activity in vivo without affecting enzyme activity of adjacent normal tissue. Upon drug exposure, telomerase decrease was consistent with a dose-dependent switch to anti-survival, cell arrest and apoptosis in our in vitro HCC models. Blocking telomerase by the specific inhibitor TMPyP4 further sensitized cancer cells to MTBITC-mediated cytotoxicity. Overexpression of hTERT, but not enzyme activity deficient DNhTERT, protected against apoptosis; neither DNA damage nor cytostasis induction by MTBITC was prevented by hTERT overexpression. These findings imply that telomerase enzyme activity does not protect against MTBITC-induced DNA damage but impacts signalling processes upstream of apoptosis execution level. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  9. Traumatic brain injury–Modeling neuropsychiatric symptoms in rodents

    Directory of Open Access Journals (Sweden)

    Oz eMalkesman

    2013-10-01

    Full Text Available Each year in the United States, approximately 1.5 million people sustain a traumatic brain injury (TBI. Victims of TBI can suffer from chronic post-TBI symptoms, such as sensory and motor deficits, cognitive impairments including problems with memory, learning, and attention, and neuropsychiatric symptoms such as depression, anxiety, irritability, aggression, and suicidal rumination. Although partially associated with the site and severity of injury, the biological mechanisms associated with many of these symptoms—and why some patients experience differing assortments of persistent maladies—are largely unknown. The use of animal models is a promising strategy for elucidation of the mechanisms of impairment and treatment, and learning, memory, sensory and motor tests have widespread utility in rodent models of TBI and psychopharmacology. Comparatively, behavioral tests for the evaluation of neuropsychiatric symptomatology are rarely employed in animal models of TBI and, as determined in this review, the results have been inconsistent. Animal behavioral studies contribute to the understanding of the biological mechanisms by which TBI is associated with neurobehavioral symptoms and offer a powerful means for pre-clinical treatment validation. Therefore, further exploration of the utility of animal behavioral tests for the study of injury mechanisms and therapeutic strategies for the alleviation of emotional symptoms are relevant and essential.

  10. Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model

    DEFF Research Database (Denmark)

    Andersson, O.; Badisco, L.; Hansen, A. H.

    2014-01-01

    In earlier studies insects were proposed as suitable models for vertebrate blood–brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain....... As in vertebrates, the locust brain–barrier function is morphologically confined to one specific cell layer and by using a whole-brain ex vivo drug exposure technique our locust model may retain the major cues that maintain and modulate the physiological function of the brain barrier. We show that the locust model...

  11. White Matter MS-Lesion Segmentation Using a Geometric Brain Model.

    OpenAIRE

    Strumia Maddalena; Schmidt Frank; Anastasopoulos Constantin; Granziera Cristina; Krueger Gunnar; Brox Thomas

    2016-01-01

    Brain magnetic resonance imaging (MRI) in patients with Multiple Sclerosis (MS) shows regions of signal abnormalities named plaques or lesions. The spatial lesion distribution plays a major role for MS diagnosis. In this paper we present a 3D MS lesion segmentation method based on an adaptive geometric brain model. We model the topological properties of the lesions and brain tissues in order to constrain the lesion segmentation to the white matter. As a result the method is independent of an ...

  12. A Nonparametric model for Brain Tumor Segmentation and Volumetry in Longitudinal MR Sequences

    OpenAIRE

    Alberts, Esther; Charpiat, Guillaume; Tarabalka, Yuliya; Huber, Thomas; Weber, Marc-André; Bauer, Jan; Zimmer, Claus; Menze, Bjoern H.

    2015-01-01

    International audience; Brain tumor image segmentation and brain tumor growth assessment are inter-dependent and benet from a joint evaluation. Starting from a generative model for multimodal brain tumor segmentation, we make use of a nonparametric growth model that is implemented as a conditional random field (CRF) including directed links with infinite weight in order to incorporate growth and inclusion constraints, reflecting our prior belief on tumor occurrence in the dierent image modali...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    : Overall, TCP curves based on ADC maps showed larger differences between individuals than those assuming uniform cell densities. The range of the dose required to reach 50% TCP across the patient cohort was 20.1 Gy, 18.7 Gy and 13.2 Gy using an MRI-based voxel density (linear, binary and sigmoid approach......) and apparent diffusion coefficient (ADC) maps-based cell density distributions. Materials and methods: ADC maps in a series of 20 prostate cancer patients were applied to estimate the initial number of cells within each voxel, using three different approaches for the relation between ADC values and cell...... density: a linear, a binary and a sigmoid relation. All TCP models were based on linear- quadratic cell survival curves assuming a/b = 1.93 Gy (consistent with a recent meta-analysis) and a set to obtain a 70% of TCP when 77 Gy was delivered to the entire prostate in 35 fractions (a = 0.18 Gy?1). Results...

  14. 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.

  15. 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

  16. 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-