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Sample records for human intracranial tumours

  1. 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...

  2. N-nitroso compounds and human intracranial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Preston-Martin, S.; Henderson, B.E.

    1984-01-01

    Experimentalists have shown that various N-nitroso compounds are potent nervous system carcinogens, particularly when animals are exposed transplacentally. Information has been obtained concerning exposure to N-nitroso compounds and their precursors in three case-control studies of intracranial tumour patients in Los Angeles County, California. A study of women (185 pairs) found that level of consumption of nitrite-cured meats was related to meningioma development (p = 0.01). In a similar study of meningiomas in men (105 pairs), the association with cured meats was not clear. The most striking results were obtained in a study of young brain tumour patients (209 matched pairs). Increased risk was associated with maternal contact, during pregnancy, with N-nitrosamine-containing substances, such as burning incense, sidestream cigarette smoke and face make-up. Increased risk was also associated with maternal use of diuretics and antihistamines and with the level of maternal consumption of cured meats. Additional epidemiological studies of nervous system tumours in young people would appear to offer considerable promise for testing the hypothesis that N-nitroso compounds are etiologically related to human neurogenic neoplasms.

  3. Occurrence studies of intracranial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Larjavaara, S.

    2011-07-01

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

  4. MRI of intracranial germ cell tumours

    Energy Technology Data Exchange (ETDEWEB)

    Sumida, M. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Uozumi, T. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Kiya, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Mukada, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Arita, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Kurisu, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Sugiyama, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Onda, J. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Satoh, H. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Ikawa, F. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Migita, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan)

    1995-01-01

    We reviewed MRI findings in proven intracranial germ cell tumours in 22 cases, 12 of whom received Gd-DTPA. On T1-weighted images, the signal intensity of the tumour parenchyma was moderately low in 19 cases and isointense in 3; on T2-weighted images, it was high in all cases. Regions of different intensity thought to be cysts were found in 17 (77 %): 7 of 12 patients with germinoma (58 %) and in all other cases. Of the 13 patients with pineal lesions T1-weighted sagittal images showed the aqueduct to be obstructed in 5, stenotic in 7 and normal in 1. Strong contrast enhancement was observed in all 12 cases. Of the 14 patients with suprasellar lesions, 5 were found to have an intrasellar extension, and in 3 of these, the normal pituitary gland, which could be distinguished from the tumour, was displaced anteriorly. Ten patients (45 %) had multiple lesions. (orig.)

  5. MRI of intracranial germ-cell tumours

    Energy Technology Data Exchange (ETDEWEB)

    Liang, L.; Korogi, Y.; Sugahara, T.; Ikushima, I.; Shigematsu, Y.; Okuda, T.; Takahashi, M. [Department of Radiology, Kumamoto University School of Medicine (Japan); Kochi, M.; Ushio, Y. [Department of Neurosurgery, Kumamoto University School of Medicine (Japan)

    2002-05-01

    Abstract. Our aim was to review the MRI appearances of primary intracranial germ-cell tumours (GCT). We reviewed the MRI studies of 32 patients: 19 with germinomas, five with teratomas, one with an embryonal carcinoma, five with mixed and two with malignant nongerminomatous GCT. Eleven were in the pineal region, 12 suprasellar, five in the both sites, two in the basal ganglia and two in the corpus callosum. Contrast-enhanced images were available for 27 patients. The solid parts of GCT were nearly isointense with grey matter on both T1- and T2-weighted images. In seven patients with nongerminomatous GCT high-signal components were found on T1-weighted images, representing haemorrhage, high-protein fluid or fat. Cystic components were detected in 17 of 27 patients; eight germinomas and all nine nongerminomatous GCT had cysts. The solid components of germinomas enhanced homogeneously in eight cases and heterogeneously in 10, while all nongerminomatous GCT showed heterogeneous enhancement. MRI features tumours can facilitate correct diagnosis of GCT, including histological subtypes. (orig.)

  6. Intracranial tumours after external fractionated radiotherapy for pituitary adenomas in northern Sweden

    Energy Technology Data Exchange (ETDEWEB)

    Norberg, Lars; Johansson, Robert; Rasmuson, Torgny (Dept. of Radiation Sciences, Oncology, Umeaa Univ., Umeaa (Sweden)), E-mail: Torgny.Rasmuson@onkologi.umu.se

    2010-11-15

    We analysed the incidence of second primary intracranial tumours in patients with pituitary adenomas treated with radiotherapy compared to the risk of patients not exposed to irradiation and to the general population. Materials and methods. This retrospective cohort study includes 298 patients with pituitary adenomas that received radiotherapy to the pituitary from 1960 to 2007. The patients were recruited from the Cancer Registry of northern Sweden and the local radiotherapy-registry of the Univ. Hospital in Umeaa. Only patients with =12 months follow-up after diagnosis of pituitary adenoma were included. A cohort of 131 patients with pituitary adenomas not treated with radiotherapy was used as reference. Standard incidence ratios (SIR) between observed and expected number of second primary intracranial tumours were calculated. Results. The median observation time after diagnosis of pituitary adenoma in 298 patients treated with radiotherapy was 14 years, and the total number of person-years at risk was 4 784. Six (2.0%) of the patients developed second primary intracranial tumours between 7 and 31 years after radiotherapy. Two patients had gliomas and four had meningiomas. The expected number of intracranial tumours was 1.15 giving a SIR of 5.20 (95% CI 1.90-11.31). No significant correlations were found between radiation technique or administered dose and the risk of developing a second primary intracranial tumour. The cumulative risk for second intracranial tumours at 10 and 20 years was 1.3%. Patients not treated with radiotherapy were followed 1 601 years and no second primary intracranial tumour occurred. Discussion. The results indicate an increased risk of second primary intracranial tumours in patients treated with radiotherapy for pituitary adenomas, compared to patients not exposed to irradiation and to the general population. Meningiomas were more frequent than gliomas and the median time interval between radiotherapy and second intracranial tumour was

  7. Intracranial recordings and human memory

    OpenAIRE

    Johnson, Elizabeth L.; Knight, Robert T.

    2014-01-01

    Recent work involving intracranial recording during human memory performance provides superb spatiotemporal resolution on mnemonic processes. These data demonstrate that the cortical regions identified in neuroimaging studies of memory fall into temporally distinct networks and the hippocampal theta activity reported in animal memory literature also plays a central role in human memory. Memory is linked to activity at multiple interacting frequencies, ranging from 1-500 Hz. High-frequency res...

  8. New evidence for the origin of intracranial germ cell tumours from primordial germ cells

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Sehested, A; Juhler, M

    2006-01-01

    Primary intracranial germ cell tumours are rare neoplasms that occur in children and adolescents. This study examined both the biology and the origin of these tumours, as it has been hypothesized that they originate from a totipotent primordial germ cell. We applied recent knowledge from gonadal...... germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children...... and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected...

  9. Intracranial recordings and human memory.

    Science.gov (United States)

    Johnson, Elizabeth L; Knight, Robert T

    2015-04-01

    Recent work involving intracranial recording during human memory performance provides superb spatiotemporal resolution on mnemonic processes. These data demonstrate that the cortical regions identified in neuroimaging studies of memory fall into temporally distinct networks and the hippocampal theta activity reported in animal memory literature also plays a central role in human memory. Memory is linked to activity at multiple interacting frequencies, ranging from 1 to 500Hz. High-frequency responses and coupling between different frequencies suggest that frontal cortex activity is critical to human memory processes, as well as a potential key role for the thalamus in neocortical oscillations. Future research will inform unresolved questions in the neuroscience of human memory and guide creation of stimulation protocols to facilitate function in the damaged brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. 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.

  11. 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.

  12. The potential of proton beam radiation therapy in intracranial and ocular tumours

    Energy Technology Data Exchange (ETDEWEB)

    Blomquist, Erik [Univ. Hospital, Uppsala (Sweden). Dept. of Oncology, Radiology and Clinical Immunology; Bjelkengren, Goeran [Univ. Hospital, Malmoe (Sweden). Dept. of Oncology; Glimelius, Bengt [Karolinska Inst., Stockholm (Sweden). Dept. of Oncology and Pathology; Akademiska sjukhuset, Uppsala (Sweden). Dept. of Oncology, Radiology and Clinical Immunology

    2005-12-01

    A group of oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In intracranial benign and malignant tumours, it is estimated that between 130 and 180 patients each year are candidates for proton beam therapy. Of these, between 50 and 75 patients have malignant glioma, 30-40 meningeoma, 20-25 arteriovenous malformations, 20-25 skull base tumours and 10-15 pituitary adenoma. In addition, 15 patients with ocular melanoma are candidates.

  13. Primary intracranial germ cell tumours: experience of a single South-East Asian institution.

    Science.gov (United States)

    Foo, Aaron S C; Lim, Cindy; Chong, Dawn Q Q; Tan, Daniel Y H; Tham, Chee Kian

    2014-10-01

    Primary intracranial germ cell tumours (ICGCT) are a rare group of brain tumours arising predominantly in the paediatric and pre-adult population, accounting for up to 9.5% of paediatric brain tumours in East Asia. The National Cancer Centre Singapore (NCCS) is a tertiary referral centre for patients from all over South-East Asia. Our study aims to describe the characteristics of ICGCT patients in South-East Asia. Data on all patients with ICGCT who were seen at the Therapeutic Radiology Department of NCCS from 2000 to 2013 were collected retrospectively. Patient demographics, disease characteristics and treatment outcomes were analysed. Characteristics and survival of our patients were similar to other centres. Pure germinomas demonstrated 5 year overall survival (OS) and disease-free survival (DFS) rates of 89.2% (95% confidence interval [CI] 60.2-97.5) and 85.2% (95%CI 60.8-95.0) respectively. Secreting germinomas, non-germinomatous germ cell tumours and mixed germ cell tumours were evaluated together and demonstrated 5 year OS of 70.6% (95%CI 41.0-87.3) and DFS of 61.4% (95%CI 31.9-81.3). Patients ⩽ 12 years had marginally better 5 year OS than their older counterparts (81.0% [95%CI 49.5-93.9] versus 77.9% [95%CI 47.3-92.0], respectively). Patients who underwent extended field radiotherapy had longer OS and DFS than those who received local field irradiation. Treatment outcomes of our ICGCT patients are comparable with those in other Asian and Western centres. Extended field radiotherapy is a pivotal component of ICGCT treatment. Adding chemotherapy confers no extra survival benefit in treating germinomas. Treatment of mixed germ cell tumours and non-germinomatous germ cell tumours involves a multidisciplinary approach that varies for each histological subtype. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. INTRACRANIAL AND INTRASPINAL TUMOURS: REVIEW OF MRI FINDINGS IN A RARE NF - 2 CASE

    Directory of Open Access Journals (Sweden)

    Sahoo

    2015-02-01

    Full Text Available Neurofibromatosis type 2 is a rare autosomal dominant syndrome, characterized by multiple intracranial and intraspinal tumours associated with ocular abnormalities. The most common tumor associated with the disease is the vestibule cochlear schwannoma, and as many as 10% of patients with this tumor have neurofibromatosis type 2. Based on clinical and imaging findings the diagnostic of neurofibromatosis type 2 can be made. In this report we aim to report a 24 - year - old male who was evaluated for progressive h earing loss, vertigo, ataxic gait and right lower limb weakness. During the workup, cranial CT, Brain and whole s pine MRI was done which showed all the findings in one patient including bilateral vestibulocochlear schwannoma, multiple meningiomas, and intr amedullary and extramedullary tumours in spinal cord.

  15. 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....

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

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 35; Issue 2 ... Human tumour xenografts; radiation; rats; tumour bed ... Dosimetry and the corresponding methodology for radiotherapy of human non-small cell lung cancer xenograft tumours transplanted to and growing subcutaneously on the right lower limb in a nude rat ...

  17. Intracranial cortical localization of the human K-complex.

    Science.gov (United States)

    Wennberg, Richard

    2010-08-01

    The K-complex was first identified in human sleep EEG more than 70years ago, but the localization of its intracranial generators is an unresolved issue. In this study, K-complexes recorded using simultaneous scalp and intracranial EEG were analyzed to discover the intracranial distribution of the human K-complex. Stereoelectroencephalographic recordings were performed in six patients with medically-refractory epilepsy. Full 10-20 scalp montages were used and intracranial macroelectrodes sampled medial, lateral and basal frontal and temporal cortices, medial and lateral parietal and occipital cortices, as well as the hippocampus and thalamus. Spontaneous K-complexes were visually identified in stage II sleep and averaged off-line. The intracranial K-complex field was maximal over the anterior and superior aspects of the medial and lateral frontal lobe cortices, consistent with the frontal midline scalp EEG maximum. The frontal maximum surface-negative field was volume conducted as an inverted, positive field posteriorly and inferiorly, the polarity reversing laterally above the inferior temporal region and medially above the cingulate cortex. As suggested by the scalp EEG topography, the intracranial distribution of the human K-complex is maximal over the anterior and superior frontal cortices. K-complex generation appears limited to cortical regions above the inferior temporal sulcus laterally, the cingulate sulcus medially and the parietooccipital junction posteriorly. The human K-complex is produced by synchronous cortical activity that appears maximal intracranially over the superior medial and lateral aspects of the frontal lobes. The cingulate cortex and functionally related mesial temporal structures appear uninvolved in human K-complex generation. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Loss of the tumour suppressor gene AIP mediates the browning of human brown fat tumours.

    Science.gov (United States)

    Magnusson, Linda; Hansen, Nils; Saba, Karim H; Nilsson, Jenny; Fioretos, Thoas; Rissler, Pehr; Nord, Karolin H

    2017-10-01

    Human brown fat tumours (hibernomas) show concomitant loss of the tumour suppressor genes MEN1 and AIP. We hypothesized that the brown fat phenotype is attributable to these mutations. Accordingly, in this study, we demonstrate that silencing of AIP in human brown preadipocytic and white fat cell lines results in the induction of the brown fat marker UCP1. In human adipocytic tumours, loss of MEN1 was found both in white (one of 51 lipomas) and in brown fat tumours. In contrast, concurrent loss of AIP was always accompanied by a brown fat morphology. We conclude that this white-to-brown phenotype switch in brown fat tumours is mediated by the loss of AIP. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  19. Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model

    Directory of Open Access Journals (Sweden)

    Carole eGrasso

    2014-12-01

    Full Text Available Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumour environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionising radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumour, glioblastoma multiforme (GBM, is very resistant to radiation; radiosensitising GBM cells will improve survival of GBM patients. Here we demonstrate that a single fraction (6 Gy of radiation combined with a one hour exposure to ascorbate (5 mM sensitised murine glioma GL261cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy of whole brain radiation combined with daily intra-peritoneal injections of ascorbate (1 mg/kg in an intra-cranial GL261 glioma mouse model. Tumour-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain eight days after tumour implantation, a second group received daily intra-peritoneal injections of ascorbate (day 8-45 after implantation, a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumour progression, intra-peritoneal ascorbate alone had no effect on tumour progression. Tumour progression was faster in tumour-bearing mice treated with radiation and daily ascorbate than those treated with radiation alone. Histological analysis showed less necrosis in tumours treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumour micro-environment which determines whether ascorbate remains outside the cell, acting as a pro-oxidant or whether it enters the cells and acts as an anti-oxidant.

  20. 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...

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

    Indian Academy of Sciences (India)

    Prakash

    for radiotherapy of human non-small cell lung cancer xenograft tumours transplanted to and growing subcutaneously on the right lower limb in a nude rat model were investigated. Procedures and results described herein prove the feasibility of use of the device, which is applicable for any investigation involving irradiation ...

  3. NOISY INTRACRANIAL TUMORS

    NARCIS (Netherlands)

    VANDOOREN, BTH; VANBRUGGEN, AC; MOOIJ, JJA; HEW, JM; JOURNEE, HL

    1994-01-01

    Transorbital sound recordings were obtained from 21 patients with intracranial tumours, 28 patients with intracranial aneurysms and 20 control patients. The group of patients with tumours consisted of 12 patients with gliomas, of whom 6 had low-grade gliomas and 6 had high-grade gliomas, and 9

  4. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  5. K ATP channels in pig and human intracranial arteries

    DEFF Research Database (Denmark)

    Ploug, Kenneth Beri; Sørensen, Mette Aaskov; Strøbech, Lotte

    2008-01-01

    Clinical trials suggest that synthetic ATP-sensitive K(+) (K(ATP)) channel openers may cause headache and migraine by dilating cerebral and meningeal arteries. We studied the mRNA expression profile of K(ATP) channel subunits in the pig and human middle meningeal artery (MMA) and in the pig middle...... cerebral artery (MCA). We determined the order of potency of four K(ATP) channel openers when applied to isolated pig MMA and MCA, and we examined the potential inhibitory effects of the Kir6.1 subunit specific K(ATP) channel blocker PNU-37883A on K(ATP) channel opener-induced relaxation of the isolated...... pig MMA and MCA. Using conventional RT-PCR, we detected the mRNA transcripts of the K(ATP) channel subunits Kir6.1 and SUR2B in all the examined pig and human intracranial arteries. Application of K(ATP) channel openers to isolated pig MMA and MCA in myographs caused a concentration...

  6. DNA alterations in Cd133+ and Cd133- tumour cells enriched from intra-operative human colon tumour biopsies.

    Science.gov (United States)

    Cervantes-Madrid, Diana; Wettergren, Yvonne; Falk, Peter; Lundholm, Kent; Asting, Annika G

    2017-03-27

    Tumour stem cells are considered important to promote disease progression, recurrence and treatment resistance following chemotherapy in colon cancer. However, genomic analyses of colorectal cancer have mainly been performed on integrated tumour tissue consisting of several different cell types in addition to differentiated tumour cells. The purpose of the present study was to compare genomic alterations in two cell fractions enriched of CD133+ and CD133-/EpCAM+ cells, respectively, obtained from fresh intraoperative human tumour biopsies. The tumour biopsies were fractionated into CD133+ and CD133-/EpCAM+ cells by immunomagnetic separation, confirmed by immunocytochemistry and Q-PCR. DNA were extracted and used for array comparative genome hybridization (aCGH) after whole genome amplification. Frozen tumour tissue biopsies were used for DNA/RNA extraction and Q-PCR analyses to check for DNA alterations detected in the cell fractions. The number and size of DNA alterations were equally distributed across the cell fractions; however, large deletions were detected on chromosome 1, 7 and 19 in CD133-/EpCAM+ cells. Deletions were frequent in both cell fractions and a deletion on chromosome 19p was confirmed in 90% of the patients. Isolation of enriched cells derived from tumour tissue revealed mainly genomic deletions, which were not observed in tumour tissue DNA analyses. CD133+ cells were genetically heterogeneous among patients without any defined profile compared to CD133-/EpCAM+ cells.

  7. 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

  8. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    Science.gov (United States)

    Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura ME; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher RK; Cuellar-Partida, Gabriel; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David CM; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Olde Loohuis, Loes M; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein MJ; Van Eijk, Kristel R; Van Erp, Theo GM; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco JC; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald HH; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, WT; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda WJH; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Valdés Hernández, Maria C; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic JA; Van Duijn, Cornelia M; Van Haren, Neeltje EM; Van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton JM; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth. PMID:27694991

  9. Time reversibility of intracranial human EEG recordings in mesial temporal lobe epilepsy

    Science.gov (United States)

    van der Heyden, M. J.; Diks, C.; Pijn, J. P. M.; Velis, D. N.

    1996-02-01

    Intracranial electroencephalograms from patients suffering from mesial temporal lobe epilepsy were tested for time reversibility. If the recorded time series is irreversible, the input of the recording system cannot be a realisation of a linear Gaussian random process. We confirmed experimentally that the measurement equipment did not introduce irreversibility in the recorded output when the input was a realisation of a linear Gaussian random process. In general, the non-seizure recordings are reversible, whereas the seizure recordings are irreversible. These results suggest that time reversibility is a useful property for the characterisation of human intracranial EEG recordings in mesial temporal lobe epilepsy.

  10. The use of intracranial recordings to decode human language: Challenges and opportunities.

    Science.gov (United States)

    Martin, Stephanie; Millán, José Del R; Knight, Robert T; Pasley, Brian N

    2016-07-01

    Decoding speech from intracranial recordings serves two main purposes: understanding the neural correlates of speech processing and decoding speech features for targeting speech neuroprosthetic devices. Intracranial recordings have high spatial and temporal resolution, and thus offer a unique opportunity to investigate and decode the electrophysiological dynamics underlying speech processing. In this review article, we describe current approaches to decoding different features of speech perception and production - such as spectrotemporal, phonetic, phonotactic, semantic, and articulatory components - using intracranial recordings. A specific section is devoted to the decoding of imagined speech, and potential applications to speech prosthetic devices. We outline the challenges in decoding human language, as well as the opportunities in scientific and neuroengineering applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The role of resection alone in select children with intracranial ependymoma: the Canadian Pediatric Brain Tumour Consortium experience.

    Science.gov (United States)

    Ailon, Tamir; Dunham, Christopher; Carret, Anne-Sophie; Tabori, Uri; Mcneely, P Daniel; Zelcer, Shayna; Wilson, Beverley; Lafay-Cousin, Lucie; Johnston, Donna; Eisenstat, David D; Silva, Marianna; Jabado, Nada; Goddard, Karen Jane; Fryer, Chris; Hendson, Glenda; Hawkins, Cynthia; Dunn, Sandra; Yip, Stephen; Singhal, Ashutosh; Hukin, Juliette

    2015-01-01

    Gross total resection (GTR) of intracranial ependymoma is an accepted goal. More controversial is radiotherapy deferral. This study reports on children treated with gross total resection who did not receive upfront adjuvant radiotherapy. We conducted a retrospective review of children with intracranial ependymoma in 12 Canadian centers. Patients who had GTR of their tumor and no upfront radiotherapy were identified. Immunostaining was performed for Ki-67, epidermal growth factor receptor (EGFR), and EZH2 on archived tissue. The Kaplan-Meier survival analysis was performed and compared with those who had GTR followed by radiation. Twenty-six children were identified treated with GTR alone at diagnosis; 12 posterior fossa ependymoma (PFE) WHO grade II, and 14 supratentorial ependymoma (STE). Progression-free survival (PFS) in ependymoma treated with GTR alone at diagnosis was inferior in those with high Ki-67 or positive EZH2 immunostaining. Survival was inferior for patients less than 2 years old at diagnosis (p = 0.002). Survival was comparable to PFE WHO grade II and STE who had GTR followed by radiation (p = 0.62). Five-year PFS and overall survival (OS) of those treated with GTR alone were 60 and 70% respectively for PFE and 45 and 70% respectively for STE (p = 0.2; 0.55). This study suggests that there is a subset of children with certain biologic features who, in the setting of a prospective clinical trial, might be candidates for observation following GTR. Good risk factors for this approach include age of 2 years or older, low Ki-67, and negative EZH2. If relapse occurs, it may be confined to the primary site, allowing for possible salvage with GTR followed by XRT.

  12. Training for planning tumour resection: augmented reality and human factors.

    Science.gov (United States)

    Abhari, Kamyar; Baxter, John S H; Chen, Elvis C S; Khan, Ali R; Peters, Terry M; de Ribaupierre, Sandrine; Eagleson, Roy

    2015-06-01

    Planning surgical interventions is a complex task, demanding a high degree of perceptual, cognitive, and sensorimotor skills to reduce intra- and post-operative complications. This process requires spatial reasoning to coordinate between the preoperatively acquired medical images and patient reference frames. In the case of neurosurgical interventions, traditional approaches to planning tend to focus on providing a means for visualizing medical images, but rarely support transformation between different spatial reference frames. Thus, surgeons often rely on their previous experience and intuition as their sole guide is to perform mental transformation. In case of junior residents, this may lead to longer operation times or increased chance of error under additional cognitive demands. In this paper, we introduce a mixed augmented-/virtual-reality system to facilitate training for planning a common neurosurgical procedure, brain tumour resection. The proposed system is designed and evaluated with human factors explicitly in mind, alleviating the difficulty of mental transformation. Our results indicate that, compared to conventional planning environments, the proposed system greatly improves the nonclinicians' performance, independent of the sensorimotor tasks performed ( ). Furthermore, the use of the proposed system by clinicians resulted in a significant reduction in time to perform clinically relevant tasks ( ). These results demonstrate the role of mixed-reality systems in assisting residents to develop necessary spatial reasoning skills needed for planning brain tumour resection, improving patient outcomes.

  13. Tumour marker expression in blood and lymphatic vessels of human ...

    African Journals Online (AJOL)

    The behaviour of tumours cannot be effectively assessed on histological tissue sections only, hence, specific bi-ological markers were used to predict tumour behaviour. The biological markers at the same time must provide prognostic information, necessary for the treatment of patients. The immunostaining of antibodies ...

  14. Cyclooxygenase-2 expression in the normal human eye and its expression pattern in selected eye tumours

    DEFF Research Database (Denmark)

    Wang, Jinmei; Wu, Yazhen; Heegaard, Steffen

    2011-01-01

    and retina. The COX-2 expression was less in tumours deriving from the ciliary epithelium and also in retinoblastoma. Conclusion: Cyclooxygenase-2 is constitutively expressed in normal human eyes. The expression of COX-2 is much lower in selected eye tumours involving COX-2 expressing cells....

  15. Expression of Selected Markers in Immunohistochemical Diagnosis of Canine and Human Testicular Tumours

    Directory of Open Access Journals (Sweden)

    Ciaputa Rafał

    2015-04-01

    Full Text Available Immunohistochemical profiles of the most common canine testicular tumours, including the Leydig cell tumours, seminomas, and Sertoli cell tumours were analysed, and the results were compared with those obtained in the corresponding types of human testicular neoplasms. The expressions of vimentin, von Willebrand factor (FVIII, chromogranin A, synaptophysin, and MCM3 were quantified. In the case of Sertoli cell tumours, only canine ones were analysed, since this type of tumour is very rarely diagnosed in men. The expression of the analysed proteins in the testicular tumours was similar. The von Willebrand factor exhibited the strongest expression in Leydig cell tumours in dogs and men, while vimentin was expressed more strongly in dogs (96.7% had an intensity at +++ than in men (62.5% had +++ in the Leydigioma. The immunoexpression of MCM3 in seminomas was high in both men and dogs – 90% +++ and 100% +++ respectively. The lack of chromogranin A and synaptophysin was observed in almost 100% of seminomas in men and dogs. This differed from the results obtained for Leydigioma, where chromogranin A was expressed in 70% of dogs at +++ and in 100% of men at ++++. The results may indicate that the antibodies were selected correctly. Their analysis and interpretation provides valuable information concerning the nature of the studied tumours.

  16. Cyclooxygenase-2 expression in the normal human eye and its expression pattern in selected eye tumours

    DEFF Research Database (Denmark)

    Wang, Jinmei; Wu, Yazhen; Heegaard, Steffen

    2011-01-01

    Purpose: Cyclooxygenase-2 (COX-2) is an enzyme involved in neoplastic processes. The purpose of the present study is to investigate COX-2 expression in the normal human eye and the expression pattern in selected eye tumours involving COX-2 expressing cells. Methods: Immunohistochemical staining...... using antibodies against COX-2 was performed on paraffin sections of normal human eyes and selected eye tumours arising from cells expressing COX-2. Results: Cyclooxygenase-2 expression was found in various structures of the normal eye. Abundant expression was seen in the cornea, iris, ciliary body...... and retina. The COX-2 expression was less in tumours deriving from the ciliary epithelium and also in retinoblastoma. Conclusion: Cyclooxygenase-2 is constitutively expressed in normal human eyes. The expression of COX-2 is much lower in selected eye tumours involving COX-2 expressing cells....

  17. Secreted and tumour targeted human carboxylesterase for activation of irinotecan

    NARCIS (Netherlands)

    Oosterhoff, D; Pinedo, HM; van der Meulen, IH; Sone, T; Kruyt, FA; van Beusechem, VW; Haisma, HJ; Gerritsen, WR

    2002-01-01

    Innotecan (CPT-II) is an anticancer agent for the treatment of colon cancer. CPT-II can be considered as a prodrug, since it needs to be activated into the toxic drug SN-38 by the enzyme carboxylesterase. An approach to achieve tumour specific activation of CPT-II is to transduce the cDNA encoding

  18. Genetically engineered mesenchymal stromal cells producing TNFα have tumour suppressing effect on human melanoma xenograft.

    Science.gov (United States)

    Tyciakova, Silvia; Matuskova, Miroslava; Bohovic, Roman; Polakova, Katarina; Toro, Lenka; Skolekova, Svetlana; Kucerova, Lucia

    2015-01-01

    Mesenchymal stromal cells (MSC) are a promising tool for targeted cancer therapy due to their tumour-homing ability. Intrinsic resistance enables the MSC to longer tolerate therapeutic factors, such as prodrug converting enzymes, cytokines and pro-apoptotic proteins. Tumour necrosis factor alpha (TNFα) is known to be cytotoxic to a variety of cancer cells and exert a tumour-destructive capacity. MSC were retrovirally transduced to stable express an exogenous gene encoding the desired therapeutic agent hTNFα. The effect of a TNFα-producing adipose tissue-derived MSC (AT-MSC/hTNFα) was tested on the tumour cell lines of different origins: melanoma (A375), breast carcinoma (SKBR3, MDA-MB-231), colon carcinoma (HT29), ovarian carcinoma (SKOV3) and glioblastoma (U87-MG) cells. The tumour suppressing effect of AT-MSC/hTNFα on A375 melanoma xenografts was monitored in an immunodeficient mouse model in vivo. Engineered AT-MSC are able to constitutively secrete human TNFα protein, induce apoptosis of tumour cell lines via caspase 3/7 activation and inhibit the tumour cell proliferation in vitro. Melanoma A375 and breast carcinoma SKBR3 cells were the most sensitive, and their proliferation in vitro was reduced by conditioned media produced by AT-MSC/hTNFα to 60% and 40%, respectively. The previously reported tumour supportive effect of AT-MSC on subcutaneous A375 melanoma xenograft growth was neutralised and suppressed by engineered AT-MSC stably producing hTNFα. When AT-MSC/hTNFα were coinjected with A375 melanoma cells, the tumour mass inhibition was up to 97.5%. The results of the present study demonstrate that tumour cells respond to hTNFα-based treatment mediated by genetically engineered AT-MSC/hTNFα both in vitro and in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Alpha-amidated peptides derived from pro-opiomelanocortin in human pituitary tumours

    DEFF Research Database (Denmark)

    Fenger, M; Johnsen, A H

    1988-01-01

    Human pituitary tumours, obtained at surgery for Cushing's disease and Nelson's syndrome, were extracted and the content and molecular forms of pro-opiomelanocortin (POMC)-derived peptides determined by radioimmunoassay, gel chromatography, reversed-phase high-performance liquid chromatography...... (HPLC) and sequence analysis. In the tumours from patients with Cushing's disease the mean concentrations of amidated peptides relative to the total amount of POMC were as follows: alpha-MSH, 1.7%; amidated gamma-MSH (gamma 1-MSH), 8.5% and the peptide linking gamma-MSH and ACTH in the precursor (hinge....... In conclusion, all the molecular forms of the amidated peptides detected in tumours from patients with Cushing's disease and Nelson's syndrome were similar to the molecular forms found in the normal human pituitary. The main difference between the tumours and the normal pituitary was the greater amount...

  20. Exploring emotions using invasive methods: review of 60 years of human intracranial electrophysiology.

    Science.gov (United States)

    Guillory, Sean A; Bujarski, Krzysztof A

    2014-12-01

    Over the past 60 years, human intracranial electrophysiology (HIE) has been used to characterize seizures in patients with epilepsy. Secondary to the clinical objectives, electrodes implanted intracranially have been used to investigate mechanisms of human cognition. In addition to studies of memory and language, HIE methods have been used to investigate emotions. The aim of this review is to outline the contribution of HIE (electrocorticography, single-unit recording and electrical brain stimulation) to our understanding of the neural representations of emotions. We identified 64 papers dating back to the mid-1950s which used HIE techniques to study emotional states. Evidence from HIE studies supports the existence of widely distributed networks in the neocortex, limbic/paralimbic regions and subcortical nuclei which contribute to the representation of emotional states. In addition, evidence from HIE supports hemispheric dominance for emotional valence. Furthermore, evidence from HIE supports the existence of overlapping neural areas for emotion perception, experience and expression. Lastly, HIE provides unique insights into the temporal dynamics of neural activation during perception, experience and expression of emotional states. In conclusion, we propose that HIE techniques offer important evidence which must be incorporated into our current models of emotion representation in the human brain. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  1. Exploring emotions using invasive methods: review of 60 years of human intracranial electrophysiology

    Science.gov (United States)

    Guillory, Sean A.

    2014-01-01

    Over the past 60 years, human intracranial electrophysiology (HIE) has been used to characterize seizures in patients with epilepsy. Secondary to the clinical objectives, electrodes implanted intracranially have been used to investigate mechanisms of human cognition. In addition to studies of memory and language, HIE methods have been used to investigate emotions. The aim of this review is to outline the contribution of HIE (electrocorticography, single-unit recording and electrical brain stimulation) to our understanding of the neural representations of emotions. We identified 64 papers dating back to the mid-1950s which used HIE techniques to study emotional states. Evidence from HIE studies supports the existence of widely distributed networks in the neocortex, limbic/paralimbic regions and subcortical nuclei which contribute to the representation of emotional states. In addition, evidence from HIE supports hemispheric dominance for emotional valence. Furthermore, evidence from HIE supports the existence of overlapping neural areas for emotion perception, experience and expression. Lastly, HIE provides unique insights into the temporal dynamics of neural activation during perception, experience and expression of emotional states. In conclusion, we propose that HIE techniques offer important evidence which must be incorporated into our current models of emotion representation in the human brain. PMID:24509492

  2. Decoding sequence learning from single-trial intracranial EEG in humans.

    Directory of Open Access Journals (Sweden)

    Marzia De Lucia

    Full Text Available We propose and validate a multivariate classification algorithm for characterizing changes in human intracranial electroencephalographic data (iEEG after learning motor sequences. The algorithm is based on a Hidden Markov Model (HMM that captures spatio-temporal properties of the iEEG at the level of single trials. Continuous intracranial iEEG was acquired during two sessions (one before and one after a night of sleep in two patients with depth electrodes implanted in several brain areas. They performed a visuomotor sequence (serial reaction time task, SRTT using the fingers of their non-dominant hand. Our results show that the decoding algorithm correctly classified single iEEG trials from the trained sequence as belonging to either the initial training phase (day 1, before sleep or a later consolidated phase (day 2, after sleep, whereas it failed to do so for trials belonging to a control condition (pseudo-random sequence. Accurate single-trial classification was achieved by taking advantage of the distributed pattern of neural activity. However, across all the contacts the hippocampus contributed most significantly to the classification accuracy for both patients, and one fronto-striatal contact for one patient. Together, these human intracranial findings demonstrate that a multivariate decoding approach can detect learning-related changes at the level of single-trial iEEG. Because it allows an unbiased identification of brain sites contributing to a behavioral effect (or experimental condition at the level of single subject, this approach could be usefully applied to assess the neural correlates of other complex cognitive functions in patients implanted with multiple electrodes.

  3. 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.

  4. Neutron autoradiography imaging of selective boron uptake in human metastatic tumours

    Energy Technology Data Exchange (ETDEWEB)

    Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, Via Bassi 6, Pavia (Italy)], E-mail: saverio.altieri@pv.infn.it; Bortolussi, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, Via Bassi 6, Pavia (Italy); Bruschi, P.; Chiari, P.; Fossati, F.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Prati, U.; Roveda, L. [Unit of cancer surgery, Cancer Center of Excellence, Foundation T. Campanella, Catanzaro (Italy); Zonta, A.; Zonta, C.; Ferrari, C.; Clerici, A. [Department of Surgery, University of Pavia, Piazza Botta, Pavia (Italy); Nano, R. [Department of Animal Biology, University of Pavia, Piazza Botta, Pavia (Italy); Pinelli, T. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, Via Bassi 6, Pavia (Italy)

    2008-12-15

    The ability to selectively hit the tumour cells is an essential characteristic of an anti-tumour therapy. In boron neutron capture therapy (BNCT) this characteristic is based on the selective uptake of {sup 10}B in the tumour cells with respect to normal tissues. An important step in the BNCT planning is the measurement of the boron concentration in the tissue samples, both tumour and healthy. When the tumour is spread through the healthy tissue, as in the case of metastases, the knowledge of the different kinds of tissues in the sample being analysed is crucial. If the percentage of tumour and normal tissues cannot be evaluated, the obtained concentration is a mean value depending on the composition of the different samples being measured. In this case an imaging method that could give information both on the morphology and on the spatial distribution of boron concentration in the sample would be a fundamental support. In this paper, the results of the boron uptake analysis in the tumour and in the healthy samples taken from human livers after boron phenylalanine (BPA) infusion are shown; boron imaging was performed using neutron autoradiography.

  5. iELVis: An open source MATLAB toolbox for localizing and visualizing human intracranial electrode data.

    Science.gov (United States)

    Groppe, David M; Bickel, Stephan; Dykstra, Andrew R; Wang, Xiuyuan; Mégevand, Pierre; Mercier, Manuel R; Lado, Fred A; Mehta, Ashesh D; Honey, Christopher J

    2017-04-01

    Intracranial electrical recordings (iEEG) and brain stimulation (iEBS) are invaluable human neuroscience methodologies. However, the value of such data is often unrealized as many laboratories lack tools for localizing electrodes relative to anatomy. To remedy this, we have developed a MATLAB toolbox for intracranial electrode localization and visualization, iELVis. NEW METHOD: iELVis uses existing tools (BioImage Suite, FSL, and FreeSurfer) for preimplant magnetic resonance imaging (MRI) segmentation, neuroimaging coregistration, and manual identification of electrodes in postimplant neuroimaging. Subsequently, iELVis implements methods for correcting electrode locations for postimplant brain shift with millimeter-scale accuracy and provides interactive visualization on 3D surfaces or in 2D slices with optional functional neuroimaging overlays. iELVis also localizes electrodes relative to FreeSurfer-based atlases and can combine data across subjects via the FreeSurfer average brain. It takes 30-60min of user time and 12-24h of computer time to localize and visualize electrodes from one brain. We demonstrate iELVis's functionality by showing that three methods for mapping primary hand somatosensory cortex (iEEG, iEBS, and functional MRI) provide highly concordant results. COMPARISON WITH EXISTING METHODS: iELVis is the first public software for electrode localization that corrects for brain shift, maps electrodes to an average brain, and supports neuroimaging overlays. Moreover, its interactive visualizations are powerful and its tutorial material is extensive. iELVis promises to speed the progress and enhance the robustness of intracranial electrode research. The software and extensive tutorial materials are freely available as part of the EpiSurg software project: https://github.com/episurg/episurg. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Polio vaccines, SV40 and human tumours, an update on false positive and false negative results.

    Science.gov (United States)

    Elmishad, A G; Bocchetta, M; Pass, H I; Carbone, M

    2006-01-01

    Simian virus 40 (SV40) has been detected in different human tumours in numerous laboratories. The detection of SV40 in human tumours has been linked to the administration of SV40-contaminated polio vaccines from 1954 until 1963. Many of these reports linked SV40 to human mesothelioma. Some studies have failed to detect SV40 in human tumours and this has caused a controversy. Here we review the current literature. Moreover, we present evidence showing how differences in the sensitivities of methodologies can lead to a very different interpretation of the same study. The same 20 mesothelioma specimens all tested negative, 2/20 tested positive or 7/20 tested positive for SV40 Tag by simply changing the detection method on the same immuno-precipitation/western blot membranes. These results provide a simple explanation for some of the apparent discordant results reported in the literature.

  7. Tumour microenvironment and radiation response in sarcomas originating from tumourigenic human mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Safwat, Akmal Ahmed; Burns, Jorge S.

    2012-01-01

    Background: Resistance to radiation therapy remains a serious impediment to cancer therapy. We previously reported heterogeneity for clonogenic survival when testing in vitro radiation resistance among single cell derived clones from a human mesenchymal cancer stem cell model (hMSC). Here we aimed...... to determine whether this heterogeneity persisted in tumours established from these clones, and whether the response to radiation treatment was principally governed by cell intrinsic qualities or by factors pertaining to the tumour microenvironment, such as the degree of hypoxia and vascularisation. Methods......: Immune deficient female mice were implanted on the backs with cells from one of the clones. The subsequent tumours were subjected to either radiation treatment or had the tumour microenvironment assayed, when they reached 400mm3. Radiation was given as a single fraction of 0 to 15 Gy and the degree...

  8. Intracranial Aneurysms Involving Circle of Willis in a Child with Human Immunodeficiency Virus Associated Vasculitis- A Rare Case Report.

    Science.gov (United States)

    Lahoti, Amol Madanlal; Taori, Abhijit Kishor; Dhok, Avinash Parashuram; Rawat, Jitesh Subhash; Chandak, Nihar Umakant

    2017-07-01

    Intracranial Arterial Aneurysms (IAAs) are relatively rare in paediatric population and they account for at least 10%-15% of haemorrhagic strokes which occur during the first two decades of life. Here we present a unique and unusual case of Human Immunodeficiency Virus (HIV) infected child who presented with intracranial aneurysms with formation of collaterals and vasculopathy, demonstrating low viral count despite receiving adequate antiretroviral treatment. Intracranial vascular involvement, their complications and its incidence in these patients may become increasingly common as the management of human immunodeficiency virus infection continues to improve and afflicted patients survive for longer periods because of advancement in the antiretroviral treatment. Diagnosing aneurysm of cerebral circulation needs high degree of suspicion and correlation between clinical and radiological findings.

  9. Significance of the detection of esters of p-hydroxybenzoic acid (parabens) in human breast tumours.

    Science.gov (United States)

    Harvey, Philip W; Everett, David J

    2004-01-01

    This issue of Journal of Applied Toxicology publishes the paper Concentrations of Parabens in Human Breast Tumours by Darbre et al. (2004), which reports that esters of p-hydroxybenzoic acid (parabens) can be detected in samples of tissue from human breast tumours. Breast tumour samples were supplied from 20 patients, in collaboration with the Edinburgh Breast Unit Research Group, and analysed by high-pressure liquid chromatography and tandem mass spectrometry. The parabens are used as antimicrobial preservatives in underarm deodorants and antiperspirants and in a wide range of other consumer products. The parabens also have inherent oestrogenic and other hormone related activity (increased progesterone receptor gene expression). As oestrogen is a major aetiological factor in the growth and development of the majority of human breast cancers, it has been previously suggested by Darbre that parabens and other chemicals in underarm cosmetics may contribute to the rising incidence of breast cancer. The significance of the finding of parabens in tumour samples is discussed here in terms of 1). Darbre et al's study design, 2). what can be inferred from this type of data (and what can not, such as the cause of these tumours), 3). the toxicology of these compounds and 4). the limitations of the existing toxicology database and the need to consider data that is appropriate to human exposures. Copyright 2004 John Wiley & Sons, Ltd.

  10. A blueprint for real-time functional mapping via human intracranial recordings.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Lachaux

    Full Text Available BACKGROUND: The surgical treatment of patients with intractable epilepsy is preceded by a pre-surgical evaluation period during which intracranial EEG recordings are performed to identify the epileptogenic network and provide a functional map of eloquent cerebral areas that need to be spared to minimize the risk of post-operative deficits. A growing body of research based on such invasive recordings indicates that cortical oscillations at various frequencies, especially in the gamma range (40 to 150 Hz, can provide efficient markers of task-related neural network activity. PRINCIPAL FINDINGS: Here we introduce a novel real-time investigation framework for mapping human brain functions based on online visualization of the spectral power of the ongoing intracranial activity. The results obtained with the first two implanted epilepsy patients who used the proposed online system illustrate its feasibility and utility both for clinical applications, as a complementary tool to electrical stimulation for presurgical mapping purposes, and for basic research, as an exploratory tool used to detect correlations between behavior and oscillatory power modulations. Furthermore, our findings suggest a putative role for high gamma oscillations in higher-order auditory processing involved in speech and music perception. CONCLUSION/SIGNIFICANCE: The proposed real-time setup is a promising tool for presurgical mapping, the investigation of functional brain dynamics, and possibly for neurofeedback training and brain computer interfaces.

  11. Gastrin: growth enhancing effects on human gastric and colonic tumour cells.

    Science.gov (United States)

    Watson, S.; Durrant, L.; Morris, D.

    1989-01-01

    Two colorectal (HT29, LoVo) and one gastric (MKN45) human tumour cell lines were examined for their in vitro trophic response to human gastrin-17. MKN45 and HT29 responded by increased 75Se selenomethionine uptake to exogenous gastrin (139 +/- 5.5% and 123 +/- 3% of control values respectively) whereas LoVo showed no significant response to this hormone. When these same cell lines were grown as xenografts in nude mice, similar responses were seen to exogenously administered human gastrin-17 (10 micrograms mouse-1 day-1, subcutaneous injection). MKN45 xenografts showed a greater response to continuously administered gastrin (osmotic mini-pumps, (10 micrograms mouse-1 day-1) when compared to the same dose given via a subcutaneous bolus injection. The hormone-treated xenografts had a two-fold increase in tumour cross-sectional area and growth rate when compared to saline-treated controls. Dose-response studies revealed that 0.4 micrograms gastrin mouse-1 day-1 appeared to be the minimally effective dose. As gastric and colorectal tumour cells show a trophic response to gastrin, antagonists of the gastrin receptor may prevent this effect causing tumour stasis. The gastric tumour cell line, MKN45, is gastrin-responsive and would be an ideal model for screening potent receptor antagonists. PMID:2713241

  12. Human intracranial high-frequency activity during memory processing: neural oscillations or stochastic volatility?

    Science.gov (United States)

    Burke, John F; Ramayya, Ashwin G; Kahana, Michael J

    2015-04-01

    Intracranial high-frequency activity (HFA), which refers to fast fluctuations in electrophysiological recordings, increases during memory processing. Two views have emerged to explain this effect: (1) HFA reflects a synchronous signal, related to underlying gamma oscillations, that plays a mechanistic role in human memory and (2) HFA reflects an asynchronous signal that is a non-specific marker of brain activation. We review recent data supporting each of these views and conclude that HFA during memory processing is more consistent with an asynchronous signal. Memory-related HFA is therefore best conceptualized as a biomarker of neural activation that can functionally map memory with high spatial and temporal precision. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

    Science.gov (United States)

    Wild, Peter J; Ikenberg, Kristian; Fuchs, Thomas J; Rechsteiner, Markus; Georgiev, Strahil; Fankhauser, Niklaus; Noske, Aurelia; Roessle, Matthias; Caduff, Rosmarie; Dellas, Athanassios; Fink, Daniel; Moch, Holger; Krek, Wilhelm; Frew, Ian J

    2012-01-01

    Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. PMID:22678923

  14. Casein kinase II is elevated in solid human tumours and rapidly proliferating non-neoplastic tissue

    DEFF Research Database (Denmark)

    Münstermann, U; Fritz, G; Seitz, G

    1990-01-01

    Protein kinase CKII (i.e. casein kinase II, CKII, NII) is expressed at a higher level in rapidly proliferating tissues and in solid human tumours (e.g. colorectal carcinomas) when compared to the corresponding non-neoplastic colorectal mucosa. This could be shown by (a) Western blotting of cellular...

  15. Alpha-amidated peptides derived from pro-opiomelanocortin in human pituitary tumours

    DEFF Research Database (Denmark)

    Fenger, M; Johnsen, A H

    1988-01-01

    Human pituitary tumours, obtained at surgery for Cushing's disease and Nelson's syndrome, were extracted and the content and molecular forms of pro-opiomelanocortin (POMC)-derived peptides determined by radioimmunoassay, gel chromatography, reversed-phase high-performance liquid chromatography...

  16. 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.

  17. Atypical imaging appearances of intracranial meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    O' Leary, S. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Adams, W.M. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Parrish, R.W. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Mukonoweshuro, W. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom)]. E-mail: William.mukonoweshuro@phnt.swest.nhs.uk

    2007-01-15

    Meningiomas are the commonest primary, non-glial intracranial tumours. The diagnosis is often correctly predicted from characteristic imaging appearances. This paper presents some examples of atypical imaging appearances that may cause diagnostic confusion.

  18. Signal Complexity of Human Intracranial EEG Tracks Successful Associative-Memory Formation across Individuals.

    Science.gov (United States)

    Sheehan, Timothy C; Sreekumar, Vishnu; Inati, Sara K; Zaghloul, Kareem A

    2018-02-14

    Memory performance is highly variable among individuals. Most studies examining human memory, however, have largely focused on the neural correlates of successful memory formation within individuals, rather than the differences among them. As such, what gives rise to this variability is poorly understood. Here, we examined intracranial EEG (iEEG) recordings captured from 43 participants (23 male) implanted with subdural electrodes for seizure monitoring as they performed a paired-associates verbal memory task. We identified three separate but related signatures of neural activity that tracked differences in successful memory formation across individuals. High-performing individuals consistently exhibited less broadband power, flatter power spectral density slopes, and greater complexity in their iEEG signals. Furthermore, within individuals across three separate time scales ranging from seconds to days, successful recall was positively associated with these same metrics. Our data therefore suggest that memory ability across individuals can be indexed by increased neural signal complexity. SIGNIFICANCE STATEMENT We show that participants whose intracranial EEG exhibits less low-frequency power, flatter power spectrums, and greater sample entropy overall are better able to memorize associations, and that the same metrics track fluctuations in memory performance across time within individuals. These metrics together signify greater neural signal complexity, which may index the brain's ability to flexibly engage with information and generate separable memory representations. Critically, the current set of results provides a unique window into the neural markers of individual differences in memory performance, which have hitherto been underexplored. Copyright © 2018 the authors 0270-6474/18/381744-12$15.00/0.

  19. Intracranial EEG fluctuates over months after implanting electrodes in human brain

    Science.gov (United States)

    Ung, Hoameng; Baldassano, Steven N.; Bink, Hank; Krieger, Abba M.; Williams, Shawniqua; Vitale, Flavia; Wu, Chengyuan; Freestone, Dean; Nurse, Ewan; Leyde, Kent; Davis, Kathryn A.; Cook, Mark; Litt, Brian

    2017-10-01

    Objective. Implanting subdural and penetrating electrodes in the brain causes acute trauma and inflammation that affect intracranial electroencephalographic (iEEG) recordings. This behavior and its potential impact on clinical decision-making and algorithms for implanted devices have not been assessed in detail. In this study we aim to characterize the temporal and spatial variability of continuous, prolonged human iEEG recordings. Approach. Intracranial electroencephalography from 15 patients with drug-refractory epilepsy, each implanted with 16 subdural electrodes and continuously monitored for an average of 18 months, was included in this study. Time and spectral domain features were computed each day for each channel for the duration of each patient’s recording. Metrics to capture post-implantation feature changes and inflexion points were computed on group and individual levels. A linear mixed model was used to characterize transient group-level changes in feature values post-implantation and independent linear models were used to describe individual variability. Main results. A significant decline in features important to seizure detection and prediction algorithms (mean line length, energy, and half-wave), as well as mean power in the Berger and high gamma bands, was observed in many patients over 100 d following implantation. In addition, spatial variability across electrodes declines post-implantation following a similar timeframe. All selected features decreased by 14–50% in the initial 75 d of recording on the group level, and at least one feature demonstrated this pattern in 13 of the 15 patients. Our findings indicate that iEEG signal features demonstrate increased variability following implantation, most notably in the weeks immediately post-implant. Significance. These findings suggest that conclusions drawn from iEEG, both clinically and for research, should account for spatiotemporal signal variability and that properly assessing the iEEG in

  20. RNA-Seq Differentiates Tumour and Host mRNA Expression Changes Induced by Treatment of Human Tumour Xenografts with the VEGFR Tyrosine Kinase Inhibitor Cediranib.

    Science.gov (United States)

    Bradford, James R; Farren, Matthew; Powell, Steve J; Runswick, Sarah; Weston, Susie L; Brown, Helen; Delpuech, Oona; Wappett, Mark; Smith, Neil R; Carr, T Hedley; Dry, Jonathan R; Gibson, Neil J; Barry, Simon T

    2013-01-01

    Pre-clinical models of tumour biology often rely on propagating human tumour cells in a mouse. In order to gain insight into the alignment of these models to human disease segments or investigate the effects of different therapeutics, approaches such as PCR or array based expression profiling are often employed despite suffering from biased transcript coverage, and a requirement for specialist experimental protocols to separate tumour and host signals. Here, we describe a computational strategy to profile transcript expression in both the tumour and host compartments of pre-clinical xenograft models from the same RNA sample using RNA-Seq. Key to this strategy is a species-specific mapping approach that removes the need for manipulation of the RNA population, customised sequencing protocols, or prior knowledge of the species component ratio. The method demonstrates comparable performance to species-specific RT-qPCR and a standard microarray platform, and allowed us to quantify gene expression changes in both the tumour and host tissue following treatment with cediranib, a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, including the reduction of multiple murine transcripts associated with endothelium or vessels, and an increase in genes associated with the inflammatory response in response to cediranib. In the human compartment, we observed a robust induction of hypoxia genes and a reduction in cell cycle associated transcripts. In conclusion, the study establishes that RNA-Seq can be applied to pre-clinical models to gain deeper understanding of model characteristics and compound mechanism of action, and to identify both tumour and host biomarkers.

  1. RNA-Seq Differentiates Tumour and Host mRNA Expression Changes Induced by Treatment of Human Tumour Xenografts with the VEGFR Tyrosine Kinase Inhibitor Cediranib.

    Directory of Open Access Journals (Sweden)

    James R Bradford

    Full Text Available Pre-clinical models of tumour biology often rely on propagating human tumour cells in a mouse. In order to gain insight into the alignment of these models to human disease segments or investigate the effects of different therapeutics, approaches such as PCR or array based expression profiling are often employed despite suffering from biased transcript coverage, and a requirement for specialist experimental protocols to separate tumour and host signals. Here, we describe a computational strategy to profile transcript expression in both the tumour and host compartments of pre-clinical xenograft models from the same RNA sample using RNA-Seq. Key to this strategy is a species-specific mapping approach that removes the need for manipulation of the RNA population, customised sequencing protocols, or prior knowledge of the species component ratio. The method demonstrates comparable performance to species-specific RT-qPCR and a standard microarray platform, and allowed us to quantify gene expression changes in both the tumour and host tissue following treatment with cediranib, a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, including the reduction of multiple murine transcripts associated with endothelium or vessels, and an increase in genes associated with the inflammatory response in response to cediranib. In the human compartment, we observed a robust induction of hypoxia genes and a reduction in cell cycle associated transcripts. In conclusion, the study establishes that RNA-Seq can be applied to pre-clinical models to gain deeper understanding of model characteristics and compound mechanism of action, and to identify both tumour and host biomarkers.

  2. Evidence of Distinct Tumour-Propagating Cell Populations with Different Properties in Primary Human Hepatocellular Carcinoma

    Science.gov (United States)

    Colombo, Federico; Baldan, Francesca; Mazzucchelli, Silvia; Martin-Padura, Ines; Marighetti, Paola; Cattaneo, Alessandra; Foglieni, Barbara; Spreafico, Marta; Guerneri, Silvana; Baccarin, Marco; Bertolini, Francesco; Rossi, Giorgio; Mazzaferro, Vincenzo; Cadamuro, Massimiliano; Maggioni, Marco; Agnelli, Luca; Rebulla, Paolo

    2011-01-01

    Background and Aims Increasing evidence that a number of malignancies are characterised by tumour cell heterogeneity has recently been published, but there is still a lack of data concerning liver cancers. The aim of this study was to investigate and characterise tumour-propagating cell (TPC) compartments within human hepatocellular carcinoma (HCC). Methods After long-term culture, we identified three morphologically different tumour cell populations in a single HCC specimen, and extensively characterised them by means of flow cytometry, fluorescence microscopy, karyotyping and microarray analyses, single cell cloning, and xenotransplantation in NOD/SCID/IL2Rγ−/− mice. Results The primary cell populations (hcc-1, -2 and -3) and two clones generated by means of limiting dilutions from hcc-1 (clone-1/7 and -1/8) differently expressed a number of tumour-associated stem cell markers, including EpCAM, CD49f, CD44, CD133, CD56, Thy-1, ALDH and CK19, and also showed different doubling times, drug resistance and tumorigenic potential. Moreover, we found that ALDH expression, in combination with CD44 or Thy-1 negativity or CD56 positivity identified subpopulations with a higher clonogenic potential within hcc-1, hcc-2 and hcc-3 primary cell populations, respectively. Karyotyping revealed the clonal evolution of the cell populations and clones within the primary tumour. Importantly, the primary tumour cell population with the greatest tumorigenic potential and drug resistance showed more chromosomal alterations than the others and contained clones with epithelial and mesenchymal features. Conclusions Individual HCCs can harbor different self-renewing tumorigenic cell types expressing a variety of morphological and phenotypical markers, karyotypic evolution and different gene expression profiles. This suggests that the models of hepatic carcinogenesis should take into account TPC heterogeneity due to intratumour clonal evolution. PMID:21731718

  3. Evidence of distinct tumour-propagating cell populations with different properties in primary human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Federico Colombo

    Full Text Available Increasing evidence that a number of malignancies are characterised by tumour cell heterogeneity has recently been published, but there is still a lack of data concerning liver cancers. The aim of this study was to investigate and characterise tumour-propagating cell (TPC compartments within human hepatocellular carcinoma (HCC.After long-term culture, we identified three morphologically different tumour cell populations in a single HCC specimen, and extensively characterised them by means of flow cytometry, fluorescence microscopy, karyotyping and microarray analyses, single cell cloning, and xenotransplantation in NOD/SCID/IL2Rγ/⁻ mice.The primary cell populations (hcc-1, -2 and -3 and two clones generated by means of limiting dilutions from hcc-1 (clone-1/7 and -1/8 differently expressed a number of tumour-associated stem cell markers, including EpCAM, CD49f, CD44, CD133, CD56, Thy-1, ALDH and CK19, and also showed different doubling times, drug resistance and tumorigenic potential. Moreover, we found that ALDH expression, in combination with CD44 or Thy-1 negativity or CD56 positivity identified subpopulations with a higher clonogenic potential within hcc-1, hcc-2 and hcc-3 primary cell populations, respectively. Karyotyping revealed the clonal evolution of the cell populations and clones within the primary tumour. Importantly, the primary tumour cell population with the greatest tumorigenic potential and drug resistance showed more chromosomal alterations than the others and contained clones with epithelial and mesenchymal features.Individual HCCs can harbor different self-renewing tumorigenic cell types expressing a variety of morphological and phenotypical markers, karyotypic evolution and different gene expression profiles. This suggests that the models of hepatic carcinogenesis should take into account TPC heterogeneity due to intratumour clonal evolution.

  4. 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...

  5. Medial frontal cortex and response conflict: Evidence from human intracranial EEG and medial frontal cortex lesion

    NARCIS (Netherlands)

    Cohen, M.X.; Ridderinkhof, K.R.; Haupt, S.; Elger, C.E.; Fell, J.

    2008-01-01

    The medial frontal cortex (MFC) has been implicated in the monitoring and selection of actions in the face of competing alternatives, but much remains unknown about its functional properties, including electrophysiological oscillations, during response conflict tasks. Here, we recorded intracranial

  6. Ruptured intracranial dermoids: magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Patkar D

    1999-04-01

    Full Text Available Rupture of intracranial dermoids tumour is rare and carries with it the risk of significant morbidity as well as fatality. Three cases that presented with varying symptoms ranging from headache to chiasmatic compression and suspected to have rupture of dermoid tumour are described. The importance of MR imaging in their diagnosis is discussed.

  7. Gastrin: growth enhancing effects on human gastric and colonic tumour cells.

    OpenAIRE

    Watson, S.; Durrant, L.; Morris, D.

    1989-01-01

    Two colorectal (HT29, LoVo) and one gastric (MKN45) human tumour cell lines were examined for their in vitro trophic response to human gastrin-17. MKN45 and HT29 responded by increased 75Se selenomethionine uptake to exogenous gastrin (139 +/- 5.5% and 123 +/- 3% of control values respectively) whereas LoVo showed no significant response to this hormone. When these same cell lines were grown as xenografts in nude mice, similar responses were seen to exogenously administered human gastrin-17 (...

  8. Idiopathic intracranial hypertension associated with anaemia, secondary to antiretroviral drug in a human immunodeficiency virus positive patient

    Directory of Open Access Journals (Sweden)

    J Vijay Ananth

    2018-01-01

    Full Text Available Papilledema in a patient with human immunodeficiency virus (HIV/acquired immune deficiency syndrome is an alarming finding. Any condition giving rise to raised intracranial tension (ICT can cause papilledema, and in these patients, it could be secondary to opportunistic infections like meningitis to neoplasm. We report a case of a 28-year old female with HIV on antiretroviral therapy, who presented to us, with papilledema. Her fundus examination revealed superficial hemorrhages and Roth's spots along with papilledema. Patient was diagnosed with idiopathic intracranial hypertension (IIH, and all other possible systemic associations were ruled out. Her blood tests showed severe anemia. The papilledema and retinal changes resolved with treatment of anemia. This is a rare presentation of IIH in HIV positive patient due to anemia, secondary to zidovudine adverse effect.

  9. Intracranial hypotension and intracranial hypertension.

    Science.gov (United States)

    Yuh, Esther L; Dillon, William P

    2010-11-01

    Intracranial pressure (ICP) is the pressure within the intracranial space. Intracranial hypotension is a clinical syndrome in which low cerebrospinal fluid volume (CSF) results in orthostatic headache. Severe cases can result in nausea, vomiting, photophobia, and, rarely, decreased level of consciousness and coma. CSF opening pressure can be within the normal range in spontaneous intracranial hypotension. Imaging tests therefore play a key and decisive role in the diagnosis, as well as treatment, of intracranial hypotension. Intracranial hypertension occurs in a chronic form known as idiopathic intracranial hypertension, as well as in a large variety of neurologic and systemic disorders. Symptoms include headache, nausea and vomiting, blurred vision, and in severe cases, altered level of consciousness that can progress to coma and death. Direct measurements of CSF pressure through lumbar puncture (in idiopathic intracranial hypotension) or invasive ICP monitoring (in acute intracranial hypertension) are the key diagnostic tests. Imaging is used primarily to determine treatable causes of increased ICP, to assess for impending brain herniation, and to evaluate ventricular size. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. 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....

  11. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    NARCIS (Netherlands)

    Adams, Hieab H H; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija|info:eu-repo/dai/nl/34549072X; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura M E; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P|info:eu-repo/dai/nl/286852071; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; Braber, Anouk Den; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R|info:eu-repo/dai/nl/344497569; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M|info:eu-repo/dai/nl/304811432; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke|info:eu-repo/dai/nl/250566370; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco J C; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Pol, Hilleke E Hulshoff|info:eu-repo/dai/nl/142348228; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S|info:eu-repo/dai/nl/073778532; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, W T; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A|info:eu-repo/dai/nl/16237299X; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic J A; Van Duijn, Cornelia M; Van Haren, Neeltje E M|info:eu-repo/dai/nl/271562161; Van T Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton J M; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously

  12. The radiological appearance of intracranial aneurysms in adults infected with the human immunodeficiency virus (HIV

    Directory of Open Access Journals (Sweden)

    Gerrit Blignaut

    2014-04-01

    Full Text Available Background: The global prevalence of intracranial aneurysms is estimated at 2.3%. Limited literature is available on intracranial aneurysms in HIV-infected patients.Objectives: To describe the radiological appearance of intracranial aneurysms in HIV-positive adults.Method: In this retrospective analysis of data, 23 HIV-positive patients, of which 15 (65.2%were female, with a total of 41 aneurysms were included. The mean age was 38 years, and their median CD4 count was 305 x 106/L. Inclusion criteria comprised subarachnoid haemorrhage and confirmed intracranial aneurysms on four-vessel angiography.Results: Fifteen (65.2% patients had a single aneurysm, of which 12 (80.0% had a saccular appearance. Seven (46.7% of the single aneurysms had a neck width larger than 50% of the transverse aneurysm sac size. The mean longitudinal diameter of the aneurysm sac was 4.9 mm and the transverse diameter 4.4 mm. More than half of these aneurysms occurred at the anterior communicating artery. The median CD4 count of single-aneurysm patients was 319 x 106 /L. Eight patients (34.8% had multiple aneurysms, with a total of 26 aneurysms (range 2–6 aneurysms per patient, of which 13 (50.0% had a complex appearance. Twenty-four (92.3% of the multiple aneurysms had a neck width larger than 50% of the transverse aneurysm sac size. The mean longitudinal diameter of the aneurysm sac was 4.0 mm and the transverse diameter 3.9 mm. The multiple aneurysms occurred more commonly in the internal carotid artery. These patients had a median CD4 count of 294 x 106/L.Conclusion: HIV-associated intracranial aneurysms occur at a younger age, appear to be saccular and complex in shape, with a wide neck, and might rupture at small sizes.

  13. Mendelian analysis of a metastasis-prone substrain of BALB/c nude mice using a subcutaneously inoculated human tumour

    DEFF Research Database (Denmark)

    Schou, M; Brünner, N; Spang-Thomsen, M

    2006-01-01

    Most nude mice do not allow the formation of metastases after heterotransplantation of human malignant tumours. Here we describe a substrain of BALB/c nude mice (BALB/c/AnNCr) that reproducibly allows some human cancers to metastasize. By Mendelian analysis of hybrids between this substrain and C57......BL/6J +/+ mice we found that the ability to allow a human tumour (MDA-MB-435 BAG) to express its metastatic phenotype is determined by a recessively inheritable trait in the mouse host. We are presently working to identify the genetics responsible for development of metastases. The study also...... includes immunohistochemical and electron microscopic analysis of the test tumour, originally assumed to be a human mammary carcinoma, but shown to possess characteristics of a malignant melanoma (1). The ultimate aim of our ongoing study is to establish a substrain of nude mice that will allow metastasis...

  14. Activation and regulation of endogenous retroviral genes in the human pituitary gland and related endocrine tumours.

    Science.gov (United States)

    Buslei, Rolf; Strissel, Pamela L; Henke, Christine; Schey, Regina; Lang, Nadine; Ruebner, Matthias; Stolt, Claus C; Fabry, Ben; Buchfelder, Michael; Strick, Reiner

    2015-02-01

    Adenohypophysis (AH) hormone-producing cells represent the origin of diverse groups of pituitary adenomas (PA). Deregulation of hypothalamic hormone receptors, growth factors and cAMP signalling have been implicated in the aetiology of PA. Endogenous retroviruses (ERVs) are derived from past exogenous retroviral infections and represent more than 8% of the human genome. Some ERV genes encode open reading frames and produce functional proteins, for example, the ERVW-1 envelope gene Syncytin-1, essential for placentogenesis, but also deregulated in human tumours. Data concerning ERV expression in the AH and related endocrine tumours are missing. Syncytin-1 protein was analysed in normal AH (n = 15) and compared with five PA subtypes (n = 117) by immunohistochemistry. Absolute gene expression of 20 ERV functional envelope genes and ERVW-5 gag was measured. PA tissues were examined for Syncytin-1 and the cAMP signalling marker phospho-CREB-Ser133 using immunohistochemistry. Isolated primary human PA cells were treated with different hormones. Murine embryonic and adult pituitary gland ERV expressions were compared with human AH. Syncytin-1 protein colocalized with corticotropic cells of AH. In contrast, all PA demonstrated significant Syncytin-1 protein overexpression, supporting deregulation. All other ERV genes showed significant up-regulations in different PA subtypes. Phospho-CREB-Ser133 and Syncytin-1 colocalized in PA cells. Cultivated primary PA cells with ACTH or CRH induced their respective receptors and ERV genes. Syncytin-A/-B, murine orthologues to human Syncytin-1/-2, localized to embryonic and adult pituitary glands demonstrating functional mammalian conservation. Deregulated ERV genes may contribute to PA development via cAMP signalling. © 2014 British Neuropathological Society.

  15. Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells).

    Science.gov (United States)

    Puthia, Manoj; Storm, Petter; Nadeem, Aftab; Hsiung, Sabrina; Svanborg, Catharina

    2014-01-01

    Most colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context. To investigate if HAMLET can be used for colon cancer treatment and prevention. Apc(Min)(/+) mice, which carry mutations relevant to hereditary and sporadic human colorectal tumours, were used as a model for human disease. HAMLET was given perorally in therapeutic and prophylactic regimens. Tumour burden and animal survival of HAMLET-treated and sham-fed mice were compared. Tissue analysis focused on Wnt/β-catenin signalling, proliferation markers and gene expression, using microarrays, immunoblotting, immunohistochemistry and ELISA. Confocal microscopy, reporter assay, immunoprecipitation, immunoblotting, ion flux assays and holographic imaging were used to determine effects on colon cancer cells. Peroral HAMLET administration reduced tumour progression and mortality in Apc(Min)(/+) mice. HAMLET accumulated specifically in tumour tissue, reduced β-catenin and related tumour markers. Gene expression analysis detected inhibition of Wnt signalling and a shift to a more differentiated phenotype. In colon cancer cells with APC mutations, HAMLET altered β-catenin integrity and localisation through an ion channel-dependent pathway, defining a new mechanism for controlling β-catenin signalling. Remarkably, supplying HAMLET to the drinking water from the time of weaning also significantly prevented tumour development. These data identify HAMLET as a new, peroral agent for colon cancer prevention and treatment, especially needed in people carrying APC mutations, where colon cancer remains a leading cause of death.

  16. 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

  17. The human EKC/KEOPS complex is recruited to Cullin2 ubiquitin ligases by the human tumour antigen PRAME.

    Directory of Open Access Journals (Sweden)

    Adalberto Costessi

    Full Text Available The human tumour antigen PRAME (preferentially expressed antigen in melanoma is frequently overexpressed during oncogenesis, and high PRAME levels are associated with poor clinical outcome in a variety of cancers. However, the molecular pathways in which PRAME is implicated are not well understood. We recently characterized PRAME as a BC-box subunit of a Cullin2-based E3 ubiquitin ligase. In this study, we mined the PRAME interactome to a deeper level and identified specific interactions with OSGEP and LAGE3, which are human orthologues of the ancient EKC/KEOPS complex. By characterizing biochemically the human EKC complex and its interactions with PRAME, we show that PRAME recruits a Cul2 ubiquitin ligase to EKC. Moreover, EKC subunits associate with PRAME target sites on chromatin. Our data reveal a novel link between the oncoprotein PRAME and the conserved EKC complex and support a role for both complexes in the same pathways.

  18. The human EKC/KEOPS complex is recruited to Cullin2 ubiquitin ligases by the human tumour antigen PRAME.

    Science.gov (United States)

    Costessi, Adalberto; Mahrour, Nawel; Sharma, Vikram; Stunnenberg, Rieka; Stoel, Marieke A; Tijchon, Esther; Conaway, Joan W; Conaway, Ronald C; Stunnenberg, Hendrik G

    2012-01-01

    The human tumour antigen PRAME (preferentially expressed antigen in melanoma) is frequently overexpressed during oncogenesis, and high PRAME levels are associated with poor clinical outcome in a variety of cancers. However, the molecular pathways in which PRAME is implicated are not well understood. We recently characterized PRAME as a BC-box subunit of a Cullin2-based E3 ubiquitin ligase. In this study, we mined the PRAME interactome to a deeper level and identified specific interactions with OSGEP and LAGE3, which are human orthologues of the ancient EKC/KEOPS complex. By characterizing biochemically the human EKC complex and its interactions with PRAME, we show that PRAME recruits a Cul2 ubiquitin ligase to EKC. Moreover, EKC subunits associate with PRAME target sites on chromatin. Our data reveal a novel link between the oncoprotein PRAME and the conserved EKC complex and support a role for both complexes in the same pathways.

  19. Ribosomal protein S6 phosphorylation and morphological changes in response to the tumour promoter 12-O-tetradecanoylphorbol 13-acetate in primary human tumour cells, established and transformed cell lines

    DEFF Research Database (Denmark)

    Rance, A J; Thönnes, M; Issinger, O G

    1985-01-01

    was about 4-6-fold. Established and transformed cell lines showed enhanced S6 phosphorylation which was not further stimulated by the addition of TPA. These findings indicated that the influence of TPA on the metabolic pathway, that finally leads to the phosphorylation of protein S6 in cells with a limited...... lifespan (fibroblasts, primary human tumour cells) can be mimicked by unknown steps also associated with immortalization (establishment function) and the transformed state of the tumour cells. Another interesting observation were morphological changes of the established and SV40-transformed cells which......The phosphorylation of ribosomal protein S6 in fibroblasts, primary human tumour cells, established and SV40-transformed human cell lines was compared after the addition of 12-O-tetradecanoylphorbol 13-acetate (TPA). In fibroblasts and primary tumour cell cultures, stimulation of S6 phosphorylation...

  20. Relative biological effectiveness of light ions in human tumoural cell lines: role of protein p53

    Science.gov (United States)

    Baggio, L.; Cavinato, M.; Cherubini, R.; Conzato, M.; Cucinotta, F.; Favaretto, S.; Gerardi, S.; Lora, S.; Stoppa, P.; Williams, J. R.

    2002-01-01

    Protons and alpha particles of high linear energy transfer (LET) have shown an increased relative biological effectiveness (RBE) with respect to X/gamma rays for several cellular and molecular endpoints in different in vitro cell systems. To contribute to understanding the biochemical mechanisms involved in the increased effectiveness of high LET radiation, an extensive study has been designed. The present work reports the preliminary result of this study on two human tumoural cell lines, DLD1 and HCT116, (with different p53 status), which indicate that for these cell lines, p53 does not appear to take a part in the response to radiation induced DNA damage, suggesting an alternative p53-independent pathway and a cell biochemical mechanism dependent on the cell type.

  1. Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy.

    Science.gov (United States)

    Di Caro, Giuseppe; Cortese, Nina; Castino, Giovanni Francesco; Grizzi, Fabio; Gavazzi, Francesca; Ridolfi, Cristina; Capretti, Giovanni; Mineri, Rossana; Todoric, Jelena; Zerbi, Alessandro; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2016-10-01

    Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX). In vitro, we dissected the synergism of CTX and TAMs. In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206(+) and IL-10(+) TAMs at the tumour-stroma interface. Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX. 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/

  2. Histological characteristics of human papilloma-virus-positive and -negative invasive and in situ squamous cell tumours of the penis

    DEFF Research Database (Denmark)

    Krustrup, Dorrit; Jensen, Helle Lone; van den Brule, Adriaan J C

    2009-01-01

    A high prevalence of cervical cancer associated high-risk types of human papillomavirus (hrHPV) has been demonstrated in premalignant and invasive squamous cell lesions of the penis, but large studies correlating histological characteristics with HPV status are few in number. Tumour tissues from...

  3. Tumour suppression associated with expression of human insulin-like growth factor II.

    OpenAIRE

    Schofield, P. N.; Lee, A.; Hill, D. J.; Cheetham, J. E.; James, D.; Stewart, C.

    1991-01-01

    Recent circumstantial evidence has implicated Insulin-like growth factor II in the genesis of several tumour types, notably developmental tumours (Scott et al., 1985; Schofield & Tate, 1987; Wilkins et al., 1989). This type of tumour, thought to originate during the defective differentiation of organ precursors (Miereau et al., 1987), often expresses greatly elevated levels of mRNA for IGF-II, a known mitogen for these cells and abundantly expressed in their presumed normal counterparts (Scot...

  4. Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in humans and nonhuman primates

    DEFF Research Database (Denmark)

    Opitz, Alexander; Falchier, Arnaud; Yan, Chao-Gan

    2016-01-01

    Transcranial electric stimulation (TES) is an emerging technique, developed to non-invasively modulate brain function. However, the spatiotemporal distribution of the intracranial electric fields induced by TES remains poorly understood. In particular, it is unclear how much current actually...... reaches the brain, and how it distributes across the brain. Lack of this basic information precludes a firm mechanistic understanding of TES effects. In this study we directly measure the spatial and temporal characteristics of the electric field generated by TES using stereotactic EEG (s-EEG) electrode...... arrays implanted in cebus monkeys and surgical epilepsy patients. We found a small frequency dependent decrease (10%) in magnitudes of TES induced potentials and negligible phase shifts over space. Electric field strengths were strongest in superficial brain regions with maximum values of about 0.5 m...

  5. Comparative analysis of peptidylarginine deiminase-2 expression in canine, feline and human mammary tumours.

    Science.gov (United States)

    Cherrington, B D; Mohanan, S; Diep, A N; Fleiss, R; Sudilovsky, D; Anguish, L J; Coonrod, S A; Wakshlag, J J

    2012-01-01

    The peptidylarginine deiminase (PAD) enzyme family converts arginine residues in proteins to citrulline. In the canine mammary gland, PAD2 expression is first detected in epithelial cells in oestrus and becomes more widely expressed during dioestrus. PAD2 appears to modify nuclear histones, suggesting a role for the enzyme in chromatin remodelling and gene regulation. Recent evidence suggests that PAD2 plays a role in gene regulation in primary human breast epithelial cells. PAD2 may therefore be involved in gene regulation as it relates to mammary development, the oestrus cycle and potentially to neoplasia. The aim of the present study was to determine whether PAD2 expression was increased or decreased in mammary carcinoma compared with normal mammary tissue. A human mammary tissue microarray and archival surgical biopsy tissues from canine and feline mammary tumours were used to demonstrate differential expression of PAD2 in mammary carcinoma that appeared to be consistent across species. Normal human and canine mammary epithelium showed strong cytoplasmic and nuclear expression of PAD2, but there was reduced PAD2 expression in mammary carcinomas from both species. Feline mammary carcinomas had complete loss of nuclear PAD2 expression. Loss of nuclear PAD2 expression may therefore represent a marker of progression towards more aggressive neoplasia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. No Evidence of Human Polyomavirus 9, WU and KI DNA in Kidney and Urinary Bladder Tumour Tissue Samples.

    Science.gov (United States)

    Csoma, Eszter; Bidiga, László; Méhes, Gábor; Gergely, Lajos

    2016-01-01

    The oncogenic potential of human polyomaviruses (HPyVs) has been proposed, but so far only Merkel cell carcinoma polyomavirus seems to be associated with a human tumour. The role of BK polyomavirus (BKPyV) in human tumourigenesis remains controversial. BKPyV establishes persistent infection in the urinary tract, and renal and bladder neoplasms have been studied extensively, but conflicting prevalence data are reported. KI, WU and HPyV9 were detected in urine samples suggesting that these viruses may also infect the urinary tract, but their presence in urinary tract tumours has not been studied. The aim of this work was to examine the prevalence of KIPyV, WUPyV, HPyV9 and BKPyV by PCR in renal and bladder neoplasms. A total of 190 formalin-fixed paraffin-embedded renal neoplasms, bladder cancer and kidney biopsy samples were analysed for the presence of BKPyV, KIPyV, WUPyV and HPyV9 DNA by real-time and nested PCR. Amplifiable DNA was extracted from all the samples, but none of the studied viruses were detected in benign renal neoplasia (0/23), malignant renal tumours (0/89) or bladder cancer (0/76). Our study did not find any evidence that BKPyV, KIPyV, WUPyV or HPyV9 are associated with bladder and renal tumours. © 2016 S. Karger AG, Basel.

  7. A Case Of Ollier′s Disease With Intracranial Enchondroma

    Directory of Open Access Journals (Sweden)

    Sidharthan Neeraj

    2005-01-01

    Full Text Available The syndrome of multiple enchondromas is known as Ollier′s disease. Enchondromas are benign tumours of hyaline cartilage arising within the medullary cavity of tubular bones. We are reporting the case of a 16 year old girl with Ollier′s disease who presented with seizures and brainstem compression. A MRI scan of brain showed an intracranial space-occupying lesion in the region of clivus. The intracranial tumour was surgically removed and the histopathology confirmed the diagnosis of enchondroma. Intracranial enchondroma is an extremely rare situation and reported for the first time from south India.

  8. Meningiomas among intracranial neoplasms in Johannesburg ...

    African Journals Online (AJOL)

    Results: The commonest histological types were meningiomas, gliomas and pituitary tumours. Forty eight (31.8%) patients had histologically confirmed intracranial meningiomas during the study period, 35 (23.2%) had pituitary adenomas and 32 (21.2%) had gliomas. The mean age of the patients was 43 years with a ...

  9. Intracranial neoplasmin Ibadan, Nigeria | Olasode | East African ...

    African Journals Online (AJOL)

    Objective: To determine the pattern of histopathological variants of intracranial neoplasms, relative distribution of the variants in the age groups and also to determine the gender differences that exist in these tumours. Design: Case control study. Setting: Department of Pathology, University College Hospital, Ibadan, Nigeria.

  10. Demographic profile of patients diagnosed with intracranial ...

    African Journals Online (AJOL)

    Background: Meningiomas are common brain tumours and display gender, racial and ethnic differences in their demographic profile. The demographic profile of our patients diagnosed with intracranial meningiomas is presented and compared with the literature. Objectives: To determine the age, gender, racial and ethnic ...

  11. Acute recurrent haemorrhage of an intracranial meningioma.

    Science.gov (United States)

    Bellut, David; Nern, Christian; Burkhardt, Jan-Karl; Könü, Dilek; Bertalanffy, Helmut; Krayenbühl, Niklaus

    2011-07-01

    Meningioma-associated haemorrhages are rare. To our knowledge this is the first report of a patient with an acute two-stage haemorrhage of a benign intracranial meningioma (World Health Organization grade I) verified by cranial CT scan and histopathological examination. Early surgery with complete tumour removal led to a good outcome for the patient. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. In vivo imaging of twist drill drainage for subdural hematoma: a clinical feasibility study on electrical impedance tomography for measuring intracranial bleeding in humans.

    Directory of Open Access Journals (Sweden)

    Meng Dai

    Full Text Available Intracranial bleeding is one of the most severe medical emergencies in neurosurgery. Early detection or diagnosis would largely reduce the rate of disability and mortality, and improve the prognosis of the patients. Electrical Impedance Tomography (EIT can non-invasively image the internal resistivity distribution within a human body using a ring of external electrodes, and is thus a promising technique to promptly detect the occurrence of intracranial bleedings because blood differs from other brain tissues in resistivity. However, so far there is no experimental study that has determined whether the intracranial resistivity changes in humans could be repeatedly detected and imaged by EIT. Hence, we for the first time attempt to clinically validate this by in vivo imaging the influx and efflux of irrigating fluid (5% dextrose in water, D5W during the twist-drill drainage operation for the patients with subdural hematoma (SDH. In this study, six patients (four male, two female with subacute or chronic SDH received the surgical operation in order to evacuate the hematoma around subdural region, and EIT measurements were performed simultaneously on each patient's head. The results showed that the resistivity significantly increased on the corresponding position of EIT images during the influx of D5W and gradually decreased back to baseline during the efflux. In the quantitative analysis, the average resistivity values demonstrated the similar results and had highly linear correlation (R(2 = 0.93 ± 0.06 with the injected D5W volumes, as well as the area of the resistivity gain(R(2 = 0.94 ± 0.05. In conclusion, it was clinically validated that intracranial resistivity changes in humans were detectable and quantifiable by the EIT method. After further technical improvements, EIT has the great potential of being a routine neuroimaging tool for early detection of intracranial bleedings.

  13. Intracranial Hypertension

    Directory of Open Access Journals (Sweden)

    Xenophon Sinopidis

    2012-01-01

    Full Text Available We present the case of a 4-year-old boy who was admitted to hospital with intracranial hypertension, headache, diplopia, papilledema, and a normal brain MRI. Brucella melitensis in the cerebrospinal fluid was confirmed with PCR assay. We believe that neurobrucellosis should be included in the differential diagnosis when headaches persist following brucellosis. In addition, we suggest that when cerebrospinal fluid culture is negative, PCR may prove to be an optimal alternative tool for an immediate and accurate diagnosis.

  14. The anti-tumour effect of a DNA vaccine carrying a fusion gene of human VEGFR2 and IL-12

    Directory of Open Access Journals (Sweden)

    Sha Wen

    2016-09-01

    Full Text Available Because of tumour dependence on angiogenesis, anti-angiogenic therapy has become the most attractive area of basic and clinical study in the field of cancer research. In order to create a synergistic effect on angiogenesis and immune regulation, we designed and constructed a new type of DNA vaccine that can express VEGFR2 (vascular endothelial growth factor receptor 2 and the prostate cancer antigen IL-12 (interleukin 12 in the same reading frame. The aim of this study was to investigate the anti-tumour activity of a eukaryotic expression plasmid carrying a fusion gene of human VEGFR2 and IL-12. According to the gene sequences in GenBank, we synthesized the human VEGFR2 and IL-12 genes. VEGFR2 and IL-12 were joined by a sequence encoding a Furin recognition site and a 2A cleavage site, and the resulting fusion gene was cloned into the eukaryotic expression vector pVAX1 to construct the expression plasmid pVAX1-VEGFR2-F2A-IL-12. The expression of VEGFR2 and IL-12 could be detected in 293T cells transfected with pVAX1-VEGFR2-F2A-IL-12 by enzyme-linked immunosorbent assay. Each of these proteins, and in particular co-expression of both proteins, can result in humoral and cellular immune responses in C57BL/6 mice. After injection into the tumour-bearing mouse model, the plasmid showed stronger inhibition of tumour growth than a plasmid expressing VEGFR2 alone. Our results demonstrate that a DNA vaccine carrying a fusion gene of human VEGFR2 and IL-12 could represent a promising approach for tumour immunotherapy.

  15. Temporal Dissociation of Neocortical and Hippocampal Contributions to Mental Time Travel Using Intracranial Recordings in Humans

    Directory of Open Access Journals (Sweden)

    Roey Schurr

    2018-02-01

    Full Text Available In mental time travel (MTT one is “traveling” back-and-forth in time, remembering, and imagining events. Despite intensive research regarding memory processes in the hippocampus, it was only recently shown that the hippocampus plays an essential role in encoding the temporal order of events remembered, and therefore plays an important role in MTT. Does it also encode the temporal relations of these events to the remembering self? We asked patients undergoing pre-surgical evaluation with depth electrodes penetrating the temporal lobes bilaterally toward the hippocampus to project themselves in time to a past, future, or present time-point, and then make judgments regarding various events. Classification analysis of intracranial evoked potentials revealed clear temporal dissociation in the left hemisphere between lateral-temporal electrodes, activated at ~100–300 ms, and hippocampal electrodes, activated at ~400–600 ms. This dissociation may suggest a division of labor in the temporal lobe during self-projection in time, hinting toward the different roles of the lateral-temporal cortex and the hippocampus in MTT and the temporal organization of the related events with respect to the experiencing self.

  16. Inferior frontal oscillations reveal visuo-motor matching for actions and speech: evidence from human intracranial recordings.

    Science.gov (United States)

    Halje, Pär; Seeck, Margitta; Blanke, Olaf; Ionta, Silvio

    2015-12-01

    The neural correspondence between the systems responsible for the execution and recognition of actions has been suggested both in humans and non-human primates. Apart from being a key region of this visuo-motor observation-execution matching (OEM) system, the human inferior frontal gyrus (IFG) is also important for speech production. The functional overlap of visuo-motor OEM and speech, together with the phylogenetic history of the IFG as a motor area, has led to the idea that speech function has evolved from pre-existing motor systems and to the hypothesis that an OEM system may exist also for speech. However, visuo-motor OEM and speech OEM have never been compared directly. We used electrocorticography to analyze oscillations recorded from intracranial electrodes in human fronto-parieto-temporal cortex during visuo-motor (executing or visually observing an action) and speech OEM tasks (verbally describing an action using the first or third person pronoun). The results show that neural activity related to visuo-motor OEM is widespread in the frontal, parietal, and temporal regions. Speech OEM also elicited widespread responses partly overlapping with visuo-motor OEM sites (bilaterally), including frontal, parietal, and temporal regions. Interestingly a more focal region, the inferior frontal gyrus (bilaterally), showed both visuo-motor OEM and speech OEM properties independent of orolingual speech-unrelated movements. Building on the methodological advantages in human invasive electrocorticography, the present findings provide highly precise spatial and temporal information to support the existence of a modality-independent action representation system in the human brain that is shared between systems for performing, interpreting and describing actions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The prognostic benefit of tumour-infiltrating Natural Killer cells in endometrial cancer is dependent on concurrent overexpression of Human Leucocyte Antigen-E in the tumour microenvironment.

    Science.gov (United States)

    Versluis, M A C; Marchal, S; Plat, A; de Bock, G H; van Hall, T; de Bruyn, M; Hollema, H; Nijman, H W

    2017-11-01

    Human Leucocyte Antigen- E (HLA-E) has been reported as both a positive and negative prognostic marker in cancer. This apparent discrepancy may be due to opposing actions of HLA-E on tumour-infiltrating immune cells. Therefore, we evaluated HLA-E expression and survival in relation to the presence of intratumoural natural killer (NK) cells and cytotoxic T cells (CTLs). Tissue microarrays (TMAs) of endometrial tumours were used for immunohistochemical staining of parameters of interest. The combined impact of clinical, pathological and immune parameters on survival was analysed using log rank testing and Cox regression analyses. Upregulation of HLA-E was associated with an improved disease-free and disease-specific survival in univariate analysis (HR 0.58 95% CI 0.37-0.89; HR 0.42 95% CI 0.25-0.73, respectively). In multivariate analysis, the presence of NK cells predicts survival with a hazard ratio (HR) 0.28 (95% confidence interval (CI) 0.09-0.91) when HLA-E expression is upregulated; but it is associated with a worse prognosis when HLA-E expression is normal (HR 13.43, 95% CI 1.70-106.14). By contrast, the prognostic benefit of T cells was not modulated by HLA-E expression. Taken together, we demonstrate that the prognostic benefit of NK cells, but not T-cells, is influenced by HLA-E expression in endometrial cancer (EC) and propose a model to explain our observations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Intracranial Hypertension Research Foundation

    Science.gov (United States)

    ... Espanol. PARTNERSHIPS Meet our Fundraising Partners Tweet Welcome Intracranial hypertension (IH) is the general term for the neurological ... too high. (Old names for IH include Benign Intracranial Hypertension and Pseudotumor Cerebri). The Intracranial Hypertension Research Foundation ...

  19. Antibodies to PAI-1 alter the invasive and migratory properties of human tumour cells in vitro.

    Science.gov (United States)

    Brooks, T D; Slomp, J; Quax, P H; De Bart, A C; Spencer, M T; Verheijen, J H; Charlton, P A

    2000-01-01

    Recent reports suggest that elevated levels of plasminogen activator inhibitor-1 (PAI-1) may contribute to tumour progression. The studies reported here were designed to help elucidate PAI-1's contribution to the invasive and migratory phenotype. Antibodies to PA-1 dose-dependently, and significantly, inhibited the invasive and migratory potential of human HT1080 fibrosarcoma cells, as did an antibody to uPA and the plasmin inhibitor aprotinin. Invasion of the human melanoma cell line, BLM, was also attenuated by the anti-PAI-1 monoclonal antibody MAI-12. The non-invasive human melanoma cell line, IF6, which does not express uPA, provided further confirmation of PAI-1 and uPA's role as, upon transfection with uPA, this cell line attained an invasive phenotype, which was again attenuated by MAI-12. Although antibodies to PAI-1 did not affect the adhesion of HT1080 cells to vitronectin, the antibody to uPA reduced their attachment. Addition of exogenous PAI-1, however, prevented HT1080 cell adhesion (IC50 180 nM) and promoted cell detachment from vitronectin. Furthermore melanoma cells transfected with a uPA variant, which had an impaired interaction with PAI-1, were not invasive and had impaired binding to vitronectin. These data highlight the importance of a balanced proteolysis and suggest an additional role for PAI-1 distinct from its role in proteolysis. These data also suggest that uPA and PAI-1 may co-operate in the migratory process by respectively facilitating the attachment to, and subsequent detachment from, vitronectin in the extracellular matrix. These results support the clinical findings and indicate that modulation of PAI-1 activity may be of therapeutic benefit for the treatment of cancer.

  20. Induction of circulating phospholipase A2 by intravenous administration of recombinant human tumour necrosis factor

    Directory of Open Access Journals (Sweden)

    Waldemar Pruzanski

    1992-01-01

    Full Text Available We have examined the effects of intravenous infusion of recombinant human tumour necrosis factor (rh-TNF on serum activity of phospholipase A2 (PLA2 in patients with malignancies. Nine patients received a 24 h continuous intravenous infusion ranging from 1.0 × 105 U/m2 to 3.0 × 105 U/m2; 14 patients received a 5 day continuous intravenous infusion ranging from 0.5 × 105 U/m2/day to 3.0 105 U/m2/day. Twenty one of 23 patients responded with marked increases in serum PLA2 activity that were detectable 3 h after the beginning of the rh-TNF infusion and reached maximum levels at 18 h with a mean increase of 16.2-fold. In patients receiving a 5 day rh-TNF infusion, the highest levels of PLA2 were observed after the first day of infusion. Serum PLA2 activity declined continuously to 2.9-fold above baseline at the end of the infusion. A significant correlation was noted between the dose of infused rh-TNF and the maximum increase in PLA2 activity. To our knowledge, this is the first time that an association between intravenous TNF administration and induction of circulating PLA2 in man has been established.

  1. Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus

    Energy Technology Data Exchange (ETDEWEB)

    Stakaitytė, Gabrielė; Wood, Jennifer J.; Knight, Laura M.; Abdul-Sada, Hussein; Adzahar, Noor Suhana; Nwogu, Nnenna; Macdonald, Andrew; Whitehouse, Adrian, E-mail: A.Whitehouse@leeds.ac.uk [School of Molecular and Cellular Biology and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT (United Kingdom)

    2014-06-27

    A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC.

  2. Three-dimensional stereotactic atlas of the adult human skull correlated with the brain, cranial nerves, and intracranial vasculature.

    Science.gov (United States)

    Nowinski, Wieslaw L; Thaung, Thant Shoon Let; Chua, Beng Choon; Yi, Su Hnin Wut; Ngai, Vincent; Yang, Yili; Chrzan, Robert; Urbanik, Andrzej

    2015-05-15

    Although the adult human skull is a complex and multifunctional structure, its 3D, complete, realistic, and stereotactic atlas has not yet been created. This work addresses the construction of a 3D interactive atlas of the adult human skull spatially correlated with the brain, cranial nerves, and intracranial vasculature. The process of atlas construction included computed tomography (CT) high-resolution scan acquisition, skull extraction, skull parcellation, 3D disarticulated bone surface modeling, 3D model simplification, brain-skull registration, 3D surface editing, 3D surface naming and color-coding, integration of the CT-derived 3D bony models with the existing brain atlas, and validation. The virtual skull model created is complete with all 29 bones, including the auditory ossicles (being among the smallest bones). It contains all typical bony features and landmarks. The created skull model is superior to the existing skull models in terms of completeness, realism, and integration with the brain along with blood vessels and cranial nerves. This skull atlas is valuable for medical students and residents to easily get familiarized with the skull and surrounding anatomy with a few clicks. The atlas is also useful for educators to prepare teaching materials. It may potentially serve as a reference aid in the reading and operating rooms. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Epigenetic inactivation of tumour suppressor coding and non-coding genes in human cancer: an update.

    Science.gov (United States)

    Llinàs-Arias, Pere; Esteller, Manel

    2017-09-01

    Cancer cells undergo many different alterations during their transformation, including genetic and epigenetic events. The controlled division of healthy cells can be impaired through the downregulation of tumour suppressor genes. Here, we provide an update of the mechanisms in which epigenetically altered coding and non-coding tumour suppressor genes are implicated. We will highlight the importance of epigenetics in the different molecular pathways that lead to enhanced and unlimited capacity of division, genomic instability, metabolic shift, acquisition of mesenchymal features that lead to metastasis, and tumour plasticity. We will briefly describe these pathways, focusing especially on genes whose epigenetic inactivation through DNA methylation has been recently described, as well as on those that are well established as being epigenetically silenced in cancer. A brief perspective of current clinical therapeutic approaches that can revert epigenetic inactivation of non-coding tumour suppressor genes will also be given. © 2017 The Authors.

  4. Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

    DEFF Research Database (Denmark)

    Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B

    2013-01-01

    Observations in patients with an activating mutation of fibroblast growth factor receptor 3 (FGFR3) suggest a role for FGFR3 signalling in promoting proliferation or survival of germ cells. In this study, we aimed to identify the FGFR3 subtype and the ontogeny of expression during human testis...... development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3...... expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression...

  5. Differentiation of tumour and inflammation: characterisation of [methyl-{sup 3}H]methionine (MET) and O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells

    Energy Technology Data Exchange (ETDEWEB)

    Stoeber, Barbara; Tanase, Ursula; Herz, Michael; Seidl, Christof; Schwaiger, Markus; Senekowitsch-Schmidtke, Reingard [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum Rechts der Isar, Munich (Germany)

    2006-08-15

    Previous studies suggest that radiolabelled amino acids could be superior to FDG in differentiating tumour and inflammation. Therefore the aim of this study was to investigate the uptake of FET and MET in human tumour and inflammatory cells and to investigate their uptake kinetics. For uptake studies, cells were incubated with 370 kBq FET or 3.7 kBq MET for 15 min. Kinetic studies were performed at variable concentrations of FET and MET. Competitive inhibition studies were done with BCH, MeAIB and L-serine. All inflammatory cells incorporated more MET than the tumour cells. The uptake of FET, in contrast, was significantly lower in all inflammatory cells than in the tumour cells. In tumour cells the uptake of MET was about five times the uptake of FET. The competitive inhibitors reduced uptake of both tracers to 20-40% in tumour cells and to 70% in inflammatory cells. Kinetic studies showed that MET and FET transport was saturable in all cells except macrophages and followed a Michaelis-Menten kinetic. Highest capacity (V{sub max}) and affinity (K{sub m}) for the uptake of MET was observed in granulocytes. Capacity and affinity for FET uptake were highest in the DHL-4 cells. In contrast to MET, FET accumulated to a significantly greater extent in tumour cells than in inflammatory cells. The marked differences between tumour and inflammatory cells concerning FET and MET uptake suggest that FET and MET are substrates of different subtypes of the L system. (orig.)

  6. Watching brain TV and playing brain ball exploring novel BCI strategies using real-time analysis of human intracranial data.

    Science.gov (United States)

    Jerbi, Karim; Freyermuth, Samson; Minotti, Lorella; Kahane, Philippe; Berthoz, Alain; Lachaux, Jean-Philippe

    2009-01-01

    A large body of evidence from animal studies indicates that motor intention can be decoded via multiple single-unit recordings or from local field potentials (LFPs) recorded not only in primary motor cortex, but also in premotor or parietal areas. In humans, reports of invasive data acquisition for the purpose of BCI developments are less numerous and signal selection for optimal control still remains poorly investigated. Here we report on our recent implementation of a real-time analysis platform for the investigation of ongoing oscillations in human intracerebral recordings and review various results illustrating its utility for the development of novel brain-computer and brain-robot interfaces. Our findings show that the insight gained both from off-line experiments and from online functional exploration can be used to guide future selection of the sites and frequency bands to be used in a translation algorithm such as the one needed for a BCI-driven cursor control. Overall, the findings reported with our online spectral analysis platforms (Brain TV and Brain Ball) indicate the feasibility of online functional exploration via intracranial recordings in humans and outline the direct benefits of this approach for the improvement of invasive BCI strategies in humans. In particular, our findings suggest that current BCI performance may be improved by using signals recorded from various systems previously unexplored in the context of BCI research such as the oscillatory activity recorded in the oculomotor networks as well as higher cognitive processes including working memory, attention, and mental calculation networks. Finally, we discuss current limitations of the methodology and outline future paths for innovative BCI research.

  7. 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.)

  8. Recombinant Kunjin virus replicon vaccines induce protective T-cell immunity against human papillomavirus 16 E7-expressing tumour.

    Science.gov (United States)

    Herd, Karen A; Harvey, Tracey; Khromykh, Alexander A; Tindle, Robert W

    2004-02-20

    The persistence of the E7 oncoprotein in transformed cells in human papillomavirus (HPV)-associated cervical cancer provides a tumour-specific antigen to which immunotherapeutic strategies may be directed. Self-replicating RNA (replicon) vaccine vectors derived from the flavivirus Kunjin (KUN) have recently been reported to induce T-cell immunity. Here, we report that inclusion of a CTL epitope of HPV16 E7 protein into a polyepitope encoded by a KUN vector induced E7-directed T-cell responses and protected mice against challenge with an E7-expressing epithelial tumour. We found replicon RNA packaged into virus-like particles to be more effective than naked replicon RNA or plasmid DNA constructed to allow replicon RNA transcription in vivo. Protective immunity was induced although the E7 CTL epitope was subdominant in the context of other CTL epitopes in the polyepitope. The results demonstrate the efficacy of the KUN replicon vector system for inducing protective immunity directed towards a virally encoded human tumour-specific antigen, and for inducing multi-epitopic CTL responses.

  9. 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

  10. High-frequency neural activity and human cognition: past, present and possible future of intracranial EEG research

    Science.gov (United States)

    Lachaux, Jean-Philippe; Axmacher, Nikolai; Mormann, Florian; Halgren, Eric; Crone, Nathan E.

    2013-01-01

    Human intracranial EEG (iEEG) recordings are primarily performed in epileptic patients for presurgical mapping. When patients perform cognitive tasks, iEEG signals reveal high-frequency neural activities (HFA, between around 40 Hz and 150 Hz) with exquisite anatomical, functional and temporal specificity. Such HFA were originally interpreted in the context of perceptual or motor binding, in line with animal studies on gamma-band (‘40Hz’) neural synchronization. Today, our understanding of HFA has evolved into a more general index of cortical processing: task-induced HFA reveals, with excellent spatial and time resolution, the participation of local neural ensembles in the task-at-hand, and perhaps the neural communication mechanisms allowing them to do so. This review promotes the claim that studying HFA with iEEG provides insights into the neural bases of cognition that cannot be derived as easily from other approaches, such as fMRI. We provide a series of examples supporting that claim, drawn from studies on memory, language and default-mode networks, and successful attempts of real-time functional mapping. These examples are followed by several guidelines for HFA research, intended for new groups interested by this approach. Overall, iEEG research on HFA should play an increasing role in cognitive neuroscience in humans, because it can be explicitly linked to basic research in animals. We conclude by discussing the future evolution of this field, which might expand that role even further, for instance through the use of multi-scale electrodes and the fusion of iEEG with MEG and fMRI. PMID:22750156

  11. {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.

  12. Disaggregation of human solid tumours by combined mechanical and enzymatic methods

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Brünner, N

    1985-01-01

    Two combined mechanical and enzymatic disaggregation techniques and a simple mechanical disaggregation procedure were compared. The combined procedures involved a mechanical comminution of the tumour tissue followed by incubation in trypsin. In one method, the tissue was subjected to long....... The combined techniques provided reproducible cell yields of 2-10 X 10(7) viable cells g-1 of tissue, whereas only a small number of tumour cells was produced by the mechanical method. DNA analysis demonstrated that only the long-term trypsinization procedure resulted in a representative cell yield from all...

  13. 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

  14. In-depth characterization of CGRP receptors in human intracranial arteries

    DEFF Research Database (Denmark)

    Jansen-Olesen, Inger; Jørgensen, Linda; Engel, Ulla

    2003-01-01

    meningeal arteries. Removal of the endothelium neither changed the maximum relaxant response nor the pIC(50) values for alpha- and beta-CGRP as compared to the responses in arteries with an intact endothelium. Human alpha-CGRP-(8-37) caused a shift of h alpha- and h beta-CGRP-induced relaxations in cerebral...

  15. Identification of common variants associated with human hippocampal and intracranial volumes

    NARCIS (Netherlands)

    Stein, Jason L.; Medland, Sarah E.; Vasquez, Alejandro Arias; Hibar, Derrek P.; Senstad, Rudy E.; Winkler, Anderson M.; Toro, Roberto; Appel, Katja; Bartecek, Richard; Bergmann, Orjan; Bernard, Manon; Brown, Andrew A.; Cannon, Dara M.; Chakravarty, M. Mallar; Christoforou, Andrea; Domin, Martin; Grimm, Oliver; Hollinshead, Marisa; Holmes, Avram J.; Homuth, Georg; Hottenga, Jouke-Jan; Langan, Camilla; Lopez, Lorna M.; Hansell, Narelle K.; Hwang, Kristy S.; Kim, Sungeun; Laje, Gonzalo; Lee, Phil H.; Liu, Xinmin; Loth, Eva; Lourdusamy, Anbarasu; Mattingsdal, Morten; Mohnke, Sebastian; Maniega, Susana Munoz; Nho, Kwangsik; Nugent, Allison C.; O'Brien, Carol; Papmeyer, Martina; Putz, Benno; Ramasamy, Adaikalavan; Rasmussen, Jerod; Rijpkema, Mark; Risacher, Shannon L.; Roddey, J. Cooper; Rose, Emma J.; Ryten, Mina; Shen, Li; Sprooten, Emma; Strengman, Eric; Teumer, Alexander; Trabzuni, Daniah; Turner, Jessica; van Eijk, Kristel; van Erp, Theo G. M.; van Tol, Marie-Jose; Wittfeld, Katharina; Wolf, Christiane; Woudstra, Saskia; Aleman, Andre; Alhusaini, Saud; Almasy, Laura; Binder, Elisabeth B.; Brohawn, David G.; Cantor, Rita M.; Carless, Melanie A.; Corvin, Aiden; Czisch, Michael; Curran, Joanne E.; Davies, Gail; de Almeida, Marcio A. A.; Delanty, Norman; Depondt, Chantal; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fagerness, Jesen; Fox, Peter T.; Freimer, Nelson B.; Gill, Michael; Goering, Harald H. H.; Hagler, Donald J.; Hoehn, David; Holsboer, Florian; Hoogman, Martine; Hosten, Norbert; Jahanshad, Neda; Johnson, Matthew P.; Kasperaviciute, Dalia; Kent, Jack W.; Kochunov, Peter; Lancaster, Jack L.; Lawrie, Stephen M.; Liewald, David C.; Mandl, Rene; Matarin, Mar; Mattheisen, Manuel; Meisenzahl, Eva; Melle, Ingrid; Moses, Eric K.; Muehleisen, Thomas W.; Nauck, Matthias; Noethen, Markus M.; Olvera, Rene L.; Pandolfo, Massimo; Pike, G. Bruce; Puls, Ralf; Reinvang, Ivar; Renteria, Miguel E.; Rietschel, Marcella; Roffman, Joshua L.; Royle, Natalie A.; Rujescu, Dan; Savitz, Jonathan; Schnack, Hugo G.; Schnell, Knut; Seiferth, Nina; Smith, Colin; Steen, Vidar M.; Hernandez, Maria C. Valdes; Van den Heuvel, Martijn; van der Wee, Nic J.; Van Haren, Neeltje E. M.; Veltman, Joris A.; Voelzke, Henry; Walker, Robert; Westlye, Lars T.; Whelan, Christopher D.; Agartz, Ingrid; Boomsma, Dorret I.; Cavalleri, Gianpiero L.; Dale, Anders M.; Djurovic, Srdjan; Drevets, Wayne C.; Hagoort, Peter; Hall, Jeremy; Heinz, Andreas; Jack, Clifford R.; Foroud, Tatiana M.; Le Hellard, Stephanie; Macciardi, Fabio; Montgomery, Grant W.; Poline, Jean Baptiste; Porteous, David J.; Sisodiya, Sanjay M.; Starr, John M.; Sussmann, Jessika; Toga, Arthur W.; Veltman, Dick J.; Walter, Henrik; Weiner, Michael W.; Bis, Joshua C.; Ikram, M. Arfan; Smith, Albert V.; Gudnason, Vilmundur; Tzourio, Christophe; Vernooij, Meike W.; Launer, Lenore J.; DeCarli, Charles; Seshadri, Sudha; Andreassen, Ole A.; Apostolova, Liana G.; Bastin, Mark E.; Blangero, John; Brunner, Han G.; Buckner, Randy L.; Cichon, Sven; Coppola, Giovanni; de Zubicaray, Greig I.; Deary, Ian J.; Donohoe, Gary; de Geus, Eco J. C.; Espeseth, Thomas; Fernandez, Guillen; Glahn, David C.; Grabe, Hans J.; Hardy, John; Pol, Hilleke E. Hulshoff; Jenkinson, Mark; Kahn, Rene S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Meyer-Lindenberg, Andreas; Morris, Derek W.; Mueller-Myhsok, Bertram; Nichols, Thomas E.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W.; Potkin, Steven G.; Saemann, Philipp G.; Saykin, Andrew J.; Schumann, Gunter; Smoller, Jordan W.; Wardlaw, Joanna M.; Weale, Michael E.; Martin, Nicholas G.; Franke, Barbara; Wright, Margaret J.; Thompson, Paul M.

    Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease(1,2) and is reduced in schizophrenia(3), major depression(4) and

  16. Deregulation of the RB pathway in human testicular germ cell tumours

    DEFF Research Database (Denmark)

    Bartkova, Jirina; Lukas, Claudia; Sørensen, Claus S

    2003-01-01

    , are differentially targeted in diverse types of cancer. An 'unorthodox' spectrum of defects within this cascade occurs in testicular germ cell tumours (TGCTs), including silencing of pRB transcription, overexpression of cyclin D2, and loss of p18INK4c. To improve understanding of the role of this pathway...

  17. Erythromycin inhibits Pseudomonas aeruginosa-induced tumour necrosis factor-alpha production in human whole blood

    NARCIS (Netherlands)

    Schultz, M. J.; Speelman, P.; van der Poll, T.

    2001-01-01

    Erythromycin has been shown to be beneficial for panbronchiolitis, a disorder linked to infection with Pseudomonas aeruginosa. Erythromycin, but not the anti-Pseudomonas antibiotics imipenem, ceftazidime, gentamicin and ciprofloxacin, caused a dose-dependent decrease in the production of tumour

  18. NMR metabolomics of human lung tumours reveals distinct metabolic signatures for adenocarcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Rocha, Cláudia M; Barros, António S; Goodfellow, Brian J; Carreira, Isabel M; Gomes, Ana; Sousa, Vitor; Bernardo, João; Carvalho, Lina; Gil, Ana M; Duarte, Iola F

    2015-01-01

    Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through (1)H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and adjacent control tissues from 56 patients undergoing surgical excision of primary lung carcinomas. Multivariate modeling allowed tumour and control tissues to be discriminated with high accuracy (97% classification rate), mainly due to significant differences in the levels of 13 metabolites. Notably, the magnitude of those differences were clearly distinct for AdC and SqCC: major alterations in AdC were related to phospholipid metabolism (increased phosphocholine, glycerophosphocholine and phosphoethanolamine, together with decreased acetate) and protein catabolism (increased peptide moieties), whereas SqCC had stronger glycolytic and glutaminolytic profiles (negatively correlated variations in glucose and lactate and positively correlated increases in glutamate and alanine). Other tumour metabolic features were increased creatine, glutathione, taurine and uridine nucleotides, the first two being especially prominent in SqCC and the latter in AdC. Furthermore, multivariate analysis of AdC and SqCC profiles allowed their discrimination with a 94% classification rate, thus showing great potential for aiding lung tumours subtyping. Overall, this study has provided new, clear evidence of distinct metabolic signatures for lung AdC and SqCC, which can potentially impact on diagnosis and provide important leads for future research on novel therapeutic targets or imaging tracers. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. 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 ...

  20. Successful inhibition of intracranial human glioblastoma multiforme xenograft growth via systemic adenoviral delivery of soluble endostatin and soluble vascular endothelial growth factor receptor-2: laboratory investigation.

    Science.gov (United States)

    Szentirmai, Oszkar; Baker, Cheryl H; Bullain, Szofia S; Lin, Ning; Takahashi, Masaya; Folkman, Judah; Mulligan, Richard C; Carter, Bob S

    2008-05-01

    Glioblastoma multiforme (GBM) is characterized by neovascularization, raising the question of whether angiogenic blockade may be a useful therapeutic strategy for this disease. It has been suggested, however, that, to be useful, angiogenic blockade must be persistent and at levels sufficient to overcome proangiogenic signals from tumor cells. In this report, the authors tested the hypothesis that sustained high concentrations of 2 different antiangiogenic proteins, delivered using a systemic gene therapy strategy, could inhibit the growth of established intracranial U87 human GBM xenografts in nude mice. Mice harboring established U87 intracranial tumors received intravenous injections of adenoviral vectors encoding either the extracellular domain of vascular endothelial growth factor receptor-2-Fc fusion protein (Ad-VEGFR2-Fc) alone, soluble endostatin (Ad-ES) alone, a combination of Ad-VEGFR2-Fc and Ad-ES, or immunoglobulin 1-Fc (Ad-Fc) as a control. Three weeks after treatment, magnetic resonance imaging-based determination of tumor volume showed that treatment with Ad-VEGFR2-Fc, Ad-ES, or Ad-VEGFR2-Fc in combination with Ad-ES, produced 69, 59, and 74% growth inhibition, respectively. Bioluminescent monitoring of tumor growth revealed growth inhibition in the same treatment groups to be 62, 74, and 72%, respectively. Staining with proliferating cell nuclear antigen and with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling showed reduced tumor cell proliferation and increased apoptosis in all antiangiogenic treatment groups. These results suggest that systemic delivery and sustained production of endostatin and soluble VEGFR2 can slow intracranial glial tumor growth by both reducing cell proliferation and increasing tumor apoptosis. This work adds further support to the concept of using antiangiogenesis therapy for intracranial GBM.

  1. Successful inhibition of intracranial human glioblastoma multiforme xenograft growth via systemic adenoviral delivery of soluble endostatin and soluble vascular endothelial growth factor receptor-2

    Science.gov (United States)

    Szentirmai, Oszkar; Baker, Cheryl H.; Bullain, Szofia S.; Lin, Ning; Takahashi, Masaya; Folkman, Judah; Mulligan, Richard C.; Carter, Bob S.

    2015-01-01

    Object Glioblastoma multiforme (GBM) is characterized by neovascularization, raising the question of whether angiogenic blockade may be a useful therapeutic strategy for this disease. It has been suggested, however, that, to be useful, angiogenic blockade must be persistent and at levels sufficient to overcome proangiogenic signals from tumor cells. In this report, the authors tested the hypothesis that sustained high concentrations of 2 different antiangiogenic proteins, delivered using a systemic gene therapy strategy, could inhibit the growth of established intracranial U87 human GBM xenografts in nude mice. Methods Mice harboring established U87 intracranial tumors received intravenous injections of adenoviral vectors encoding either the extracellular domain of vascular endothelial growth factor receptor-2-Fc fusion protein (Ad-VEGFR2-Fc) alone, soluble endostatin (Ad-ES) alone, a combination of Ad-VEGFR2-Fc and Ad-ES, or immunoglobulin 1-Fc (Ad-Fc) as a control. Results Three weeks after treatment, magnetic resonance imaging-based determination of tumor volume showed that treatment with Ad-VEGFR2-Fc, Ad-ES, or Ad-VEGFR2-Fc in combination with Ad-ES, produced 69, 59, and 74% growth inhibition, respectively. Bioluminescent monitoring of tumor growth revealed growth inhibition in the same treatment groups to be 62, 74, and 72%, respectively. Staining with proliferating cell nuclear antigen and with terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling showed reduced tumor cell proliferation and increased apoptosis in all antiangiogenic treatment groups. Conclusions These results suggest that systemic delivery and sustained production of endostatin and soluble VEGFR2 can slow intracranial glial tumor growth by both reducing cell proliferation and increasing tumor apoptosis. This work adds further support to the concept of using antiangiogenesis therapy for intracranial GBM. PMID:18447716

  2. Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers.

    Science.gov (United States)

    Dallol, Ashraf; Forgacs, Eva; Martinez, Alonso; Sekido, Yoshitaka; Walker, Rosemary; Kishida, Takeshi; Rabbitts, Pamela; Maher, Eamonn R; Minna, John D; Latif, Farida

    2002-05-02

    The human homologue of the Drosophila Roundabout gene DUTT1 (Deleted in U Twenty Twenty) or ROBO1 (Locus Link ID 6091), a member of the NCAM family of receptors, was recently cloned from the lung cancer tumour suppressor gene region 2 (LCTSGR2 or U2020 region) at 3p12. DUTT1 maps within a region of overlapping homozygous deletions characterized in both small cell lung cancer lines (SCLC) and in a breast cancer line. In this report we (a) defined the genomic organization of the DUTT1 gene, (b) performed mutation and expression analysis of DUTT1 in lung, breast and kidney cancers, (c) identified tumour specific promoter region methylation of DUTT1 in human cancers. The gene was found to contain 29 exons and spans at least 240 kb of genomic sequence. The 5' region contains a CpG island, and the poly(A)(+) tail has an atypical 5'-GATAAA-3' signal. We analysed DUTT1 for mutations in lung, breast and kidney cancers, no inactivating mutations were detected by PCR-SSCP. However, seven germline missense changes were found and characterized. DUTT1 expression was not detectable in one out of 18 breast tumour lines analysed by RT-PCR. Bisulfite sequencing of the promoter region of DUTT1 gene in the HTB-19 breast tumour cell line (not expressing DUTT1) showed complete hypermethylation of CpG sites within the promoter region of the DUTT1 gene (-244 to +27 relative to the translation start site). The expression of DUTT1 gene was reactivated in HTB-19 after treatment with the demethylating agent 5-aza-2'-deoxycytidine. The same region was also found to be hypermethylated in six out of 32 (19%) primary invasive breast carcinomas and eight out of 44 (18%) primary clear cell renal cell carcinomas (CC-RCC) and in one out of 26 (4%) primary NSCLC tumours. Furthermore 80% of breast and 75% of CC-RCC tumours showing DUTT1 methylation had allelic losses for 3p12 markers hence obeying Knudson's two hit hypothesis. Our findings suggest that DUTT1 warrants further analysis as a candidate for

  3. Intracranial germ cell tumor mimicking anorexia nervosa.

    Science.gov (United States)

    Andreu Martínez, F J; Martínez Mateu, J M

    2006-12-01

    We report on a case of a 23 year-old female diagnosed as having a germ-cell tumour located in the sellar region. The patient referred anorexia, psychic disorders, weight loss of 15 kilograms and secondary amenorrhea during the previous three years. This is the reason why the patient was diagnosed as having anorexia nervosa. Subsequently, the patient presented some endocrine dysfunction. MRI revealed the existence of a lesion located in suprasellar and hypothalamic regions. This case shows that the presence of intracranial tumours next to the hypothalamus must be borne in mind as a rare but real possibility in cases of anorexia nervosa, specially in those non-typical cases.

  4. Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3 in colon cancer serum and tumours: a biomarker study

    Directory of Open Access Journals (Sweden)

    Olsen Jesper

    2005-01-01

    Full Text Available Abstract Background Molecular markers for localized colon tumours and for prognosis following therapy are needed. Proteomics research is currently producing numerous biomarker studies with clinical potential. We investigate the protein composition of plasma and of tumour extracts with the aim of identifying biomarkers for colon cancer. Methods By Surface Enhanced Laser Desorption/Ionisation – Time Of Flight / Mass spectrometry (SELDI-TOF/MS we compare the protein profiles of colon cancer serum with serum from healthy individuals and the protein profiles of colon tumours with normal colon tissue. By size exclusion chromatography, we investigate the binding of HNP 1-3 to high mass plasma proteins. By microflow we investigate the effect of HNP 1-3 on mammalian cells. Results Human Neutrophil Peptides -1, -2 and -3 (HNP 1-3, also known as alfa-defensin-1, -2 and -3, are present in elevated concentrations in serum from colon cancer patients and in protein extracts from colon tumours. A fraction of HNP 1-3 in serum is bound to unidentified high mass plasma proteins. HNP 1-3 purified from colon tumours are lethal to mammalian cells. Conclusions HNP 1-3 may serve as blood markers for colon cancer in combination with other diagnostic tools. We propose that HNP 1-3 are carried into the bloodstream by attaching to high mass plasma proteins in the tumour microenvironment. We discuss the effect of HNP 1-3 on tumour progression.

  5. Elastase-induced intracranial aneurysms in hypertensive mice

    Science.gov (United States)

    Nuki, Yoshitsugu; Tsou, Tsung-Ling; Kurihara, Chie; Kanematsu, Miyuki; Kanematsu, Yasuhisa; Hashimoto, Tomoki

    2009-01-01

    Mechanisms of formation and growth of intracranial aneurysms are poorly understood. To investigate the pathophysiology of intracranial aneurysms, an animal model of intracranial aneurysm yielding high incidence of large aneurysm formation within a short incubation period is needed. We combined two well-known clinical factors associated with human intracranial aneurysms—hypertension and the degeneration of elastic lamina— to induce intracranial aneurysm formation in mice. Roles of matrix metalloproteinases (MMPs) in this model were investigated utilizing doxycycline, a broad-spectrum MMP inhibitor, and MMP knockout mice. Hypertension was induced by continuous infusion of angiotensin-II for two weeks. The disruption of elastic lamina was achieved by a single stereotaxic injection of elastase into the cerebrospinal fluid at the right basal cistern. 77% of the mice that received 35 milli-units of elastase and 1000 ng/kg/min angiotensin-II developed intracranial aneurysms in two weeks. There were dose-dependent effects of elastase and angiotensin-II on the incidence of aneurysms. Histologically, intracranial aneurysms observed in this model closely resembled human intracranial aneurysms. Doxycycline, a broad-spectrum MMP inhibitor, reduced the incidence of aneurysm to 10%. MMP-9 knockout mice, but not MMP-2 knockout mice, had reduced the incidence of intracranial aneurysms. In summary, a stereotaxic injection of elastase into the basal cistern in hypertensive mice resulted in intracranial aneurysms that closely resembled human intracranial aneurysms. The intracranial aneurysm formation in this model appeared to be dependent on MMP activation. PMID:19884566

  6. Human papillomavirus tumour status is not associated with a positive depression screen for patients with oropharyngeal cancer.

    Science.gov (United States)

    Qualliotine, J R; Califano, J A; Li, R J; Gold, D; Messing, B; Lee, G; Ha, P; Fakhry, C

    2017-09-01

    Several risk factors for depression in patients with oropharyngeal cancer have been determined. However, it is unknown whether human papillomavirus associated oropharyngeal cancer, which has a distinct clinico-demographic profile, modulates this risk. A retrospective analysis was conducted of patients with oropharyngeal cancer. These patients had completed a 10-item depression screening questionnaire before receiving treatment for their disease from 2011 to 2014. Associations between patient or disease characteristics and depression screening questionnaire results were investigated. The study comprised 69 patients, 31 (44.9 per cent) of whom screened positive for depression. There were no significant differences in distributions of clinico-demographic or histopathological characteristics, including human papillomavirus tumour status, by depression screen result. This population has a high risk for depression, but no obvious risk factors, including human papillomavirus tumour status, were associated with an elevated risk. This inability to risk-stratify patients by clinico-demographic or disease characteristics emphasises the importance of regular depression screening for all patients in this population.

  7. Tumour dosimetry and response in patients with metastatic differentiated thyroid cancer using recombinant human thyrotropin before radioiodine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Keizer, Bart de; Hoekstra, Anne; Rijk, Peter P. van; Klerk, John M.H. de [Department of Nuclear Medicine, Room E02.222, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht (Netherlands); Brans, Boudewijn; Dierckx, Rudi A. [Department of Nuclear Medicine, Ghent University Hospital, Ghent (Belgium); Zelissen, Pierre M.J.; Koppeschaar, Hans P.F.; Lips, Cees J.M. [Department of Endocrinology, University Medical Center Utrecht (Netherlands)

    2003-03-01

    The development of recombinant human thyrotropin (rhTSH) has given clinicians new options for diagnostic follow-up and treatment of patients with differentiated thyroid cancer (DTC). This paper evaluates the tumour dosimetry and response following -iodine-131 treatment of metastatic thyroid cancer patients after rhTSH stimulation instead of classical hormone withdrawal-induced hypothyroidism. Nineteen consecutive {sup 131}I treatments in 16 patients were performed after rhTSH stimulation. All patients had undergone a near-total thyroidectomy followed by an ablative dosage of {sup 131}I. They all suffered from metastatic or recurrent disease showing tumoral {sup 131}I uptake on previous post-treatment scintigraphy. Dosimetric calculations were performed using {sup 131}I tumour uptake measurements from post-treatment {sup 131}I scintigrams and tumour volume estimations from radiological images. Response was assessed by comparing pre-treatment serum thyroglobulin (Tg) level with the Tg level 3 months post treatment. In 18 out of 19 treatments, uptake of {sup 131}I in metastatic or recurrent lesions was seen. The median tumour radiation dose was 26.3 Gy (range 1.3-368 Gy), and the median effective half-life was 2.7 days (range 0.5-6.5 days). Eleven of 19 treatments (10/16 patients) were evaluable for response after 3 months. {sup 131}I therapy with rhTSH resulted in a biochemical partial response in 3/11 or 27% of treatments (two patients), biochemical stable disease in 2/11 or 18% of treatments and biochemical progressive disease in 6/11 or 55% of treatments. Our study showed that although tumour doses in DTC patients treated with {sup 131}I after rhTSH were highly variable, 45% of treatments led to disease stabilisation or partial remission when using rhTSH in conjunction with {sup 131}I therapy, without serious side-effects and with minimal impact on quality of life. RhTSH is therefore adequately satisfactory as an adjuvant tool in therapeutic settings and is

  8. POSTERIOR CRANIAL FOSSA TUMOURS IN CHILDREN AT ...

    African Journals Online (AJOL)

    hi-tech

    2004-05-05

    May 5, 2004 ... symptoms were the most common mode of presentation (30%) followed by headaches and vomiting. Twenty percent of our patients ... paediatric posterior fossa tumours are medulloblastoma. (20%) astrocytoma (15%) ... cranial nerve palsies, headaches, vomiting and blindness due to raised intracranial ...

  9. Cystic lesions accompanying extra-axial tumours

    NARCIS (Netherlands)

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

    We examined the mechanism of cyst formation in extra-axial tumours in the central nervous system (CNS). Cyst fluid, cerebrospinal fluid (CSF) and blood plasma were analysed in eight patients with nine peritumoral cysts: four with meningiomas, two with intracranial and two spinal intradural

  10. 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.

  11. Interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells.

    Science.gov (United States)

    Stec, Małgorzata; Szatanek, Rafał; Baj-Krzyworzeka, Monika; Baran, Jarosław; Zembala, Maria; Barbasz, Jakub; Waligórska, Agnieszka; Dobrucki, Jurek W; Mytar, Bożenna; Szczepanik, Antoni; Siedlar, Maciej; Drabik, Grażyna; Urbanowicz, Barbara; Zembala, Marek

    2015-12-01

    Tumour cells release membrane micro(nano)fragments called tumour-derived microvesicles (TMV) that are believed to play an important role in cancer progression. TMV suppress/modify antitumour response of the host, but there is also some evidence for their direct interaction with cancer cells. In cancer patients TMV are present in body fluid and tumour microenvironment. The present study aimed at characterization of whole types/subpopulations, but not only exosomes, of TMV from newly established gastric cancer cell line (called GC1415) and to define their interactions with autologous cells. TMV were isolated from cell cultures supernatants by centrifugation at 50,000×g and their phenotype was determined by flow cytometry. The size of TMV was analysed by dynamic light scattering and nanoparticle tracking analysis, while morphology by transmission electron microscopy and atomic force microscopy. Interactions of TMV with cancer cells were visualized using fluorescence-activated cell sorter, confocal and atomic force microscopy, biological effects by xenografts in NOD SCID mice. Isolated TMV showed expression of CD44H, CD44v6 (hyaluronian receptors), CCR6 (chemokine receptor) and HER-2/neu molecules, exhibited different shapes and sizes (range 60-900 nm, highest frequency of particles with size range of 80-120 nm). TMV attached to autologous cancer cells within 2 h and then were internalized by them at 24 h. CD44H, CD44v6 and CCR6 molecules may play a role in attachment of TMV to cancer cells, while HER-2 associated with CD24 be involved in promoting cancer cells growth. Pre-exposure of cancer cells to TMV resulted in enhancement of tumour growth and cancer cell-induced angiogenesis in NOD SCID mice model. TMV interact directly with cancer cells serving as macro-messengers and molecular cargo transfer between gastric cancer cells resulting in enhancement of tumour growth. TMV should be considered in future as target of anticancer therapy.

  12. A pharmacokinetic and pharmacodynamic study In vivo of human HT29 tumours using {sup 19}F and {sup 31}P magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Griffiths, J.R. [CRC Biomedical Magnetic Resonance Research Unit, Department of Cell and Molecular Sciences, St. George' s Hospital Medical School, Cranmer Terrace, London (United Kingdom); Judson, I.R. [CRC Centre for Cancer Therapeutics, Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, Surrey (United Kingdom); Leach, M.O. [CRC Clinical Magnetic Resonance Research Group, Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, Surrey (United Kingdom); Rodrigues, L.M.; Ojugo, A.S.E. [CRC Biomedical Magnetic Resonance Research Unit, Department of Cell and Molecular Sciences, St. George' s Hospital Medical School, Cranmer Terrace, London (United Kingdom); Seymour, M.T. [University of Leeds, Cancer Medicine Research Unit, Cookridge Hospital, Leeds (United Kingdom); McSheehy, P.M.J. [CRC Biomedical Magnetic Resonance Research Unit, Department of Cell and Molecular Sciences, St. George' s Hospital Medical School, Cranmer Terrace, London (United Kingdom)

    1997-12-01

    {sup 19}F-MRS (magnetic resonance spectroscopy) was used to study the pharmacokinetics of 5-fluorouracil (5-FU) in human (HT29) tumour xenografts, with and without pretreatment of the mice using either thymidine (40 min) or interferon-{alpha} (2 and 24 h). A 200 mg/kg i.p. bolus dose of 5-FU was eliminated from control tumours with a t{sub 1/2} of 25.4 {+-} 2 min (mean {+-} SEM, n = 11), while both thymidine (500 mg/kg) and interferon (50 000 IU/mouse) significantly increased t{sub 1/2} to 36.5 {+-} 6.1 (n = 5) and 48.1 {+-} 13.6 min (n = 4), respectively (P = 0.04, Gabriel's ANOVA). Thymidine increased 5-FU anabolism to cytotoxic 5-fluoronucleotides, and decreased the amount of tumour catabolites; the latter probably recirculated from liver since isolated HT29 cells did not catabolise 5-FU. These in vivo observations were confirmed by {sup 19}F-MRS quantification of tumour extracts. Interferon did not significantly affect 5-FU metabolism in the tumour or liver, nor the 5-FU t{sub 1/2} in liver. Treatment of tumours with 5-FU or interferon had no effect on tumour growth, whereas the combination strongly inhibited growth. {sup 31}P-MRS of HT29 tumours showed that 2 and 24 h after i.p. injections of interferon there was a significant increase in the pH{sub int} of 0.3 {+-} 0.04 units (P = 0.002), while pH{sub ext} and the tumour NTP/Pi ratio were unchanged. The large increase in the negative pH gradient (-{delta} pH) across the tumour plasma membrane caused by interferon suggests the {delta} pH may be a factor in tumour retention of 5-FU, as recently shown in isolated tumour cells. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  13. 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.

  14. Monoclonal antibody Po66 uptake by human lung tumours implanted in nude mice: effect of co-administration with doxorubicin.

    OpenAIRE

    Desrues, B.; L?na, H.; Brichory, F.; Ram?e, M. P.; Toujas, L; Delaval, P.; Dazord, L

    1995-01-01

    The efficacy of radioimmunotherapy of tumours with radiolabelled monoclonal antibodies (MAbs) depends on the amount of antibody taken up by the tumour and on its intratumoral distribution. In the case of MAbs directed against intracellular antigens, increasing the permeability of the cytoplasmic membrane may augment the bioavailability of the antigen for the antibody. This raises the question whether the induction of tumour necrosis by chemotherapy can enhance the tumour uptake of radiolabell...

  15. AZFa protein DDX3Y is differentially expressed in human male germ cells during development and in testicular tumours

    DEFF Research Database (Denmark)

    Gueler, B; Sonne, S B; Zimmer, J

    2012-01-01

    BACKGROUNDDDX3Y (DBY), located within AZoospermia Factor a (AZFa) region of the human Y chromosome (Yq11), encodes a conserved DEAD-box RNA helicase expressed only in germ cells and with a putative function at G1-S phase of the cell cycle. Deletion of AZFa results most often in germ cell aplasia, i.......e. Sertoli-cell-only syndrome. To investigate the function of DDX3Y during human spermatogenesis, we examined its expression during development and maturation of the testis and in several types of testicular germ cell tumours (TGCTs), including the pre-invasive carcinoma in situ (CIS) precursor cells which......, but not in somatically differentiated non-seminomas, consistent with its germ-cell specific function.CONCLUSIONSThe fetal germ cell DDX3Y expression suggests a role in early spermatogonial proliferation and implies that, in men with AZFa deletion, germ cell depletion may begin prenatally. The strong expression of DDX3Y...

  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. Monitoring of Intracranial Pressure During Intracranial Endoscopy

    Directory of Open Access Journals (Sweden)

    Rajeev Kumar

    2013-08-01

    Full Text Available Background: Intracranial endoscopy is a minimum invasive procedure, which reduces trauma to the brain, is cost-effective, and carries a shortened hospital stay with an improved postoperative outcome. Objective: To monitor intracranial pressure changes during intracranial endoscopy among children and adults under general anesthesia/sedation, and to compare the intracranial pressure changes between children and adults receiving general anesthesia and among adults receiving general anesthesia and sedation. Methods: The present cross-sectional study was conducted in one of the tertiary care hospitals of Lucknow. This was carried out in the department of neurosurgery from January 2008 to December 2008. Patients who were not fit for general anesthesia received local anesthesia under sedation. Patients participating in the study were divided into three groups. Intracranial pressure was recorded at specific intervals. Parametric data were subjected to statistical analysis using a student\\s t test. Result: A total of 70 patients were undergoing intracranial endoscopy under general anesthesia during the study period. In both groups A and B, intracranial pressure increases the maximum during inflation of the balloon. In group C, all the variations in ICP were found to be statistically significant. In the comparison of intracranial pressure changes between groups A and B, no significant difference was found. All correlations in the comparison of groups B and C were found to be statistically significant (p< 0.001. Conclusion: There is a need for continuous intraoperative monitoring of ICP intracranial endoscopy, because ICP increases in various stages of the procedure, which can be detrimental to the perfusion of the brain. [Arch Clin Exp Surg 2013; 2(4.000: 240-245

  18. Heterochromatin marks HP1γ, HP1α and H3K9me3, and DNA damage response activation in human testis development and germ cell tumours

    DEFF Research Database (Denmark)

    Bartkova, J; Moudry, P; Hodny, Z

    2011-01-01

    Heterochromatinization has been implicated in fundamental biological and pathological processes including differentiation, senescence, ageing and tumourigenesis; however, little is known about its regulation and roles in human cells and tissues in vivo. Here, we show distinct cell-type- and cancer...... protein and without DDR activation. Overall, these results provide novel insights into cell-related and tumour-related diversity of heterochromatin in human tissues in vivo, relevant for andrology and intrinsic anti-tumour defence roles attributed to activated DDR and cellular senescence.......-invasive carcinoma in situ (CIS; n=26) lesions and a series of overt germ cell tumours, including seminomas (n=26), embryonal carcinomas (n=18) and teratomas (n=11). Among striking findings were high levels of HP1γ in foetal gonocytes, CIS and seminomas; enhanced multimarker heterochromatinization without DDR...

  19. 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.

  20. Mitochondrial modulation of oxygen-dependent radiosensitivity in some human tumour cell lines.

    LENUS (Irish Health Repository)

    Anoopkumar-Dukie, S

    2009-10-01

    Oxygen-dependent radiosensitivity of tumour cells reflects direct oxidative damage to DNA, but non-nuclear mechanisms including signalling pathways may also contribute. Mitochondria are likely candidates because not only do they integrate signals from each of the main kinase pathways but mitochondrial kinases responsive to oxidative stress communicate to the rest of the cell. Using pharmacological and immunochemical methods, we tested the role of mitochondrial permeability transition (MPT) and the Bcl-2 proteins in oxygen-dependent radiosensitivity. Drug-treated or untreated cervical cancer HeLa, breast cancer MCF-7 and melanoma MeWo cell lines were irradiated at 6.2 Gy under normoxic and hypoxic conditions then allowed to proliferate for 7 days. The MPT blocker cyclosporin A (2 microM) strongly protected HeLa but not the other two lines against oxygen-dependent radiosensitivity. By contrast, bongkrekic acid (50 microM), which blocks MPT by targeting the adenine nucleotide transporter, had only marginal effect and calcineurin inhibitor FK-506 (0.1 microM) had none. Nor was evidence found for the modulation of oxygen-dependent radiosensitivity by Bax\\/Bcl-2 signalling, mitochondrial ATP-dependent potassium (mitoK(ATP)) channels or mitochondrial Ca(2+) uptake. In conclusion, calcineurin-independent protection by cyclosporin A suggests that MPT but not mitoK(ATP) or the mitochondrial apoptosis pathway plays a causal role in oxygen-dependent radiosensitivity of HeLa cells. Targeting MPT may therefore improve the effectiveness of radiotherapy in some solid tumours.

  1. The tumour-targeting human L19-IL2 immunocytokine: preclinical safety studies, phase I clinical trial in patients with solid tumours and expansion into patients with advanced renal cell carcinoma.

    Science.gov (United States)

    Johannsen, Manfred; Spitaleri, Gianluca; Curigliano, Giuseppe; Roigas, Jan; Weikert, Steffen; Kempkensteffen, Carsten; Roemer, Andreas; Kloeters, Christian; Rogalla, Patrik; Pecher, Gabriele; Miller, Kurt; Berndt, Alexander; Kosmehl, Hartwig; Trachsel, Eveline; Kaspar, Manuela; Lovato, Valeria; González-Iglesias, Reinerio; Giovannoni, Leonardo; Menssen, Hans D; Neri, Dario; de Braud, Filippo

    2010-11-01

    L19-IL2, a tumour-targeting immunocytokine composed of the recombinant human antibody fragment L19 (specific to the alternatively-spliced EDB domain of fibronectin, a well characterised marker of tumour neo-vasculature) and of human IL2, has demonstrated strong therapeutic activity in animal cancer models. This phase I/II trial was performed to evaluate safety, tolerability, recommended phase II dose (RD) and early signs of activity of L19-IL2. Five cohorts of patients with progressive solid tumours (n=21) received an intravenous infusion of L19-IL2 (from 5 to 30 Mio IU IL2 equivalent dose) on days 1, 3 and 5 every 3 weeks. This treatment cycle was repeated up to six times. In the following expansion phase, patients with metastatic renal cell carcinoma (RCC) (n=12) were treated at the RD of L19-IL2. Clinical data and laboratory findings were analysed for safety, tolerability and activity. Preclinical studies in rats and monkeys did not raise any safety concerns. The RD was defined to be 22.5 Mio IU IL2 equivalent. Pharmacokinetics of L19-IL2 was dose proportional over the tested range, with a terminal half-life of 2-3h. Toxicities were manageable and reversible with no treatment-related deaths. We observed stable disease in 17/33 patients (51%) and 15/18 with mRCC (83%) after two cycles. Median progression-free survival of RCC patients in the expansion phase of the study was 8 months (1.5-30.5). L19-IL2 can be safely and repeatedly administered at the RD of 22.5 Mio IU IL2 equivalent in advanced solid tumours. Preliminary evaluation suggests clinical activity of L19-IL2 in patients with mRCC. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Cytogenetic and molecular characterization of human radio-induced tumours; Caracterisation cytogenetique et moleculaire de tumeurs radio-induites humaines

    Energy Technology Data Exchange (ETDEWEB)

    Lefevre, S.

    2002-09-15

    After a brief recall of some fundamentals regarding radiobiology, this research thesis discusses some epidemiological aspects of radio carcinogenesis, based on epidemiological studies performed on people having survived to Hiroshima, Nagasaki and Chernobyl, but also performed on people submitted to domestic or professional exposures to radon, or to medicine-related exposures. The author highlights some predispositions to radio-induced cancers. Then, she discusses the genetic mechanisms of radio-induced carcinogenesis and the genetic alterations observed in human radio-induced tumours. She discusses and comments the genomic instability, its mechanisms and some models observed on mice, and describes the various forms of radio-induced genomic instability. After a discussion of all these aspects, the author draws some perspectives for future research works

  3. Tumour procurement, DNA extraction, coverage analysis and optimisation of mutation-detection algorithms for human melanoma genomes.

    Science.gov (United States)

    Wilmott, James S; Field, Matthew A; Johansson, Peter A; Kakavand, Hojabr; Shang, Ping; De Paoli-Iseppi, Ricardo; Vilain, Ricardo E; Pupo, Gulietta M; Tembe, Varsha; Jakrot, Valerie; Shang, Catherine A; Cebon, Jonathan; Shackleton, Mark; Fitzgerald, Anna; Thompson, John F; Hayward, Nicholas K; Mann, Graham J; Scolyer, Richard A

    2015-12-01

    Whole genome sequencing (WGS) of cancer patients' tumours offers the most comprehensive method of identifying both novel and known clinically-actionable genomic targets. However, the practicalities of performing WGS on clinical samples are poorly defined.This study was designed to test sample preparation, sequencing specifications and bioinformatic algorithms for their effect on accuracy and cost-efficiency in a large WGS analysis of human melanoma samples.WGS was performed on melanoma cell lines (n = 15) and melanoma fresh frozen tumours (n = 222). The appropriate level of coverage and the optimal mutation detection algorithm for the project pipeline were determined.An incremental increase in sequencing coverage from 36X to 132X in melanoma tissue samples and 30X to 103X for cell lines only resulted in a small increase (1-2%) in the number of mutations detected, and the quality scores of the additional mutations indicated a low probability that the mutations were real. The results suggest that 60X coverage for melanoma tissue and 40X for melanoma cell lines empower the detection of 98-99% of informative single nucleotide variants (SNVs), a sensitivity level at which clinical decision making or landscape research projects can be carried out with a high degree of confidence in the results. Likewise the bioinformatic mutation analysis methodology strongly influenced the number and quality of SNVs detected. Detecting mutations in the blood genomes separate to the tumour genomes generated 41% more SNVs than if the blood and melanoma tissue genomes were analysed simultaneously. Therefore, simultaneous analysis should be employed on matched melanoma tissue and blood genomes to reduce errors in mutation detection.This study provided valuable insights into the accuracy of SNV with WGS at various coverage levels in human clinical cancer specimens. Additionally, we investigated the accuracy of the publicly available mutation detection algorithms to detect cancer

  4. Sound identification in human auditory cortex: Differential contribution of local field potentials and high gamma power as revealed by direct intracranial recordings.

    Science.gov (United States)

    Nourski, Kirill V; Steinschneider, Mitchell; Rhone, Ariane E; Oya, Hiroyuki; Kawasaki, Hiroto; Howard, Matthew A; McMurray, Bob

    2015-09-01

    High gamma power has become the principal means of assessing auditory cortical activation in human intracranial studies, albeit at the expense of low frequency local field potentials (LFPs). It is unclear whether limiting analyses to high gamma impedes ability of clarifying auditory cortical organization. We compared the two measures obtained from posterolateral superior temporal gyrus (PLST) and evaluated their relative utility in sound categorization. Subjects were neurosurgical patients undergoing invasive monitoring for medically refractory epilepsy. Stimuli (consonant-vowel syllables varying in voicing and place of articulation and control tones) elicited robust evoked potentials and high gamma activity on PLST. LFPs had greater across-subject variability, yet yielded higher classification accuracy, relative to high gamma power. Classification was enhanced by including temporal detail of LFPs and combining LFP and high gamma. We conclude that future studies should consider utilizing both LFP and high gamma when investigating the functional organization of human auditory cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Increased detectability of somatic changes in the DNA from human tumours after probing with "synthetic" and "genome-derived" hypervariable multilocus probes

    DEFF Research Database (Denmark)

    Lagoda, P J; Seitz, G; Epplen, J T

    1989-01-01

    DNA fingerprinting with two minisatellite (33.15, M13) and two simple repeat probes [(GACA)4, (CAC)5/(GTG)s] was performed to screen for somatic changes in the DNA from various solid human tumours in comparison with constitutional DNA from the same patient. Loss of bands or changes in band intens...

  6. The relation between deoxycytidine kinase activity and the radiosensitising effect of gemcitabine in eight different human tumour cell lines

    Directory of Open Access Journals (Sweden)

    Peters Godefridus J

    2006-05-01

    Full Text Available Abstract Background Gemcitabine (dFdC is an active antitumour agent with radiosensitising properties, shown both in preclinical and clinical studies. In the present study, the relation between deoxycytidine kinase (dCK activity and the radiosensitising effect of gemcitabine was investigated in eight different human tumour cell lines. Methods Tumour cells were treated with dFdC (0–100 nM for 24 h prior to radiotherapy (RT (γ-Co60, 0–6 Gy, room temperature. Cell survival was determined 7, 8, or 9 days after RT by the sulforhodamine B test. dCK activity of the cells was determined by an enzyme activity assay. Results A clear concentration-dependent radiosensitising effect of dFdC was observed in all cell lines. The degree of radiosensitisation was also cell line dependent and seemed to correlate with the sensitivity of the cell line to the cytotoxic effect of dFdC. The dCK activity of our cell lines varied considerably and differed up to three fold from 5 to 15 pmol/h/mg protein between the tested cell lines. In this range dCK activity was only weakly related to radiosensitisation (correlation coefficient 0.62, p = 0.11. Conclusion Gemcitabine needs to be metabolised to the active nucleotide in order to radiosensitise the cells. Since dFdCTP accumulation and incorporation into DNA are concentration dependent, the degree of radiosensitisation seems to be related to the extent of dFdCTP incorporated into DNA required to inhibit DNA repair. The activity of dCK does not seem to be the most important factor, but is clearly a major factor. Other partners of the intracellular metabolism of gemcitabine in relation to the cell cycle effects and DNA repair could be more responsible for the radiosensitising effect than dCK activity.

  7. Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

    Science.gov (United States)

    ... Asked Questions Español Condiciones Chinese Conditions Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) En Español Read in Chinese What is idiopathic intracranial hypertension? Idiopathic intracranial hypertension (IIH) is a disorder that ...

  8. Cancer cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts.

    Science.gov (United States)

    Lau, Tat-San; Chung, Tony Kwok-Hung; Cheung, Tak-Hong; Chan, Loucia Kit-Ying; Cheung, Leonard Wing-Hong; Yim, So-Fan; Siu, Nelson Shing-Shun; Lo, Kwok-Wai; Yu, May Mei-Yung; Kulbe, Hagen; Balkwill, Frances R; Kwong, Joseph

    2014-01-01

    We have investigated the role of cytokine lymphotoxin in tumour-stromal interactions in human ovarian cancer. We found that lymphotoxin overexpression is commonly shared by the cancer cells of various ovarian cancer subtypes, and lymphotoxin-beta receptor (LTBR) is expressed ubiquitously in both the cancer cells and cancer-associated fibroblasts (CAFs). In monoculture, we showed that ovarian cancer cells are not the major lymphotoxin-responsive cells. On the other hand, our co-culture studies demonstrated that the cancer cell-derived lymphotoxin induces chemokine expression in stromal fibroblasts through LTBR-NF-κB signalling. Amongst the chemokines being produced, we found that fibroblast-secreted CXCL11 promotes proliferation and migration of ovarian cancer cells via the chemokine receptor CXCR3. CXCL11 is highly expressed in CAFs in ovarian cancer biopsies, while CXCR3 is found in malignant cells in primary ovarian tumours. Additionally, the overexpression of CXCR3 is significantly associated with the tumour grade and lymph node metastasis of ovarian cancer, further supporting the role of CXCR3, which interacts with CXCL11, in promoting growth and metastasis of human ovarian cancer. Taken together, these results demonstrated that cancer-cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts. Our findings suggest that lymphotoxin-LTBR and CXCL11-CXCR3 signalling represent therapeutic targets in ovarian cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  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. Associations between the uptake of {sup 111}In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts

    Energy Technology Data Exchange (ETDEWEB)

    McLarty, Kristin; Cornelissen, Bart; Scollard, Deborah A. [University of Toronto, Department of Pharmaceutical Sciences, Toronto, ON (Canada); Done, Susan J. [University of Toronto, Department of Medical Biophysics, Toronto, ON (Canada)]|[University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, ON (Canada)]|[University Health Network, Department of Pathology, Toronto, ON (Canada); Chun, Kathy [North York General Hospital, Genetics Program, Toronto, ON (Canada); Reilly, Raymond M. [University of Toronto, Department of Pharmaceutical Sciences, Toronto, ON (Canada)]|[University of Toronto, Department of Medical Imaging, Toronto, ON (Canada)]|[University Health Network, Toronto General Research Institute, Toronto, ON (Canada)]|[University of Toronto, Leslie Dan Faculty of Pharmacy, Toronto, ON (Canada)

    2009-01-15

    The purpose of the study was to investigate the associations between uptake of {sup 111}In-DTPA-trastuzumab, tumour HER2 density and response to trastuzumab (Herceptin) of human breast cancer (BC) xenografts in athymic mice. The tumour uptake of {sup 111}In-DTPA-trastuzumab in athymic mice bearing BC xenografts with increasing HER2 density (0 to 3+) was evaluated. Specific uptake ratios were established in biodistribution (SUR) and imaging studies (ROI-SUR) using {sup 111}In-labeled mouse IgG ({sup 111}In-DTPA-mIgG). Further corrections were made for circulating radioactivity using tumour-to-blood ratios defined as a localization index (LI) and region-of-interest localization index (ROI-LI), respectively. Mice were treated with trastuzumab (Herceptin). A tumour growth inhibition index (TGI) was calculated and relative TGIs calculated by dividing the TGI of control by that of trastuzumab-treated mice. Strong, nonlinear associations with HER2 density were obtained if the uptake of {sup 111}In-DTPA-trastuzumab was corrected for nonspecific IgG localization (i.e., SUR; r{sup 2}=0.99) and circulating radioactivity (i.e., LI; r{sup 2} =0.87), but without these corrections, the association between HER2 density and tumour uptake was poor (r{sup 2}=0.22). There was a strong association between ROI-SUR and ROI-LI values and HER2 expression (r{sup 2}=0.90 and r{sup 2}=0.95), respectively. All tumours were imaged. Relative TGI values were associated with increasing uncorrected tumour uptake of {sup 111}In-DTPA-trastuzumab but not always with HER2 density (i.e., MCF-HER2-18 cells with trastuzumab-resistance). HER2 expression (0 to 3+) can be differentiated using {sup 111}In-DTPA-trastuzumab, but requires correction of tumour uptake for nonspecific IgG localization and circulating radioactivity. The uncorrected uptake of {sup 111}In-DTPA-trastuzumab was associated with tumour response to trastuzumab. (orig.)

  11. Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts.

    Science.gov (United States)

    McLarty, Kristin; Cornelissen, Bart; Scollard, Deborah A; Done, Susan J; Chun, Kathy; Reilly, Raymond M

    2009-01-01

    The purpose of the study was to investigate the associations between uptake of (111)In-DTPA-trastuzumab, tumour HER2 density and response to trastuzumab (Herceptin) of human breast cancer (BC) xenografts in athymic mice. The tumour uptake of (111)In-DTPA-trastuzumab in athymic mice bearing BC xenografts with increasing HER2 density (0 to 3+) was evaluated. Specific uptake ratios were established in biodistribution (SUR) and imaging studies (ROI-SUR) using (111)In-labeled mouse IgG ((111)In-DTPA-mIgG). Further corrections were made for circulating radioactivity using tumour-to-blood ratios defined as a localization index (LI) and region-of-interest localization index (ROI-LI), respectively. Mice were treated with trastuzumab (Herceptin). A tumour growth inhibition index (TGI) was calculated and relative TGIs calculated by dividing the TGI of control by that of trastuzumab-treated mice. Strong, nonlinear associations with HER2 density were obtained if the uptake of (111)In-DTPA-trastuzumab was corrected for nonspecific IgG localization (i.e., SUR; r (2) = 0.99) and circulating radioactivity (i.e., LI; r (2) = 0.87), but without these corrections, the association between HER2 density and tumour uptake was poor (r (2) = 0.22). There was a strong association between ROI-SUR and ROI-LI values and HER2 expression (r (2) = 0.90 and r (2) = 0.95, respectively. All tumours were imaged. Relative TGI values were associated with increasing uncorrected tumour uptake of (111)In-DTPA-trastuzumab but not always with HER2 density (i.e., MCF-HER2-18 cells with trastuzumab-resistance). HER2 expression (0 to 3+) can be differentiated using (111)In-DTPA-trastuzumab, but requires correction of tumour uptake for nonspecific IgG localization and circulating radioactivity. The uncorrected uptake of (111)In-DTPA-trastuzumab was associated with tumour response to trastuzumab.

  12. Intracranial hypertension in pediatric patients treated with recombinant human growth hormone: data from 25 years of the Genentech National Cooperative Growth Study.

    Science.gov (United States)

    Noto, Richard; Maneatis, Thomas; Frane, James; Alexander, Kimberly; Lippe, Barbara; Davis, D Aaron

    2011-01-01

    Intracranial hypertension (IH) is a rare condition in children. However, a relationship between recombinant human growth hormone (rhGH) therapy and IH has been well documented. Risk factors were assessed for 70 rhGH-naive patients enrolled in the National Cooperative Growth Study with reports of IH after treatment initiation. Patients with severe growth hormone deficiency, Turner syndrome, chronic renal insufficiency (CRI), and obesity (particularly in the CRI group) were at highest risk of developing IH during the first year of therapy, suggesting initiation of careful early monitoring. In some patients, factors such as corticosteroid use or other chromosomal abnormalities appear to confer a delayed risk of IH, and these patients should be monitored long-term for signs and symptoms of IH.

  13. Global gene expression analysis reveals reduced abundance of putative microRNA targets in human prostate tumours

    Directory of Open Access Journals (Sweden)

    Xie Yi

    2009-02-01

    Full Text Available Abstract Background Recently, microRNAs (miRNAs have taken centre stage in the field of human molecular oncology. Several studies have shown that miRNA profiling analyses offer new possibilities in cancer classification, diagnosis and prognosis. However, the function of miRNAs that are dysregulated in tumours remains largely a mystery. Global analysis of miRNA-target gene expression has helped illuminate the role of miRNAs in developmental gene expression programs, but such an approach has not been reported in cancer transcriptomics. Results In this study, we globally analysed the expression patterns of miRNA target genes in prostate cancer by using several public microarray datasets. Intriguingly, we found that, in contrast to global mRNA transcript levels, putative miRNA targets showed a reduced abundance in prostate tumours relative to benign prostate tissue. Additionally, the down-regulation of these miRNA targets positively correlated with the number of types of miRNA target-sites in the 3' untranslated regions of these targets. Further investigation revealed that the globally low expression was mainly driven by the targets of 36 specific miRNAs that were reported to be up-regulated in prostate cancer by a miRNA expression profiling study. We also found that the transcript levels of miRNA targets were lower in androgen-independent prostate cancer than in androgen-dependent prostate cancer. Moreover, when the global analysis was extended to four other cancers, significant differences in transcript levels between miRNA targets and total mRNA backgrounds were found. Conclusion Global gene expression analysis, along with further investigation, suggests that miRNA targets have a significantly reduced transcript abundance in prostate cancer, when compared with the combined pool of all mRNAs. The abnormal expression pattern of miRNA targets in human cancer could be a common feature of the human cancer transcriptome. Our study may help to shed new

  14. Spontaneous intracranial hypotension.

    LENUS (Irish Health Repository)

    Fullam, L

    2012-01-31

    INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

  15. Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Bøgebo, Rikke; Gammeltoft, Steen

    2005-01-01

    BACKGROUND: Molecular markers for localized colon tumours and for prognosis following therapy are needed. Proteomics research is currently producing numerous biomarker studies with clinical potential. We investigate the protein composition of plasma and of tumour extracts with the aim of identify......BACKGROUND: Molecular markers for localized colon tumours and for prognosis following therapy are needed. Proteomics research is currently producing numerous biomarker studies with clinical potential. We investigate the protein composition of plasma and of tumour extracts with the aim...... of identifying biomarkers for colon cancer. METHODS: By Surface Enhanced Laser Desorption/Ionisation--Time Of Flight/Mass spectrometry (SELDI-TOF/MS) we compare the protein profiles of colon cancer serum with serum from healthy individuals and the protein profiles of colon tumours with normal colon tissue...... concentrations in serum from colon cancer patients and in protein extracts from colon tumours. A fraction of HNP 1-3 in serum is bound to unidentified high mass plasma proteins. HNP 1-3 purified from colon tumours are lethal to mammalian cells. CONCLUSIONS: HNP 1-3 may serve as blood markers for colon cancer...

  16. Tumour-Derived Interleukin-1 Beta Induces Pro-inflammatory Response in Human Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Alajez, Nehad M; Al-toub, Mashael; Almusa, Abdulaziz

    ’ secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs. Background Over the past several years, significant amount of research has emerged......, the goal of this study was to assess the cellular and molecular changes in MSCs in response to secreted factors present in conditioned media (CM) from a panel of human tumor cell lines covering a spectrum of human cancers (Breast, Prostate, Lung, colon, and head and neck). Research Morphological changes...... with bipolar processes. In association with phenotypic changes, genome-wide gene expression and bioinformatics analysis revealed an enhanced pro-inflammatory response of those MSCs. Pharmacological inhibitions of FAK and MAPKK severely impaired the pro-inflammatory response of MSCs to tumor CM (~80-99%, and 55...

  17. Tumour necrosis factor-alpha (TNFα stimulates the growth of human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    F. Rougier

    1997-01-01

    Full Text Available This study reports that TNF-α is a potent mitogen for human bone marrow sternal cells in vitro (assessed by [3H]-thymidine incorporation into DNA and cell counts. In contrast, cytokines such as IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, LIF, SCF, M-CSF, G-CSF and GM-CSF had no effect. The effect of TNF-α on the growth of human bone marrow stromal cells could be of importance during inflammatory processes which take place in the marrow, for example marrow fibrosis.

  18. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

    Science.gov (United States)

    Glenn, Wendy K; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J; Lawson, James S

    2012-01-01

    The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

  19. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

    Directory of Open Access Journals (Sweden)

    Wendy K Glenn

    Full Text Available BACKGROUND: The purpose of this investigation is to determine if Epstein Barr virus (EBV, high risk human papillomavirus (HPV, and mouse mammary tumour viruses (MMTV co-exist in some breast cancers. MATERIALS AND METHODS: All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis and 14 were predominantly invasive ductal carcinomas (idc. RESULTS: EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%, HPV, 20% and MMTV (32% of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. CONCLUSIONS: We conclude that (i EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

  20. Human papillomavirus and Epstein-Barr virus in the etiology of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Hørding, U; Nielsen, H W

    1994-01-01

    sequences of two viruses with known transforming abilities, human papillomavirus (HPV) and Epstein-Barr virus (EBV). The polymerase chain reaction (PCR) technique was used. In none of the 19 successfully amplified samples were DNA sequences of HPV type 16 or type 18 detected. In six cases a faint trace...

  1. Correlation between human papillomavirus and p16 overexpression in oropharyngeal tumours

    DEFF Research Database (Denmark)

    Grønhøj Larsen, C; Gyldenløve, M; Jensen, D H

    2014-01-01

    A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based...

  2. Deregulated expression of hnRNP A/B proteins in human non-small cell lung cancer: parallel assessment of protein and mRNA levels in paired tumour/non-tumour tissues

    Directory of Open Access Journals (Sweden)

    Boukakis Georgios

    2010-08-01

    Full Text Available Abstract Background Heterogeneous nuclear ribonucleoproteins (hnRNPs of the A/B type (hnRNP A1, A2/B1, A3 are highly related multifunctional proteins participating in alternative splicing by antagonising other splicing factors, notably ASF/SF2. The altered expression pattern of hnRNP A2/B1 and/or splicing variant B1 alone in human lung cancer and their potential to serve as molecular markers for early diagnosis remain issues of intense investigation. The main objective of the present study was to use paired tumour/non-tumour biopsies from patients with non-small cell lung cancer (NSCLC to investigate the expression profiles of hnRNP A1, A2/B1 and A3 in conjunction with ASF/SF2. Methods We combined western blotting of tissue homogenates with immunohistochemical examination of fixed tissue sections and quantification of mRNA expression levels in tumour versus adjacent normal-looking areas of the lung in the same patient. Results Our study, in addition to clear evidence of mostly uncoupled deregulation of hnRNPs A/B, has revealed hnRNP A1 to be the most deregulated protein with a high frequency of over-expression (76%, followed by A3 (52% and A2/B1 (43%. Moreover, direct comparison of protein/mRNA levels showed a lack of correlation in the case of hnRNP A1 (as well as of ASF/SF2, but not of A2/B1, suggesting that different mechanisms underlie their deregulation. Conclusion Our results provide strong evidence for the up-regulation of hnRNP A/B in NSCLC, and they support the existence of distinct mechanisms responsible for their deregulated expression.

  3. Cyclic nucleotides differentially regulate the synthesis of tumour necrosis factor-alpha and interleukin-1 beta by human mononuclear cells

    NARCIS (Netherlands)

    Endres, S; Fülle, H J; Sinha, B; Stoll, D; Dinarello, C A; Gerzer, R; Weber, P.C.

    Recent reports have shown that phosphodiesterase (PDE) inhibitors suppress production of tumour necrosis factor-alpha (TNF-alpha) in mouse macrophages. In the present study we show that theophylline, pentoxifylline and 3-isobutyl-1-methylxanthine markedly suppress the lipopolysaccharide

  4. Low expression of DNA polymerase beta in human testicular germ cell tumours--impact on foetal gonocytic origin theory.

    Science.gov (United States)

    Nowak, Radosława; Grzybowska, Ewa A; Wilczyńska, Anna; Pykało, Roman; Siedlecki, Janusz A

    2002-01-01

    Different models of pathogenesis of adult testicular germ cell tumours (TGCTs) are presented. Analysis of telomeric length and DNA polymerase beta expression suggests that seminoma and nonseminoma, two main histological types of TGCTs, derive independently from transformed foetal primordial cells.

  5. Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater: expression differences in tumour histotypes

    Directory of Open Access Journals (Sweden)

    G. Perrone

    2010-09-01

    Full Text Available The human equilibrative nucleoside transporter 1 (hENT1 is the major means by which gemcitabine enters human cells; recent evidence exists that hENT1 is expressed in carcinoma of the ampulla of Vater and that it should be considered as a molecular prognostic marker for patients with resected ampullary cancer. Aim of the present study is to evaluate the variations of hENT1 expression in ampullary carcinomas and to correlate such variations with histological subtypes and clinicopathological parameters. Forty-one ampullary carcinomas were histologically classified into intestinal, pancreaticobiliary and unusual types. hENT1 and Ki67 expression were evaluated by immunohistochemistry, and apoptotic cells were identified by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL method. hENT1 overexpression was detected in 63.4% ampullary carcinomas. A significant difference in terms of hENT1 and Ki67 expression was found between intestinal vs. pancreaticobiliary types (P=0.03 and P=0.009 respectively. Moreover, a significant statistical positive correlation was found between apoptotic and proliferative Index (P=0.036, while no significant correlation was found between hENT1 and apoptosis. Our results on hENT1 expression suggest that classification of ampullary carcinoma by morphological subtypes may represent an additional tool in prospective clinical trials aimed at examining treatment efficacy; in addition, data obtained from Ki67 and TUNEL suggest a key role of hENT1 in tumour growth of ampullary carcinoma.

  6. Irreversible but not reversible pulpitis is associated with up-regulation of tumour necrosis factor-alpha gene expression in human pulp.

    Science.gov (United States)

    Kokkas, A B; Goulas, A; Varsamidis, K; Mirtsou, V; Tziafas, D

    2007-03-01

    To analyse the gene expression of tumour necrosis factor-alpha (TNF-alpha) in human dental pulps, under normal and inflammatory conditions and to examine the association between any observed alterations in the expression of this cytokine with the severity of the clinical symptoms. Eighteen pulpal samples were obtained from single-rooted human teeth. Six of the teeth were normal (group A), six had been diagnosed with reversible pulpitis (group B), and the remaining six were from teeth diagnosed with irreversible pulpitis (group C). TNF-alpha gene expression was semi-quantitatively analysed in each sample with RT-PCR, and the results from each group of teeth were compared with the Kruskal-Wallis and Mann-Whitney tests. Tumour necrosis factor-alpha was detected in all three groups of dental pulp. Statistical analysis provided evidence of a significant increase of TNF-alpha gene expression associated with irreversible inflammation compared with healthy controls (P = 0.002). No such difference was detected in reversibly inflamed pulp in comparison to healthy teeth (P = 0.699). Tumour necrosis factor-alpha gene expression in inflamed human dental pulp tissue is positively associated with the severity of clinical symptoms.

  7. Human Fibronectin Extra-Domain B (EDB)-Specific Aptide (APTEDB) Radiolabelling with Technetium-99m as a Potent Targeted Tumour-Imaging Agent.

    Science.gov (United States)

    Mohammadgholi, Mohsen; Sadeghzadeh, Nourollah; Erfani, Mostafa; Abediankenari, Saeid; Abedi, Seyed Mohammad; Emrarian, Iman; Jafari, Narjes; Behzadi, Ramezan

    2017-09-18

    Human fibronectin extra-domain B (EDB) is particularly expressed during angiogenesis progression. It is, thus, a promising marker of tumour growth. Aptides are a novel class of peptides with high-affinity binding to specific protein targets. APTEDB is an antagonist-like ligand that especially interacts with human fibronectin EDB. This study was the first attempt in which the hydrazinonicotinamide (HYNIC)-conjugated APTEDB was labelled with technetium-99m (99mTc) as an appropriate radiotracer and tricine/EDDA exchange labeling . Method: Radiochemical purity, normal saline, and serum stability were evaluated by HPLC and radio-isotope TLC scanner. Other examinations, such as protein-binding calculation, dissociation radioligand binding assay, and partition coefficient constant determination, were also carried out. The cellular-specific binding of 99mTc-HYNIC-conjugated APTEDB was assessed in two EDB-positive (U87MG) and EDB-negative (U373MG) cell lines. Bio-distribution was investigated in normal mice as well as in U87MG and U373MG tumour-bearing mice. Eventually, the radiolabelled APTEDB was used for tumour imaging using planar SPECT. Results: Radiolabelling was achieved with high purity (up to 97%) and accompanied by high solution (Over 90% after overnight) and serum (80% after 2 hours) stability. The obtained cellular-specific binding ratio was greater than nine-fold. In-vivo experiments showed rapid blood clearance with mainly renal excretion and tumour uptake specificity (0.48±0.03% ID/g after 1h ). The results of the imaging also confirmed considerable tumour uptake for EDB-positive cell lines compared with the EDB-negative ones. Conclusion: Aptides are considered to be a potent candidate for biopharmaceutical applications. They can be modified with imaging or therapeutic agents. This report shows the capability of 99mTc-HYNIC-APTEDB for human EDB-expressing tumour detection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. 21 CFR 882.1620 - Intracranial pressure monitoring device.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intracranial pressure monitoring device. 882.1620 Section 882.1620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... for short-term monitoring and recording of intracranial pressures and pressure trends. The device...

  9. Increased intracranial pressure

    Science.gov (United States)

    ... by pressing on important structures and by restricting blood flow into the brain. Many conditions can increase intracranial pressure. Common causes include: Aneurysm rupture and subarachnoid hemorrhage Brain tumor Encephalitis Head ...

  10. Understanding idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Markey, Keira A; Mollan, Susan P; Jensen, Rigmor H

    2016-01-01

    Idiopathic intracranial hypertension is a disorder characterised by raised intracranial pressure that predominantly affects young, obese women. Pathogenesis has not been fully elucidated, but several causal factors have been proposed. Symptoms can include headaches, visual loss, pulsatile tinnitus...... of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) reported beneficial effects of acetazolamide in patients with mild visual loss. Studies have also established weight loss as an effective disease-modifying treatment, and further clinical trials to investigate new treatments are underway....... The incidence of idiopathic intracranial hypertension is expected to increase as rates of obesity increase; efforts to reduce diagnostic delays and identify new, effective approaches to treatment will be key to meeting the needs of a growing number of patients....

  11. Pediatric Intracranial Hypertension.

    Science.gov (United States)

    Sivaswamy, Lalitha

    2016-10-01

    Investigators from the Ohio State University, Oregon Health and Science University and Rosalind Franklin School of Medicine examined the presenting manifestations, demographics and treatment strategies in children enrolled in the Intracranial Hypertension Registry (IHR).

  12. Idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Yri, Hanne M; Jensen, Rigmor H

    2015-01-01

    AIMS: The aims of this article are to characterize the headache in idiopathic intracranial hypertension (IIH) and to field-test the ICHD diagnostic criteria for headache attributed to IIH. MATERIALS AND METHODS: We included 44 patients with new-onset IIH. Thirty-four patients with suspected...... tinnitus may suggest intracranial hypertension. Based on data from a well-defined IIH cohort, we propose a revision of the ICDH-3 beta diagnostic criteria with improved clinical applicability and increased sensitivity and specificity....

  13. Molecular evidence of high-risk human papillomavirus infection in colorectal tumours from Cuban patients

    Directory of Open Access Journals (Sweden)

    Yudira Soto

    Full Text Available The association between colorectal cancer and human papillomavirus (HPV infection is still unproven. The aim of this study was to investigate the presence of high-risk HPV (HR-HPV DNA in colorectal tissues from Cuban patients. A total of 63 colorectal formalin-fixed paraffin-embedded tissues were studied (24 adenocarcinoma, 18 adenoma, and 21 colorectal tissues classified as benign colitis. DNA from colorectal samples was analysed by quantitative real-time polymerase chain reaction to detect the most clinically relevant high HR-HPV types (HPV-16, -18, -31, -33, -45, -52, and -58. Associations between histologic findings and other risk factors were also analysed. Overall, HPV DNA was detected in 23.8% (15/63 of the samples studied. Viral infections were detected in 41.7% of adenocarcinoma (10/24 and 27.7% of adenoma cases (5/18. HPV DNA was not found in any of the negative cases. An association between histological diagnosis of adenocarcinoma and HPV infection was observed (odd ratio = 4.85, 95% confidence interval = 1.40-16.80, p = 0.009. The only genotypes identified were HPV 16 and 33. Viral loads were higher in adenocarcinoma, and these cases were associated with HPV 16. This study provides molecular evidence of HR-HPV infection in colorectal adenocarcinoma tissues from Cuban patients.

  14. Cerebellopontine angle tumours in black South Africans - how rare ...

    African Journals Online (AJOL)

    Previous reports of Intracranial neoplasms from Africa have all shown a very low incidence of acoustic schwannomas (neuromas). In this series a group of 11 cerebellopontine angle solid tumours from black Africans were studied. On conventional histological examination only 3 had the features of a schwannoma. However ...

  15. Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation.

    Science.gov (United States)

    Gardiol, D; Kühne, C; Glaunsinger, B; Lee, S S; Javier, R; Banks, L

    1999-09-30

    Previous studies have shown that the oncogenic HPV E6 proteins form a complex with the human homologue of the Drosophila tumour suppressor protein, discs large (Dlg). This is mediated by the carboxy terminus of the E6 proteins and involves recognition of at least one PDZ domain of Dlg. This region of E6 is not conserved amongst E6 proteins from the low risk papillomavirus types and, hence, binding of HPV E6 proteins to Dlg correlates with the oncogenic potential of these viruses. We have performed studies to investigate the consequences of the interaction between E6 and Dlg. Mutational analysis of both the HPV18 E6 and Dlg proteins has further defined the regions of E6 and Dlg necessary for complex formation. Strikingly, co-expression of wild type HPV18 E6 with Dlg in vitro or in vivo results in a dramatic decrease in the amount of Dlg protein, whereas mutants of E6 which fail to complex with Dlg have minimal effect on Dlg protein levels. The oncogenic HPV16 E6 also decreased the Dlg levels, but this was not observed with the low risk HPV11 E6 protein. Moreover, a region within the first 544 amino acids of Dlg containing the three PDZ domains confers susceptibility to E6 mediated degradation. Finally, treatment of cells with a proteasome inhibitor overrides the capacity of E6 to degrade Dlg. These results demonstrate that Dlg is targeted by high risk HPV E6 proteins for proteasome mediated degradation.

  16. Correlation between human papillomavirus and p16 overexpression in oropharyngeal tumours: a systematic review

    Science.gov (United States)

    Grønhøj Larsen, C; Gyldenløve, M; Jensen, D H; Therkildsen, M H; Kiss, K; Norrild, B; Konge, L; von Buchwald, C

    2014-01-01

    Background: A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based on diagnostic measures and definition of p16 overexpression. We evaluated means of p16 and HPV diagnostics, and quantified overexpression of p16 in HPV-positive and -negative OP-SCCs by mode of immunohistochemical staining of carcinoma cells. Methods: PubMed, Embase, and the Cochrane Library were searched from 1980 until October 2012. We applied the following inclusion criteria: a minimum of 20 cases of site-specific OP-SCCs, and HPV and p16 results present. Studies were categorised into three groups based on their definition of p16 overexpression: verbal definition, nuclear and cytoplasmatic staining between 5 and 69%, and ⩾70% staining. Results: We identified 39 studies with available outcome data (n=3926): 22 studies (n=1980) used PCR, 6 studies (n=688) used ISH, and 11 studies (n=1258) used both PCR and ISH for HPV diagnostics. The methods showed similar HPV-positive results. Overall, 52.5% of the cases (n=2062) were HPV positive. As to p16 overexpression, 17 studies (n=1684) used a minimum of 5–69% staining, and 7 studies (n=764) used ⩾70% staining. Fifteen studies (n=1478) referred to a verbal definition. Studies showed high heterogeneity in diagnostics of HPV and definition of p16. The correlation between HPV positivity and p16 overexpression proved best numerically in the group applying ⩾70% staining for p16 overexpression. The group with verbal definitions had a significantly lower false-positive rate, but along with the group applying 5–69% staining showed a worse sensitivity compared with ⩾70% staining. Conclusions: There are substantial differences in how studies diagnose HPV and define p16 overexpression. Numerically, p16 staining is better to

  17. 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.

  18. Congenital tumours involving the head, neck and central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Vazquez, Elida; Castellote, Amparo; Mayolas, Nuria; Enriquez, Goya [Hospital Universitario Vall d' Hebron, Department of Pediatric Radiology, Barcelona (Spain); Carreras, Elena [Hospital Universitario Vall d' Hebron, Fetal Medicine Unit, Barcelona (Spain); Peiro, Jose Luis [Hospital Universitario Vall d' Hebron, Department of Paediatric Surgery, Barcelona (Spain)

    2009-11-15

    Congenital intracranial tumours are uncommon and differ from those occurring in older children in clinical presentation, imaging characteristics and prognosis. These tumours are often detected incidentally on routine prenatal US and/or fetal MRI. Hence, the paediatric radiologist should be familiar with the features of those lesions that should be included in the differential diagnosis. In general, the prognosis of these conditions is poor owing to large tumour size and the limitations of adjuvant therapy at such a young age. Congenital lesions involving the head and neck region require a meticulous imaging approach using both US and MRI techniques to better guide prenatal planning and fetal or neonatal surgical procedures. (orig.)

  19. 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....

  20. FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression

    DEFF Research Database (Denmark)

    Tornehave, D; Jensen, Charlotte Harken; Teisner, B

    1996-01-01

    tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing...... development, gradually disappeared from these cells and became restricted to insulin-producing beta cells. Throughout development FA1 was not detected in endocrine glucagon, somatostatin or pancreatic polypeptide cells. Moreover, developing insulin cells that coexpressed glucagon were negative for FA1. Thus......, there was a negative correlation between FA1 and glucagon both in tumours and during development. These results, together with FA1/dlk's similarity with homeotic proteins, point to a role of FA1 in islet cell differentiation. Udgivelsesdato: 1996-Dec...

  1. Carcino-embryonic antigen in monitoring the growth of human colon adenocarcinoma tumour cells SK-CO-1 and HT-29 in vitro and in nude mice

    DEFF Research Database (Denmark)

    Sölétormos, G; Fogh, J M; Sehested-Hansen, B

    1997-01-01

    A set of experimental model systems were designed to investigate (a) the inter-relationship between growth of two human cancer cell lines (SK-CO-1, HT-29) and carcino-embryonic antigen (CEA) kinetics; and (b) whether neoplastic growth or CEA concentration is modulated by human growth hormone (h....... In conclusion, our results suggest that experimental models may be useful for investigating the role of serological markers as monitors of increasing tumour burden. It will be of interest to investigate the performance of those model systems in examining the effect of cytotoxic agents in neoplastic growth....

  2. Manifestations of Pediatric Intracranial Hypertension From the Intracranial Hypertension Registry.

    Science.gov (United States)

    Aylward, Shawn C; Waslo, Carin S; Au, Johnathan N; Tanne, Emanuel

    2016-08-01

    The purpose of this study was to examine the presenting symptoms, demographics, and interventions in pediatric patients enrolled in the Intracranial Hypertension Registry. We analyzed confirmed intracranial hypertension patients ≤18 years at the time of initial diagnosis who were enrolled in the registry. A total of 203 patients met the criteria for inclusion; 142 (70%) were considered primary intracranial hypertension. Females made up 72.5% (103 of 142) and 75.8% (47 of 61) in the primary intracranial hypertension and secondary intracranial hypertension groups, respectively. There were no clinically significant differences in age, body mass index, or opening pressure between the primary intracranial hypertension and secondary intracranial hypertension groups. Symptoms most often reported were headache and blurred vision. Bilateral optic disc edema occurred in 89.3% of primary intracranial hypertension and 78.7% of secondary intracranial hypertension patients. When divided into pre- and postpubertal status, 32.5% of patients were classified prepubertal; 77.3% of these had primary intracranial hypertension. This resulted in a female to male ratio of 1:1.04 for prepubertal and 6:1 for postpubertal primary intracranial hypertension patients. The body mass index was significantly higher in the postpubertal primary intracranial hypertension group (P = 0.0014). There was no significant difference in opening pressure. The common symptoms of intracranial hypertension, including headache, optic disc edema, and vision changes, occurred with similar frequencies in our cohort to those reported in the literature. In separate subanalyses, we found significantly higher rates of obesity in postpubertal females with primary intracranial hypertension. The female-to-male ratios in the postpubertal primary intracranial hypertension and secondary intracranial hypertension groups were higher than reported in the literature. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 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.

  4. [Acute intracranial hypertension].

    Science.gov (United States)

    Gilo Arrojo, F; Herrera Muñoz, A; Anciones, B

    2010-10-01

    Acute intracranial hypertension is a syndrome with multiple etiologies. Diagnosis and treatment must be performed urgently to save the patient's life and prevent the development of significant disabilities. The appearance of this syndrome is due to intracraincreased volumes and -in turn- the pressure of the intracranial contents, either through an increase in the physiological components (blood, cerebrospinal fluid and brain parenchyma), or through the appearance of a volume in the form of added mass. The underlying brain edema in this condition may be of several types: cytotoxic, vasogenic, interstitial, or hydrostatic. Increased intracranial pressure decreases cerebral perfusion pressure, creating a vicious cycle because of the resulting cerebral ischemia, which progressively increases cerebral blood volume by decreasing resistance and further increases intracranial pressure. Treatment depends on the etiology and will generally require medical and surgical care. Patient management is usually carried out in neurocritical units and involves intracranial pressure monitoring to guide treatment. Correction of all hemostasis disorders is also crucial to patient survival. Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  5. A human tRNA methyltransferase 9-like protein prevents tumour growth by regulating LIN9 and HIF1-α

    Science.gov (United States)

    Begley, Ulrike; Sosa, Maria Soledad; Avivar-Valderas, Alvaro; Patil, Ashish; Endres, Lauren; Estrada, Yeriel; Chan, Clement TY; Su, Dan; Dedon, Peter C; Aguirre-Ghiso, Julio A; Begley, Thomas

    2013-01-01

    Emerging evidence points to aberrant regulation of translation as a driver of cell transformation in cancer. Given the direct control of translation by tRNA modifications, tRNA modifying enzymes may function as regulators of cancer progression. Here, we show that a tRNA methyltransferase 9-like (hTRM9L/KIAA1456) mRNA is down-regulated in breast, bladder, colorectal, cervix and testicular carcinomas. In the aggressive SW620 and HCT116 colon carcinoma cell lines, hTRM9L is silenced and its re-expression and methyltransferase activity dramatically suppressed tumour growth in vivo. This growth inhibition was linked to decreased proliferation, senescence-like G0/G1-arrest and up-regulation of the RB interacting protein LIN9. Additionally, SW620 cells re-expressing hTRM9L did not respond to hypoxia via HIF1-α-dependent induction of GLUT1. Importantly, hTRM9L-negative tumours were highly sensitive to aminoglycoside antibiotics and this was associated with altered tRNA modification levels compared to antibiotic resistant hTRM9L-expressing SW620 cells. Our study links hTRM9L and tRNA modifications to inhibition of tumour growth via LIN9 and HIF1-α-dependent mechanisms. It also suggests that aminoglycoside antibiotics may be useful to treat hTRM9L-deficient tumours. PMID:23381944

  6. Sesquiterpene Lactones Isolated from Elephantopus scaber L. Inhibits Human Lymphocyte Proliferation and the Growth of Tumour Cell Lines and Induces Apoptosis In Vitro

    Science.gov (United States)

    Geetha, B. S.; Nair, Mangalam S.; Latha, P. G.; Remani, P.

    2012-01-01

    This study was designed to isolate the compounds responsible for the cytotoxic properties of South Indian Elephantopus scaber L. and further investigate their effects on quiescent and proliferating cells. Bioassay-guided isolation of the whole plant of chloroform extract of South Indian Elephantopus scaber afforded the known sesquiterpene lactone, deoxyelephantopin, and isodeoxyelephantopin whose structures were determined by spectroscopic methods. These compounds caused a dose dependent reduction in the viability of L-929 tumour cells in 72 h culture (IC50 value of 2.7 μg/mL and 3.3 μg/mL) by the cell viability assay. Both the compounds act selectively on quiescent and PHA-stimulated proliferating human lymphocytes and inhibited tritiated thymidine incorporation into cellular DNA of DLA tumour cells. The compound deoxyelephantopin at a concentration of 3 μg/mL caused maximum apoptotic cells. It also exhibited significant in vivo antitumour efficacy against DLA tumour cells. The results, therefore, indicate that the antiproliferative property of deoxyelephantopin and isodeoxyelephantopin could be used in regimens for treating tumors with extensive proliferative potencies. PMID:22500104

  7. Sesquiterpene Lactones Isolated from Elephantopus scaber L. Inhibits Human Lymphocyte Proliferation and the Growth of Tumour Cell Lines and Induces Apoptosis In Vitro

    Directory of Open Access Journals (Sweden)

    B. S. Geetha

    2012-01-01

    Full Text Available This study was designed to isolate the compounds responsible for the cytotoxic properties of South Indian Elephantopus scaber L. and further investigate their effects on quiescent and proliferating cells. Bioassay-guided isolation of the whole plant of chloroform extract of South Indian Elephantopus scaber afforded the known sesquiterpene lactone, deoxyelephantopin, and isodeoxyelephantopin whose structures were determined by spectroscopic methods. These compounds caused a dose dependent reduction in the viability of L-929 tumour cells in 72 h culture (IC50 value of 2.7 μg/mL and 3.3 μg/mL by the cell viability assay. Both the compounds act selectively on quiescent and PHA-stimulated proliferating human lymphocytes and inhibited tritiated thymidine incorporation into cellular DNA of DLA tumour cells. The compound deoxyelephantopin at a concentration of 3 μg/mL caused maximum apoptotic cells. It also exhibited significant in vivo antitumour efficacy against DLA tumour cells. The results, therefore, indicate that the antiproliferative property of deoxyelephantopin and isodeoxyelephantopin could be used in regimens for treating tumors with extensive proliferative potencies.

  8. Intracranial Hypertension: Medication and Surgery

    Science.gov (United States)

    ... have little effect on headaches caused by intracranial hypertension, they may temporarily affect the intensity of a ... study in which 26 patients with idiopathic intracranial hypertension (IIH) were treated with octreotide, a synthetic hormone ...

  9. Pseudotumour cerebri Idiopathic intracranial hypertension and vascular intracranial hypertension

    Directory of Open Access Journals (Sweden)

    Iencean St. M.

    2015-12-01

    Full Text Available From the first to use of “pseudotumor cerebri” by Nonne in 1904, the historic evolution of the knowledge on pseudotumor cerebri has been marked by several periods (the otologic stage, the neurosurgical stage, the neuro-ophthalmologic stage; today there are clear diagnosis criteria for the idiopathic intracranial hypertension, there is a clear differentiation between idiopathic intracranial hypertension and vascular intracranial hypertension, also the comprehension of the illness pathogeny is based on the dynamics of the intracranial fluids, which allows the auto-regulation of the cerebral circulation within quasi-normal limits, despite the very high intracranial pressure.

  10. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Almstrup, K; Nielsen, J E

    2005-01-01

    AIMS: NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and pluripotency. Our recent genome-wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG...... earlier than for OCT-4. We detected no expression at the protein level in normal testis. CONCLUSIONS: NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT-4 are determinants of the stem cell-like pluripotency of the preinvasive CIS cell. Timing of NANOG......; seminoma and embryonal carcinoma were strongly positive, differentiated somatic elements of teratoma were negative. We provide evidence for the fetal origin of testicular cancer as we detected strong expression of NANOG in fetal gonocytes up to gestational week 20, with subsequent down-regulation occurring...

  11. Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation.

    Science.gov (United States)

    Winship, Amy Louise; Rainczuk, Kate; Ton, Amanda; Dimitriadis, Eva

    2016-07-01

    Endometrial cancer is the most common invasive gynaecological malignancy. While endocrine, genetic and inflammatory factors are thought to contribute to its pathogenesis, its precise etiology and molecular regulators remain poorly understood. Fibulin-5 is an extracellular matrix (ECM) protein that inhibits cell growth and invasion in several cancer cell types and is downregulated in a number of types of human cancer. However, it is unknown whether fibulin-5 plays a role in endometrial tumourigenesis. In the current report, the expression and localisation of fibulin-5 in type I endometrioid human endometrial cancers of grades (G) 1-3 was investigated using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Fibulin-5 mRNA was found to be significantly reduced in whole tumour tissues from women across G1-3 compared with benign endometrium (Pendometrial epithelial cancer cells expressing fibulin-5 stimulated cell adhesion and proliferation in vitro . Fibulin-5 mRNA expression in Ishikawa cells was induced by transforming growth factor-β and fibulin-5 in turn activated extracellular signal-regulated kinases (ERK1/2), suggesting that it may act via the mitogen-activated protein kinase pathway. In summary, the present study identified fibulin-5 as a downregulated ECM gene in human endometrial cancer and observed a shift from epithelial to stromal protein localisation with increasing tumour grade in women. These data suggest that loss of fibulin-5 function may promote endometrial cancer progression by enhancing epithelial cell adhesion and proliferation.

  12. Semantic category-based decoding of human brain activity using a Gabor-based model by estimating intracranial field potential range in temporal cortex.

    Science.gov (United States)

    Jahromy, Fateme Zareayan; Daliri, Mohammed Reza

    2017-01-01

    Predicting and decoding the recorded neural activity for visual stimuli is the topic of many studies. This prediction can be made by comparing the model's responses to different stimuli with the available recorded brain signal. The neural activities can be decoded then by finding the stimulus which has generated the nearest model's response to the recorded signal. In this study, a model is proposed which can estimate the response of human brain to images from different conceptual categories by inserting the visual stimuli as the model input after filtering by Gabor wavelets. This helped us to find each image's low level visual features. Afterward, the extracted image features were applied to the input of a curve fitting neural network. As the output, the range of intracranial field potential was estimated. This was performed separately for each pixel of the image. To evaluate the model's accuracy, two factors were used, namely the Pearson correlation and Normalized root mean square error. The results show that the proposed model can accurately estimate the brain's response to conceptual categories To decode the brain' activity based on the observed semantic category in each test observations by using of the model, we calculated the distance between the recorded signal and the model responses to all stimuli from different categories and assigned the category of the nearest model response to brain's response in that trial. To this end, a K-nearest neighbors classifier based on Euclidean distance was used. This leaded to a classification accuracy which was significantly higher than chance level. So, the proposed model can be used to decode the activity of the brain in response to the visual stimuli.

  13. Extracellular RNAs: development as biomarkers of human disease

    Directory of Open Access Journals (Sweden)

    Joseph F. Quinn

    2015-08-01

    Full Text Available Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

  14. Intracranial artery dissection

    NARCIS (Netherlands)

    Sikkema, T.; Uyttenboogaart, Maarten; Eshghi, O.; De Keyser, J.; Brouns, R.; van Dijk, J.M.C.; Luijckx, G. J.

    The aim of this narrative review is to evaluate the pathogenesis, clinical features, diagnosis, treatment and prognosis of intracranial artery dissection (IAD). IAD is a rare and often unrecognized cause of stroke or subarachnoid haemorrhage (SAH), especially in young adults. Two types of IAD can be

  15. Intracranial saccular aneurysm

    Directory of Open Access Journals (Sweden)

    J. R. Pinto

    1992-12-01

    Full Text Available The authors report the cases of three patients from the same family, all with intracranial saccular aneurysm (left carotid artery, anterior communicating artery, and middle cerebral artery. All three patients were operated on with good recovery and no complications. The authors call attention for some etipathogenic aspects of familial saccular aneurysms.

  16. Intracranial tuberculoma: MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Salgado, P.; Zenteno, M.A.; Rodriguez-Carbajal, J.; Brutto, O.H. del; Talamas, O.

    1989-09-01

    MR studies of 6 patients with intracranial tuberculoma are reviewed. All patients also underwent CT scans which showed hypo- or isodense lesions with abnormal enhancement following contrast administration. MR showed lesions with prolongation of the T1 relaxation time in every case. On the T2-weighted sequences, the signal properties of the tuberculoma varied according to the stage of evolution of the lesion. Incipient tuberculomas appeared as scattered areas of hypointensity surrounded by edema. Mature tuberculomas were composed of a dark necrotic center surrounded by an isointense capsule which was, in turn, surrounded by edema. In one patient, the center of the lesion was hyperintense probably because of liquefaction and pus formation (tuberculous abscess). While both, CT and MR, were equally sensitive in visualizing the intracranial tuberculoma in every patient, MR was slightly superior in demonstrating the extent of the lesion, especially for brainstem tuberculomas. Nevertheless, the potential role for MR diagnosis of intracranial tuberculoma is limited by the fact that other infectious or neoplasic diseases may present similar findings. The diagnosis of intracranial tuberculoma should rest on a proper integration of data from clinical manifestations, cerebrospinal fluid analysis, and neuroimaging studies. (orig.).

  17. Intracranial Pressure Monitoring

    DEFF Research Database (Denmark)

    Raboel, P H; Bartek, J; Andresen, M

    2012-01-01

    Monitoring of intracranial pressure (ICP) has been used for decades in the fields of neurosurgery and neurology. There are multiple techniques: invasive as well as noninvasive. This paper aims to provide an overview of the advantages and disadvantages of the most common and well-known methods...

  18. 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

  19. Mapping effective connectivity in the human brain with concurrent intracranial electrical stimulation and BOLD-fMRI.

    Science.gov (United States)

    Oya, Hiroyuki; Howard, Matthew A; Magnotta, Vincent A; Kruger, Anton; Griffiths, Timothy D; Lemieux, Louis; Carmichael, David W; Petkov, Christopher I; Kawasaki, Hiroto; Kovach, Christopher K; Sutterer, Matthew J; Adolphs, Ralph

    2017-02-01

    Understanding brain function requires knowledge of how one brain region causally influences another. This information is difficult to obtain directly in the human brain, and is instead typically inferred from resting-state fMRI. Here, we demonstrate the safety and scientific promise of a novel and complementary approach: concurrent electrical stimulation and fMRI (es-fMRI) at 3T in awake neurosurgical patients with implanted depth electrodes. We document the results of safety testing, actual experimental setup, and stimulation parameters, that safely and reliably evoke activation in distal structures through stimulation of amygdala, cingulate, or prefrontal cortex. We compare connectivity inferred from the evoked patterns of activation with that estimated from standard resting-state fMRI in the same patients: while connectivity patterns obtained with each approach are correlated, each method produces unique results. Response patterns were stable over the course of 11min of es-fMRI runs. COMPARISON WITH EXISTING METHOD: es-fMRI in awake humans yields unique information about effective connectivity, complementing resting-state fMRI. Although our stimulations were below the level of inducing any apparent behavioral or perceptual effects, a next step would be to use es-fMRI to modulate task performances. This would reveal the acute network-level changes induced by the stimulation that mediate the behavioral and cognitive effects seen with brain stimulation. es-fMRI provides a novel and safe approach for mapping effective connectivity in the human brain in a clinical setting, and will inform treatments for psychiatric and neurodegenerative disorders that use deep brain stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. 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.

  1. In vivo 1H-spectroscopy of human intracranial tumors at 1.5 tesla. Preliminary experience at a clinical installation

    DEFF Research Database (Denmark)

    Henriksen, O; Wieslander, S; Gjerris, F

    1991-01-01

    Magnetic resonance spectroscopy (MRS) may contribute to the characterization of intracranial tumors in vivo. Volume selective water suppressed proton spectroscopy offers the possibility to study a number of metabolites in the brain including choline (CHO), creatinine/phosphocreatinine (CR/PCR), N....... However, further research is warranted before a definite conclusion can be drawn....

  2. In vivo 1H-spectroscopy of human intracranial tumors at 1.5 tesla. Preliminary experience at a clinical installation

    DEFF Research Database (Denmark)

    Henriksen, O; Wieslander, S; Gjerris, F

    1991-01-01

    Magnetic resonance spectroscopy (MRS) may contribute to the characterization of intracranial tumors in vivo. Volume selective water suppressed proton spectroscopy offers the possibility to study a number of metabolites in the brain including choline (CHO), creatinine/phosphocreatinine (CR/PCR), N...

  3. 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)

  4. Anaesthetic management for caesarean section in a case of previously operated with residual pituitary tumour

    Directory of Open Access Journals (Sweden)

    Prerana N Shah

    2011-01-01

    Full Text Available Successful anaesthetic management for caesarean section in a case with previous pituitary tumour resection, with residual tumour, is reported. The pituitary gland undergoes global hyperplasia during pregnancy. Functional pituitary tumours may exhibit symptomatic enlargement during pregnancy. Growth hormone secreting tumour is associated with acromegaly which has associated anaesthetic implications of difficult airway, systemic hypertension, and diabetes and electrolyte imbalance. Intracranial space occupying lesions can increase intra cranial pressure and compromise cerebral perfusion or cause herniation. We report management of this case.

  5. MRI of intracranial calcifications

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Jin Wha; Chang, Kee Hyun; Park, Jung Mi; Han, Moon Hee; Han, Man Chung; Kim, Chu Wan [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1988-12-15

    Recently computed tomography(CT) has been rapidly replaced by magnetic resonance imaging (MRI) in diagnosis of majority of intracranial diseases. But MRI still has some limitation, one of which is its inferiority in detecting calcification. MRI of intracranial calcification has been known to be variable in signal intensity. We retrospectively analyzed the MRI of 26 patients with intracranial calcified lesions in order to evaluate the MR intensity of calcification and to assess the capability of MRI in detecting calcification in various intracranial lesions. All the MRI were obtained using routine T1-and T2-weighted spin eco pulse sequences on 2.0T superconducting system. The 26 patients consisted of 13 brain tumors (4 oligodendrogliomas, 2 craniopharyngiomas, 2 astrocytomas, 1 gem cell tumor, 1 medulloblastoma, 1 ependympma, and pathologically unconfirmed 2 cases), 11 infectious diseases (1 paragonimiasis, 1 sparganosis, 2 cysticercosis, 3 tuberculosis, and 4 unknown cases), and 2 undetermined pathologies. Eighty-two percent (9/11) of infections disease, and 50% (1/2) of undetermined group showed signal diminution or signal void on both T1-and T2-weighted image (T1W1, T2W1). Twenty-four percent (3/13) of brain tumors showed signal diminution on both T1W1 and T2W1. In 46% (6/13) and 61% (8/13) of brain tumors the signal intensities were isointense on T1W1 and T1W1, respectively. Unexpectedly, 3 oligodendrogliomas showed high signal intensity on T1W1, two of which showed com plexed signal intensity mixed with high, iso, and low signal intensities on T2W1. In remained cases (18% (2/11) of infectious diseases and 50% (1/2) of undetermined group) the signal intensities were mixed. With simultaneous review of CT and MRI in each case, the calcification (at least one in cases showing multiple ones) was identifiable on MRI in 62% (8/13) of rumors, 82% (9/11) of infectious diseases, and 100% (2/2) in undetermined group. In 36% (4/11) of infectious diseases, fewer number of

  6. 123I-2-iodo-tyrosine, a new tumour imaging agent: human biodistribution, dosimetry and initial clinical evaluation in glioma patients.

    Science.gov (United States)

    Keyaerts, Marleen; Lahoutte, Tony; Neyns, Bart; Caveliers, Vicky; Vanhove, Chris; Everaert, Hendrik; Kersemans, Ken; Franken, Philippe R; Mertens, John; Bossuyt, Axel

    2007-07-01

    123I-2-iodo-tyrosine (123I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients. For the biodistribution study, six male volunteers received 60-95 MBq 123I-2IT. Whole-body scans and blood and urine samples were obtained up to 24 h after injection; dosimetry was calculated using OLINDA 1.0 software. Initial clinical evaluation of 123I-2IT SPECT was performed in 35 patients with suspected or known glioma, either as primary diagnosis or for detection of recurrence. Tumour-to-background (T/B) ratios were calculated for semi-quantitative analysis. The results were correlated with clinical and MRI follow-up data or histology. 123I-2IT showed both renal and intestinal clearance. Bladder (0.12 mGy/MBq) and small intestine (0.03 mGy/MBq) received the highest absorbed doses. The effective dose equivalent and effective dose were estimated at 0.020 and 0.016 mSv/MBq, respectively. In patients, 123I-2IT SPECT did not differentiate between neoplastic and non-neoplastic lesions after an indeterminate MRI. In follow-up of known glioma, 13/15 patients with disease recurrence had increased T/B values (range 1.39-3.91). Out of seven recurrence-negative patients, two showed an important increase in T/B, in one case due to radionecrosis (T/B 1.59) and in the other probably due to residual but stable disease (T/B 2.07). 123I-2IT has a favourable biodistribution for a tumour imaging agent. It shows increased uptake in central nervous system glioma and is potentially useful in the follow-up of glioma patients.

  7. 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.

  8. Ochratoxin A in human blood in relation to Balkan endemic nephropathy and urinary tract tumours in Bulgaria.

    Science.gov (United States)

    Petkova-Bocharova, T; Castegnaro, M

    1991-01-01

    Ochratoxin A is suspected of being one of the etiological agents responsible for Balkan endemic nephropathy and the associated urinary tract tumours. Contamination of cereals by this mycotoxin has been found to be more frequent in areas of endemic nephropathy than in areas where the disease is absent. As ochratoxin A binds to serum albumin, it should be detectable in biological fluids from exposed populations. A survey was thus conducted to determine the occurrence of ochratoxin A in blood from people living in the endemic area who were either affected or unaffected by the two diseases and in blood from people living in control regions where these diseases do not occur. Blood samples were collected in 1984, 1986, 1989 and 1990. Ochratoxin A was found more frequently and at higher levels in blood from patients with Balkan endemic nephropathy and/or urinary tract tumours than in blood from unaffected people from endemic and control areas. These findings suggest further that ochratoxin A is involved in the etiology of the two diseases.

  9. Intracranial Atherosclerotic Disease

    Directory of Open Access Journals (Sweden)

    Maria Khan

    2011-01-01

    Full Text Available Intracranial atherosclerotic disease (ICAD is the most common proximate mechanism of ischemic stroke worldwide. Approximately half of those affected are Asians. For diagnosis of ICAD, intra-arterial angiography is the gold standard to identify extent of stenosis. However, noninvasive techniques including transcranial ultrasound and MRA are now emerging as reliable modalities to exclude moderate to severe (50%–99% stenosis. Little is known about measures for primary prevention of the disease. In terms of secondary prevention of stroke due to intracranial atherosclerotic stenosis, aspirin continues to be the preferred antiplatelet agent although clopidogrel along with aspirin has shown promise in the acute phase. Among Asians, cilostazol has shown a favorable effect on symptomatic stenosis and is of benefit in terms of fewer bleeds. Moreover, aggressive risk factor management alone and in combination with dual antiplatelets been shown to be most effective in this group of patients. Interventional trials on intracranial atherosclerotic stenosis have so far only been carried out among Caucasians and have not yielded consistent results. Since the Asian population is known to be preferentially effected, focused trials need to be performed to establish treatment modalities that are most effective in this population.

  10. {sup 213}Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience

    Energy Technology Data Exchange (ETDEWEB)

    Kratochwil, C.; Giesel, F.L.; Mier, W.; Haberkorn, U. [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Bruchertseifer, F.; Apostolidis, C.; Morgenstern, A. [European Commission, Institute for Transuranium Elements, Karlsruhe (Germany); Boll, R.; Murphy, K. [Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    2014-11-15

    Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as {sup 90}Y/{sup 177}Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with {sup 213}Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with {sup 90}Y/{sup 177}Lu-DOTATOC were treated with an intraarterial infusion of {sup 213}Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of {sup 213}Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and {sup 68}Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. The biodistribution of {sup 213}Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses. (orig.)

  11. European Organisation for Research and Treatment of Cancer (EORTC) Pathobiology Group standard operating procedure for the preparation of human tumour tissue extracts suited for the quantitative analysis of tissue-associated biomarkers.

    Science.gov (United States)

    Schmitt, Manfred; Mengele, Karin; Schueren, Elisabeth; Sweep, Fred C G J; Foekens, John A; Brünner, Nils; Laabs, Juliane; Malik, Abha; Harbeck, Nadia

    2007-03-01

    With the new concept of 'individualized treatment and targeted therapies', tumour tissue-associated biomarkers have been given a new role in selection of cancer patients for treatment and in cancer patient management. Tumour biomarkers can give support to cancer patient stratification and risk assessment, treatment response identification, or to identifying those patients who are expected to respond to certain anticancer drugs. As the field of tumour-associated biomarkers has expanded rapidly over the last years, it has become increasingly apparent that a strong need exists to establish guidelines on how to easily disintegrate the tumour tissue for assessment of the presence of tumour tissue-associated biomarkers. Several mechanical tissue (cell) disruption techniques exist, ranging from bead mill homogenisation and freeze-fracturing through to blade or pestle-type homogenisation, to grinding and ultrasonics. Still, only a few directives have been given on how fresh-frozen tumour tissues should be processed for the extraction and determination of tumour biomarkers. The PathoBiology Group of the European Organisation for Research and Treatment of Cancer therefore has devised a standard operating procedure for the standardised preparation of human tumour tissue extracts which is designed for the quantitative analysis of tumour tissue-associated biomarkers. The easy to follow technical steps involved require 50-300 mg of deep-frozen cancer tissue placed into small size (1.2 ml) cryogenic tubes. These are placed into the shaking flask of a Mikro-Dismembrator S machine (bead mill) to pulverise the tumour tissue in the capped tubes in the deep-frozen state by use of a stainless steel ball, all within 30 s of exposure. RNA is isolated from the pulverised tissue following standard procedures. Proteins are extracted from the still frozen pulverised tissue by addition of Tris-buffered saline to obtain the cytosol fraction of the tumour or by the Tris buffer supplemented with

  12. Molecular Genetics of Intracranial Meningiomas with Emphasis on Canonical Wnt Signalling

    Directory of Open Access Journals (Sweden)

    Nives Pećina-Šlaus

    2016-07-01

    Full Text Available Research over the last decade recognized the importance of novel molecular pathways in pathogenesis of intracranial meningiomas. In this review, we focus on human brain tumours meningiomas and the involvement of Wnt signalling pathway genes and proteins in this common brain tumour, describing their known functional effects. Meningiomas originate from the meningeal layers of the brain and the spinal cord. Most meningiomas have benign clinical behaviour and are classified as grade I by World Health Organization (WHO. However, up to 20% histologically classified as atypical (grade II or anaplastic (grade III are associated with higher recurrent rate and have overall less favourable clinical outcome. Recently, there is emerging evidence that multiple signalling pathways including Wnt pathway contribute to the formation and growth of meningiomas. In the review we present the synopsis on meningioma histopathology and genetics and discuss our research regarding Wnt in meningioma. Epithelial-to-mesenchymal transition, a process in which Wnt signalling plays an important role, is shortly discussed.

  13. Nuclear localization of E-cadherin but not beta-catenin in human ovarian granulosa cell tumours and normal ovarian follicles and ovarian stroma.

    Science.gov (United States)

    Ohishi, Yoshihiro; Oda, Yoshinao; Kurihara, Shuichi; Kaku, Tsunehisa; Kobayashi, Hiroaki; Wake, Norio; Tsuneyoshi, Masazumi

    2011-02-01

    The role of misregulated Wnt/beta-catenin signalling in human ovarian granulosa cell tumour (GCT) has not been well characterized. The aim of this study was to confirm subcellular localization of key molecules of Wnt signalling (beta-catenin and E-cadherin) in human ovarian GCTs. Tissue samples taken from 32 human ovarian GCTs and 19 human normal ovaries containing 68 follicles were stained immunohistochemically using monoclonal anti-beta-catenin and anti-E-cadherin antibodies. None of the 32 GCTs and none of the 68 ovarian follicles showed beta-catenin nuclear expression (0%). On the other hand, 28 of 32 GCTs (88%) and 53 of 68 normal ovarian follicles (78%) showed nuclear expression of E-cadherin in granulosa cells. The ovarian stroma in all 19 normal ovaries showed nuclear expression of E-cadherin but not beta-catenin. Membranous and cytoplasmic expression was observed variously in ovarian GCT, follicles and stroma. We have confirmed frequent nuclear localization of E-cadherin but not beta-catenin in human ovarian GCT, ovarian follicles and stroma. There is no evidence of misregulated Wnt/beta-catenin signalling (represented by nuclear expression of beta-catenin) in human ovarian GCT. Nuclear translocation of E-cadherin might contribute to ovarian folliculogenesis or granulosa/stromal cell differentiation. © 2011 Blackwell Publishing Limited.

  14. 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

  15. 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

  16. Intracranial germinoma with ventricular system dissemination

    Directory of Open Access Journals (Sweden)

    Shi-yun CHEN

    2014-05-01

    Full Text Available Objective To study the clinical, neuroimaging and histopathological features of intracranial germinoma.  Methods One case of intracranial germinoma with ventricular system dissemination was reported, and related literatures were reviewed.  Results A 34-year-old male complained of progressive dizziness for 30 d and manifested unsteady gait for 45 d. Radiological examinations revealed low signal intensity on T1WI and hyperintense on T2WI in the corpus callosum, left cerebellum, around the fourth ventricle, aqueduct mesencephalon, the ventral pons and pineal region, with even or uneven enhancement after contrast. The clinical initial diagnosis was "intracranial multiple focal lesions and high possibility of multiple sclerosis". After well response to glucocorticoid impact and dehydration, the patient stopped taking drugs but presented relapse and exacerbation. Later, he underwent biopsy on pineal region and was diagnosed as intracranial germinoma. Microscopically, the big germ cells and lymphocytes coexisted. Tumor cells were epithelioid cells with transparent cytoplasm, prominent nuclei and mitotic activity. Lymphocytes were distributed along interstitial substance of vessel and fiber, and individual syncytiotrophoblasts were sprasely distributed. Immunohistochemical staining showed tumor cells were positive for CD117 and OCT3/4, and the syncytiotrophoblasts were positive for β-human chorionic gonadotropin ( β-hCG. The clinical symptoms were completely alleviated after radiotherapy and chemotherapy.  Conclusions Because of the sensitivity for radiotherapy and chemotherapy, intracranial germinoma can be diagnosed and treated early to improve its prognosis. However, it is very easy to disseminate along with ventricular system and form multiple lesions, leading to atypical clinical and imaging manifestations, which is a big challenge for clinical diagnosis. doi: 10.3969/j.issn.1672-6731.2014.05.010

  17. Rebound intracranial hypertension: a complication of epidural blood patching for intracranial hypotension.

    Science.gov (United States)

    Kranz, P G; Amrhein, T J; Gray, L

    2014-06-01

    Rebound intracranial hypertension is a complication of epidural blood patching for treatment of intracranial hypotension characterized by increased intracranial pressure, resulting in potentially severe headache, nausea, and vomiting. Because the symptoms of rebound intracranial hypertension may bear some similarity to those of intracranial hypotension and literature reports of rebound intracranial hypertension are limited, it may be mistaken for refractory intracranial hypotension, leading to inappropriate management. This clinical report of 9 patients with confirmed rebound intracranial hypertension reviews the clinical characteristics of patients with this condition, emphasizing factors that can be helpful in discriminating rebound intracranial hypertension from refractory spontaneous intracranial hypotension, and discusses treatment. © 2014 by American Journal of Neuroradiology.

  18. INTRACRANIAL PRESSURE MONITORING

    Directory of Open Access Journals (Sweden)

    Retno Widiyanthi

    2013-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Intracranial pressure is total of pressure that is produced by brain, blood, and cerebrospinal fluid/CSF in the tight cranial space. As a respon to intracranial pressure increasing, compensation begin by movement of CSF from ventricle to cerebral subarachnoidal space, and increase the absorption of CSF. Increasing of ICP usually caused by increasing of brain volume (cerebral oedem, blood (intracranial bleeding, space occupying lesion, or CSF (hidrocephalus. Indication in ICP monitoring can be seen from : neurological criteria, abnormal CT-scan result when admission, normal CT-scan result, but had more two risk factors. According to the procedure that must be done, there are two methods in ICP monitoring: invasive ICP monitoring methodes and non-invasive measuring method. Increasing of ICP will decrease the compliance of brain, pulsation of artery more clearly, and the component of vein is lost. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  19. Sinogenic intracranial complications

    DEFF Research Database (Denmark)

    Kofoed, Mikkel Seremet; Fisker, Niels; Christensen, Anne Estmann

    2018-01-01

    and subcortical abscesses in combination with sinusitis. She was treated with endoscopic sinus surgery and intravenous antibiotics. Both patients had developed psoriasis and episodes of infection during treatment. They were non-septic and had low fever on presentation. None of the patients suffered any long......We present two 11-year-old girls with chronic recurrent multifocal osteomyelitis, treated with adalimumab. Both developed severe intracranial complications to sinusitis. Patient 1 had been treated with adalimumab for 15 months when she developed acute sinusitis complicated by an orbital abscess...

  20. Effects of treatment with a fully human anti-tumour necrosis factor alpha monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNFalpha in patients with rheumatoid arthritis.

    NARCIS (Netherlands)

    Barrera Rico, P.; Joosten, L.A.B.; Broeder, A. den; Putte, L.B.A. van de; Riel, P.L.C.M. van; Berg, W.B. van den

    2001-01-01

    OBJECTIVES: To study the short term effects of a single dose of D2E7, a fully human anti-tumour necrosis factor (TNFalpha) monoclonal antibody (mAb), on the local and systemic homeostasis of interleukin 1beta (IL1beta) and TNFalpha in patients with rheumatoid arthritis (RA). METHODS: All patients

  1. Comparison of the monoclonal antibodies 17-1A and 323/A3 : The influence of the affinity on tumour uptake and efficacy of radioimmunotherapy in human ovarian cancer xenografts

    NARCIS (Netherlands)

    Kievit, E; Pinedo, HM; Schluper, HMM; Haisma, HJ; Boven, E

    The low-affinity monoclonal antibody (MAb) chimeric 17-1A(c-17-1A) and the high-affinity MAb mouse 323/A3 (m-323/A3) were used to study the effect of the MAb affinity on the tumour uptake and efficacy of radioimmunotherapy in nude mice bearing subcutaneously the human ovarian cancer xenografts FMa,

  2. Sertoliform cystadenoma: a rare benign tumour of the rete testis.

    Science.gov (United States)

    Bremmer, Felix; Schweyer, Stefan; Behnes, Carl Ludwig; Blech, Manfred; Radzun, Heinz Joachim

    2013-02-14

    Sertoliform cystadenoma of the rete testis represents an uncommon benign tumour. They appear in patients from 26 to 62 years of age. We describe a case of a 66-year-old man with a tumour in the area of the epididymal head. The tumour markers were not increased. Under the assumption of a malignant testicular tumour an inguinal orchiectomy was performed. The cut surface of this tumour was of grey/white color and showed small cysts. The tumour consisted of two compartments. The epithelial like tumour cells showed a sertoliform growth pattern and cystic dilatations. In between the tumour cells repeatedly actin expressing sclerotic areas could be recognized as the second tumour component. Proliferative activity was not increased. Immunohistochemically the tumour cells were positiv for inhibin, S-100, and CD 99. Alpha feto protein (AFP), human chorionic gonadotropin (ß-HCG) and placental alkaline phosphatase (PLAP) as well as synaptophysin, epithelial membrane antigene (EMA), and BCL-2 were not expressed. As far as we know this is the sixth reported case of this tumour. Because of the benign nature of this tumour the correct diagnosis is important for the intra- and postoperative management. Here we present a case of this rare tumour and discuss potential differential diagnosis. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956026143857335.

  3. Effect of an anti-human Co-029/tspan8/Tspan8 mouse monoclonal antibody on tumour growth in a nude mouse model

    Directory of Open Access Journals (Sweden)

    Naouel eAilane

    2014-09-01

    Full Text Available New therapeutic agents are needed in digestive tract tumours. Co-029/tspan8 is a tetraspanin frequently expressed on human colorectal tumours, In this work, we report the effects of the monoclonal antibody Ts29.2, targeting Co-029/tspan8, on colorectal tumor cells in vitro and after implantation in nude mice. HT29, Isreco1 and SW480 colorectal tumor cell lines were used for this study. HT29 has a strong endogenous expression of Co-029/tspan8, whereas Isreco1 cells don’t express Co-029/tspan8 and SW480 has only a weak expression. Isreco1 and SW480 were transduced to express Co-029/tspan8 at the same level as HT29. In order to check the specificity of the effect of monoclonal antibody Ts29.2, low Co029/tspan8 expressing SW480 cells were injected simultaneously with transduced cells in the back, on the left and right sides of the mice. With an early treatment, Ts29.2 mAb inhibited growth of tumors expressing Co-029/tspan8 up to 70%, whereas a delayed treatment was less efficient. No effect of the antibody on cell proliferation or apoptosis induction was detected in vitro. No increase of activated caspase 3 labeling was observed in vivo and areas occupied by vessels were not significantly different between treated mice and controls. This suggests that the action of Ts29.2 is linked neither to cellular toxicity nor to the inhibition of the previously reported angiogenic properties of Co-029/tspan8. An inhibition of cell proliferation in vivo is demonstrated by a reduction of the mitotic index in HT29 tumors of Ts29.2 treated mice. The discrepancy between in vitro and in vivo data on cell proliferation suggests that the binding of Ts29.2 to tumour cells may modify their response to signals issued from the microenvironment. Given the restricted pattern of tissue expression of the tetraspanin Co-029/tspan8, these preliminary results put forth for consideration the antibody targeting of this tetraspanin in further investigations for therapeutic

  4. {sup 123}I-2-iodo-tyrosine, a new tumour imaging agent: human biodistribution, dosimetry and initial clinical evaluation in glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Keyaerts, Marleen; Lahoutte, Tony; Caveliers, Vicky; Vanhove, Chris; Franken, Philippe R.; Bossuyt, Axel [Academic Hospital, Vrije Universiteit Brussel AZ-VUB, Department of Nuclear Medicine, Brussels (Belgium); ICMIC Brussels, Vrije Universiteit Brussel VUB, In Vivo Cellular and Molecular Imaging Center, Brussels (Belgium); Neyns, Bart [Academic Hospital, Vrije Universiteit Brussel AZ-VUB, Department of Medical Oncology, Oncologisch Centrum, Brussels (Belgium); Everaert, Hendrik; Kersemans, Ken; Mertens, John [Academic Hospital, Vrije Universiteit Brussel AZ-VUB, Department of Nuclear Medicine, Brussels (Belgium)

    2007-07-15

    {sup 123}I-2-iodo-tyrosine ({sup 123}I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients. For the biodistribution study, six male volunteers received 60-95 MBq {sup 123}I-2IT. Whole-body scans and blood and urine samples were obtained up to 24 h after injection; dosimetry was calculated using OLINDA 1.0 software. Initial clinical evaluation of {sup 123}I-2IT SPECT was performed in 35 patients with suspected or known glioma, either as primary diagnosis or for detection of recurrence. Tumour-to-background (T/B) ratios were calculated for semi-quantitative analysis. The results were correlated with clinical and MRI follow-up data or histology. {sup 123}I-2IT showed both renal and intestinal clearance. Bladder (0.12 mGy/MBq) and small intestine (0.03 mGy/MBq) received the highest absorbed doses. The effective dose equivalent and effective dose were estimated at 0.020 and 0.016 mSv/MBq, respectively. In patients, {sup 123}I-2IT SPECT did not differentiate between neoplastic and non-neoplastic lesions after an indeterminate MRI. In follow-up of known glioma, 13/15 patients with disease recurrence had increased T/B values (range 1.39-3.91). Out of seven recurrence-negative patients, two showed an important increase in T/B, in one case due to radionecrosis (T/B 1.59) and in the other probably due to residual but stable disease (T/B 2.07). {sup 123}I-2IT has a favourable biodistribution for a tumour imaging agent. It shows increased uptake in central nervous system glioma and is potentially useful in the follow-up of glioma patients. (orig.)

  5. Pediatric Intracranial Hypertension.

    Science.gov (United States)

    Aylward, Shawn C; Reem, Rachel E

    2017-01-01

    Primary (idiopathic) intracranial hypertension has been considered to be a rare entity, but with no precise estimates of the pediatric incidence in the United States. There have been attempts to revise the criteria over the years and adapt the adult criteria for use in pediatrics. The clinical presentation varies with age, and symptoms tending to be less obvious in younger individuals. In the prepubertal population, incidentally discovered optic disc edema is relatively common. By far the most consistent symptom is headache; other symptoms include nausea, vomiting tinnitus, and diplopia. Treatment mainstays include weight loss when appropriate and acetazolamide. Furosemide may exhibit a synergistic benefit when used in conjunction with acetazolamide. Surgical interventions are required relatively infrequently, but include optic nerve sheath fenestration and cerebrospinal fluid shunting. Pain and permanent vision loss are the two major complications of this disorder and these manifestations justify aggressive treatment. Once intracranial hypertension has resolved, up to two thirds of patients develop a new or chronic headache type that is different from their initial presenting headache. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Intracranial Infections: Clinical and Imaging Characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Foerster, B.R.; Thurnher, M.M.; Malani, P.N.; Petrou, M.; Carets-Zumelzu, F.; Sundgren, P.C. [Dept. of Radiology, and Divisions of Infectious Diseases and G eriatric Medicine, Dept. of Internal Medicine, Univ. of Michigan Medical Center, Ann Arbor, MI (United States)

    2007-10-15

    The radiologist plays a crucial role in identifying and narrowing the differential diagnosis of intracranial infections. A thorough understanding of the intracranial compartment anatomy and characteristic imaging findings of specific pathogens, as well incorporation of the clinical information, is essential to establish correct diagnosis. Specific types of infections have certain propensities for different anatomical regions within the brain. In addition, the imaging findings must be placed in the context of the clinical setting, particularly in immunocompromised and human immunodeficiency virus (HIV)-positive patients. This paper describes and depicts infections within the different compartments of the brain. Pathology-proven infectious cases are presented in both immunocompetent and immunocompromised patients, with a discussion of the characteristic findings of each pathogen. Magnetic resonance spectroscopy (MRS) characteristics for several infections are also discussed.

  7. Tumour viruses and innate immunity.

    Science.gov (United States)

    Hopcraft, Sharon E; Damania, Blossom

    2017-10-19

    Host cells sense viral infection through pattern recognition receptors (PRRs), which detect pathogen-associated molecular patterns (PAMPs) and stimulate an innate immune response. PRRs are localized to several different cellular compartments and are stimulated by viral proteins and nucleic acids. PRR activation initiates signal transduction events that ultimately result in an inflammatory response. Human tumour viruses, which include Kaposi's sarcoma-associated herpesvirus, Epstein-Barr virus, human papillomavirus, hepatitis C virus, hepatitis B virus, human T-cell lymphotropic virus type 1 and Merkel cell polyomavirus, are detected by several different PRRs. These viruses engage in a variety of mechanisms to evade the innate immune response, including downregulating PRRs, inhibiting PRR signalling, and disrupting the activation of transcription factors critical for mediating the inflammatory response, among others. This review will describe tumour virus PAMPs and the PRRs responsible for detecting viral infection, PRR signalling pathways, and the mechanisms by which tumour viruses evade the host innate immune system.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).

  8. 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.)

  9. Gestational trophoblastic tumours: an update for 2014.

    Science.gov (United States)

    Froeling, Fieke E M; Seckl, Michael J

    2014-11-01

    Gestational trophoblastic disease describes a variety of pregnancy-related diseases including the premalignant conditions of a partial and complete hydatidiform mole and the malignant disorders of invasive mole, choriocarcinoma and the rare placental-site trophoblastic tumour and epithelioid trophoblastic tumour. The availability of a highly sensitive tumour marker in the form of human chorionic gonadotrophin, the chemosensitive character of the disease with effective treatment strategies and centralization of care of a rare group of diseases has resulted in excellent survival rates, which can exceed 98 %. This review gives a general overview of gestational trophoblastic disease, the most recent insights in aetiology and pathology and a summary of the different management strategies.

  10. Manifestations of Pediatric Intracranial Hypertension From the Intracranial Hypertension Registry

    OpenAIRE

    Sivaswamy, Lalitha

    2016-01-01

    Investigators from the Ohio State University, Oregon Health and Science University and Rosalind Franklin School of Medicine examined the presenting manifestations, demographics and treatment strategies in children enrolled in the Intracranial Hypertension Registry (IHR).

  11. Management of intracranial hypertension.

    Science.gov (United States)

    Singhi, Sunit C; Tiwari, Lokesh

    2009-05-01

    Raised intracranial pressure (ICP) is a life threatening condition that is common to many neurological and non-neurological illnesses. Unless recognized and treated early it may cause secondary brain injury due to reduced cerebral perfusion pressure (CPP), and progress to brain herniation and death. Management of raised ICP includes care of airway, ventilation and oxygenation, adequate sedation and analgesia, neutral neck position, head end elevation by 20 degrees-30 degrees, and short-term hyperventilation (to achieve PCO(2) 32-35 mm Hg) and hyperosmolar therapy (mannitol or hypertonic saline) in critically raised ICP. Barbiturate coma, moderate hypothermia and surgical decompression may be helpful in refractory cases. Therapies aimed directly at keeping ICP pressure targeted therapy may offer better outcome than ICP targeted therapies.

  12. 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.

  13. The effects of dexamethasone and chlorpromazine on tumour necrosis factor-alpha, interleukin-1 beta, interleukin-1 receptor antagonist and interleukin-10 in human volunteers.

    Science.gov (United States)

    Bleeker, M W; Netea, M G; Kullberg, B J; Van der Ven-Jongekrijg, J; Van der Meer, J W

    1997-01-01

    Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are pro-inflammatory cytokines that play an important role in severe infections, whereas IL-1 receptor antagonist (IL-1ra) and IL-10 are anti-inflammatory cytokines that counteract their effects. Chlorpromazine and dexamethasone protect mice against lethal endotoxaemia by decreasing circulating concentrations of TNF-alpha and IL-1 beta. We investigated whether administration of chlorpromazine or dexamethasone to human volunteers is able to modulate the lipopolysaccharide (LPS)-stimulated cytokine production capacity in whole blood. Blood samples were taken before and several time-points after medication. Circulating cytokine concentrations were low in all samples. LPS-induced TNF-alpha and IL-1 beta production in whole blood was inhibited by dexamethasone treatment, while chlorpromazine had no effect. When peripheral blood mononuclear cells were stimulated in vitro with LPS, the addition of chlorpromazine (1-100 ng/ml) had no modulatory action on TNF-alpha, IL-1 beta, IL-1ra or IL-10 synthesis. The chlorpromazine concentrations measured in circulation of volunteers were eight to 40 times lower than the concentrations shown to be effective in mice. In conclusion, chlorpromazine inhibits TNF-alpha and IL-1 beta production in mice at concentrations that cannot be reached in humans, thus precluding its usage in clinical anti-cytokine strategies. In contrast, dexamethasone is an effective inhibitor of pro-inflammatory cytokine production. PMID:9378493

  14. Engineering human tumour-associated chromosomal translocations with the RNA-guided CRISPR-Cas9 system

    National Research Council Canada - National Science Library

    Torres, R; Martin, M C; Garcia, A; Cigudosa, Juan C; Ramirez, J C; Rodriguez-Perales, S

    2014-01-01

    .... Here we present a strategy for generating cancer-related human chromosomal translocations in vitro based on the ability of the RNA-guided CRISPR-Cas9 system to induce DSBs at defined positions...

  15. Intracranial Birth Injury of Newborns

    National Research Council Canada - National Science Library

    T.I. Shevtsova

    2015-01-01

    The lecture presents the modern views on the problem of intracranial birth injury, considers risk factors, features of clinical manifestations at different types of this trauma, issues of diagnosis...

  16. What Is IH (Intracranial Hypertension)?

    Science.gov (United States)

    ... But when the body cannot effectively absorb or drain CSF, intracranial pressure increases within the skull, which is made of bone and cannot expand. And since the brain and the vasculature can only be compressed so ...

  17. Update on idiopathic intracranial hypertension.

    Science.gov (United States)

    Bruce, Beau B; Biousse, Valérie; Newman, Nancy J

    2011-08-01

    To provide an update on various features of idiopathic intracranial hypertension. Perspective. Selected articles on the epidemiology, clinical and imaging features, natural history, pathophysiology, and treatment of idiopathic intracranial hypertension were reviewed and interpreted in the context of the authors' clinical and research experience. Idiopathic intracranial hypertension primarily is a disease of obese women of childbearing age, but it can affect patients of any weight, sex, and age. Although a relatively rare disorder, idiopathic intracranial hypertension's associated costs in the United States entail hundreds of millions of dollars. Even after treatment, headaches frequently are persistent and may require the continued involvement of a neurologist. Quality-of-life reductions and depression are common among idiopathic intracranial hypertension patients. However, visual dysfunction, especially visual field abnormalities, represents the major morbidity of this disorder, and serial automated perimetry remains the primary method of patient monitoring. Patients who are men, black, very obese, or anemic are at higher risk of visual loss. Vitamin A metabolism, adipose tissue as an actively secreting endocrine tissue, and cerebral venous abnormalities are areas of active study regarding the pathophysiology of idiopathic intracranial hypertension. Treatment studies show that lumbar puncture is a valuable treatment (in addition to its crucial diagnostic role), and that weight management is critical. However, open questions remain regarding the efficacy of acetazolamide, cerebrospinal fluid diversion procedures, and cerebral venous stenting. Many questions remain unanswered about idiopathic intracranial hypertension. Ongoing studies, especially an ongoing National Institutes of Health-funded clinical trial of acetazolamide, should provide more insight into this important, yet poorly understood, syndrome of isolated intracranial hypertension. Copyright © 2011

  18. Syphilis mimicking idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Yri, Hanne; Wegener, Marianne; Jensen, Rigmor

    2011-01-01

    Idiopathic intracranial hypertension (IIH) is a condition of yet unknown aetiology affecting predominantly obese females of childbearing age. IIH is a diagnosis of exclusion as raised cerebrospinal fluid pressure may occur secondary to numerous other medical conditions. An atypical phenotype or a...... antibiotic treatment, signs and symptoms of elevated intracranial pressure resolved completely. Syphilis is a rare, but very important, differential diagnosis that in this case was clinically indistinguishable from IIH....

  19. EWS-Oct-4B, an alternative EWS-Oct-4 fusion gene, is a potent oncogene linked to human epithelial tumours

    Science.gov (United States)

    Kim, S; Lim, B; Kim, J

    2010-01-01

    Background: Characterisation of EWS-Oct-4 translocation fusion product in bone and soft-tissue tumours revealed a chimeric gene resulting from an in-frame fusion between EWS (Ewing's sarcoma gene) exons 1–6 and Oct-4 exons 1–4. Recently, an alternative form of the fusion protein between the EWS and Oct-4 genes, named EWS-Oct-4B, was reported in two types of epithelial tumours, a hidradenoma of the skin and a mucoepidermoid carcinoma of the salivary glands. As the N-terminal and POU domains of the EWS-Oct-4 and EWS-Oct-4B proteins are not structurally identical, we decided to investigate the functional consequences of the EWS-Oct-4B fusion. Methods: In this report, we have characterised the EWS-Oct-4B fusion protein. To investigate how the EWS-Oct-4B protein contributes to tumourigenesis in human cancers, we analysed its DNA-binding activity, subcellular localisation, transcriptional activation behaviour, and oncogenic properties. Results: We found that this new chimeric gene encodes a nuclear protein that binds DNA with the same sequence specificity as the parental Oct-4 protein or the fusion EWS-Oct-4 protein. We show that the nuclear localisation signal of EWS-Oct-4B is dependent on the POU DNA-binding domain, and we identified a cluster of basic amino acids, 269RKRKR273, in the POU domain that specifically mediates the nuclear localisation of EWS-Oct-4B. Comparison of the properties of EWS-Oct-4B and EWS-Oct-4 indicated that EWS-Oct-4B is a less-potent transcriptional activator of a reporter construct carrying the Oct-4-binding sites. Deletion analysis of the functional domains of EWS-Oct-4B revealed that the EWS N-terminal domain (NTD)B, POU, and C-terminal domain (CTD) are necessary for its full transactivation potential. Despite its reduced activity as a transcriptional activator, EWS-Oct-4B regulated the expression of fgf-4 (fibroblast growth factor-4) and nanog, which are potent mitogens, as well as of Oct-4 downstream target genes, the promoters of

  20. Alveolar soft part sarcoma: the new primary intracranial malignancy : A case report and review of the literature.

    Science.gov (United States)

    Kumar, Aditaya; Alrohmain, B; Taylor, W; Bhattathiri, P

    2017-07-26

    The purpose of this paper is to serve as a reference to aid in the management of this poorly understood intracranial malignancy. The authors report their experience treating the eighth ostensible case of a primary intracranial alveolar soft part sarcoma (ASPS). A 21-year-old man presented to hospital after collapsing. He gave a 1-year history of headache, a 2-month history of reduced visual acuity and on examination had left facial paraesthesia with left-sided incoordination. MRI of the brain revealed a large left posterior fossa mass. The patient underwent resection of the tumour with good recovery in function. Immunohistochemical analysis of the tumour specimen confirmed an ASPS, and multimodal imaging in search of an extra-cranial disease primary was negative. A review of the literature yielded only seven other cases of primary intracranial ASPS. A variety of diagnostic imaging modalities were employed in search of a disease primary, as were various combinations of surgical resection, chemotherapy and radiotherapy as treatment. Half of the cases documented delayed disease recurrence. The authors discuss the following: the unique radiological and immunohistological characteristics of this disease including the potential for its misdiagnosis; the investigations required to diagnose a primary intracranial ASPS; the efficacy of current medical and surgical treatment options and the factors that will aid in prognostication. This is the first review of this new primary intracranial malignancy. From our analysis, we offer a joint radiological and immunohistochemical algorithm for the diagnosis of primary intracranial ASPS and specific operative considerations prior to resection.

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

    Directory of Open Access Journals (Sweden)

    Dewi Y Bisri

    2017-01-01

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

  2. 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

  3. 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.

  4. 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.

  5. Dienogest improves human leucocyte antigen-DR underexpression and reduces tumour necrosis factor-α production in peritoneal fluid cells from women with endometriosis.

    Science.gov (United States)

    Maeda, N; Izumiya, C; Taniguchi, K; Matsushima, S; Mita, S; Shimizu, Y; Fukaya, T

    2014-06-01

    To determine the immunological effect of dienogest (DNG), an oral anti-endometriosis drug, on peritoneal fluid (PF) macrophages collected from women with endometriosis. Although it has been suggested that DNG has direct effects on endometriotic cells, including decreased cell proliferation and decreased anti-inflammatory cytokine production, the effects of DNG on PF cells are unclear. The effects of DNG on PF cells from 34 women with endometriosis and 22 women without endometriosis (controls) were investigated. Expression of human leucocyte antigen (HLA)-DR in PF macrophages, obtained from the peritoneal cavity during laparoscopic surgery, was determined by flow cytometry. HLA-DR expression was measured again after PF cells had been cultured for 72 h in a humidified atmosphere at 37 °C in 5% CO₂-95% air with or without DNG. After 72 h of incubation, the concentration of pro-inflammatory tumour necrosis factor (TNF)-α in the media was measured by enzyme-linked immunosorbent assay. HLA-DR expression was lower in PF macrophages from women with endometriosis compared with controls. However, after DNG treatment, HLA-DR expression in PF macrophages from women with endometriosis was increased to the same level as in controls. The TNF-α concentration in the media was decreased by DNG. DNG can restore the antigen-presenting ability of PF macrophages by increased HLA-DR expression, and may have an anti-inflammatory effect on PF macrophages in women with endometriosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. [Malignant peripheral nerve sheath tumour of the infra-orbital nerve].

    Science.gov (United States)

    González-Orús Álvarez-Morujo, Ricardo; García Leal, Roberto; Lasso Vázquez, José María; Scola Yurrita, Barolomé

    2014-01-01

    A malignant peripheral nerve sheath tumour (MPNST) is an uncommon neoplasm that rarely involves the head and neck region. It is even more infrequent for these tumours to affect cranial nerves. We report the case of a 53-year-old man who presented a MPNST involving the infra-orbital nerve, which extended through the orbit and the base of the skull, progressing intracranially. Histological studies identified the tumour as an MPNST. Response to radiotherapy was not complete and radical surgical resection was impossible, so the patient died 10months later. This rare case of MPNST with intracranial involvement illustrates the dismal prognosis for patients with these lesions. Prognosis is poor because of the difficulty of performing radical surgery with free margins in these locations. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  7. 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.

  8. Spontaneous intracranial hypotension

    Energy Technology Data Exchange (ETDEWEB)

    Haritanti, A. [Department of Radiology, Aristotele' s University School of Medicine, AHEPA University Hospital, 54636 Thessaloniki (Greece); Karacostas, D. [Department of Neurology, Aristotele' s University School of Medicine, AHEPA University Hospital, 54636 Thessaloniki (Greece)], E-mail: bneurol@med.auth.gr; Drevelengas, A. [Department of Radiology, Aristotele' s University School of Medicine, AHEPA University Hospital, 54636 Thessaloniki (Greece); Kanellopoulos, V. [Department of Radiology, Aristotele' s University School of Medicine, AHEPA University Hospital, 54636 Thessaloniki (Greece)], E-mail: vasikanel@hotmail.com; Paraskevopoulou, E. [Department of Neurology, Aristotele' s University School of Medicine, AHEPA University Hospital, 54636 Thessaloniki (Greece); Lefkopoulos, A.; Economou, I.; Dimitriadis, A.S. [Department of Radiology, Aristotele' s University School of Medicine, AHEPA University Hospital, 54636 Thessaloniki (Greece)

    2009-02-15

    Spontaneous intracranial hypotension (SIH) is an uncommon but increasingly recognized syndrome. Orthostatic headache with typical findings on magnetic resonance imaging (MRI) are the key to diagnosis. Delayed diagnosis of this condition may subject patients to unnecessary procedures and prolong morbidity. We describe six patients with SIH and outline the important clinical and neuroimaging findings. They were all relatively young, 20-54 years old, with clearly orthostatic headache, minimal neurological signs (only abducent nerve paresis in two) and diffuse pachymeningeal gadolinium enhancement on brain MRI, while two of them presented subdural hygromas. Spinal MRI was helpful in detecting a cervical cerebrospinal fluid leak in three patients and dilatation of the vertebral venous plexus with extradural fluid collection in another. Conservative management resulted in rapid resolution of symptoms in five patients (10 days-3 weeks) and in one who developed cerebral venous sinus thrombosis, the condition resolved in 2 months. However, this rapid clinical improvement was not accompanied by an analogous regression of the brain MR findings that persisted on a longer follow-up. Along with recent literature data, our patients further point out that SIH, to be correctly diagnosed, necessitates increased alertness by the attending physician, in the evaluation of headaches.

  9. Nonlocal Intracranial Cavity Extraction

    Science.gov (United States)

    Manjón, José V.; Eskildsen, Simon F.; Coupé, Pierrick; Romero, José E.; Collins, D. Louis; Robles, Montserrat

    2014-01-01

    Automatic and accurate methods to estimate normalized regional brain volumes from MRI data are valuable tools which may help to obtain an objective diagnosis and followup of many neurological diseases. To estimate such regional brain volumes, the intracranial cavity volume (ICV) is often used for normalization. However, the high variability of brain shape and size due to normal intersubject variability, normal changes occurring over the lifespan, and abnormal changes due to disease makes the ICV estimation problem challenging. In this paper, we present a new approach to perform ICV extraction based on the use of a library of prelabeled brain images to capture the large variability of brain shapes. To this end, an improved nonlocal label fusion scheme based on BEaST technique is proposed to increase the accuracy of the ICV estimation. The proposed method is compared with recent state-of-the-art methods and the results demonstrate an improved performance both in terms of accuracy and reproducibility while maintaining a reduced computational burden. PMID:25328511

  10. Co-Expression of Plexin-B1 and Met in Human Breast and Ovary Tumours Enhances the Risk of Progression

    Directory of Open Access Journals (Sweden)

    Guido Valente

    2009-01-01

    Full Text Available Background: Plex-B1, the receptor of Sema4D, has been implicated in tumour growth, angiogenesis and metastasis. The binding of Sema4D to Plex-B1 can trigger the activation of Met tyrosine kinase, thereby promoting cell dissociation and invasive growth. We tested the hypothesis that the expression of Plex-B1, either alone or in association with Met, can be of predictive value for tumour progression.

  11. Production of a tumour-targeting antibody with a human-compatible glycosylation profile in N. benthamiana hairy root cultures.

    Science.gov (United States)

    Lonoce, Chiara; Salem, Reda; Marusic, Carla; Jutras, Philippe V; Scaloni, Andrea; Salzano, Anna Maria; Lucretti, Sergio; Steinkellner, Herta; Benvenuto, Eugenio; Donini, Marcello

    2016-09-01

    Hairy root (HR) cultures derived from Agrobacterium rhizogenes transformation of plant tissues are an advantageous biotechnological manufacturing platform due to the accumulation of recombinant proteins in an otherwise largely protein free culture medium. In this context, HRs descending from transgenic Nicotiana tabacum plants were successfully used for the production of several functional mAbs with plant-type glycans. Here, we expressed the tumor-targeting monoclonal antibody mAb H10 in HRs obtained either by infecting a transgenic N. tabacum line expressing H10 with A. rhizogenes or a glyco-engineered N. benthamiana line (ΔXTFT) with recombinant A. rhizogenes carrying mAb H10 heavy and light chain cDNAs. Selected HR clones derived from both plants accumulated mAb H10 in the culture medium with similar yields (2-3 mg/L). N-glycosylation profiles of antibodies purified from HR supernatant revealed the presence of plant-typical complex structures for N. tabacum-derived mAb H10 and of GnGn structures lacking xylose and fucose for the ΔXTFT-derived counterpart. Both antibody glyco-formats exhibited comparable antigen binding activities. Collectively, these data demonstrate that the co-infection of ΔXTFT Nicotiana benthamiana with recombinant A. rhizogenes is an efficient procedure for the generation of stable HR cultures expressing the tumor-targeting mAb H10 with a human-compatible glycosylation profile, thus representing an important step towards the exploitation of root cultures for the production of 'next generation' human therapeutic antibodies. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Soma-to-germline transmission of RNA in mice xenografted with human tumour cells: possible transport by exosomes.

    Directory of Open Access Journals (Sweden)

    Cristina Cossetti

    Full Text Available Mendelian laws provide the universal founding paradigm for the mechanism of genetic inheritance through which characters are segregated and assorted. In recent years, however, parallel with the rapid growth of epigenetic studies, cases of inheritance deviating from Mendelian patterns have emerged. Growing studies underscore phenotypic variations and increased risk of pathologies that are transgenerationally inherited in a non-Mendelian fashion in the absence of any classically identifiable mutation or predisposing genetic lesion in the genome of individuals who develop the disease. Non-Mendelian inheritance is most often transmitted through the germline in consequence of primary events occurring in somatic cells, implying soma-to-germline transmission of information. While studies of sperm cells suggest that epigenetic variations can potentially underlie phenotypic alterations across generations, no instance of transmission of DNA- or RNA-mediated information from somatic to germ cells has been reported as yet. To address these issues, we have now generated a mouse model xenografted with human melanoma cells stably expressing EGFP-encoding plasmid. We find that EGFP RNA is released from the xenografted human cells into the bloodstream and eventually in spermatozoa of the mice. Tumor-released EGFP RNA is associated with an extracellular fraction processed for exosome purification and expressing exosomal markers, in all steps of the process, from the xenografted cancer cells to the spermatozoa of the recipient animals, strongly suggesting that exosomes are the carriers of a flow of information from somatic cells to gametes. Together, these results indicate that somatic RNA is transferred to sperm cells, which can therefore act as the final recipients of somatic cell-derived information.

  13. [Intracranial carotid artery bifurcation aneurysms].

    Science.gov (United States)

    Vega-Basulto, S D; Montejo-Montejo, J

    Intracranial carotid artery bifurcation aneurysms are infrequent but its clinical behavior, high risk of bleeding and complex anatomic relationships of the sac permit to consider these lesions as a challenge cases. 497 patients harboring intracranial aneurysms were operated on at Manuel Ascunce Domenech Hospital, Camagüey, Cuba between January 1982 to august 2001. We utilized microsurgical procedures, optical magnification, specialized neuroanesthesia and Intensive Care Unit postoperatory following. All patients were evaluated clinically with World Federation Neurological Surgeon Scale and Glasgow Outcome Scale. There were 16 patients with intracranial carotid artery bifurcation aneurysms (3.2 %). 12 patients were under 40 years and 50% were between 16 and 30 years old. All patients present intracranial bleeding. There was 87.5% of total or partial recuperation. There was one death only. Postoperative deficit were observed at 44% but 31% disappeared three month later. Intracranial carotid artery bifurcation aneurysms are complex anatomoclinical lesions. Clinically, we observed high tendency to bleed and multiplicity. Anatomically, these sacs have complex arterial relationship that difficult dissection and clipping. They have frequent postoperative morbidity. Multiple or bilateral aneurysmal sacs will be clipped by one surgical procedure.

  14. Papilledema and idiopathic intracranial hypertension.

    Science.gov (United States)

    Friedman, Deborah I

    2014-08-01

    Papilledema is one of the most concerning physical examination findings in neurology: it has a broad differential diagnosis of intracranial (and occasionally spinal) pathology associated with increased intracranial pressure. Papilledema impairs axoplasmic flow within the optic nerves and compresses the optic nerves externally; it may lead to profound visual loss. Thus, detection of papilledema and assessment of visual function are essential to patient management. This article reviews the treatment of papilledema-related visual loss in pseudotumor cerebri syndrome, one of the most common causes of papilledema encountered by neurologists. Results from the Idiopathic Intracranial Hypertension Trial (IIHTT), the first randomized, double-masked, placebo-controlled trial for the treatment of patients with mild visual loss from idiopathic intracranial hypertension, were published in April 2014. The IIHTT provides the first evidence-based treatment recommendations, showing the benefit of acetazolamide and weight loss for improving visual status in patients with mild visual field loss from idiopathic intracranial hypertension. A detailed ophthalmic examination, including perimetry, is critical to the evaluation, treatment, and assessment of treatment response in patients with papilledema.

  15. Intracranial dural metastases.

    Science.gov (United States)

    Nayak, Lakshmi; Abrey, Lauren E; Iwamoto, Fabio M

    2009-05-01

    : Intracranial dural metastases (IDM) are found at autopsy in 9% of patients with advanced systemic cancer. However, to the authors' knowledge, IDM have not been studied systematically in the modern neuroimaging era. The objective of the current study was to evaluate the demographics, clinical presentation, imaging, treatment, and prognosis of patients with IDM. : The current study was a retrospective review of 122 patients with IDM diagnosed at Memorial Sloan-Kettering Cancer Center between 1999 and 2006. Patients with concurrent brain or leptomeningeal metastases were excluded. : Sixty-one percent of the patients were women; the median age at diagnosis was 59 years, the median Karnofsky performance scale (KPS) at diagnosis was 80, and the median time to IDM diagnosis from initial cancer diagnosis was 37 months. Breast (34%) and prostate (17%) cancers were the most frequent primary tumors associated with IDM. Fifty-six percent of patients had a single dural metastasis. On imaging, 70% had metastases of the overlying skull, 44% had dural tail metastases, 53% had vasogenic edema, and 34% had brain invasion. Direct extension from skull metastases was the most common mode of spread. Eighty-three percent of patients had active systemic disease at the time of IDM diagnosis. A lower KPS and lung cancer were associated with worse overall survival. Surgical resection and chemotherapy improved progression-free survival, but only resection was found to be associated with improved overall survival. : IDM affect a significant proportion of cancer patients. KPS and status of systemic cancer should guide treatment decisions. Cancer 2009. (c) 2009 American Cancer Society.

  16. The radiological appearance of intracranial aneurysms in adults ...

    African Journals Online (AJOL)

    2014-04-04

    Apr 4, 2014 ... http://sajr.org.za. The radiological appearance of intracranial aneurysms in adults infected with the human immunodeficiency virus (HIV). Authors: ... Method: In this retrospective analysis of data, 23 HIV-positive patients, of which 15 (65.2%) ..... muscularis layer.14 HIV viral proteins have been associated.

  17. Multiple intracranial hydatid cysts: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Pumar, J. [Dept. of Diagnostic Radiology, University Hospital, Santiago de Compostela (Spain); Alvarez, M. [Dept. of Diagnostic Radiology, University Hospital, Santiago de Compostela (Spain); Leira, R. [Dept. of Neurology, University Hospital, Santiago de Compostela (Spain); Prieto, J.M. [Dept. of Neurology, University Hospital, Santiago de Compostela (Spain); Arrojo, L. [Dept. of Diagnostic Radiology, University Hospital, Santiago de Compostela (Spain); Pereira, J. [Dept. of Diagnostic Radiology, University Hospital, Santiago de Compostela (Spain); Vidal, J. [Dept. of Diagnostic Radiology, University Hospital, Santiago de Compostela (Spain)

    1992-08-01

    Multiple intracranial hydatid cysts are uncommon and usually localized in the supratentorial compartment. We report a case studied by CT and MR of multiple intracranial hydatid cysts scattered in various anatomic sites: supratentorial, infratentorial and also intraventricular. (orig.)

  18. New Phage Display-Isolated Heptapeptide Recognizing the Regulatory Carboxy-Terminal Domain of Human Tumour Protein p53.

    Science.gov (United States)

    Ben Abid, Sihem; Sahnoun, Mouna; Yacoubi-Hadj Amor, Ines; Abdelmoula-Souissi, Salma; Hassairi, Hajer; Mokdad-Gargouri, Raja; Gargouri, Ali

    2017-10-01

    The transcription factor tumor protein p53 (P53) controls a variety of genes most involved in cell cycle and is at the origin of apoptosis when DNA is irreparably damaged. We planned to select novel tumor protein p53-interacting peptides through the screening of hepta-peptide phage-display libraries. For this aim, human tumor suppressor protein p53 was expressed in Escherichia coli as Glutathione S-transferase fusion and purified by affinity chromatography. The phage library was then screened on this immobilized protein target. After three rounds of panning, phages were sequenced and shown to contain a consensus sequence NPNSAQG. Thereafter, either free p53 liberated from the fusion protein through thrombin treatment or Histidine-tagged p53 were recognized efficiently by the selected phage. To locate the p53-binding epitope of the selected hepta-peptide, three long peptides parts of the three known domains of the protein were synthesized and screened by the selected phage/peptide. Thus, the Carboxy-terminal p53 region was shown to be the target of the isolated phage as well as by its derived Fluorescein isothiocyanate-peptide. Molecular docking showed Lysine 386 as an important residue potentially engaged in this interaction. The selected hepta-peptide is a novel p53-interacting peptide, not described by other studies, and could be used as therapeutic tool in the future.

  19. The major influence of the atmosphere on intracranial pressure: an observational study

    Science.gov (United States)

    Herbowski, Leszek

    2017-01-01

    The impact of the atmosphere on human physiology has been studied widely within the last years. In practice, intracranial pressure is a pressure difference between intracranial compartments and the surrounding atmosphere. This means that gauge intracranial pressure uses atmospheric pressure as its zero point, and therefore, this method of pressure measurement excludes the effects of barometric pressure's fluctuation. The comparison of these two physical quantities can only take place through their absolute value relationship. The aim of this study is to investigate the direct effect of barometric pressure on the absolute intracranial pressure homeostasis. A prospective observational cross-sectional open study was conducted in Szczecin, Poland. In 28 neurosurgical patients with suspected normal-pressure hydrocephalus, intracranial intraventricular pressure was monitored in a sitting position. A total of 168 intracranial pressure and atmospheric pressure measurements were performed. Absolute atmospheric pressure was recorded directly. All values of intracranial gauge pressure were converted to absolute pressure (the sum of gauge intracranial pressure and local absolute atmospheric pressure). The average absolute mean intracranial pressure in the patients is 1006.6 hPa (95 % CI 1004.5 to 1008.8 hPa, SEM 1.1), and the mean absolute atmospheric pressure is 1007.9 hPa (95 % CI 1006.3 to 1009.6 hPa, SEM 0.8). The observed association between atmospheric and intracranial pressure is strongly significant (Spearman correlation r = 0.87, p pressure are related to seasonal variation. Absolute intracranial pressure is shown to be impacted positively by atmospheric pressure.

  20. Sex differences in intracranial arterial bifurcations

    DEFF Research Database (Denmark)

    Lindekleiv, Haakon M; Valen-Sendstad, Kristian; Morgan, Michael K

    2010-01-01

    Subarachnoid hemorrhage (SAH) is a serious condition, occurring more frequently in females than in males. SAH is mainly caused by rupture of an intracranial aneurysm, which is formed by localized dilation of the intracranial arterial vessel wall, usually at the apex of the arterial bifurcation. T....... The female preponderance is usually explained by systemic factors (hormonal influences and intrinsic wall weakness); however, the uneven sex distribution of intracranial aneurysms suggests a possible physiologic factor-a local sex difference in the intracranial arteries....

  1. Dexmedetomidine for Refractory Intracranial Hypertension.

    Science.gov (United States)

    Schomer, Kendra J; Sebat, Christian M; Adams, Jason Y; Duby, Jeremiah J; Shahlaie, Kiarash; Louie, Erin L

    2017-01-01

    Dexmedetomidine (DEX) is a selective α2 adrenergic agonist that is commonly used for sedation in the intensive care unit (ICU). The role of DEX for adjunctive treatment of refractory intracranial hypertension is poorly defined. The primary objective of this study was to determine the effect of DEX on the need for rescue therapy (ie, hyperosmolar boluses, extraventricular drain [EVD] drainages) for refractory intracranial hypertension. Secondary objectives included the number of intracranial pressure (ICP) excursions, bradycardic, hypotensive, and compromised cerebral perfusion pressure episodes. This retrospective cohort study evaluated patients admitted to the neurosurgical ICU from August 1, 2009, to July 29, 2015, and who received DEX for refractory intracranial hypertension. The objectives were compared between the 2 time periods-before (pre-DEX) and during therapy (DEX). Twenty-three patients with 26 episodes of refractory intracranial hypertension met the inclusion criteria. The number of hyperosmolar boluses was decreased after DEX therapy was initiated. Mannitol boluses required were statistically reduced (1 vs 0.5, P = .03); however, reduction in hypertonic boluses was not statistically significant (1.3 vs 0.9, P = .2). The mean number of EVD drainages per 24 hours was not significantly different between the time periods (15.7 vs 14.0, P = .35). The rate of ICP excursions did not differ between the 2 groups (24.3 vs 22.5, P = .62). When compared to pre-DEX data, there was no difference in the median number of hypotensive (0 vs 0), bradycardic (0 vs 0), or compromised cerebral perfusion pressure episodes (0.5 vs 1.0). Dexmedetomidine may avoid increases in the need for rescue therapy when used as an adjunctive treatment of refractory intracranial hypertension without compromising hemodynamics.

  2. Clinical application of proton magnetic resonance spectroscopy in the diagnosis of intracranial mass lesions

    Energy Technology Data Exchange (ETDEWEB)

    Moeller-Hartmann, W.; Krings, T. [Department of Neuroradiology, University Hospital of Aachen University of Technology (Germany); Herminghaus, S.; Lanfermann, H.; Pilatus, U.; Zanella, F.E. [Department of Neuroradiology, University Hospital of Johann Wolfgang von Goethe-University, Frankfurt Main (Germany); Marquardt, G. [Clinic of Neurosurgery, University Hospital of Johann Wolfgang von Goethe-University, Frankfurt Main (Germany)

    2002-05-01

    Diagnosis of primary and secondary brain tumours and other focal intracranial mass lesions based on imaging procedures alone is still a challenging problem. Proton magnetic resonance spectroscopy ({sup 1}H-MRS) gives completely different information related to cell membrane proliferation, neuronal damage, energy metabolism and necrotic transformation of brain or tumour tissues. Our purpose was to evaluate the clinical utility of {sup 1}H-MRS added to MRI for the differentiation of intracranial neoplastic and non-neoplastic mass lesions. 176 mostly histologically verified lesions were studied with a constant clinically available single volume {sup 1}H-MRS protocol following routine MRI. 12 spectra (6.8%) were not of satisfactory diagnostic quality; 164 spectroscopic data sets were therefore available for definitive evaluation. Our study shows that spectroscopy added to MRI helps in tissue characterization of intracranial mass lesions, thereby leading to an improved diagnosis of focal brain disease. Non-neoplastic lesions such as cerebral infarctions and brain abscesses are marked by decreases in choline (Cho), creatine (Cr) and N-acetyl-aspartate (NAA), while tumours generally have elevated Cho and decreased levels of Cr and NAA. Gliomas exhibit significantly increased Cho and lipid formation with higher WHO tumour grading. Metastases have elevated Cho similar to anaplastic astrocytomas, but can be differentiated from high-grade gliomas by their higher lipid levels. Extra-axial tumours, i.e. meningiomas and neurinomas, are characterized by a nearly complete absence of the neuronal marker NAA. The additive information of {sup 1}H-MRS led to a 15.4%-higher number of correct diagnoses, to 6.2% fewer incorrect and 16% fewer equivocal diagnoses than with structural MRI data alone. (orig.)

  3. Pseudoarachnoiditis in Spontaneous Intracranial Hypotension

    Directory of Open Access Journals (Sweden)

    Özlem Alkan

    2011-03-01

    Full Text Available Spontaneous intracranial hypotension is an important cause of new daily persistent headaches in young and middle-aged individuals. The diagnosis is made based on low cerebrospinal fluid pressure with characteristic findings upon brain and spinal magnetic resonance imaging (MRI. We present the case of a 15-year-old boy with spontaneous intracranial hypotension. Although his brain MRI was normal, his lumbar spinal MRI showed clustering of the nerve roots characteristic of arachnoiditis. Radionuclide cisternography revealed an epidural leak, which was treated with an epidural blood patch. The patient reached a near-full recovery within 24 h, and the lumbar spinal MRI findings mimicking arachnoiditis disappeared.

  4. Syphilis mimicking idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Yri, Hanne; Wegener, Marianne; Jensen, Rigmor

    2011-01-01

    Idiopathic intracranial hypertension (IIH) is a condition of yet unknown aetiology affecting predominantly obese females of childbearing age. IIH is a diagnosis of exclusion as raised cerebrospinal fluid pressure may occur secondary to numerous other medical conditions. An atypical phenotype...... or an atypical disease course should alert the physician to reevaluate a presumed IIH-diagnosis. The authors report a case of a 32-year-old non-obese male with intracranial hypertension, secondary to a syphilitic central nervous system infection, initially misdiagnosed as being idiopathic. Upon relevant...

  5. Intracranial Complications of Pediatric Sinusitis.

    Science.gov (United States)

    Wiersma, Alexandria J; Vu, Tien

    2017-06-13

    "Headache and fever" is a common presentation to the urgent care and emergency department setting and can have many etiologies. We present a case of a 10-year-old girl who presented with headache and fever and was found to have intracranial extension of sinusitis despite lack of typical sinus or chronic upper respiratory tract infection symptoms. This case illustrates the need in the emergency department or urgent care to keep a broad differential diagnosis for pediatric headache, especially when initial interventions are unsuccessful. We also review the epidemiology of pediatric sinusitis, age at sinus development, and associated intracranial complications.

  6. Intracranial calcification in central diabetes insipidus

    Energy Technology Data Exchange (ETDEWEB)

    Al-Kandari, Salwa R. [Al Razi Hospital, Department of Clinical Radiology, Kuwait (Kuwait); Pandey, Tarun [Al Razi Hospital, Department of Clinical Radiology, Kuwait (Kuwait); University of Arkansas for Medical Sciences, Radiology Department, Little Rock, AR (United States); Badawi, Mona H. [Al-Adan Hospital, Department of Paediatrics, Kuwait (Kuwait)

    2008-01-15

    Intracranial calcification is a known but extremely rare complication of diabetes insipidus. To date, only 16 patients have been reported and all had the peripheral (nephrogenic) type of diabetes insipidus. We report a child with intracranial calcification complicating central diabetes insipidus. We also report a child with nephrogenic diabetes insipidus, and compare the patterns of intracranial calcification. (orig.)

  7. Intracranial elastance is increased in idiopathic intracranial hypertension.

    Science.gov (United States)

    Chisholm, J T; Sudhakar, P; Alhajeri, A N; Smith, J H

    2017-12-01

    To date, no pathophysiological model has sufficiently accounted for all the findings encountered in patients with idiopathic intracranial hypertension (IIH). Intracranial elastance is an index of volume-buffering capacity known to play a role in certain disorders of cerebrospinal fluid (CSF) dynamics, which has not been previously investigated in relation to IIH patients. This was a single-center retrospective cohort study from 1 July 2011 to 1 July 2016. Values for opening pressure (PO ), closing pressure (PC ) and volume (V) of CSF removed were collected, as well as demographic and clinical covariates. Intracranial elastance (E) and pressure-volume index (PVI) were calculated according to established equations: E = (PO -PC )/V and PVI = V/log10 (PO /PC ), respectively. Those with an alternative central nervous system pathology, including meningitis, encephalitis and normal pressure hydrocephalus were excluded. Eligible patients were subdivided into two groups based on final diagnosis: a control group and an IIH group. In our cohort (n = 49), a significant association of both E (P intracranial elastance is increased in IIH, reflecting a novel insight into disease pathogenesis. © 2017 EAN.

  8. Antigens in human glioblastomas and meningiomas: Search for tumour and onco-foetal antigens. Estimation of S-100 and GFA protein

    DEFF Research Database (Denmark)

    Dittmann, L; Axelsen, N H; Norgaard-Pedersen, B

    1977-01-01

    Extracts of glioblastomas and meningiomas were analysed by quantitative immunoelectrophoresis for the presence of foetal brain antigens and tumour-associated antigens, and levels of 2 normal brain-specific proteins were also determined. The following antibodies were used: monospecific anti-S-100......-alpha-foetoprotein; and monospecific anti-ferritin. Using the antibodies raised against the tumours, several antigens not present in foetal or adult normal brain were found in the glioblastomas and the meningiomas. These antigens cross-reacted with antigens present in normal liver and were therefore not tumour-associated. S-100...... was found in glioblastomas in approximately one tenth the amount in whole brain homogenate, whereas GFA was found 2-4 times enriched. The 2 proteins were absent in meningiomas. The possible use of the GFA protein as a marker for astroglial neoplasia is discussed. Five foetal antigens were found in foetal...

  9. [Multiple intracranial tuberculomas in infancy].

    Science.gov (United States)

    Serrano, M; Campistol, J; Chávez, B; Caritg, J; Fortuny, C; Costa, J M

    Tuberculous involvement of the CNS is most frequent in children aged between 6 months and 6 years, although it may occur at any age. It may present as meningoencephalitis, basal arachnoiditis or intracranial tuberculomas. Whilst meningitis is typical of infancy, tuberculomas and arachnoiditis are commoner in adults. It has been estimated that tuberculomas make up 3% of the cases of neurotuberculosis. The increasing use of CAT and MR has been a great help for diagnosis of this serious complication of tuberculosis. A 5 month old patient presented with tuberculous meningitis which had been treated with streptomycin, isoniazid, pyrazinamide and rifampicin at the usual dosage. One month later, after good initial progress, triventricular hydrocephaly was diagnosed and a ventriculoperitoneal shunt inserted. Three months after this, there was an episode of intracranial hypertension. Cranial CAT showed considerable zones of hypodense parenchyma without ventricle dilatation. On MR there were multiple, disseminated, rounded areas which were hyperintense on T2 and compatible with intracranial tuberculomas. After fresh insertion of a ventricular shunt, the patient progressed but still had a residual right hemiparesia and retarded development. Although intracranial tuberculomas usually occur in adults, they may be seen in children following meningoencephalitis. Occasionally, following a good initial response to tuberculostatic drugs, tuberculomas appear, although not present before, as happened in our patient. This usually occurs within the first three months, and although the mechanism is unknown, it is believed to be due to the accumulation of lymphocytes and macrophages at preexisting microscopic foci when treatment is started.

  10. Haemorrhage in intracranial tuber- culosis

    African Journals Online (AJOL)

    lous meningitis (TBM).1-5 TBM is thought to arise from cerebrospinal ... patients are on treatment for TB.6. The co-occurrence of .... erebral, intraventricular, and sub- arachnoid spaces. Our case highlights intracranial haemorrhage as a potential additional cause of death in TBM. Treatment would require search for an ...

  11. Intracranial hemorrhage alters scalp potential distribution in bioimpedance cerebral monitoring: Preliminary results from FEM simulation on a realistic head model and human subjects.

    Science.gov (United States)

    Atefi, Seyed Reza; Seoane, Fernando; Kamalian, Shervin; Rosenthal, Eric S; Lev, Michael H; Bonmassar, Giorgio

    2016-02-01

    Current diagnostic neuroimaging for detection of intracranial hemorrhage (ICH) is limited to fixed scanners requiring patient transport and extensive infrastructure support. ICH diagnosis would therefore benefit from a portable diagnostic technology, such as electrical bioimpedance (EBI). Through simulations and patient observation, the authors assessed the influence of unilateral ICH hematomas on quasisymmetric scalp potential distributions in order to establish the feasibility of EBI technology as a potential tool for early diagnosis. Finite element method (FEM) simulations and experimental left-right hemispheric scalp potential differences of healthy and damaged brains were compared with respect to the asymmetry caused by ICH lesions on quasisymmetric scalp potential distributions. In numerical simulations, this asymmetry was measured at 25 kHz and visualized on the scalp as the normalized potential difference between the healthy and ICH damaged models. Proof-of-concept simulations were extended in a pilot study of experimental scalp potential measurements recorded between 0 and 50 kHz with the authors' custom-made bioimpedance spectrometer. Mean left-right scalp potential differences recorded from the frontal, central, and parietal brain regions of ten healthy control and six patients suffering from acute/subacute ICH were compared. The observed differences were measured at the 5% level of significance using the two-sample Welch t-test. The 3D-anatomically accurate FEM simulations showed that the normalized scalp potential difference between the damaged and healthy brain models is zero everywhere on the head surface, except in the vicinity of the lesion, where it can vary up to 5%. The authors' preliminary experimental results also confirmed that the left-right scalp potential difference in patients with ICH (e.g., 64 mV) is significantly larger than in healthy subjects (e.g., 20.8 mV; P potential distributions. Pilot clinical observations with the authors

  12. Intracranial hypertension: classification and patterns of evolution

    Science.gov (United States)

    Iencean, SM

    2008-01-01

    Intracranial hypertension (ICH) was systematized in four categories according to its aetiology and pathogenic mechanisms: parenchymatous ICH with an intrinsic cerebral cause; vascular ICH, which has its aetiology in disorders of cerebral blood circulation; ICH caused by disorders of cerebro–spinal fluid dynamics and idiopathic ICH. The increase of intracranial pressure is the first to happen and then intracranial hypertension develops from this initial effect becoming symptomatic; it then acquires its individuality, surpassing the initial disease. The intracranial hypertension syndrome corresponds to the stage at which the increased intracranial pressure can be compensated and the acute form of intracranial hypertension is equivalent to a decompensated ICH syndrome. The decompensation of intracranial hypertension is a condition of instability and appears when the normal intrinsic ratio of intracranial pressure – time fluctuation is changed. The essential conditions for decompensation of intracranial hypertension are: the speed of intracranial pressure increase over normal values, the highest value of abnormal intracranial pressure and the duration of high ICP values. Medical objectives are preventing ICP from exceeding 20 mm Hg and maintaining a normal cerebral blood flow. The emergency therapy is the same for the acute form but each of the four forms of ICH has a specific therapy, according to the pathogenic mechanism and if possible to aetiology. PMID:20108456

  13. Transcranial Doppler Ultrasound Examination in Dogs with Suspected Intracranial Hypertension Caused by Neurologic Diseases.

    Science.gov (United States)

    Sasaoka, K; Nakamura, K; Osuga, T; Morita, T; Yokoyama, N; Morishita, K; Sasaki, N; Ohta, H; Takiguchi, M

    2017-12-19

    Transcranial Doppler ultrasound examination (TCD) is a rapid, noninvasive technique used to evaluate cerebral blood flow and is useful for the detection of intracranial hypertension in humans. However, the clinical usefulness of TCD in diagnosing intracranial hypertension has not been demonstrated for intracranial diseases in dogs. To determine the association between the TCD variables and intracranial hypertension in dogs with intracranial diseases. Fifty client-owned dogs with neurologic signs. Cross-sectional study. All dogs underwent TCD of the basilar artery under isoflurane anesthesia after magnetic resonance imaging (MRI). Dogs were classified into 3 groups based on MRI findings: no structural diseases (group I), structural disease without MRI evidence of intracranial hypertension (group II), and structural disease with MRI evidence of intracranial hypertension (group III). The TCD vascular resistance variables (resistive index [RI], pulsatility index [PI], and the ratio of systolic to diastolic mean velocity [Sm/Dm]) were measured. Fifteen, 22, and 13 dogs were classified into groups I, II, and III, respectively. Dogs in group III had significantly higher Sm/Dm (median, 1.78; range, 1.44-2.58) than those in group I (median, 1.63; range, 1.43-1.75) and group II (median, 1.62; range, 1.27-2.10). No significant differences in RI and PI were identified among groups. Our findings suggest that increased Sm/Dm is associated with MRI findings of suspected intracranial hypertension in dogs with intracranial diseases and that TCD could be a useful tool to help to diagnose intracranial hypertension. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  14. 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

  15. The role of methylation in urological tumours

    NARCIS (Netherlands)

    Heijden, A.G. van der

    2013-01-01

    Alterations in DNA methylation have been described in human cancer for more than thirty years now. Since the last decade DNA methylation gets more and more important in cancer research. In this review the different alterations of DNA methylation are discussed in testicular germ cell tumours,

  16. 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.

  17. The value of MRI in angiogram-negative intracranial haemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Renowden, S.A. (Dept. of Neuroradiology, Radcliffe Infirmary, Oxford (United Kingdom)); Molyneux, A.J. (Dept. of Neuroradiology, Radcliffe Infirmary, Oxford (United Kingdom)); Anslow, P. (Dept. of Neuroradiology, Radcliffe Infirmary, Oxford (United Kingdom)); Byrne, J.V. (Dept. of Neuroradiology, Radcliffe Infirmary, Oxford (United Kingdom))

    1994-08-01

    In one year, cerebral angiograms were performed for intracranial haemorrhage (ICH) on 334 patients. No cause for haemorrhage could be identified in 41 (12 %), 30 of whom had predominantly subarachnoid (SAH) and 11 predominantly parenchymal haemorrhage (PH). These patients were prospectively examined by cranial MRI 1-6 weeks after the ictus. The MRI studies were positive in 7 patients (17 %). In the 30 patients examined after SAH, 2 studies were positive, showing an aneurysm in one case and a brain stem lesion of uncertain aetiology in the other. In those examined after PH, cavernous angiomas were shown in 2, a tumour in 1 and a vascular malformation in another; useful diagnostic information was thus obtained in 36 % of this group. (orig.)

  18. Cerebral haemodynamics during experimental intracranial hypertension.

    Science.gov (United States)

    Donnelly, Joseph; Czosnyka, Marek; Harland, Spencer; Varsos, Georgios V; Cardim, Danilo; Robba, Chiara; Liu, Xiuyun; Ainslie, Philip N; Smielewski, Peter

    2017-02-01

    Intracranial hypertension is a common final pathway in many acute neurological conditions. However, the cerebral haemodynamic response to acute intracranial hypertension is poorly understood. We assessed cerebral haemodynamics (arterial blood pressure, intracranial pressure, laser Doppler flowmetry, basilar artery Doppler flow velocity, and vascular wall tension) in 27 basilar artery-dependent rabbits during experimental (artificial CSF infusion) intracranial hypertension. From baseline (∼9 mmHg; SE 1.5) to moderate intracranial pressure (∼41 mmHg; SE 2.2), mean flow velocity remained unchanged (47 to 45 cm/s; p = 0.38), arterial blood pressure increased (88.8 to 94.2 mmHg; p intracranial pressure (∼75 mmHg; SE 3.7), both mean flow velocity and laser Doppler flowmetry decreased (45 to 31.3 cm/s p intracranial hypertension demonstrated two intracranial pressure-dependent cerebroprotective mechanisms: with moderate increases in intracranial pressure, wall tension decreased, and arterial blood pressure increased, while with severe increases in intracranial pressure, an arterial blood pressure increase predominated. Clinical monitoring of such phenomena could help individualise the management of neurocritical patients.

  19. 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.

  20. Visual Impairment/Intracranial Pressure Risk Assessment

    Science.gov (United States)

    Fogarty, Jennifer A.; Durham, T.; Otto, C.; Grounds, D.; Davis, J. R.

    2010-01-01

    Since 2006 there have been 6 reported cases of altered visual acuity and intracranial pressure (ICP) in long duration astronauts. In order to document this risk and develop an integrated approach to its mitigation, the NASA Space Life Sciences Directorate (SLSD) and Human Research Program (HRP) have chosen to use the Human System Risk Board (HSRB) and the risk management analysis tool (RMAT). The HSRB is the venue in which the stakeholders and customers discuss and vet the evidence and the RMAT is the tool that facilitates documentation and comparison of the evidence across mission profiles as well as identification of risk factors, and documentation of mitigation strategies. This process allows for information to be brought forward and dispositioned so that it may be properly incorporated into the RMAT and contribute to the design of the research and mitigation plans. The evidence thus far has resulted in the identification of a visual impairment/intracranial pressure (VIIP) project team, updating of both short and long duration medical requirements designed to assess visual acuity, and a research plan to characterize this issue further. In order to understand this issue more completely, a plan to develop an Accelerated Research Collaboration (ARC) has been approved by the HSRB. The ARC is a novel research model pioneered by the Myelin Repair Foundation. It is a patient centered research model that brings together researchers and clinicians, under the guidance of a scientific advisory panel, to collaborate and produce results much quickly than accomplished through traditional research models. The data and evidence from the updated medical requirements and the VIIP ARC will be reviewed at the HSRB on a regular basis. Each review package presented to the HSRB will include an assessment and recommendation with respect to continuation of research, countermeasure development, occupational surveillance modalities, selection criteria, etc. This process will determine the

  1. Melanotic neuroectodermal tumour of infancy: CT and MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Haque, Saira; Sebire, Neil; McHugh, Kieran [Great Ormond Street Hospital, Department of Radiology, London (United Kingdom); McCarville, Mary Beth [St. Jude Children' s Research Hospital, Memphis, TN (United States)

    2012-06-15

    Melanotic neuroectodermal tumour of infancy (MNTI) is a rare neoplasm of neural crest origin. To describe three further cases of MNTI, with emphasis on CT and MRI findings. Data for children with histologically confirmed MNTI following biopsy or surgery were retrieved. Three children with available imaging at the time of diagnosis were included in the study. All three children had primary tumour in the head and neck region: one in the maxilla, one in the occipital bone (extra-axial but with intracranial extension) and one with an unusual tumour growing exophytically from the subcutaneous tissues adjacent to the occipital bone. All tumours were iso/hypointense both on T1- and T2-weighted MRI, and showed marked contrast enhancement in their non-ossified components. CT allowed identification of bone destruction and remodelling. Our findings are consistent with previously reported cases of MNTI regarding age at presentation and location in the head and neck region. Our MR findings did not demonstrate the typical pattern of T1-shortening expected from melanin deposition. (orig.)

  2. 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

  3. 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.

  4. 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 ...

  5. [Intracranial hypertension in Proteus syndrome].

    Science.gov (United States)

    Dandine, J-B; James, S; Van Garsse, A; Born, J-D

    2007-11-01

    Proteus syndrome, described for the first time in 1979, is a sporadic congenital poly-malformation syndrome named for its highly variable manifestations. We report the case of a 36-year-old male patient with several malformations including skull hyperostosis and huge frontal sinus hypertrophy compressing the brain. He complained of increasing headache for 5 years. Cerebrospinal fluid pressure monitoring revealed severe hypertension. The patient underwent frontoparietal craniectomy, which allowed partial decompression. Postoperatively headaches decreased and the intracranial pressure normalized. Proteus syndrome is a genetic disease with a mosaic pattern. Only a hundred cases have been reported, mostly in childhood. Common manifestations include disproportionate overgrowth of the limbs and the skull, various subcutaneous tumors, vascular, renal and pulmonary malformations. Brain abnormalities are not common in this syndrome. When present, retardation or seizure disorders are typically seen. Intracranial hypertension is described for the first time in this syndrome.

  6. Bilateral disease and new trends in Wilms tumour

    Energy Technology Data Exchange (ETDEWEB)

    Owens, Catherine M.; Olsen, Oeystein E. [Great Ormond Street Hospital for Children NHS Trust, Department of Radiology, London (United Kingdom); Brisse, Herve J. [Institut Curie, Service de Radiodiagnostic, Paris (France); Begent, Joanna [University College Hospital, Paediatric Oncology, London (United Kingdom); Smets, Anne M. [Academic Medical Center Amsterdam, Department of Radiology, Amsterdam (Netherlands)

    2008-01-15

    Wilms tumour is a great therapeutic success story within paediatric oncology; its prognosis is excellent. Although mainly sporadic, occurring in otherwise well children, it occurs in a small number of genetically predisposed children. Thus regular surveillance imaging is performed in predisposed children in parts of the USA and Europe. The risks and benefits of surveillance are unclear, as the existing ad-hoc surveillance protocols are lacking in consistency of practice and equity of provision. We present guidelines for Wilms tumour surveillance based on a review of current practice and available evidence, outlined by a multidisciplinary working group in the UK. Wilms tumours are bilateral in 4-13% of affected children. Bilateral synchronous nephroblastomas are observed in 5% of affected children and are usually associated with the presence of nephrogenic rests, congenital malformations and predisposing syndromes. The major challenge in bilateral disease is to achieve a cure and at the same time to preserve sufficient functional renal tissue for normal growth and development. The association among Wilms tumour, nephrogenic rests and nephroblastomatosis makes detection and characterization of renal lesions with imaging extremely important. We discuss the relative strengths and weaknesses of the different modalities used for diagnosis and follow-up in bilateral renal disease. We also discuss newly emerging diagnostic imaging tests such as {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET). This technique, when fused with CT (PET-CT), allows accelerated metabolic activity to be accurately anatomically localised and so is potentially useful for staging, assessment of treatment response, and for surgical and radiotherapy planning. In addition, quantitative MRI techniques have been proved to be valuable in intracranial tumours, but no such role has been validated in abdominal disease. Diffusion-weighted imaging with calculation of ADC maps is feasible in

  7. Intracranial MR imaging of achondroplasia

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Shinichi; Ootsuka, Ryouichi; Hayashi, Yoshinori; Nishitani, Hiromu; Shirakawa, Norihisa; Hashimoto, Toshiaki (Tokushima Univ. (Japan). School of Medicine)

    1992-10-01

    Intracranial MR imaging was performed in five patients with achondroplasia. All patients had narrowing of the subarachnoid space at the level of the formen magnum that was mainly due to protrusion of the posterior aspect. Three patients had compressive deformities of the brainstem and/or upper cervical spine. Among them, two patients had deformities of the pons. Relative upward displacement of the brainstem was seen in all patients. Hydrocephalus was seen in three patients. (author).

  8. Primary liver tumour of intermediate (hepatocyte-bile duct cell) phenotype: a progenitor cell tumour?

    Science.gov (United States)

    Robrechts, C; De Vos, R; Van den Heuvel, M; Van Cutsem, E; Van Damme, B; Desmet, V; Roskams, T

    1998-08-01

    A 57-year-old female patient presented with painless obstructive jaundice and mild mesogastric pain; she was in good general condition on admission. Abdominal ultrasonography revealed diffuse tumoral invasion of the liver, suggesting diffuse metastases. A liver biopsy showed a tumour with a trabecular growth pattern, composed of uniform relatively small cells, very suggestive of an endocrine carcinoma. Additional immunohistochemical stains, however, did not show any endocrine differentiation, but showed positivity for both hepatocyte-type cytokeratins (cytokeratin 8 and 18) and bile duct-type cytokeratins (cytokeratin 7 and 19). In addition, parathyroid hormone-related peptide, shown to be a good marker for cholangiocarcinoma, was immunoreactive. Electron microscopy revealed tumour cells with an intermediate phenotype: the cells clearly showed hepatocyte features on one hand and bile duct cell features on the other hand. Nine days after admission, the patient died due to liver failure and hepatic encephalopathy. Autopsy excluded another primary tumour site. Overall, this tumour was a primary liver tumour with an intermediate phenotype and with a very rapid clinical course. The intermediate (between hepatocyte and bile duct cell) phenotype suggests an immature progenitor cell origin, which is concordant with a rapid clinical course. This type of tumour has not been described previously and provides additional evidence for the existence of progenitor cells in human liver.

  9. Meningoceles in Idiopathic Intracranial Hypertension

    Science.gov (United States)

    Bialer, Omer Y.; Rueda, Mario Perez; Bruce, Beau B.; Newman, Nancy J.; Biousse, Valérie; Saindane, Amit M.

    2014-01-01

    OBJECTIVE MRI abnormalities have been described in patients with increased intracranial pressure (ICP), including in those with idiopathic intracranial hypertension (IIH). Spontaneous cerebral spinal fluid (CSF)-filled outpouchings of the dura (meningoceles), and secondary CSF leaks can occur from elevated ICP in patients with IIH, however, few studies have evaluated these findings. Our objective was to evaluate the frequency of spontaneous intracranial meningoceles among IIH patients and determine their association with visual outcome. SUBJECTS AND METHODS We performed a retrospective case-control study of consecutive IIH patients between 2000 and 2011 who underwent MRI including T2-weighted imaging. Demographics, presenting symptoms, CSF opening pressure, and visual outcome were collected for the first and last evaluations. Controls included patients without headache or visual complaints with normal brain MRIs. Stratified analysis was used to control for potential confounding by age, gender, race, and body mass index. RESULTS We included 79 IIH patients and 76 controls. Meningoceles were found in 11% of IIH patients versus 0% of controls (pmeningoceles were found in 9% of IIH patients versus 0% of controls (pmeningocele or prominent Meckel’s caves was not associated with demographics, symptoms, degree of papilledema, CSF opening pressure, visual acuity, or visual field defect severity. CONCLUSION Meningoceles are significantly more common in IIH patients than in controls, and can be considered an additional imaging sign for IIH. Meningoceles are not, however, associated with decreased CSF opening pressure or better visual outcome in IIH. PMID:24555598

  10. Intracranial pressure in patients with the empty sella syndrome without benign intracranial hypertension.

    OpenAIRE

    Kaye, A H; Tress, B M; Brownbill, D; King, J

    1982-01-01

    The intracranial pressure was monitored continuously for at least 48 hours in five patients with empty sella syndrome, who did not have clinical benign intracranial hypertension (BIH). It has been suggested that the empty sella syndrome is a result of chronically elevated intracranial pressure in the presence of a congenitally deficient diaphragma sellae. However, whilst the intracranial pressure in two of the five patients was abnormally high, in three patients in whom it was monitored, the ...

  11. Intracranial hypertension: classification and patterns of evolution

    OpenAIRE

    Iencean, SM; Ciurea, AV

    2008-01-01

    Intracranial hypertension (ICH) was systematized in four categories according to its aetiology and pathogenic mechanisms: parenchymatous ICH with an intrinsic cerebral cause; vascular ICH, which has its aetiology in disorders of cerebral blood circulation; ICH caused by disorders of cerebro–spinal fluid dynamics and idiopathic ICH. The increase of intracranial pressure is the first to happen and then intracranial hypertension develops from this initial effect becoming symptomatic; it then acq...

  12. 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

  13. Benzene-induced mutational pattern in the tumour suppressor gene TP53 analysed by use of a functional assay, the functional analysis of separated alleles in yeast, in human lung cells.

    Science.gov (United States)

    Billet, Sylvain; Paget, Vincent; Garçon, Guillaume; Heutte, Natacha; André, Véronique; Shirali, Pirouz; Sichel, François

    2010-02-01

    Recent concern has centred on the effects of continuous exposure to low concentrations of benzene, both occupationally and environmentally. Although benzene has for a long time been recognised as a carcinogen for humans, its mechanistic pathway remains unclear. Since mutations in the tumour suppressor gene TP53 are the most common genetic alterations involved in human cancer, our objective was to establish the first mutational pattern induced by benzene on the TP53 gene in human type II-like alveolar epithelial A549 cells by using the Functional Analysis of Separated Alleles in Yeast (FASAY). Seventeen mutations linked to benzene exposure were found: 3 one- or two-base deletions, and 14 single nucleotide substitutions (1 nonsense and 13 missense mutations). A>G and G>A transitions were the most prevalent (23.5% for both). Other mutations included A>C transversions and deletions (3/17, 17.6% for both), G>T transversions (2/17, 11.8%) and A>T transversions (1/17, 5.9%). Data arising from this benzene-induced mutational pattern affecting TP53, a critical target gene in human carcinogenesis, have been compared with those reported in human acute myeloid leukaemia, the aetiology of which is clearly linked to benzene exposure, and in experimental benzene-induced carcinoma. This comparison suggests that A>G transition could be a fingerprint of benzene exposure in tumours. Furthermore, our results demonstrate that FASAY is a promising tool for the study of the carcinogenic potency of benzene in the human lung.

  14. Nephrogenic Diabetes Insipidus with Intracranial Calcifications in a ...

    African Journals Online (AJOL)

    Nephrogenic Diabetes Insipidus with Intracranial Calcifications in a Child with Thalassemia Minor. ... Introduction: There are numerous causes for intracranial calcification in children. We describe an ... Keywords: Developmental Delay; Intracranial Calcifications; Nephrogenic Diabetes Insipidus; Seizures; Thalassemia Minor ...

  15. 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.

  16. Diffusion-weighted images of intracranial cyst-like lesions

    Energy Technology Data Exchange (ETDEWEB)

    Bergui, M.; Zhong, J.; Sales, S. [Dept. of Neuroradiology, University of Turin (Italy); Bradac, G.B. [Dept. of Neuroradiology, University of Turin (Italy); Neuroradiologia Universitaria, Ospedale S. G. Battista, Turin (Italy)

    2001-10-01

    Magnetic resonance sequences may be designed to evaluate the diffusion movements of the protons (diffusion-weighted images, DWI). In these images, a bright signal identifies a region where the diffusion along a spatial axis is restricted. The contents of a cystic lesion frequently have the signal intensities of a generic homogeneous hyperproteinic fluid (hypointensity in T1-, hyperintensity in T2-weighted images). DWI may give further information about the microscopic organisation of these fluids: a hyperintense signal indicates the presence of a restricted diffusion, due to some kind of microscopic organisation, at the cellular or macromolecular level. This may provide additional information useful for clinical purposes. We obtained DWI in 24 consecutive patients with intracranial cystic lesions, (19 intra-axial: five abscesses, five gliomas, six metastases, two demyelinating lesions, one neurocysticercosis; five extra-axial: two arachnoid cysts, two epidermoid cysts, one cholesteatoma). We found a strongly hyperintense signal, indicating restricted diffusion, in brain abscesses, epidermoid cysts and cholesteatoma; all the remaining lesions were hypointense or mildly hyperintense. We found these data useful in critical diagnoses, such as in differentiating abscesses from tumours, and in identifying elusive tumours such as epidermoid cysts. (orig.)

  17. Intracranial hemorrhage due to intracranial hypertension caused by the superior vena cava syndrome.

    Science.gov (United States)

    Bartek, Jiri; Abedi-Valugerdi, Golbarg; Liska, Jan; Nyström, Harriet; Andresen, Morten; Mathiesen, Tiit

    2013-07-01

    We report a patient with intracranial hemorrhage secondary to venous hypertension as a result of a giant aortic pseudoaneurysm that compressed the superior vena cava and caused obstruction of the venous return from the brain. To our knowledge, this is the first patient reported to have an intracranial hemorrhage secondary to a superior vena cava syndrome. The condition appears to be caused by a reversible transient rise in intracranial pressure, as a result of compression of the venous return from the brain. Treatment consisted of surgery for the aortic pseudoaneurysm, which led to normalization of the intracranial pressure and resorption of the intracranial hemorrhage. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    OBJECTIVE: To investigate the effect of different cytokines that are present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland. MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231. Interventions: Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. RESULTS: tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05). CONCLUSION: These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.

  19. Idiopathic intracranial hypertension: case report

    Directory of Open Access Journals (Sweden)

    Iacob G.

    2015-12-01

    Full Text Available Idiopathic intracranial hypertension - IIH (synonymous old terms: benign intracranial hypertension - BIH, pseudotumor-cerebri - PTC it’s a syndrome, related to elevated intracranial pressure, of unknown cause, sometimes cerebral emergency, occuring in all age groups, especially in children and young obese womans, in the absence of an underlying expansive intracranial lesion, despite extensive investigations. Although initial symptoms can resolve, IIH displays a high risk of recurrence several months or years later, even if initial symptoms resolved. Results: A 20-year-old male, obese since two years (body mass index 30, 9, was admitted for three months intense headache, vomiting, diplopia, progressive visual acuity loss. Neurologic examination confirmed diplopia by left abducens nerve palsy, papilledema right > left. At admission, cerebral CT scan and cerebral MRI with angio MRI 3DTOF and 2D venous TOF was normal. Despite treatment with acetazolamide (Diamox, corticosteroid, antidepressants (Amitriptyline, anticonvulsivants (Topiramate three weeks later headache, diplopia persist and vision become worse, confirmed by visual field assessment, visual evoked potential (VEP. A cerebral arteriography demonstrate filling defect of the superior sagittal sinus in the 1/3 proximal part and very week filling of the transverse right sinus on venous time. Trombophylic profile has revealed a heterozygote V factor Leyden mutation, a homozygote MTHFR and PAI mutation justifying an anticoagulant treatment initiated to the patient. The MRI showed a superior sagittal sinus, right transverse and sigmoid sinus thrombosis, dilatation and buckling of the optic nerve sheaths with increased perineural fluid especially retrobulbar, discrete flattening of the posterior segment of the eyeballs, spinal MRI showed posterior epidural space with dilated venous branches, with mass effect on the spinal cord, that occurs pushed anterior on sagittal T1/T2 sequences cervical and

  20. Testicular germ cell tumours in dogs are predominantly of spermatocytic seminoma type and are frequently associated with somatic cell tumours

    DEFF Research Database (Denmark)

    Bush, J M; Gardiner, D W; Palmer, J S

    2011-01-01

    Unlike seminomas in humans, seminomas in animals are not typically sub-classified as classical or spermatocytic types. To compare testicular germ cell tumours (TGCT) in dogs with those of men, archived tissues from 347 cases of canine testicular tumours were morphologically evaluated and characte......Unlike seminomas in humans, seminomas in animals are not typically sub-classified as classical or spermatocytic types. To compare testicular germ cell tumours (TGCT) in dogs with those of men, archived tissues from 347 cases of canine testicular tumours were morphologically evaluated...... in canine TGCT. None of the canine TGCT evaluated demonstrated the presence of carcinoma in situ cells, a standard feature of human classical seminomas, suggesting that classical seminomas either do not occur in dogs or are rare in occurrence. Canine spermatocytic seminomas may provide a useful model...

  1. Phase contrast MRI in intracranial aneurysms

    NARCIS (Netherlands)

    van Ooij, P.

    2012-01-01

    Intracranial aneurysms are outpouchings of intracranial arteries that cause brain hemorrhage after rupture. Unruptured aneurysms can be treated but the risk of treatment may outweigh the risk of rupture. Local intra-aneurysmal hemodynamics can contribute substantially to the rupture risk estimation

  2. Acute surgical management in idiopathic intracranial hypertension.

    LENUS (Irish Health Repository)

    Zakaria, Zaitun

    2012-01-01

    Idiopathic intracranial hypertension is a headache syndrome with progressive symptoms of raised intracranial pressure. Most commonly, it is a slow process where surveillance and medical management are the main treatment modalities. We describe herein an acute presentation with bilateral sixth nerve palsies, papilloedema and visual deterioration, where acute surgical intervention was a vision-saving operation.

  3. Demographic profile of patients diagnosed with intracranial ...

    African Journals Online (AJOL)

    Objectives: To determine the age, gender, racial and ethnic distribution of our patients diagnosed with intracranial menin- giomas. ... intracranial meningiomas were more in frequency among Black Africans, the racial distribution mirrored our population distribution .... Hinojosa et al14 in US (9.6 patients per year), Jaggon.

  4. Is "benign intracranial hypertension" really benign?

    OpenAIRE

    Barber, S G; Garvan, N

    1980-01-01

    Hypothalamic-hypophyseal insufficiency has been found in seven of eight patients with so-called benign intracranial hypertension, of whom four showed an inadequate adrenal response to stress. The syndrome of benign intracranial hypertension cannot therefore be considered entirely benign and patients should receive full endocrinological assessment and follow up.

  5. Migraine before rupture of intracranial aneurysms

    DEFF Research Database (Denmark)

    Lebedeva, Elena R; Gurary, Natalia M; Sakovich, Vladimir P

    2013-01-01

    Rupture of a saccular intracranial aneurysm (SIA) causes thunderclap headache but it remains unclear whether headache in general and migraine in particular are more prevalent in patients with unruptured SIA.......Rupture of a saccular intracranial aneurysm (SIA) causes thunderclap headache but it remains unclear whether headache in general and migraine in particular are more prevalent in patients with unruptured SIA....

  6. Intracranial hypertension and HIV associated meningoradiculitis.

    OpenAIRE

    Prevett, M C; Plant, G T

    1997-01-01

    Two patients with meningoradiculitis associated with HIV presented with symptoms and signs of intracranial hypertension. In the patients described, the raised intracranial pressure resolved after lumbar puncture. After exclusion of opportunistic infection, such patients may be managed with therapeutic lumbar puncture alone.

  7. Computerised tomographic detection of intracranial complications of ...

    African Journals Online (AJOL)

    These include cerebral, subdural and epidural abscesses, frontal bone osteomyelitis. The maxillary and ethmoidal sinuses were mostly involved and can be implicated as the sinogenic causes of intracranial infections. Sphenoidal sinus was not involved in any of the patients. Key Words: Intracranial Complications, Sinusitis, ...

  8. Intracranial alveolar echinococcosis: CT and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Bensaid, A.H. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Dietemann, J.L. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Filippi de la Palavesa, M.M. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Klinkert, A. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Kastler, B. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Gangi, A. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Jacquet, G. (Dept. of Neurosurgery, Univ. Hospital, Besancon (France)); Cattin, F. (Dept. of Radiology, Univ. Hospital, Besancon (France))

    1994-05-01

    Intracranial alveolar echinococcosis is uncommon. We report a patient with right frontal lobe and palpebral lesions secondary to a primary hepatic focus with secondary lesion in the lung. The intracranial and palpebral cystic masses were totally removed and both proved to be alveolar hydatid cysts. An unusual feature in this case is CT and MRI demonstration of dural and bony extension. (orig.)

  9. Radiobiological hypoxia, histological parameters of tumour microenvironment and local tumour control after fractionated irradiation.

    Science.gov (United States)

    Yaromina, Ala; Thames, Howard; Zhou, Xuanjing; Hering, Sandra; Eicheler, Wolfgang; Dörfler, Annegret; Leichtner, Thomas; Zips, Daniel; Baumann, Michael

    2010-07-01

    To investigate the relationships between radiobiological hypoxic fraction (rHF), pimonidazole hypoxic fraction (pHF) as well as other histological parameters of the tumour microenvironment, and local tumour control after fractionated irradiation in human squamous cell carcinomas (hSCCs). Ten different hSCC cell lines were transplanted into nude mice and rHF was calculated from local tumour control rates after single dose irradiation under normal or clamped blood flow conditions. In parallel, tumours were irradiated with 30 fractions within 6 weeks. Radiation response was quantified as dose required to cure 50% of tumours (TCD(50)). Unirradiated tumours were excised for histological evaluation including relative hypoxic area (pHF), relative vascular area (RVA), and fraction of perfused vessels (PF). A weak but significant positive correlation between rHF (R(2)=0.6, p=0.014) and TCD(50) after fractionated irradiation was found. The pHF did not correlate with rHF but was significantly associated with the TCD(50) after single dose clamp (R(2)=0.8, p=0.003) and showed a trend for an association with TCD(50) after fractionated irradiation (R(2)=0.4, p=0.067). Relative vascular area and fraction of perfused vessels did not show an association with rHF or TCD(50) after fractionated irradiation. Our data suggest that radiobiological hypoxia contributes to the response after fractionated irradiation but that also other radiobiological mechanisms are involved. In the present study, pimonidazole labelling does not reflect rHF and has a limited value to predict local tumour control after fractionated irradiation. The association between pHF and TCD(50) after single dose clamp warrants further investigation. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Ultra-wideband sensors for improved magnetic resonance imaging, cardiovascular monitoring and tumour diagnostics.

    Science.gov (United States)

    Thiel, Florian; Kosch, Olaf; Seifert, Frank

    2010-01-01

    The specific advantages of ultra-wideband electromagnetic remote sensing (UWB radar) make it a particularly attractive technique for biomedical applications. We partially review our activities in utilizing this novel approach for the benefit of high and ultra-high field magnetic resonance imaging (MRI) and other applications, e.g., for intensive care medicine and biomedical research. We could show that our approach is beneficial for applications like motion tracking for high resolution brain imaging due to the non-contact acquisition of involuntary head motions with high spatial resolution, navigation for cardiac MRI due to our interpretation of the detected physiological mechanical contraction of the heart muscle and for MR safety, since we have investigated the influence of high static magnetic fields on myocardial mechanics. From our findings we could conclude, that UWB radar can serve as a navigator technique for high and ultra-high field magnetic resonance imaging and can be beneficial preserving the high resolution capability of this imaging modality. Furthermore it can potentially be used to support standard ECG analysis by complementary information where sole ECG analysis fails. Further analytical investigations have proven the feasibility of this method for intracranial displacements detection and the rendition of a tumour's contrast agent based perfusion dynamic. Beside these analytical approaches we have carried out FDTD simulations of a complex arrangement mimicking the illumination of a human torso model incorporating the geometry of the antennas applied.

  11. Intracranial metastases: spectrum of MR imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Kyoung; Lee, Eun Ja; Lee, Yong Seok [Department of Radiology, Dongguk University Ilsan Hospital, Goyang-shi (Korea, Republic of)], E-mail: ejl1048@hanmail.net; Kim, Mi Sung; Park, No Hyuck [Department of Radiology, Kwandong University, College of Medicine, Myongji Hospital, Goyang-shi (Korea, Republic of); Park, Hee-Jin [Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); II, Sung Park [Department of Diagnostic Radiology, Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

    2012-12-15

    Intracranial metastatic lesions arise through a number of routes. Therefore, they can involve any part of the central nervous system and their imaging appearances vary. Magnetic resonance imaging (MRI) plays a key role in lesion detection, lesion delineation, and differentiation of metastases from other intracranial disease processes. This article is a reasoned pictorial review illustrating the many faces of intracranial metastatic lesions based on the location - intra-axial metastases, calvarial metastases, dural metastases, leptomeningeal metastases, secondary invasion of the meninges by metastatic disease involving the calvarium and skull base, direct or perineural intracranial extension of head and neck neoplasm, and other unusual manifestations of intracranial metastases. We also review the role of advanced MRI to distinguish metastases from high-grade gliomas, tumor-mimicking lesions such as brain abscesses, and delayed post-radiation changes in radiosurgically treated patients.

  12. Ultrasensitive tumour-penetrating nanosensors of protease activity.

    Science.gov (United States)

    Kwon, Ester J; Dudani, Jaideep S; Bhatia, Sangeeta N

    2017-01-01

    The ability to identify cancer lesions with endogenous biomarkers is currently limited to tumours ~1 cm in diameter. We recently reported an exogenously administered tumour-penetrating nanosensor that sheds, in response to tumour-specific proteases, peptide fragments that can then be detected in the urine. Here, we report the optimization, informed by a pharmacokinetic mathematical model, of the surface presentation of the peptide substrates to both enhance on-target protease cleavage and minimize off-target cleavage, and of the functionalization of the nanosensors with tumour-penetrating ligands that engage active trafficking pathways to increase activation in the tumour microenvironment. The resulting nanosensor discriminated sub-5 mm lesions in human epithelial tumours and detected nodules with median diameters smaller than 2 mm in an orthotopic model of ovarian cancer. We also demonstrate enhanced receptor-dependent specificity of signal generation in the urine in an immunocompetent model of colorectal liver metastases, and in situ activation of the nanosensors in human tumour microarrays when re-engineered as fluorogenic zymography probes.

  13. 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.

  14. 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.

  15. Desmopressin Acetate in Intracranial Haemorrhage

    Directory of Open Access Journals (Sweden)

    Thomas Kapapa

    2014-01-01

    Full Text Available Introduction. The secondary increase in the size of intracranial haematomas as a result of spontaneous haemorrhage or trauma is of particular relevance in the event of prior intake of platelet aggregation inhibitors. We describe the effect of desmopressin acetate as a means of temporarily stabilising the platelet function. Patients and Methods. The platelet function was analysed in 10 patients who had received single (N=4 or multiple (N=6 doses of acetylsalicylic acid and 3 patients (control group who had not taken acetylsalicylic acid. All subjects had suffered intracranial haemorrhage. Analysis was performed before, half an hour and three hours after administration of desmopressin acetate. Statistical analysis was performed by applying a level of significance of P≤0.05. Results. (1 Platelet function returned to normal 30 minutes after administration of desmopressin acetate. (2 The platelet function worsened again after three hours. (3 There were no complications related to electrolytes or fluid balance. Conclusion. Desmopressin acetate can stabilise the platelet function in neurosurgical patients who have received acetylsalicylic acid prior to surgery without causing transfusion-related side effects or a loss of time. The effect is, however, limited and influenced by the frequency of drug intake. Further controls are needed in neurosurgical patients.

  16. Tumour biology: Herceptin acts as an anti-angiogenic cocktail

    Science.gov (United States)

    Izumi, Yotaro; Xu, Lei; di Tomaso, Emmanuelle; Fukumura, Dai; Jain, Rakesh K.

    2002-03-01

    Malignant tumours secrete factors that enable them to commandeer their own blood supply (angiogenesis), and blocking the action of these factors can inhibit tumour growth. But because tumours may become resistant to treatments that target individual angiogenic factors by switching over to other angiogenic molecules, a cocktail of multiple anti-angiogenic agents should be more effective. Here we show that herceptin, a monoclonal antibody against the cell-surface receptor HER2 (for human epidermal growth factor receptor-2; ref. 4), induces normalization and regression of the vasculature in an experimental human breast tumour that overexpresses HER2 in mice, and that it works by modulating the effects of different pro- and anti-angiogenic factors. As a single agent that acts against multiple targets, herceptin, or drugs like it, may offer a simple alternative to combination anti-angiogenic treatments.

  17. Benign intracranial hypertension: atypical presentation of Miller Fisher syndrome?

    OpenAIRE

    Mewasingh, Leena D; Sekhara, Tayeb; Dachy, Bernard; Djeunang, Maurice; Dan, Bernard

    2002-01-01

    Acute ocular paresis, nausea, vomiting, and headaches associated with high intracranial pressure without obvious intracranial pathology are typical features of benign intracranial hypertension. We describe two young children whose presentation, initially suggestive of idiopathic or benign intracranial hypertension, evolved to comprise ophthalmoplegia, ataxia, and areflexia. This triad characterizes Miller Fisher syndrome, a clinical variant of Guillain-Barré syndrome that occurs rarely among ...

  18. Scalp spindles are associated with widespread intracranial activity with unexpectedly low synchrony

    Science.gov (United States)

    Frauscher, Birgit; von Ellenrieder, Nicolás; Dubeau, François; Gotman, Jean

    2015-01-01

    In humans, the knowledge of intracranial correlates of spindles is mainly gathered from noninvasive neurophysiologic and functional imaging studies which provide an indirect estimate of neuronal intracranial activity. This potential limitation can be overcome by intracranial electroencephalography used in presurgical epilepsy evaluation. We investigated the intracranial correlates of scalp spindles using combined scalp and intracerebral depth electrodes covering the frontal, parietal and temporal neocortex, and the scalp and intracranial correlates of hippocampal and insula spindles in 35 pre-surgical epilepsy patients. Spindles in the scalp were accompanied by widespread cortical increases in sigma band energy (10–16 Hz): the highest percentages were observed in the frontoparietal lateral and mesial cortex, whereas in temporal lateral and mesial structures only a low or no simultaneous increase was present. This intracranial involvement during scalp spindles showed no consistent pattern, and exhibited unexpectedly low synchrony across brain regions. Hippocampal spindles were shorter and spatially restricted with a low synchrony even within the temporal lobe. Similar results were found for the insula. We suggest that the generation of spindles is under a high local cortical influence contributing to the concept of sleep as a local phenomenon and challenging the notion of spindles as widespread synchronous oscillations. PMID:25450108

  19. Intracranial stenosis in cognitive impairment and dementia.

    Science.gov (United States)

    Hilal, Saima; Xu, Xin; Ikram, M Kamran; Vrooman, Henri; Venketasubramanian, Narayanaswamy; Chen, Christopher

    2017-06-01

    Intracranial stenosis is a common vascular lesion observed in Asian and other non-Caucasian stroke populations. However, its role in cognitive impairment and dementia has been under-studied. We, therefore, examined the association of intracranial stenosis with cognitive impairment, dementia and their subtypes in a memory clinic case-control study, where all subjects underwent detailed neuropsychological assessment and 3 T neuroimaging including three-dimensional time-of-flight magnetic resonance angiography. Intracranial stenosis was defined as ≥50% narrowing in any of the intracranial arteries. A total of 424 subjects were recruited of whom 97 were classified as no cognitive impairment, 107 as cognitive impairment no dementia, 70 vascular cognitive impairment no dementia, 121 Alzheimer's Disease, and 30 vascular dementia. Intracranial stenosis was associated with dementia (age/gender/education - adjusted odds ratios (OR): 4.73, 95% confidence interval (CI): 1.93-11.60) and vascular cognitive impairment no dementia (OR: 3.98, 95% CI: 1.59-9.93). These associations were independent of cardiovascular risk factors and MRI markers. However, the association with Alzheimer's Disease and vascular dementia became attenuated in the presence of white matter hyperintensities. Intracranial stenosis is associated with vascular cognitive impairment no dementia independent of MRI markers. In Alzheimer's Disease and vascular dementia, this association is mediated by cerebrovascular disease. Future studies focusing on perfusion and functional markers are needed to determine the pathophysiological mechanism(s) linking intracranial stenosis and cognition so as to identify treatment strategies.

  20. Spontaneous intracranial hypotension: diagnosis to management.

    Science.gov (United States)

    Limaye, Kaustubh; Samant, Rohan; Lee, Ricky W

    2016-06-01

    Spontaneous Intracranial Hypotension typically occurs from spontaneous CSF leak. CSF volume depletion rather than decrease in CSF pressure is thought to be the main causative feature for intracranial hypotension. More and more cases of intracranial hypotension are getting diagnosed with the advances in the imaging. The advances in the imaging have also led to the better understanding of the dynamic changes that occur with intracranial hypotension. The old theories of CSF overproduction or CSF underproduction have not been substantially associated with intracranial hypotension. It has also led to the fore different atypical clinical features and presentations. Although, it has been known for a long time, the diagnosis is still challenging and dilemma persists over one diagnostic modality over other and the subsequent management. Spontaneous CSF leaks occur at the spinal level and the skull base and other locations are rare. The anatomy of spontaneous intracranial hypotension is a very complex process with significant overlap in connective tissue disorders, previous dural weakness or meningeal diverticula. To localize the location of the CSF leak-CT myelography is the modality of choice. CSF cysternography may provide additional confirmation in uncertain cases and also MRI spine imaging may be of significant help in some cases. Spontaneous intracranial hypotension continues to be a diagnostic dilemma and our effort was to consolidate available information on the clinical features, diagnostics, and management for a practicing neurologist for a "15-20 min quick update of the topic".

  1. SPECTRUM OF NEUROENDOCRINE TUMOURS- A TERTIARY CARE CENTRE EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Pasupuleti Prathima

    2016-11-01

    Full Text Available BACKGROUND Neuroendocrine tumours occur at various sites in the human body. They are considered as one of the close differentials for many tumours. Various benign and malignant tumours undergo neuroendocrine differentiation. Its incidence is slightly increasing due to advanced imaging modalities. Although rare, they can be seen in breast, gallbladder and skin. The aim of the study is to study the spectrum of neuroendocrine tumours from various sites, their clinical presentation, histomorphological features with immunohistochemistry and review of literature. MATERIALS AND METHODS This is a retrospective study for a period of 3 years (June 2013-June 2016. Surgical resection specimens were included in the study. Out of the total specimens received, 24 cases were of neuroendocrine tumours. Differential diagnosis of small round cell tumours also was considered and a panel of immunohistochemical markers were included to rule out them. Biopsy specimens were excluded from the study. RESULTS Out of the 24 cases, 18 cases were benign lesions. 6 cases were malignant lesions. Female preponderance was noted. Peak incidence was seen in 20-30 years of age group. CONCLUSION Neuroendocrine tumours can occur anywhere in the body and it should be considered in one of the differential diagnosis. Diagnosis must be accurately made.

  2. Intracranial pathology of the visual pathway

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Forell, W. E-mail: mueller-forell@neuroradio.klinik.uni-mainz.de

    2004-02-01

    Intracranial pathologies involving the visual pathway are manifold. Aligning to anatomy, the most frequent and/or most important extrinsic and intrinsic intracranial lesions are presented. Clinical symptoms and imaging characteristics of lesions of the sellar region are demonstrated in different imaging modalities. The extrinsic lesions mainly consist of pituitary adenomas, meningeomas, craniopharyngeomas and chordomas. In (asymptomatic and symptomatic) aneurysms, different neurological symptoms depend on the location of aneurysms of the circle of Willis. Intrinsic tumors as astrocytoma of any grade, ependymoma and primary CNS-lymphoma require the main pathology in the course of the visual pathway. Vascular and demyelinating diseases complete this overview of intracranial lesions.

  3. Reye's syndrome: assessment of intracranial monitoring.

    Science.gov (United States)

    Jenkins, J G; Glasgow, J F; Black, G W; Fannin, T F; Hicks, E M; Keilty, S R; Crean, P M

    1987-01-01

    Direct measurements of arterial blood pressure and intracranial pressure were recorded in 39 patients aged 3.6 months to 5 years 11 months with Reye's syndrome judged to be stage 2 or beyond. Of 33 patients who survived, 27 made a full recovery and six were severely handicapped. Measurement of cerebral perfusion pressure, which is greatly reduced in the more severe forms of Reye's syndrome, was a better guide to prognosis and management than intracranial pressure alone. The findings emphasise that maintenance of cerebral perfusion pressure is essential if mortality and morbidity are to be reduced. Intracranial monitoring is mandatory in all but the mildest cases of Reye's syndrome. PMID:3101864

  4. Pediatric intracranial primary anaplastic ganglioglioma.

    Science.gov (United States)

    Lüdemann, Wolf; Banan, Rouzbeh; Hartmann, Christian; Bertalanffy, Helmut; Di Rocco, Concezio

    2017-02-01

    Primary intracranial anaplastic gangliogliomas are rare tumors in the pediatric patient group. Most of them present with symptoms of elevated pressure or symptomatic epilepsy. Extraaxial location is far more common than axial location. On MRI examination, they mimic pilocytic astrocytomas. The outcome after surgery depends mainly on the possible amount of surgical resection, and oncological therapy is necessary to prevent recurrence of the disease. An 11-year-old boy presented with headache and double vision due to obstructive hydrocephalus. MRI of the brain revealed an axial partially contrast enhancing lesion in the quadrigeminal plate extending from the cerebellum to the pineal gland and causing hydrocephalus. Subtotal removal of the lesion was performed, and the diagnosis of an anaplastic ganglioglioma was established and confirmed by the reference center. At the latest follow up (3 months), the boy is without any neurological symptoms and scheduled for radiation therapy as well as chemotherapy.

  5. Immunohistochemical characterization of N-methyl-N-nitrosourea-induced mammary tumours of Sprague-Dawley rats.

    Science.gov (United States)

    Pula, Bartosz; Malicka, Iwona; Pawlowska, Katarzyna; Paslawska, Urszula; Cegielski, Marek; Podhorska-Okolow, Marzena; Dziegiel, Piotr; Wozniewski, Marek

    2013-01-01

    Single dose of N-methyl-N-nitrosourea (MNU) was shown to induce malignant tumours in susceptible rat strains. However, such tumours are not well-characterized. We characterized MNU-induced tumours in Sprague-Dawley rats using ultrasonographic, radiographic and immunohistochemical (IHC) methods. In 27 rats, 41 tumours developed, appearing ultrasonographically as hypodense, non-homogenic areas with signal enhancement at their periphery. Out of these, 39 were of malignant epithelial origin, with an IHC phenotype closely-resembling that of human invasive ductal breast carcinoma. One case was diagnosed as carcinosarcoma. IHC analysis revealed that Ki-67 antigen expression correlated positively with tumour volume (r=0.40, p=0.0079). Moreover, tumours with α-smooth muscle actin in the tumour stroma were characterized by a higher proliferative rate as compared to those without its expression (p<0.05). This rat model of chemical carcinogenesis may be suitable for examining breast cancer development and progression.

  6. Are tumours angiogenesis-dependent?

    NARCIS (Netherlands)

    Verheul, H. M. W.; Voest, E. E.; Schlingemann, R. O.

    2004-01-01

    The final proof of principle that cancer patients can be effectively treated with angiogenesis inhibitors is eagerly awaited. Various preclinical in vivo experiments have proven that most tumours need new vessel formation in order to grow and to form metastases. First of all, tumours do not grow in

  7. Tumours in the Small Bowel

    Directory of Open Access Journals (Sweden)

    N. Kurniawan

    2014-01-01

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

  8. Intracranial hypertension after surgical correction for craniosynostosis: a systematic review.

    Science.gov (United States)

    Christian, Eisha A; Imahiyerobo, Thomas A; Nallapa, Swathi; Urata, Mark; McComb, J Gordon; Krieger, Mark D

    2015-05-01

    OBJECT The authors' aim was perform a systematic review on the incidence of intracranial hypertension (IH) after surgery for craniosynostosis. METHODS A systematic literature review was conducted using PubMed to assess the rate of postoperative IH in studies published between 1985 and 2014. Inclusion criteria were 1) English-language literature; 2) human subjects; 3) pediatric cases; and 4) postoperative IH confirmed with invasive intracranial pressure monitoring. RESULTS Seven studies met inclusion criteria. IH was reported to be present in 5% of patients postoperatively with sagittal synostosis and 4% of patients with all forms of nonsyndromic craniosynostosis. Inadequate numbers were available to determine the incidence of postoperative IH for syndromic and individual nonsyndromic sutural synostosis based on the inclusion criteria. Surgical groups were subdivided into cranial remodeling procedures without orbital advancement and craniofacial procedures with orbital advancement. IH was reported to be present in 5% of patients with all forms of nonsyndromic sutural stenosis after cranial remodeling procedures and 1% after craniofacial advancement. CONCLUSIONS Postoperative development of elevated intracranial pressure has been described by multiple institutions, but the variation in how IH is determined and the multiple surgical procedures to correct craniosynostosis has limited the number of studies subject to a meta-analysis. Nonetheless, this entity deserves special attention, and further studies are required to determine the true incidence of postoperative IH, including the role of various surgical procedures on its incidence. The long-term consequences of chronic IH in this group of patients also need to be evaluated.

  9. Clonal nature of odontogenic tumours.

    Science.gov (United States)

    Gomes, Carolina Cavaliéri; Oliveira, Carla da Silveira; Castro, Wagner Henriques; de Lacerda, Júlio César Tanos; Gomez, Ricardo Santiago

    2009-04-01

    Although clonal origin is an essential step in the comprehension of neoplasias, there have been no studies to examine whether odontogenic tumours are derived from a single somatic progenitor cell. The purpose of this study was to investigate the clonal origin of odontogenic tumours. Fresh samples of seven ameloblastomas, two odontogenic mixomas, two adenomatoid odontogenic tumour, one calcifying odontogenic cyst, one calcifying epithelial odontogenic tumour (CEOT) and six odontogenic keratocyst (OKC) of female patients were included in this study. After DNA extraction, the HUMARA gene polymorphism assay was performed. Most of the informative odontogenic lesions studied (12 out of 16) showed a monoclonal pattern. Among the polyclonal cases, two were OKC, one CEOT and one odontogenic mixoma. Our results suggest that most odontogenic tumours are monoclonal.

  10. MR angiography after coiling of intracranial aneurysms

    NARCIS (Netherlands)

    Schaafsma, J.D.

    2012-01-01

    Introduction Endovascular occlusion with detachable coils has become an alternative treatment to neurosurgical clipping of intracranial aneurysms over the last two decades. Its minimal invasiveness is the most important advantage of this treatment compared to clipping. The disadvantage of occlusion

  11. The commonly missed diagnosis of intracranial hypotension

    Directory of Open Access Journals (Sweden)

    Ashlee N. Ruggeri-McKinley, BSN, RN

    2016-06-01

    Full Text Available We report a 28 year old female who presented with a subacute onset of a severe throbbing and stabbing headache after a morning spin class 9 months ago. We confirmed the diagnosis of spontaneous intracranial hypotension cause by a cerebrospinal fluid leak. The headache finally resolved after a 55 ml blood patch. Affecting an estimated 5/100,000 patients, spontaneous intracranial hypotension is considered rare in medical literature. Many patients with spontaneous intracranial hypotension are incapacitated for years and even decades. The misdiagnosis of intracranial hypotension can have serious consequences and lead to unnecessary testing and treatment. Healthcare professionals need to be aware of this diagnosis when evaluating a patient with acute head pain. Considering that physical exams are usually normal, clinicians must focus on the patient history and physical. Clues in the patient interviewing process can lead to an immediate and accurate diagnosis.

  12. Intracranial aneurysm associated with relapsing polychondritis

    Energy Technology Data Exchange (ETDEWEB)

    Coumbaras, M.; Boulin, A.; Pierot, L. [Dept. of Neuroradiology, Hopital Foch, Suresnes (France); Piette, A.M.; Bletry, O. [Dept. of Medicine, Hopital Foch, Suresnes (France); Graveleau, P. [Dept. of Neurology, Hopital Foch, Suresnes (France)

    2001-07-01

    We describe a 50-year-old man with relapsing polychondritis (RP) involving auricular cartilage, uveitis and hearing loss, who had an aneurysm of the anterior cerebral artery. Intracranial aneurysm is a rare manifestation of RP. (orig.)

  13. Multiple intracranial arteriovenous malformations: case report.

    Science.gov (United States)

    Zellem, R T; Buchheit, W A

    1985-07-01

    The authors describe a case of multiple supratentorial intracranial arteriovenous malformations in a patient with a family history of cerebrovascular disease. There was no sign of any other vascular dysplasia. A brief review of this rare entity is given.

  14. Assessing Chemical Constituents of Mimosa caesalpiniifolia Stem Bark: Possible Bioactive Components Accountable for the Cytotoxic Effect of M. caesalpiniifolia on Human Tumour Cell Lines

    Directory of Open Access Journals (Sweden)

    Nayana Bruna Nery Monção

    2015-03-01

    Full Text Available Mimosa caesalpiniifolia is a native plant of the Brazilian northeast, and few studies have investigated its chemical composition and biological significance. This work describes the identification of the first chemical constituents in the ethanolic extract and fractions of M. caesalpiniifolia stem bark based on NMR, GC-qMS and HRMS analyses, as well as an assessment of their cytotoxic activity. GC-qMS analysis showed fatty acid derivatives, triterpenes and steroid substances and confirmed the identity of the chemical compounds isolated from the hexane fraction. Metabolite biodiversity in M. caesalpiniifolia stem bark revealed the differentiated accumulation of pentacyclic triterpenic acids, with a high content of betulinic acid and minor amounts of 3-oxo and 3β-acetoxy derivatives. Bioactive analysis based on total phenolic and flavonoid content showed a high amount of these compounds in the ethanolic extract, and ESI-(−-LTQ-Orbitrap-MS identified caffeoyl hexose at high intensity, as well as the presence of phenolic acids and flavonoids. Furthermore, the evaluation of the ethanolic extract and fractions, including betulinic acid, against colon (HCT-116, ovarian (OVCAR-8 and glioblastoma (SF-295 tumour cell lines showed that the crude extract, hexane and dichloromethane fractions possessed moderate to high inhibitory activity, which may be related to the abundance of betulinic acid. The phytochemical and biological study of M. caesalpiniifolia stem bark thus revealed a new alternative source of antitumour compounds, possibly made effective by the presence of betulinic acid and by chemical co-synergism with other compounds.

  15. Spontaneous intracranial epidural hematoma during rivaroxaban treatment

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    Ruschel, Leonardo Gilmone; Rego, Felipe Marques Monteiro do; Milano, Jeronimo Buzetti; Jung, Gustavo Simiano; Silva Junior, Luis Fernando; Ramina, Ricardo, E-mail: leonardoruschel@yahoo.com.br [Instituto de Neurologia de Curitiba (INC), Curitiba, PR (Brazil)

    2016-11-15

    According to our research, this is the first case described in the literature of spontaneous intracranial epidural hematoma secondary to the use of Xarelto®. Spontaneous intracranial epidural hematomas are rarely described in the literature. They are associated with infectious diseases of the skull, coagulation disorders, vascular malformations of the dura mater and metastasis to the skull. Long-term post-marketing monitoring and independent reports will probably detect the full spectrum of hemorrhagic complications of the use of rivaroxaban. (author)

  16. Perspective: Update on Idiopathic Intracranial Hypertension

    Science.gov (United States)

    Bruce, Beau B.; Biousse, Valérie; Newman, Nancy J.

    2011-01-01

    Purpose Provide an update on various features of idiopathic intracranial hypertension. Design Perspective. Methods Selected articles on the epidemiology, clinical and imaging features, natural history, pathophysiology, and treatment of idiopathic intracranial hypertension were reviewed and interpreted in the context of the authors’ clinical and research experience. Results Idiopathic intracranial hypertension is primarily a disease of obese women of childbearing age, but it can affect patients of any weight, sex, and age. Although a relatively rare disorder, idiopathic intracranial hypertension’s associated costs in the U.S. entail hundreds of millions of dollars. Even following treatment, headaches are frequently persistent and may require the continued involvement of a neurologist. Quality of life reductions and depression are common among idiopathic intracranial hypertension patients. However, visual dysfunction, especially visual field abnormalities, represents the major morbidity of this disorder, and serial automated perimetry remains the primary mode of patient monitoring. Patients who are men, black, very obese, or anemic are at higher risk of visual loss. Vitamin A metabolism, adipose tissue as an actively secreting endocrine tissue, and cerebral venous abnormalities are areas of active study regarding idiopathic intracranial hypertension’s pathophysiology. Treatment studies show that lumbar puncture is a valuable treatment (in addition to its crucial diagnostic role) and that weight management is critical. However, open questions remain regarding the efficacy of acetazolamide, CSF diversion procedures, and cerebral venous stenting. Conclusions Many questions remain unanswered about idiopathic intracranial hypertension. Ongoing studies, especially an ongoing NIH-funded clinical trial of acetazolamide, should provide more insight into this important, yet poorly understood syndrome of isolated intracranial hypertension. PMID:21696699

  17. Rupture of intracranial aneurysm and full moon

    OpenAIRE

    Ottomann, Christian

    2010-01-01

    ABSTRACT OBJECTIVE: To test the hypothesis that the incidence of intracranial aneurysm rupture increases at the time of a full moon period. DESIGN: Retrospective analysis SETTING: Time of rupture and neurosurgical treatment at a university hospital in the capital city of Germany. SETTING: 486 consecutive patients, irrespective of age and sex. MAIN OUTCOME MEASURES: Number of patients who attended an rupture of an intracranial aneurysm and surgical treatment during 1990 to 1998. Th...

  18. Recurrent inverted papilloma with intracranial and temporal fossa involvement: A case report and review of the literature;Papillome inverse recidivant avec extension temporale et intracranienne: cas clinique et revue de la litterature

    Energy Technology Data Exchange (ETDEWEB)

    Acevedo-Henao, C.M.; Pradier, O. [Department of Radiotherapy, Morvan Hospital, CHU de Brest, Brest University, 29 - Brest (France); Talagas, M. [Department of Pathology, Morvan Hospital, CHU de Brest, 29 - Brest (France); Marianowski, R. [Department of Head and Neck Surgery, Morvan Hospital, CHU de Brest, 29 - Brest (France)

    2010-06-15

    Inverted papilloma (I.P.) is a rare naso-sinusal benign tumour, with epithelium surface inversion to inside the stroma. Extension to intracranial temporal fossa and middle ear has been reported in few cases in the literature. This involvement may be derived from either direct extension from sino-nasal cavity via the Eustachian tube or primary middle ear involvement secondary to meta-plastic changes of the middle ear mucosa. Here, we report a case of inverted papilloma in a male patient, with multiple recurrences, middle ear and intracranial involvement into the temporal fossa with posterior development of malignancy. This patient had received multiple surgeries and radiotherapy but despite of that, his disease recurred several times. As a conclusion, inverted papilloma is a benign tumour with an aggressive course, tendency to recurrence and progression to malignancy. Intracranial and temporal fossa involvements are rare and the treatment depends of the symptoms and the severity of the disease. (authors)

  19. Reproductive tract tumours: the scourge of woman reproduction ails Indian rhinoceroses.

    Directory of Open Access Journals (Sweden)

    Robert Hermes

    Full Text Available In Indian rhinoceros, extensive leiomyoma, a benign smooth muscle tumour, was sporadically diagnosed post mortem and commonly thought of as contributing factor for reduced fecundity of this species in captivity. However, to date, the prevalence of reproductive tract tumours and their relevance for fecundity are unknown. Our analysis of the international studbook now reveals that females cease reproducing at the age of 18.1±1.2 years; equivalent to a reproductive lifespan of just 9.5±1.3 years. This short reproductive life is in sharp contrast to their longevity in captivity of over 40 years. Here we show, after examining 42% of the captive female population, that age-related genital tract tumours are highly prevalent in this endangered species. Growth and development of these tumours was found to be age-related, starting from the age of 10 years. All females older than 12 years had developed genital tumours, just 7-9 years past maturity. Tumour sizes ranged from 1.5-10 cm. With age, tumours became more numerous, sometimes merging into one large diffuse tumour mass. These tumours, primarily vaginal and cervical, presumably cause widespread young-age infertility by the age of 18 years. In few cases, tumour necrosis suggested possible malignancy of tumours. Possible consequences of such genital tract tumour infestation are hindered intromission, pain during mating, hampered sperm passage, risk of ascending infection during pregnancy, dystocia, or chronic vaginal bleeding. In humans, leiomyoma affect up to 80% of pre-menopause women. While a leading cause for infertility, pregnancy is known to reduce the risk of tumour development. However, different from human, surgical intervention is not a viable treatment option in rhinoceroses. Thus, in analogy to humans, we suggest early onset and seamless consecutive pregnancies to help reduce prevalence of this disease, better maintain a self-sustained captive population and improve animal welfare.

  20. Incidence and Demographics of Pediatric Intracranial Hypertension.

    Science.gov (United States)

    Gillson, Natalie; Jones, Charlotte; Reem, Rachel E; Rogers, David L; Zumberge, Nicholas; Aylward, Shawn C

    2017-08-01

    We analyzed the incidence and demographic features of pediatric intracranial hypertension. Inpatient and outpatient encounters of children aged 18 years or younger who were diagnosed with primary (idiopathic) or secondary intracranial hypertension between January 2010 and December 2013 were identified. Data were collected from a subspecialty clinic devoted to intracranial hypertension and the sole children's hospital in a large Midwestern city of the United States. Estimated incidence rates were calculated based on the number of newly diagnosed patients in our hospital's primary service area, which includes seven central Ohio counties. Sex, race, body mass index, socioeconomic status, and geographic distribution were also noted. A total of 74 pediatric patients were diagnosed with intracranial hypertension (49 primary/idiopathic and 25 secondary) between January 2010 and December 2013. Using census data, we determined the pediatric population in our service area during the four-year period. The Ohio Hospital Association's database indicated that 92.3% of patients aged 0 to 17 years residing in the region sought care at our institution. By combining these data, we calculated an annual incidence of primary and secondary intracranial hypertension of 0.63 and 0.32 per 100,000 children, respectively. The estimated annual incidence of pediatric primary intracranial hypertension in our seven county service area in central Ohio is similar to previous pediatric reports from other countries and is 67% of that reported in the US adult population. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Detection of Intracranial Hypertension using Deep Learning.

    Science.gov (United States)

    Quachtran, Benjamin; Hamilton, Robert; Scalzo, Fabien

    2016-12-01

    Intracranial Hypertension, a disorder characterized by elevated pressure in the brain, is typically monitored in neurointensive care and diagnosed only after elevation has occurred. This reaction-based method of treatment leaves patients at higher risk of additional complications in case of misdetection. The detection of intracranial hypertension has been the subject of many recent studies in an attempt to accurately characterize the causes of hypertension, specifically examining waveform morphology. We investigate the use of Deep Learning, a hierarchical form of machine learning, to model the relationship between hypertension and waveform morphology, giving us the ability to accurately detect presence hypertension. Data from 60 patients, showing intracranial pressure levels over a half hour time span, was used to evaluate the model. We divided each patient's recording into average normalized beats over 30 sec segments, assigning each beat a label of high (i.e. greater than 15 mmHg) or low intracranial pressure. The model was tested to predict the presence of elevated intracranial pressure. The algorithm was found to be 92.05± 2.25% accurate in detecting intracranial hypertension on our dataset.

  2. Intracranial Aneurysms in Adult Moyamoya Disease.

    Science.gov (United States)

    Kim, Jang Hun; Kwon, Taek-Hyun; Kim, Jong Hyun; Chong, Kyuha; Yoon, Wonki

    2018-01-01

    The prevalence of aneurysm formation in adults with moyamoya disease (MMD) is approximately 14%, and it represents a major potential hemorrhagic risk. We aimed to study the characteristics of intracranial aneurysms occurring in patients with MMD. We retrospectively reviewed our 10-year experience of patients with intracranial aneurysms and a diagnosis of MMD at our hospital. Imaging studies and clinical records of 211 patients who were admitted to our hospital between January 2007 and December 2016 and were diagnosed with MMD were retrospectively reviewed. Patients were divided into 2 groups: 1) MMD without intracranial aneurysms and 2) MMD with intracranial aneurysms. The 2 groups were compared using statistical analysis. Angiographic findings and clinical features of MMD-associated aneurysms were reviewed. There were significant differences between the 2 groups, including age and clinical presentation. Among all enrolled patients (N = 132), 11 aneurysms were discovered in 11 patients. Prevalence of intracranial aneurysms in patients with MMD was 8.3%, and the rupture rate of these aneurysms was 63.6%. We classified the 10 MMD-associated aneurysms (excluding 1 incidentally found paraclinoid aneurysm) as follows: 4 dissecting aneurysms or pseudoaneurysms and 6 hemodynamic true aneurysms. MMD-associated intracranial aneurysms frequently occur in patients presenting with hemorrhagic MMD and are associated with an extremely high rate of rupture. Long-standing hemodynamic stress as well as pathologic and anatomic factors might contribute to the formation of an aneurysm. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Orbital and intracranial complications after acute rhinosinusitis.

    Science.gov (United States)

    Kastner, Jan; Taudy, Milos; Lisy, Jiri; Grabec, Paul; Betka, Jan

    2010-12-01

    Nowadays, intracranial abscess is a rare complication of acute rhinosinusitis. The consequent orbital and intracranial complications of acute rhinosinusitis are rare but must be mutually excluded in complicated rhinosinusitis even when proper surgical and medical treatment tend to efficiently heal the orbital complication. We report a case of a patient who primarily revealed symptoms of orbitocellulitis as a complication of odontogenous rhinosinusitis. Proper diagnostic and therapeutical measures were undertaken to manage the disease immediately after stationary admission. Two weeks after an inconspicuous healing period, hemiparesis due to formation of an intracranial abscess developed. An emergent situation reveals which was unusual to the clinical situation. The possible role of underlying mechanisms of intracranial abscess formation is discussed and review of literature concerning orbital and intracranial rhinosinusitis complications is performed. The correct indication of imaging methods and accurate evaluation of diminutive symptoms are essential. We assume that performance of a complementary CT of the brain or MRI even when previous CT scan of the orbit/paranasal sinuses reveals no cerebral pathology should be done to avoid or minimize future patients with consecutive orbital and intracranial complications of acute rhinosinusitis.

  4. 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.

  5. [Historic malignant tumour: 27 observations].

    Science.gov (United States)

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

    2012-03-01

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

  6. STUDY OF INTRAOPERATIVE SQUASH CYTOLOGY OF INTRACRANIAL AND SPINAL CORD LESIONS WITH HISTOPATHOLOGICAL AND IHC STUDY

    Directory of Open Access Journals (Sweden)

    Naval Kishore Bajaj

    2016-07-01

    Full Text Available BACKGROUND The causes of discordant diagnoses achieved at squash cytology of intracranial and spinal cord tumours were ascertained. Lesions having the advantage of diagnostic accuracy by squash cytology of intracranial and spinal cord lesions was also determined. METHODS Squash preparations of 72 patients suspected to have neoplasia were made and stained with rapid haematoxylin and eosin stain and toluidine blue stain. The smears were classified according to the cytomorphological criteria and the squash cytodiagnoses were compared. RESULTS Total 72 cases were studied, 93.9% were neoplastic and 6.1% non-neoplastic on histopathology. Amongst neoplasms, Astrocytic tumours constituted 26.3% of cases followed by Meningiomas comprising 20.8%. Amongst the benign lesions, Tuberculoma was seen most frequently (6.95%. Overall diagnostic accuracy of squash was 98.65%. On statistical analysis, Sensitivity, Specificity, Positive Predictive value (PPV and Negative Predictive Value (NPV of squash cytology were 98.6%, 100%, 100% and 80% respectively. CONCLUSION Intraoperative Squash is reliable, accurate, cost effective diagnostic modality when combined with histopathological and immunohistochemical techniques.

  7. CT appearances of pleural tumours

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

    2009-09-15

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

  8. Deducing the stage of origin of Wilms' tumours from a developmental series of Wt1-mutant mice

    Directory of Open Access Journals (Sweden)

    Rachel L. Berry

    2015-08-01

    Full Text Available Wilms' tumours, paediatric kidney cancers, are the archetypal example of tumours caused through the disruption of normal development. The genetically best-defined subgroup of Wilms' tumours is the group caused by biallelic loss of the WT1 tumour suppressor gene. Here, we describe a developmental series of mouse models with conditional loss of Wt1 in different stages of nephron development before and after the mesenchymal-to-epithelial transition (MET. We demonstrate that Wt1 is essential for normal development at all kidney developmental stages under study. Comparison of genome-wide expression data from the mutant mouse models with human tumour material of mutant or wild-type WT1 datasets identified the stage of origin of human WT1-mutant tumours, and emphasizes fundamental differences between the two human tumour groups due to different developmental stages of origin.

  9. 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.

  10. Diagnostic value of optical coherence tomography for intracranial pressure in idiopathic intracranial hypertension

    DEFF Research Database (Denmark)

    Skau, Maren; Yri, Hanne; Sander, Birgit

    2013-01-01

    BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition of raised intracranial pressure (ICP) in the absence of space-occupying lesions or other known etiology. It primarily affects young obese females, and potentially causes permanent visual loss due to papilledema and secondary op...

  11. Base changes in tumour DNA have the power to reveal the causes and evolution of cancer

    OpenAIRE

    Hollstein, M; Alexandrov, L.B.; Wild, C. P.; Ardin, M; J. Zavadil

    2016-01-01

    Next-generation sequencing (NGS) technology has demonstrated that the cancer genomes are peppered with mutations. Although most somatic tumour mutations are unlikely to have any role in the cancer process per se, the spectra of DNA sequence changes in tumour mutation catalogues have the potential to identify the mutagens, and to reveal the mutagenic processes responsible for human cancer. Very recently, a novel approach for data mining of the vast compilations of tumour NGS data succeeded in ...

  12. Personalization of the medical treatment of solid tumours using patient-derived tumour explants (Review).

    Science.gov (United States)

    Louandre, Christophe; Donnadieu, Jérome; Lachaier, Emma; Page, Cyril; Chauffert, Bruno; Galmiche, Antoine

    2016-03-01

    Improving the pre-clinical characterization of therapeutic approaches and developing new biological assays that will enable treatment personalization for individual patients are promising developments in oncology. Here we describe a new approach consisting of culturing human tumour explants. This approach involves the preparation of slices from freshly-obtained, surgically-resected material that can be maintained ex vivo for several days. Recent studies have provided proof of principle that this approach can be easily implemented in order to explore the mode of action of various anticancer drugs and the responses of 'real' tumours at the individual patient level. We present the practical aspects and highlight the versatility of this approach, which allows for the analysis of the susceptibility of any individual tumour to multiple anticancer drugs in parallel. We discuss its potential as a companion assay in the design of optimal clinical trials and as a guide for the prescription of medical treatment. We discuss which future clinical and biological studies are needed to validate the information gathered from cultured tumour explants, and to integrate this information with that gathered from other assays in order to optimize the medical treatment of cancer.

  13. Recombinant human alpha fetoprotein synergistically potentiates the anti-cancer effects of 1′-S-1′-acetoxychavicol acetate when used as a complex against human tumours harbouring AFP-receptors

    OpenAIRE

    Arshad, Norhafiza M.; In, Lionel L.A.; Soh, Tchen Lin; Azmi, Mohamad Nurul; Ibrahim, Halijah; Awang, Khalijah; Dudich, Elena; Tatulov, Eduard; Nagoor, Noor Hasima

    2015-01-01

    Purpose Previous in vitro and in vivo studies have reported that 1′-S-1′-acetoxychavicol acetate (ACA) isolated from rhizomes of the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) induces apoptosis-mediated cell death in tumour cells via dysregulation of the NF-κB pathway. However there were some clinical development drawbacks such as poor in vivo solubility, depreciation of biological activity upon exposure to an aqueous environment and non-specific targeting of tum...

  14. Intracranial Vascular Malformations and Epilepsy.

    Science.gov (United States)

    Josephson, Colin B; Rosenow, Felix; Al-Shahi Salman, Rustam

    2015-06-01

    Among the spectrum of intracranial vascular malformations (IVMs), arteriovenous malformations (AVMs), and cavernous malformations (CCMs) are of particular importance for epilepsy. Seizures are a common mode of presentation for both conditions. Seizures may occur de novo or secondary to intracerebral hemorrhage. Timely imaging is thus crucial for patients with seizures and AVMs or CCMs. Patients with a first-ever AVM- or CCM-related seizure can now be considered to have epilepsy according to the International League Against Epilepsy criteria. Observational studies and case series suggest that between 45 to 78% of patients with AVM-related epilepsy and 47 to 60% of patients with CCM-related epilepsy may achieve seizure freedom through antiepileptic drugs (AEDs) alone. Invasive procedures are available although current evidence suggests that epilepsy-specific preintervention evaluations are underused. Randomized controlled trials and population-based studies have demonstrated worse short-term functional outcomes after routine intervention on unruptured AVMs or CCMs when compared with conservative management. The role of invasive therapy for IVM-related epilepsy has yielded mixed results. Case series have reported high estimates of seizure freedom although these results have not been replicated in controlled observational studies. Randomized controlled trials of immediate invasive therapy versus conservative management, in addition to usual care with AEDs and of different types of treatment and their timing, are warranted for AVMs and CCM-related epilepsy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Tumour exosome integrins determine organotropic metastasis.

    Science.gov (United States)

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

    2015-11-19

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

  16. Tumour exosome integrins determine organotropic metastasis

    Science.gov (United States)

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

    2015-01-01

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

  17. European Organisation for Research and Treatment of Cancer (EORTC) Pathobiology Group standard operating procedure for the preparation of human tumour tissue extracts suited for the quantitative analysis of tissue-associated biomarkers.

    NARCIS (Netherlands)

    Schmitt, M.; Mengele, K.; Schueren, E. van der; Sweep, C.G.J.; Foekens, J.A.; Brunner, N.; Laabs, J.; Malik, A.; Harbeck, N.

    2007-01-01

    With the new concept of 'individualized treatment and targeted therapies', tumour tissue-associated biomarkers have been given a new role in selection of cancer patients for treatment and in cancer patient management. Tumour biomarkers can give support to cancer patient stratification and risk

  18. Intratumoral delivery of bortezomib: impact on survival in an intracranial glioma tumor model.

    Science.gov (United States)

    Wang, Weijun; Cho, Hee-Yeon; Rosenstein-Sisson, Rachel; Marín Ramos, Nagore I; Price, Ryan; Hurth, Kyle; Schönthal, Axel H; Hofman, Florence M; Chen, Thomas C

    2017-04-14

    OBJECTIVE Glioblastoma (GBM) is the most prevalent and the most aggressive of primary brain tumors. There is currently no effective treatment for this tumor. The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for GBM. The authors' goal was to demonstrate that bortezomib can be effective in the orthotopic GBM murine model if the appropriate method of drug delivery is used. In this study the Alzet mini-osmotic pump was used to bring the drug directly to the tumor in the brain, circumventing the blood-brain barrier; thus making bortezomib an effective treatment for GBM. METHODS The 2 human glioma cell lines, U87 and U251, were labeled with luciferase and used in the subcutaneous and intracranial in vivo tumor models. Glioma cells were implanted subcutaneously into the right flank, or intracranially into the frontal cortex of athymic nude mice. Mice bearing intracranial glioma tumors were implanted with an Alzet mini-osmotic pump containing different doses of bortezomib. The Alzet pumps were introduced directly into the tumor bed in the brain. Survival was documented for mice with intracranial tumors. RESULTS Glioma cells were sensitive to bortezomib at nanomolar quantities in vitro. In the subcutaneous in vivo xenograft tumor model, bortezomib given intravenously was effective in reducing tumor progression. However, in the intracranial glioma model, bortezomib given systemically did not affect survival. By sharp contrast, animals treated with bortezomib intracranially at the tumor site exhibited significantly increased survival. CONCLUSIONS Bypassing the blood-brain barrier by using the osmotic pump resulted in an increase in the efficacy of bortezomib for the treatment of intracranial tumors. Thus, the intratumoral administration of bortezomib into the cranial cavity is an effective approach for glioma therapy.

  19. The Heidelberg classification of renal cell tumours

    NARCIS (Netherlands)

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

    1997-01-01

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

  20. Structure-cytotoxicity relationships of a series of natural and semi-synthetic simple coumarins as assessed in two human tumour cell lines

    NARCIS (Netherlands)

    Kolodziej, H; Kayser, O; Woerdenbag, HJ; vanUden, W; Pras, N

    1997-01-01

    The cytotoxicity of 22 natural and semi-synthetic simple coumarins was evaluated in GLC(4), a human small cell lung carcinoma cell line, and in COLO 320, a human colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. With IC50 values > 100 mu M, following a continuous (96h)

  1. Comparative oncology: what dogs and other species can teach us about humans with cancer.

    Science.gov (United States)

    Schiffman, Joshua D; Breen, Matthew

    2015-07-19

    Over 1.66 million humans (approx. 500/100,000 population rate) and over 4.2 million dogs (approx. 5300/100,000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  2. Paediatric laryngeal granular cell tumour

    Directory of Open Access Journals (Sweden)

    Dauda Ayuba

    2009-01-01

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

  3. Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8+Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region.

    Science.gov (United States)

    Sivars, Lars; Landin, David; Grün, Nathalie; Vlastos, Andrea; Marklund, Linda; Nordemar, Sushma; Ramqvist, Torbjörn; Munck-Wikland, Eva; Näsman, Anders; Dalianis, Tina

    2017-02-01

    Human papillomavirus (HPV) is a favourable prognostic factor in oropharyngeal cancer. Moreover, we and others reported that HPV-positive cancer of unknown primary in the head and neck region (HNCUP) has better outcome than HPV-negative HNCUP. However, not all studies concord. Here, our previous finding was investigated in a new cohort and additional biomarkers were analyzed. A total of 19 HNCUPs diagnosed 2008-2013 were analyzed for HPV DNA by polymerase chain reaction assay (PCR) and p16 by immunohistochemistry (IHC). Thereafter, 69 HNCUPs diagnosed between 2000-2013 were analyzed for HPV16 mRNA by PCR (if HPV16DNA-positive) and cluster of differentiation 8 positive (CD8 + ) tumour-infiltrating lymphocytes (TILs) and human leukocyte antigen (HLA) class I-expression using IHC. HPV DNA, alone and in combination with p16 overexpression, was validated as a favourable prognostic factor in HNCUP. HPV16 mRNA was present in most HPV16 DNA-positive cases, confirming HPV-driven carcinogenesis in HNCUP. High CD8 + TIL counts indicated favourable prognosis. HPV status is useful for the management of patients with HNCUP and the role of CD8 + TILs should be further explored. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. MRI characteristics of midbrain tumours

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-03-01

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

  5. Intracranial neoplasmin Ibadan, Nigeria | Olasode | East African ...

    African Journals Online (AJOL)

    There was no gender difference, the ratio being 1:1. Gliomas accounted for the largest group of tumours followed by metastases to the brain. Of the gliomas, astrocytoma was the commonest. Craniopharyngiomas were found to becommon in children. Germ cell tumours were found to be uncommon. Conclusion: Gliomas are ...

  6. 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.

  7. 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.

  8. IgG4-Related Disease: A New Etiology Underlying Diffuse Intracranial Dilating Vasculopathy.

    Science.gov (United States)

    Marlin, Evan S; Dornbos, David; Ikeda, Daniel S; Lehman, Norman L; Powers, Ciarán J

    2017-11-01

    Diffuse intracranial aneurysmal vasculopathy is a rare condition, previously described in patients with human immunodeficiency virus infection. IgG4-related disease (IgG4-RD) is a recognized inflammatory disease of systemic organs, leading to fibrosis of connective tissues. It also has been linked to inflammatory dilating aortic aneurysms, coronary vascular disease, hypophysitis, orbital pseudotumor, and pachymeningitis. It has not yet been described as a cause of diffuse intracranial dilating vasculopathy. Histologically, this disease is characterized by IgG4-plasma cell infiltration, fibrosis, and phlebitis. A 40-year-old woman presented with acute heart failure, valvular insufficiency, and mycotic coronary aneurysms, concerning for endocarditis. Infectious workup was negative. Concurrent neurovascular workup revealed intracranial aneurysms, appearing mycotic in origin. Despite aggressive treatment for more than 5 years, she suffered multiple episodes of subarachnoid hemorrhage from a progressive dilating intracranial vasculopathy. Serum IgG levels and aneurysm wall pathology were consistent with IgG4-RD. This is the first reported case of a diffuse intracranial dilating vasculopathy secondary to IgG4-RD. Recognition of similar pathologic findings in clinical presentation and radiologic workup should prompt further rheumatologic workup and possible immunosuppressive therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Animal tumour registry of two provinces in northern Italy: incidence of spontaneous tumours in dogs and cats

    Directory of Open Access Journals (Sweden)

    Carminato Antonio

    2009-10-01

    Full Text Available Abstract Background Cancer is a major cause of death in domestic animals. Furthermore, many forms of pet neoplasm resemble that of their human counterparts in biologic behaviour, pathologic expression, and recognised risk factors. In April 2005, a pilot project was activated so as to establish a dog and cat tumour registry living in the Venice and Vicenza provinces (Veneto Region, north-eastern Italy, with the aim of estimating the incidence of spontaneous tumours. Results Through a telephone survey, the estimates of canine and feline populations of the catchment area turned out to be of 296,318 (CI +/- 30,201 and 214,683 (CI +/- 21,755 subjects, respectively. During the first three years, overall 2,509 canine and 494 feline cases of neoplasia were diagnosed. In dogs, the estimated annual incidence rate (IR per 100,000 dogs for all tumours was 282 in all the catchment area, whereas in cats the IR was much lower (IR = 77. Malignant and benign tumours were equally distributed in male and female dogs, whereas cats had a 4.6-fold higher incidence of malignant tumours than benign. In both dogs and cats, purebreds had an almost 2-fold higher incidence of malignant tumours than mixed breeds. Tumour incidence increased with age in both dog and cat populations. Conclusion This study has provided estimates of incidence of spontaneous neoplasm in companion animals. Further attempts will be made to increase the accuracy in the population size assessment and to ascertain the real gap with the official regional canine demographic registry. Veterinary practitioners may also benefit from the tumour registry insofar they may obtain data for specific breeds, age groups or geographical areas.

  10. Optimizing clinical performance and geometrical robustness of a new electrode device for intracranial tumor electroporation

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Gehl, Julie

    2011-01-01

    and genes to intracranial tumors in humans, and demonstrate a method to optimize the design (i.e. geometry) of the electrode device prototype to improve both clinical performance and geometrical tolerance (robustness). We have employed a semiempirical objective function based on constraints similar to those...

  11. Reply: Very low prevalence of intracranial hypertension in trigonocephaly

    NARCIS (Netherlands)

    M.J. Cornelissen (Martijn); I.M.J. Mathijssen (Irene)

    2017-01-01

    markdownabstract_Sir:_ We read with interest the letter by Dr. Rogers regarding our article on the prevalence of intracranial hypertension in trigonocephaly. This article describes the occurrence of intracranial hypertension, assessed through funduscopy, and its relation

  12. Predictors of severe complications in intracranial meningioma surgery

    DEFF Research Database (Denmark)

    Bartek, Jiri; Sjåvik, Kristin; Förander, Petter

    2015-01-01

    OBJECTIVE: To investigate predictors of complications after intracranial meningioma resection using a standardized reporting system for adverse events. METHODS: A retrospective review was conducted in a Scandinavian population-based cohort of 979 adult operations for intracranial meningioma perfo...

  13. The radiological appearance of intracranial aneurysms in adults ...

    African Journals Online (AJOL)

    %. Limited literature is available on intracranial aneurysms in HIV-infected patients. Objectives: To describe the radiological appearance of intracranial aneurysms in HIV positive adults. Method: In this retrospective analysis of data, ...

  14. 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.

  15. Intracranial Hypertension Without Papilledema in Children.

    Science.gov (United States)

    Aylward, Shawn C; Aronowitz, Catherine; Roach, E Steve

    2016-02-01

    This study aims to determine the frequency of intracranial hypertension without papilledema in children. Charts of patients evaluated in a pediatric intracranial hypertension clinic at our institution were retrospectively reviewed. The patients were divided into 2 groups depending on whether they had presence or absence of optic nerve edema at the time of presentation. Age, body mass index, and opening cerebrospinal fluid pressures were considered continuous variables and compared by Wilcoxon rank sum test because of non-normality. A P-value of 0.05 was considered significant. A total of 228 charts were reviewed; 152 patients met the criteria for intracranial hypertension, and 27 patients (17.8%) met the criteria of headache without optic nerve edema. There was no clinically significant difference in age, body mass index, opening pressure, and modified opening pressure between the 2 groups. © The Author(s) 2015.

  16. Intracranial hypertension without headache in children.

    Science.gov (United States)

    Aylward, Shawn C; Aronowitz, Catherine; Reem, Rachel; Rogers, David; Roach, E Steve

    2015-05-01

    We aimed to determine the frequency of intracranial hypertension without headache in children. We retrospectively analyzed patients evaluated in a pediatric intracranial hypertension referral center. Patients were divided into 2 groups depending on whether they complained of headache at the time of presentation. Age, body mass index, and opening cerebrospinal fluid pressures were considered continuous variables and compared by Wilcoxon rank-sum test because of non-normality. A P value of .05 was considered significant. A total of 228 charts were reviewed; 152 patients met the criteria for intracranial hypertension and 22/152 patients (14.5%) met the criteria of optic nerve edema without headache. There were clinically significant differences in age and body mass index between the 2 groups. The group without headache was typically younger and not obese. The opening pressure and modified opening pressure were not clinically significant between the 2 groups. © The Author(s) 2014.

  17. Minocycline-induced fulminant intracranial hypertension.

    Science.gov (United States)

    Fraser, Clare L; Biousse, Valerie; Newman, Nancy J

    2012-08-01

    To describe the clinical course of an unusually severe case of minocycline-induced intracranial hypertension. Case study. Academic medical center. Twelve-year-old girl with a fulminant course of intracranial hypertension. Magnetic resonance imaging and venography of the brain, lumbar puncture, and optic nerve sheath fenestration. Although the patient ceased minocycline treatment, there was ongoing and rapid worsening of symptoms and vision loss. Lumbar puncture, which normally acts as a temporizing measure to preserve vision, failed to prevent, and may even have precipitated, further deterioration in vision, necessitating surgical intervention with optic nerve sheath fenestration. Minocycline can cause a fulminant syndrome of elevated intracranial pressure, with severe vision loss, even after the medication has been discontinued.

  18. Augmentation of alphavirus vector-induced human papilloma virus-specific immune and anti-tumour responses by co-expression of interleukin-12

    NARCIS (Netherlands)

    Riezebos-Brilman, Annelies; Regts, Joke; Chen, Margaret; Wilschut, Jan; Daemen, Toos

    2009-01-01

    To enhance the efficacy of a therapeutic immunisition strategy against human papillomavirus-induced cervical cancer we evaluated the adjuvant effect of interleukin-12 (IL12) expressed by a Semliki Forest virus vector (SFV) in mice. Depending on the dose and schedule. SFV-IL12 Stimulated

  19. Immunoglobulin V(H) gene sequence analysis of spontaneous murine immunoglobulin secreting B-cell tumours with clinical features of human disease

    NARCIS (Netherlands)

    Zhu, D.; Arkel, C. van; King, C.A.; Meirvenne, S. van; Greef, C. de; Thielemans, K.; Radl, J.; Stevenson, F.K.

    1998-01-01

    The 5T series of multiple myelomas (MM) and Waldenstrsom's macroglobulinaemia-like lymphomas (WM), which developed spontaneously in ageing mice of the C57BL/KaLwRij strain, shows clinical and biological features that closely resemble their corresponding human diseases. In order to compare the

  20. Superior therapeutic efficacy of alphavirus-mediated immunization against human papilloma virus type 16 antigens in a murine tumour model : effects of the route of immunization

    NARCIS (Netherlands)

    Daemen, T; Riezebos-Brilman, A; Regts, J; Dontje, B; van der Zee, A; Wilschut, J

    2004-01-01

    In our efforts to develop a strong, effective immune response against cervical carcinoma and premalignant disease, we study the use of recombinant Semliki Forest virus (SFV) encoding the oncoproteins E6 and E7 from high-risk human papilloma viruses (HPVs). Optimal immunization conditions are

  1. Maturation of human dendritic cells by monocyte-conditioned medium is dependent upon trace amounts of lipopolysaccharide inducing tumour necrosis factor alpha

    DEFF Research Database (Denmark)

    Nersting, Jacob; Svenson, Morten; Andersen, Vagn

    2003-01-01

    We investigated the ability of monocyte-conditioned medium (MCM), generated by monocytes cultured on plastic-immobilised immunoglobulin, to stimulate maturation of human monocyte-derived dendritic cells (DC). Earlier reports suggest that MCM is a strong inducer of irreversible DC maturation, wher...

  2. Zr-89-trastuzumab PET visualises HER2 downregulation by the HSP90 inhibitor NVP-AUY922 in a human tumour xenograft

    NARCIS (Netherlands)

    Munnink, Thijs H. Oude; de Korte, Maarten A.; Nagengast, Wouter B.; Timmer-Bosscha, Hetty; Schroder, Carolina P.; de Jong, Johan R.; van Dongen, Guus A. M. S.; Jensen, Michael Rugaard; Quadt, Cornelia; Lub-de Hooge, Marjolijn N.; de Vries, Elisabeth G. E.

    NVP-AUY922, a potent heat shock protein (HSP) 90 inhibitor, downregulates the expression of many oncogenic proteins, including the human epidermal growth factor receptor-2 (HER2). Because HER2 downregulation is a potential biomarker for early response to HSP90-targeted therapies, we used the

  3. Effect of gravity and microgravity on intracranial pressure.

    Science.gov (United States)

    Lawley, Justin S; Petersen, Lonnie G; Howden, Erin J; Sarma, Satyam; Cornwell, William K; Zhang, Rong; Whitworth, Louis A; Williams, Michael A; Levine, Benjamin D

    2017-03-15

    Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure on Earth. Gravity has a profound effect on fluid distribution and pressure within the human circulation. In contrast to prevailing theory, we observed that microgravity reduces central venous and intracranial pressure. This being said, intracranial pressure is not reduced to the levels observed in the 90 deg seated upright posture on Earth. Thus, over 24 h in zero gravity, pressure in the brain is slightly above that observed on Earth, which may explain remodelling of the eye in astronauts. Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure (ICP). This syndrome is considered the most mission-critical medical problem identified in the past decade of manned spaceflight. We recruited five men and three women who had an Ommaya reservoir inserted for the delivery of prophylactic CNS chemotherapy, but were free of their malignant disease for at least 1 year. ICP was assessed by placing a fluid-filled 25 gauge butterfly needle into the Ommaya reservoir. Subjects were studied in the upright and supine position, during acute zero gravity (parabolic flight) and prolonged simulated microgravity (6 deg head-down tilt bedrest). ICP was lower when seated in the 90 deg upright posture compared to lying supine (seated, 4 ± 1 vs. supine, 15 ± 2 mmHg). Whilst lying in the supine posture, central venous pressure (supine, 7 ± 3 vs. microgravity, 4 ± 2 mmHg) and ICP (supine, 17 ± 2 vs. microgravity, 13 ± 2 mmHg) were reduced in acute zero gravity, although not to the levels observed in the 90 deg seated upright posture on Earth. Prolonged periods of simulated microgravity did not cause progressive elevations in ICP (supine, 15 ± 2 vs. 24 h head-down tilt, 15 ± 4 mmHg). Complete removal of gravity does not

  4. Development of intracranial hypertension after surgical management of intracranial arachnoid cyst: report of three cases and review of the literature.

    LENUS (Irish Health Repository)

    Kaliaperumal, Chandrasekaran

    2013-11-12

    To describe three cases of delayed development of intracranial hypertension (IH) after surgical treatment of intracranial arachnoid cyst, including the pathogenesis of IH and a review of the literature.

  5. Primary intracranial leiomyoma in renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Upasana Patel

    2017-01-01

    Full Text Available Leiomyoma, the benign tumor of smooth muscle cell origin, is commonly seen in genitourinary and gastrointestinal tracts. Primary intracranial leiomyoma, however, is extremely rare occurrence. We hereby report a case of Epstein-Barr negative primary intracranial leiomyoma in a middle-aged renal transplant recipient, which mimicked left frontal parasagittal meningioma on neuroimaging. The tumor was completely excised and diagnosis of leiomyoma was clinched on pathological analysis with immunohistochemistry. The patient improved after tumor removal, and no evidence of tumor recurrence was noted on follow-up study after 10 months postsurgically.

  6. Undiagnosed intracranial lipoma associated with sudden death

    Directory of Open Access Journals (Sweden)

    Carlos Durão

    2017-03-01

    Full Text Available Intracranial lipomas represent less than 0.1% of all intracranial tumors. They are usually located in the callus area and often asymptomatic. This paper presents a sudden death case after an episode of convulsions on a 39 years old woman with a history of migraines and seizures since adolescence. The autopsy revealed the presence of an undiagnosed massive brain lipoma (60 × 35 mm associated with atrophy of the corpus callosum. Although very rare and seldom malignant these may be associated with seizures and sudden death.

  7. Idiopathic Intracranial Hypertension – Pathophysiology Based on Case Series

    Directory of Open Access Journals (Sweden)

    Ljubisavljević Srdjan

    2016-09-01

    Full Text Available According to the definition, idiopathic intracranial hypertension (IIH is a pathological state characterized by an increase in intracranial pressure; however, there are no obvious intracranial pathological processes. The pathophysiology of this disorder is not clear, although there are many reports related to it.

  8. Epilepsy in primary intracranial tumors in a neurosurgical hospital in ...

    African Journals Online (AJOL)

    2015-04-06

    Apr 6, 2015 ... Background: Seizures may be manifestation of intracranial tumor (IT) and demand thorough neurological evaluation. This paper examines ... lobe most often. Key words: Intracranial tumors, postoperative seizure outcome, seizures ... and other associated symptoms such as raised intracranial pressure and ...

  9. Intracranial meningiomas in the present era of modern neuroimaging

    African Journals Online (AJOL)

    Background: Intracranial meningioma is the most common primary, intracranial, extra-axial neoplasm. It is mesenchymal in origin and arises from meningothelial cells of arachnoid villi of meninges. Objectives: To re-emphasize the regional anatomic localisation and diagnostic radiological features of intracranial ...

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

    Science.gov (United States)

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

    2015-01-01

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

  11. A STUDY ON OPHTHALMIC MANIFESTATIONS IN PITUITARY GLAND TUMOURS

    Directory of Open Access Journals (Sweden)

    Chitra Munusamy Rajendran

    2017-09-01

    Full Text Available BACKGROUND Pituitary adenoma is a benign tumour that originates from the adenohypophyseal cells of the anterior lobe of pituitary gland. It accounts for 12% to 15% of all intracranial tumours. A spectrum of ocular manifestations are seen with these tumours ranging from the absence of any visual symptoms to severe visual field defects and loss of vision. The aim of the study is to study the various ocular features and its effect on vision, visual fields and ocular motility in cases of pituitary adenoma diagnosed on CT or MRI. MATERIALS AND METHODS This is a prospective study for a period of 1 year and 8 months conducted in Regional Institute of Ophthalmology, Madras Medical College. 25 patients aged between 25 to 65 years diagnosed as pituitary adenomas on radiological imaging who presented to squint clinic were evaluated after detailed history with visual acuity, pupillary reaction, colour vision, extraocular movements, slit lamp and fundus examination. Visual field examination was done with Octopus field analyser. RESULTS In our study, 25 patients of pituitary adenoma diagnosed on radio imaging were enrolled and evaluated. Most patients were above 50 years, 15 patients of the 25 were above 50 yrs. (60%. Females were predominantly affected (76%. Visual acquity of the patient was between 6/12-6/6 (62% on presentation. Headache was the commonest mode of presentation (80%. 76% showed field defects of which bitemporal hemianopia was the commonest in 52.9%. Pituitary macroadenoma 96% was the commonest type. Optic atrophy was seen only in 4 cases. Others had normal fundus. CONCLUSION Neuro-ophthalmic evaluation plays a major role not only in early detection, planning of treatment and further follow up, but also prevents visual loss if intervened early.

  12. CT differential diagnosis of tumour of the cranium with intracranial spread - a case report

    Energy Technology Data Exchange (ETDEWEB)

    Trittmacher, S.; Purmann, H.; Schmid, A.

    1988-01-01

    A report on patient presenting in the cranial computer tomogram with changes in the cranium in the left temporal region typical of a meningioma, as well as with changes in the floor of the middle cranial fossa. Correct diagnosis was obtained only by the overall assessment comprising anamnesis, laboratory findings and state of the skeletal structure: namely, a plasmacytoma involving the calotte of the cranium.

  13. 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

    The neutrophil-lymphocyte count ratio (NLCR) is an established prognostic marker for renal, lung and colorectal carcinomas and has been suggested to be predictive of histological grade and outcome in adult intracranial tumours. The purpose of this study was to determine whether a correlation of the pre-operative neutrophil count (NC) and NLCR with the final histological grade exists in paediatric intracranial tumours. A retrospective analysis was undertaken at a single centre. Patients less than 18 years old at the time of surgery who underwent tumour-related procedures from 2006 to 2015 were included. Patients with recurrent tumours, previous bone marrow transplant and metastases were excluded. Pre-operative full blood counts (FBC), collected before the diagnosis of intracranial pathology and before administration of steroids, were matched with histological diagnosis for each patient. Post-operative FBC was also recorded, together with survival data where applicable. A total of 116 patients (74 male, 42 female; mean age, 8 ± 0.9 years) with a diagnosis of primary intracranial tumours had pre-operative FBC that could be matched to final histological grade. Pre-operative NC and NLCR were higher with increasing grade of tumour: grade 1 (NC 4.29 109/l, NLCR 2.26), grade 2 (NC 4.59 109/l, NLCR 2.38), grade 3 (NC 5.67 109/l, NLCR 2.72) and grade 4 (NC 6.59 109/l, NLCR 3.31). Patients with WHO grade 1 and 2 tumours pooled together had a lower NC (4.37 95% CI ± 0.67 109/l) compared to WHO grade 3 and 4 patients (6.41 95% CI ± 0.99 109/l, p = 0.0013). The NLCR was lower in grade 1 and 2 tumours (2.29 ± 0.59) (compared to grade 3 and 4 tumours; 3.20 ± 0.76) but this did not reach significance (p = 0.069). The subgroup of patients with pilocytic astrocytoma had a significantly lower NC when compared to patients with high-grade tumours (p = 0.005). Medulloblastoma and supratentorial PNET subgroups had significantly higher NC compared to the low

  14. Pitfalls in colour photography of choroidal tumours.

    Science.gov (United States)

    Schalenbourg, A; Zografos, L

    2013-02-01

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

  15. Pitfalls in colour photography of choroidal tumours

    Science.gov (United States)

    Schalenbourg, A; Zografos, L

    2013-01-01

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

  16. Intracranial hemorrhage due to intracranial hypertension caused by the superior vena cava syndrome

    DEFF Research Database (Denmark)

    Bartek, Jiri; Abedi-Valugerdi, Golbarg; Liska, Jan

    2013-01-01

    We report a patient with intracranial hemorrhage secondary to venous hypertension as a result of a giant aortic pseudoaneurysm that compressed the superior vena cava and caused obstruction of the venous return from the brain. To our knowledge, this is the first patient reported to have an intracr......We report a patient with intracranial hemorrhage secondary to venous hypertension as a result of a giant aortic pseudoaneurysm that compressed the superior vena cava and caused obstruction of the venous return from the brain. To our knowledge, this is the first patient reported to have...... an intracranial hemorrhage secondary to a superior vena cava syndrome. The condition appears to be caused by a reversible transient rise in intracranial pressure, as a result of compression of the venous return from the brain. Treatment consisted of surgery for the aortic pseudoaneurysm, which led...

  17. Interleukin-10-regulated tumour tolerance in non-small cell lung cancer.

    Science.gov (United States)

    Vahl, Julius Malte; Friedrich, Juliane; Mittler, Susanne; Trump, Sonja; Heim, Lisanne; Kachler, Katerina; Balabko, Liubov; Fuhrich, Nicole; Geppert, Carol-Immanuel; Trufa, Denis Iulian; Sopel, Nina; Rieker, Ralf; Sirbu, Horia; Finotto, Susetta

    2017-11-21

    Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape. Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer. Here we discovered a positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the lung with tumour diameter in patients with lung cancer (non-small cell lung cancer), the most life-threatening cancer type worldwide. IL-10 and IL-10R were found induced in cells surrounding the lung tumour cells, and IL-10R was mainly expressed on the surface of Foxp-3 + T-regulatory lymphocytes infiltrating the tumour of these patients where its expression inversely correlated with programmed cell death 1. These findings were confirmed in translational studies. In a human lung adenocarcinoma cell line, IL-10R was found induced under metabolic restrictions present during tumour growth, whereby IL-10 inhibited PDL1 and tumour cell apoptosis. These new findings suggest that IL-10 counteracts IFN-γ effects on PD1/PDL1 pathway, resulting in possible resistance of the tumour to anti-PD1/PDL1 immunotherapy.

  18. Imaging Features of Idiopathic Intracranial Hypertension in Children.

    Science.gov (United States)

    Hartmann, Alexander J P W; Soares, Bruno P; Bruce, Beau B; Saindane, Amit M; Newman, Nancy J; Biousse, Valérie; Peragallo, Jason H

    2017-01-01

    Magnetic resonance imaging (MRI) signs of elevated intracranial pressure and idiopathic intracranial hypertension have been well characterized in adults but not in children. The MRIs of 50 children with idiopathic intracranial hypertension and 46 adults with idiopathic intracranial hypertension were reviewed for optic nerve head protrusion, optic nerve head enhancement, posterior scleral flattening, increased perioptic cerebrospinal fluid, optic nerve tortuosity, empty or partially empty sella, tonsillar herniation, enlargement of Meckel's cave meningoceles, and transverse venous sinus stenosis(TSS). Compared to adolescents (11-17 years, n = 40) and adults (>17 years, n = 46), prepubescent children (intracranial hypertension have similar MRI findings as adults, but they are less frequent in prepubescent children.

  19. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

    Science.gov (United States)

    Moch, Holger; Cubilla, Antonio L; Humphrey, Peter A; Reuter, Victor E; Ulbright, Thomas M

    2016-07-01

    The fourth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "blue book"), published in 2016, contains significant revisions. These revisions were performed after consideration by a large international group of pathologists with special expertise in this area. A subgroup of these persons met at the WHO Consensus Conference in Zurich, Switzerland, in 2015 to finalize the revisions. This review summarizes the most significant differences between the newly published classification and the prior version for renal, penile, and testicular tumours. Newly recognized epithelial renal tumours are hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome-associated RCC, succinate dehydrogenase-deficient RCC, tubulocystic RCC, acquired cystic disease-associated RCC, and clear cell papillary RCC. The WHO/International Society of Urological Pathology renal tumour grading system was recommended, and the definition of renal papillary adenoma was modified. The new WHO classification of penile squamous cell carcinomas is based on the presence of human papillomavirus and defines histologic subtypes accordingly. Germ cell neoplasia in situ (GCNIS) of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours, and testicular germ cell tumours are now separated into two fundamentally different groups: those derived from GCNIS and those unrelated to GCNIS. Spermatocytic seminoma has been designated as a spermatocytic tumour and placed within the group of non-GCNIS-related tumours in the 2016 WHO classification. The 2016 World Health Organization (WHO) classification contains new renal tumour entities. The classification of penile squamous cell carcinomas is based on the presence of human papillomavirus. Germ cell neoplasia in situ of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All

  20. Calcification of intracranial vessels in neurocysticercosis

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Bouzas, A. [ENEP Iztacala, Universidad Nacional Autonoma de Mexico, Mexico (Mexico); Ballesteros-Maresma, A. [Radiologia Clinica de Cuernavaca (Mexico); Casian, G.; Hernandez-Martinez, P. [Hospital Juarez de Mexico S. S. (Mexico); Martinez-Lopez, M. [Fundacion Clinica Medica Sur (Mexico)

    2000-07-01

    We report calcification of intracranial vessels in neurocysticercosis. Calcification was observed in the middle cerebral arteries in two patients, and the circle of Willis in two others. The patients with middle cerebral artery calcification underwent CT with inhaled stable xenon and an area of mild hypoperfusion was observed in the ipsilateral cerebral hemisphere. (orig.)

  1. Update on intracranial hypertension and hypotension.

    Science.gov (United States)

    Hoffmann, Jan; Goadsby, Peter J

    2013-06-01

    The aim of this article is to review recent findings on the pathophysiology of idiopathic changes in intracranial pressure. The review will focus on idiopathic intracranial hypertension (IIH) and spontaneous intracranial hypotension (SIH). Substantial evidence indicates that IIH is associated with delayed absorption of cerebrospinal fluid (CSF). Stenoses of the transverse sinus are common in IIH, but their clinical significance has not been entirely clarified. Despite the observed efficacy of endovascular treatment in some IIH patients, a correlation between the extent of observed stenoses and the clinical course of the disease could not be demonstrated. The underlying cause of SIH is a spontaneous CSF leakage into the epidural space. Conservative treatment and the epidural blood patch remain the treatment of choice for this rare syndrome. Recent clinical evidence indicates that IIH is probably a result of CSF outflow abnormality rather than of CSF production. Further research is needed to elucidate the causes of elevated intracranial pressure and the mechanism leading to visual loss. Prospective randomized clinical trials are needed to clarify a possible therapeutic potential of endovascular treatment. Research efforts on SIH should focus further on associated connective tissue disorders predisposing to CSF leaks.

  2. Management of Intracranial Ventriculitis caused by Multidrug ...

    African Journals Online (AJOL)

    SITWALA COMPUTERS

    from AB meningitis was 30% (four of 13 patients died) compared with 29.4% (20 of 68 patients) from other. 3 causes of Gram-negative meningitis. Timely recognition and effective treatment of intracranial ventriculitis caused by AB, has been of concern due to high motility rates. In this case report, we document a case of a ...

  3. Idiopathic intracranial hypertension is not benign

    DEFF Research Database (Denmark)

    Yri, Hanne M; Wegener, Marianne; Sander, Birgit

    2012-01-01

    Idiopathic intracranial hypertension (IIH) primarily affects young obese females, and potentially causes visual loss and severe headache. The aim of this experiment is to examine relapse rate and long-term outcome in IIH patients. The methods involved in this experiment include a prospective cont...

  4. Growth rates of intracranial aneurysms : exploring constancy

    NARCIS (Netherlands)

    Koffijberg, Hendrik; Buskens, Erik; Algra, Ale; Wermer, Marieke J. H.; Rinkel, Gabriel J. E.

    Object. The annual rate of rupture of intracranial aneurysms is often assumed to be constant, but it is unknown whether this assumption is true. Recent case reports have suggested that aneurysms grow fast in a short period of time. The authors of the present report investigated the plausibility of a

  5. Recognizable phenotypes associated with intracranial calcification

    NARCIS (Netherlands)

    Livingston, J.H.; Stivaros, S.; van der Knaap, M.S.; Crow, Y.J.

    2013-01-01

    Aim In this observational study, we adopted a systematic approach to the radiological phenotyping of disorders associated with intracranial calcification, with the aim of determining if characteristic patterns could be defined as an aid to the future diagnosis of known conditions and the

  6. Intracranial arteriovenous malformation with maternal carbamazepine use.

    Science.gov (United States)

    Narang, Manish; Shah, Dheeraj; Natasha, Gupta

    2007-01-01

    1 1/2 month old child born to primigravida mother on prolonged carbamazepine therapy presented with recurrent seizures. The child had abnormal facies and was diagnosed to be having arteriovenous malformation with intracranial hemorrhage on neuroimaging. This case suggests that development of arteriovenous malformation in a child with maternal carbamazepine therapy may occur as a part of clinical profile of 'fetal anticonvulsant syndrome'.

  7. [Intracranial plasmocytomas: biology, diagnosis, and treatment].

    Science.gov (United States)

    Belov, A I; Gol'bin, D A

    2006-01-01

    Intracranial plasmocytomas are a rare abnormality in a neurosurgeon's practice. The plasmocytomas may originate from the skull bones or soft tissue intracranial structures; they may be solitary or occur as a manifestation of multiple myeloma, this type being typical of most intracranial plasmocytomas. Progression of solitary plasmocytoma to multiple myeloma is observed in a number of cases. Preoperative diagnosis involves computed tomography or magnetic resonance imaging; angiography is desirable. The final diagnosis of plasmocytoma is chiefly based on a morphological study. Special immunohistochemical studies yield very promising results; these are likely to be of high prognostic value. Intracranial plasmocytomas require a differential approach and a meticulous examination since the presence or absence of multiple myeloma radically affects prognosis. There are well-defined predictors; however, it is appropriate that craniobasal plasmocytomas show a worse prognosis than plasmocytomas of the skull vault and more commonly progress to multiple myeloma. Plasmocytomas respond to radiotherapy very well. The gold standard of treatment for plasmocytoma is its total removal and adjuvant radiation therapy; however, there is evidence for good results when it is partially removed and undergoes radiotherapy or after radical surgery without subsequent radiation. The role of chemotherapy has not been defined today.

  8. Antimicrobial activity, growth inhibition of human tumour cell lines, and phytochemical characterization of the hydromethanolic extract obtained from Sapindus saponaria L. aerial parts.

    Science.gov (United States)

    Rashed, Khaled N; Ćirić, Ana; Glamočlija, Jasmina; Calhelha, Ricardo C; Ferreira, Isabel C F R; Soković, Marina

    2013-01-01

    The hydromethanolic extract of Sapindus saponaria L. aerial parts was investigated for antimicrobial activity (against several Gram-positive and Gram-negative bacteria and fungi) and capacity to inhibit the growth of different human tumor cell lines as also nontumor liver cells. The evaluated extract was further characterized in terms of phytochemicals using UV, (1)H-NMR, (13)C-NMR, and MS spectroscopic tools. The extract has shown a significant antimicrobial activity on all tested bacterial and fungal species. The best activity was achieved against Bacillus cereus and Staphylococcus aureus among bacteria and against all three Penicillium species tested. It also revealed cytotoxicity against human colon (HCT-15), cervical (HeLa), breast (MCF-7), and lung (NCI-H460) carcinoma cell lines, with HeLa being the most susceptible tumor cell line. The extract was not toxic for nontumor liver cells. Chromatographic separation of the extract resulted in the isolation and identification of stigmasterol, oleanolic acid, luteolin, luteolin 8-C-β-glucoside (orientin), luteolin 6-C-β-glucoside (isoorientin), luteolin 7-O-β-glucuronide, and rutin. The results of the present findings may be useful for the discovery of novel antitumor and antimicrobial agents from plant origin.

  9. Antimicrobial Activity, Growth Inhibition of Human Tumour Cell Lines, and Phytochemical Characterization of the Hydromethanolic Extract Obtained from Sapindus saponaria L. Aerial Parts

    Directory of Open Access Journals (Sweden)

    Khaled N. Rashed

    2013-01-01

    Full Text Available The hydromethanolic extract of Sapindus saponaria L. aerial parts was investigated for antimicrobial activity (against several Gram-positive and Gram-negative bacteria and fungi and capacity to inhibit the growth of different human tumor cell lines as also nontumor liver cells. The evaluated extract was further characterized in terms of phytochemicals using UV, 1H-NMR, 13C-NMR, and MS spectroscopic tools. The extract has shown a significant antimicrobial activity on all tested bacterial and fungal species. The best activity was achieved against Bacillus cereus and Staphylococcus aureus among bacteria and against all three Penicillium species tested. It also revealed cytotoxicity against human colon (HCT-15, cervical (HeLa, breast (MCF-7, and lung (NCI-H460 carcinoma cell lines, with HeLa being the most susceptible tumor cell line. The extract was not toxic for nontumor liver cells. Chromatographic separation of the extract resulted in the isolation and identification of stigmasterol, oleanolic acid, luteolin, luteolin 8-C-β-glucoside (orientin, luteolin 6-C-β-glucoside (isoorientin, luteolin 7-O-β-glucuronide, and rutin. The results of the present findings may be useful for the discovery of novel antitumor and antimicrobial agents from plant origin.

  10. Prediction of intracranial hypertension through noninvasive intracranial pressure waveform analysis in pediatric hydrocephalus.

    Science.gov (United States)

    Ballestero, Matheus Fernando Manzolli; Frigieri, Gustavo; Cabella, Brenno Caetano Troca; de Oliveira, Sergio Mascarenhas; de Oliveira, Ricardo Santos

    2017-09-01

    The purpose of this study is to evaluate a noninvasive device to assess intracranial pressure wave form in children with hydrocephalus. A prospective and non-experimental descriptive-analytic study was performed. Fifty-six patients were enrolled in this study. They were divided in four groups: group A, children with clinically compensated hydrocephalus; B, surgically treated hydrocephalus; C, patients with acute intracranial hypertension due to hydrocephalus; and D, children without neurological disease (control). Data were collected through the installation of an extracranial deformation sensor, coupled to the children's scalp, which allowed registration of noninvasive intracranial pressure curves. Parameters obtained were analyzed: P2/P1 ratio, "classification P1 and P2 and P1 slope. P2/P1 index and "classification of P1 and P2" had a sensitivity of 80% and specificity of 100% for predicting intracranial hypertension. "P1 slope" presented no statistical difference. This study showed a useful and noninvasive method for monitoring intracranial pressure, which was able to indicate the intracranial hypertension in children with hydrocephalus and, thus, should be further investigated for clinical applications.

  11. Sodium hyaluronate enhances colorectal tumour cell metastatic potential in vitro and in vivo.

    LENUS (Irish Health Repository)

    Tan, B

    2012-02-03

    BACKGROUND: Sodium hyaluronate has been used intraperitoneally to prevent postoperative adhesions. However, the effect of sodium hyaluronate on tumour growth and metastasis in vitro and in vivo is still unknown. METHODS: Human colorectal tumour cell lines SW480, SW620 and SW707 were treated with sodium hyaluronate (10-500 microg\\/ml) and carboxymethylcellulose (0.125-1 per cent), and tumour cell proliferation and motility were determined in vitro. For the in vivo experiments male BD IX rats were randomized to a sodium hyaluronate group (n = 11; intraperitoneal administration of 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml 0.4 per cent sodium hyaluronate) or a phosphate-buffered saline group (n = 11; 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml phosphate-buffered saline intraperitoneally). Four weeks later the intraperitoneal tumour load was visualized directly. RESULTS: In vitro sodium hyaluronate increased tumour cell proliferation and motility significantly. Sodium hyaluronate-induced tumour cell motility appeared to be CD44 receptor dependent, whereas sodium hyaluronate-induced tumour cell proliferation was CD44 receptor independent. In vivo there was a significantly higher total tumour nodule count in the peritoneal cavity of the sodium hyaluronate-treated group compared with the control (P = 0.016). CONCLUSION: Sodium hyaluronate enhances tumour metastatic potential in vitro and in vivo, which suggests that use of sodium hyaluronate to prevent adhesions in colorectal cancer surgery may also potentiate intraperitoneal tumour growth. Presented to the Patey Prize Session of the Surgical Research Society and the annual scientific meeting of the Association of Surgeons of Great Britain and Ireland, Brighton, UK, 4-7 May 1999

  12. Override of the radiation-induced mitotic block in human tumour cells by methylxanthines and its relationship to the potentiation of cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Musk, S.R.R.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1990-06-01

    Caffeine, theophylline, theobromine and paraxanthine, were tested for ability to override mitotic block induced by ionizing radiation in the human bladder carcinoma cell line RT112. All were found to partially override the block, at a concentration of 1mM in the order caffeine > theophylline > theobromine = paraxanthine. At a concentration of 1 mM only caffeine was found to potentiate cell killing as well as causing block override; at higher concentrations all had a significant effect on survival but little or no further influence on the degree of block override. It is concluded that override of a mitotic block is not in itself sufficient to cause increased killing when irradiated cells are incubated in the presence of caffeine, and that caffeine exerts its potentiating effect by directly inhibiting repair of damage in DNA or by causing override of radiation-induced inhibition of DNA synthesis. (author).

  13. Sixth Nerve Palsy in Paediatric Intracranial Hypertension.

    Science.gov (United States)

    Reid, Julia E; Reem, Rachel E; Aylward, Shawn C; Rogers, David L

    2016-02-01

    The purpose of this study was to report the incidence and describe the characteristics of sixth cranial nerve (CN VI) palsy in paediatric patients with intracranial hypertension (IH). A retrospective chart review of central Ohio children diagnosed with IH over the 3-year period from 2010 to 2013 was conducted. IH without identifiable cause was defined as idiopathic intracranial hypertension (IIH), whereas IH with identifiable pathologic aetiology was deemed secondary intracranial hypertension (SIH). A subset of patients with CN VI palsy was identified. Data collected included patient age, gender, past medical history, aetiology of SIH, ophthalmic examination, lumbar puncture results, neuroimaging results, and response to treatment. Seventy-eight children with intracranial hypertension were included in the study. Nine (11.5%) children (four males, five females; median age 14, range: 3-18) were found to have a unilateral (n = 2) or bilateral (n = 7) CN VI palsy. Five children had IIH; the remaining four had SIH from cerebral venous sinus thrombosis (n = 2) and infection (n = 2). The mean lumbar puncture opening pressure for the nine patients with CN VI palsy was 40 cm H2O (range: 21-65 cm H2O). Papilloedema was present in 8/9 (89%) patients. One patient required a lumboperitoneal shunt, and two others required optic nerve sheath fenestrations in addition to medical management. All cases of CN VI palsy resolved with treatment. In our primary service area, the incidence of CN VI palsy is approximately 12% among paediatric IH patients. The majority of cases with CN VI palsy presented with papilloedema and all cases resolved with treatment of intracranial hypertension.

  14. CANCER Escape from senescence boosts tumour growth

    NARCIS (Netherlands)

    Medema, Jan Paul

    2018-01-01

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

  15. Follicular infundibulum tumour presenting as cutaneous horn

    Directory of Open Access Journals (Sweden)

    Jayaraman M

    1996-01-01

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

  16. Molecular mimics of the tumour antigen MUC1.

    Directory of Open Access Journals (Sweden)

    Tharappel C James

    Full Text Available A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as "self", and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as 'proof of principle' we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1 from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides.

  17. 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.

  18. 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

  19. Overexpression of Eag1 potassium channels in clinical tumours.

    Science.gov (United States)

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

    2006-10-05

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

  20. 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.)

  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. Scintigraphy in benign bone tumours

    African Journals Online (AJOL)

    1989-08-05

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

  3. Neuropathological diagnosis of brain tumours.

    Science.gov (United States)

    Pollo, Bianca

    2011-11-01

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

  4. Induction of in situ DNA double-strand breaks and apoptosis by 200 MeV protons and 10 MV X-rays in human tumour cell lines.

    Science.gov (United States)

    Gerelchuluun, Ariungerel; Hong, Zhengshan; Sun, Lue; Suzuki, Kenshi; Terunuma, Toshiyuki; Yasuoka, Kiyoshi; Sakae, Takeji; Moritake, Takashi; Tsuboi, Koji

    2011-01-01

    To clarify the properties of clinical high-energy protons by comparing with clinical high-energy X-rays. Human tumor cell lines, ONS76 and MOLT4, were irradiated with 200 MeV protons or 10 MV X-rays. In situ DNA double-strand breaks (DDSB) induction was evaluated by immunocytochemical staining of phosphorylated histone H2AX (γ-H2AX). Apoptosis was measured by flow-cytometry after staining with Annexin V. The relative biological effectiveness (RBE) was obtained by clonogenic survival assay. DDSB induction was significantly higher for protons than X-rays with average ratios of 1.28 (ONS76) and 1.59 (MOLT4) at 30 min after irradiation. However the differences became insignificant at 6 h. Also, apoptosis induction in MOLT4 cells was significantly higher for protons than X-rays with an average ratio of 2.13 at 12 h. However, the difference became insignificant at 20 h. RBE values of protons to X-rays at 10% survival were 1.06 ± 0.04 and 1.02 ± 0.15 for ONS76 and MOLT4, respectively. Cell inactivation may differ according to different timings and/or endpoints. Proton beams demonstrated higher cell inactivation than X-rays in the early phases. These data may facilitate the understanding of the biological properties of clinical proton beams.

  5. Melanotic neuroectodermal tumour of the pineal region

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-11-01

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

  6. Radiofrequency for the treatment of liver tumours

    NARCIS (Netherlands)

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

    2005-01-01

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

  7. Radiofrequency for the treatment of liver tumours.

    NARCIS (Netherlands)

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

    2005-01-01

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

  8. Mohs micrographic surgery of rare cutaneous tumours

    NARCIS (Netherlands)

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

    2017-01-01

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

  9. REPORT OF SEVEN CASES OF METASTATIC TUMOURS

    African Journals Online (AJOL)

    Major Adebayo

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

  10. Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth

    Directory of Open Access Journals (Sweden)

    Hiroaki Haga

    2015-01-01

    Full Text Available The contributions of mesenchymal stem cells (MSCs to tumour growth and stroma formation are poorly understood. Tumour cells can transfer genetic information and modulate cell signalling in other cells through the release of extracellular vesicles (EVs. We examined the contribution of EV-mediated inter-cellular signalling between bone marrow MSCs and tumour cells in human cholangiocarcinoma, highly desmoplastic cancers that are characterized by tumour cells closely intertwined within a dense fibrous stroma. Exposure of MSCs to tumour cell–derived EVs enhanced MSC migratory capability and expression of alpha-smooth muscle actin mRNA, in addition to mRNA expression and release of CXCL-1, CCL2 and IL-6. Conditioned media from MSCs exposed to tumour cell–derived EVs increased STAT-3 phosphorylation and proliferation in tumour cells. These effects were completely blocked by anti-IL-6R antibody. In conclusion, tumour cell–derived EVs can contribute to the generation of tumour stroma through fibroblastic differentiation of MSCs, and can also selectively modulate the cellular release of soluble factors such as IL-6 by MSCs that can, in turn, alter tumour cell proliferation. Thus, malignant cells can “educate” MSCs to induce local microenvironmental changes that enhance tumour cell growth.

  11. Imaging of salivary gland tumours

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-06-15

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

  12. Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies.

    LENUS (Irish Health Repository)

    Moran, Ellen M

    2009-01-01

    INTRODUCTION: The aim of this study was to examine IL-17A in patients, following anti-TNF-alpha therapy and the effect of IL-17A on matrix turnover and cartilage degradation. METHODS: IL-17A expression was examined by ELISA and immunohistology in the rheumatoid arthritis (RA) joints. RA whole synovial tissue explant (RA ST), primary synovial fibroblasts (RASFC), human cartilage and chondrocyte cultures were stimulated with IL-17A +\\/- TNF-alpha and Oncostatin M (OSM). Matrix metalloproteinase (MMP) and tissue inhibitor (TIMP-1) were assessed by ELISA and zymography. Cartilage proteoglycan release was assessed histologically by Safranin-O staining. Clinical parameters, IL-17A, MMP\\/TIMP were assessed in patients pre\\/post biologic therapy. RESULTS: IL-17A levels were higher in RA vs osteoarthritis (OA)\\/normal joints (P < 0.05). IL-17A up-regulated MMP-1, -2, -9, and -13 in RA ST, RASFC, cartilage and chondrocyte cultures (P < 0.05). In combination with TNF-alpha and OSM, IL-17A shifted the MMP:TIMP-1 ratio in favor of matrix degradation (all P < 0.05). Cartilage proteoglycan depletion in response to IL-17A was mild; however, in combination with TNF-alpha or OSM showed almost complete proteoglycan depletion. Serum IL-17A was detected in 28% of patients commencing biologic therapy. IL-17A negative patients demonstrated reductions post therapy in serum MMP1\\/TIMP4, MMP3\\/TIMP1 and MMP3\\/TIMP4 ratios and an increase in CS846 (all P < 0.05). No significant changes were observed in IL-17A positive patients. CONCLUSIONS: IL-17A is produced locally in the inflamed RA joint. IL-17A promotes matrix turnover and cartilage destruction, especially in the presence of other cytokines, mimicking the joint environment. IL-17A levels are modulated in vivo, following anti-TNF therapy, and may reflect changes in matrix turnover.

  13. Epidemiology and genetics of intracranial aneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Caranci, F., E-mail: ferdinandocaranci@libero.it [Unit of Neuroradiology, Department of Diagnostic Radiology and Radiotherapy, Federico II University, Naples (Italy); Briganti, F., E-mail: frabriga@unina.it [Unit of Neuroradiology, Department of Diagnostic Radiology and Radiotherapy, Federico II University, Naples (Italy); Cirillo, L.; Leonardi, M. [Neuroradiology service, Bellaria Hospital, Bologna (Italy); Muto, M., E-mail: mutomar@tiscali.it [Neuroradiology Service Cardarelli Hospital Naples (Italy)

    2013-10-01

    Intracranial aneurysms are acquired lesions (5–10% of the population), a fraction of which rupture leading to subarachnoid hemorrhage with devastating consequences. Until now, the exact etiology of intracranial aneurysms formation remains unclear. The low incidence of subarachnoid hemorrhage in comparison with the prevalence of unruptured IAs suggests that the vast majority of intracranial aneurysms do not rupture and that identifying those at highest risk is important in defining the optimal management. The most important factors predicting rupture are aneurysm size and site. In addition to ambiental factors (smoking, excessive alcohol consumption and hypertension), epidemiological studies have demonstrated a familiar influence contributing to the pathogenesis of intracranial aneurysms, with increased frequency in first- and second-degree relatives of people with subarachnoid hemorrhage. In comparison to sporadic aneurysms, familial aneurysms tend to be larger, more often located at the middle cerebral artery, and more likely to be multiple. Other than familiar occurrence, there are several heritable conditions associated with intracranial aneurysm formation, including autosomal dominant polycystic kidney disease, neurofibromatosis type I, Marfan syndrome, multiple endocrine neoplasia type I, pseudoxanthoma elasticum, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II and IV. The familial occurrence and the association with heritable conditions indicate that genetic factors may play a role in the development of intracranial aneurysms. Genome-wide linkage studies in families and sib pairs with intracranial aneurysms have identified several loci on chromosomes showing suggestive evidence of linkage, particularly on chromosomes 1p34.3–p36.13, 7q11, 19q13.3, and Xp22. For the loci on 1p34.3–p36.13 and 7q11, a moderate positive association with positional candidate genes has been demonstrated (perlecan gene, elastin gene, collagen type 1 A2

  14. Functional Analysis of Chromosome 18 in Pancreatic Cancer: Strong Evidence for New Tumour Suppressor Genes

    Directory of Open Access Journals (Sweden)

    Liviu P. Lefter

    2004-04-01

    Conclusion: These data represent strong functional evidence that chromosome 18q encodes strong tumour and metastasis suppressor activity that is able to switch human pancreatic cancer cells to a dormant phenotype.

  15. Tumour gastrin expression and serum gastrin concentrations in dogs with gastric carcinoma are poor diagnostic indicators

    DEFF Research Database (Denmark)

    Seim-Wikse, T.; Kolbjørnsen, Ø.; Jörundsson, E.

    2014-01-01

    Hypergastrinaemia is observed commonly in human patients with gastric carcinoma and is associated with atrophic gastritis and Helicobacter pylori infection, both of which predispose to development of gastric tumours. Increased expression of gastrin is also described as a prognostic indicator...

  16. in vitro anti-tumour activity of some nigerian euphorbiaceae plants

    African Journals Online (AJOL)

    tumor activities involving a panel of solid tumours of human origin and the P-388 lymophocytic leukemia system. Selective cytotoxicity was observed for four of the plant species namely. Spondianthus preussii Engl. (Melanoma), Elaeophorbia ...

  17. Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression

    National Research Council Canada - National Science Library

    Halime Kalkavan; Piyush Sharma; Stefan Kasper; Iris Helfrich; Aleksandra A Pandyra; Asmae Gassa; Isabel Virchow; Lukas Flatz; Tim Brandenburg; Sukumar Namineni; Mathias Heikenwalder; Bastian Höchst; Percy A Knolle; Guido Wollmann; Dorothee Von Laer; Ingo Drexler; Jessica Rathbun; Paula M Cannon; Stefanie Scheu; Jens Bauer; Jagat Chauhan; Dieter Häussinger; Gerald Willimsky; Max Löhning; Dirk Schadendorf; Sven Brandau; Martin Schuler; Philipp A Lang; Karl S Lang

    2017-01-01

    ...) preferentially replicate in tumour cells in a variety of murine and human cancer models. Viral replication leads to prolonged local immune activation, rapid regression of localized and metastatic cancers, and long-term disease control...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-15

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

  19. Tumours of the fetal body: a review

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-11-15

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

  20. 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.

  1. ROLE OF MAGNETIC RESONANCE SPECTROSCOPY IN INTRACRANIAL LESIONS- A STUDY OF 75 CASES

    Directory of Open Access Journals (Sweden)

    Rajendra N. Solank

    2017-10-01

    Full Text Available BACKGROUND Our study have shown the role of MR spectroscopy in lesions whenever results are equivocal or non-conclusive even on MRI. MR spectroscopy can differentiate the lesions, particularly intracranial lesions on the basis of various metabolites. The aims of this study is to diagnose the intracranial lesions and to show the advantage of MR spectroscopy over the conventional MRI, to differentiate the neoplastic from non-neoplastic lesion, to prove the reliability of MR spectroscopy in identifying the different grades of glioma with histopathological correlation as well as to differentiate recurrent tumour from post-operative changes or radiation necrosis. MATERIALS AND METHODS During the period of August 2009 to July 2011, a prospective study of 75 patients was carried out at Department of Radiodiagnosis, Civil Hospital and BJ Medical College, Ahmedabad, Gujarat. MRI was performed on 1.5 Tesla MR scanner (GE HDXT using dedicated head coil. Conventional MR imaging was performed followed by MR spectroscopy using point resolved spectroscopy. After deciding the region of interest voxel was kept and 2D multivoxel proton spectroscopy (TR- 1000 msec, TE- 144 msec, voxel size 20 x 20 mm or single voxel proton spectroscopy (TR- 1500 msec, TE- 35 msec, voxel size 20 x 20 mm was performed and spectra obtained. RESULTS In the present study of 75 patients, the maximum number of patients were between 31 to 50 years of age. The approximate ratio of male: female was 2: 1. In our study sensitivity, specificity, positive predictive value, negative predictive value of MRI are 89%, 87%, 87% and 89% respectively and of MRI + MRS are 100%, 97%, 97% and 100% respectively in tumours. CONCLUSION MRS (Magnetic Resonance Spectroscopy is a non-invasive imaging technique that studies the chemical activity in the brain and detects the presence of certain chemical substances. Through this imaging technique, images and graphs of the brain can be obtained.

  2. Neuroradiological aspects of intracranial epidermoids; Zur neuroradiologischen Diagnostik der intrakraniellen Epidermoide

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    Hagen, T. [Universitaetskliniken des Saarlandes, Homburg/Saar (Germany). Inst. fuer Neuroradiologie; Kujat, C. [Universitaetskliniken des Saarlandes, Homburg/Saar (Germany). Inst. fuer Neuroradiologie; Donauer, E. [Universitaet des Saarlandes, Homburg/Saar (Germany). Neurochirurgische Klinik; Piepgras, U. [Universitaetskliniken des Saarlandes, Homburg/Saar (Germany). Inst. fuer Neuroradiologie

    1994-11-01

    Intracranial epidermoids are primarily extracerebral congenital cysts. Intra- and extradural types are differentiated: intradural lesions originate in the intracranial CSF spaces, and extradural lesions in the bony skull. Epidermoids increase in size passively as the results of an increase in the cyst volume and not because of active growth. Clinically epidermoids behave like benign, slow-growing cerebral tumours. Differential diagnosis includes other cysts and cystic tumours. Neuroradiologically epidermoids present as polycystic lesions showing extensive growth in the extracerebral CSF spaces and secondary invagination of the brain. On CT and MR, despite the high cholesterol content, epidermoids show the characteristics of liquor and not those of fat. It can be shown that he typical CT and MR appearance of an epidermoid is due to the different proportions of CSF in the cyst content, which results from diffusion of dehiscence of te cyst capsule. The present study was based on analysis of 6 cases selected from a total of 29 patients with CNS epidermoids. (orig.) [Deutsch] Intrakranielle Epidermoide sind primaer extrazerebrale kongenitale Zysten. Es sind intra- von extraduralen Formen zu unterscheiden. Intradurale Epidermoide entstehen in den intrakraniellen Liquorraeumen, extradurale im Schaedelknochen. Epidermoide vergroessern sich nicht aktiv durch autonomes Wachstum, sondern passiv durch Zunahme des Zysteninhalts. Klinisch verhalten sie sich wie gutartige, langsam wachsende Hirntumoren. Differential-diagnostisch sind sie gegenueber anderen Zysten und zystischen Tumoren abzugrenzen. Neuroradiologisch sind Epidermoide durch ihre polyzyklische Konfiguration und ihre extensive Ausdehnung in den extrazerebralen Liquorraeumen mit sekundaerer Invagination in das Gehirn gekennzeichnet. Im MR und im CT stellen sich Epidermoidzysten trotz des hohen Gehaltes an Cholesterin nicht fett-, sondern liquoraequivalent dar. Es kann nachgewiesen werden, dass die Ursache fuer die

  3. Intracranial neurenteric cyst traversing the brainstem

    Directory of Open Access Journals (Sweden)

    Jasmit Singh

    2015-01-01

    Full Text Available Neurenteric cysts (NECs, also called enterogenous cysts, are rare benign endodermal lesions of the central nervous system that probably result from separation failure of the notochord and upper gastrointestinal tract. Most frequently they are found in the lower cervical spine or the upper thoracic spine. Intracranial occurrence is rare and mostly confined to infratentorial compartment, in prepontine region [51%]. Other common locations are fourth ventricle and cerebellopontine angle. There are few reports of NEC in medulla or the cerebellum. Because of the rarity of the disease and common radiological findings, they are misinterpreted as arachnoid or simple cysts until the histopathological confirmation, unless suspected preoperatively. We herein report a rare yet interesting case of intracranial NEC traversing across the brainstem.

  4. [Rol of pituitary tumour-transforming gene (PTTG) in the pituitary adenomas].

    Science.gov (United States)

    Sánchez-Ortiga, Ruth; Sánchez Tejada, Laura; Peiró Cabrera, Gloria; Moreno-Pérez, Oscar; Arias Mendoza, Nieves; Aranda López, F Ignacio; Picó Alfonso, Antonio

    2010-01-01

    The pathogenesis of pituitary tumours is far to be understood. Pituitary transforming tumour gene (PTTG), a gen that induces aneuploidy, genetic instability, cellular proliferation and to stimulate angiogenesis, has been involved in neoplasic transformation and shown overexpressed in many neoplasm as lung, breast, endometrium, thyroid and colon malignant tumours. On the other hand, PTTG has been inconsistently studied in pituitary tumours. The majority of studies have been performed in animals and there is a great variability in the methods used in its determination. The goal of this review is to resume the role of PTTG in tumourogenesis and critically to revise the studies published in humans in order to advance in the knowledge of the pathogenesis of pituitary adenomas and to find clinical useful predictors of the behavior of these tumours. Copyright 2010 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

  5. Leukaemia cell of origin identified by chromatin landscape of bulk tumour cells.

    Science.gov (United States)

    George, Joshy; Uyar, Asli; Young, Kira; Kuffler, Lauren; Waldron-Francis, Kaiden; Marquez, Eladio; Ucar, Duygu; Trowbridge, Jennifer J

    2016-07-11

    The precise identity of a tumour's cell of origin can influence disease prognosis and outcome. Methods to reliably define tumour cell of origin from primary, bulk tumour cell samples has been a challenge. Here we use a well-defined model of MLL-rearranged acute myeloid leukaemia (AML) to demonstrate that transforming haematopoietic stem cells (HSCs) and multipotent progenitors results in more aggressive AML than transforming committed progenitor cells. Transcriptome profiling reveals a gene expression signature broadly distinguishing stem cell-derived versus progenitor cell-derived AML, including genes involved in immune escape, extravasation and small GTPase signal transduction. However, whole-genome profiling of open chromatin reveals precise and robust biomarkers reflecting each cell of origin tested, from bulk AML tumour cell sampling. We find that bulk AML tumour cells exhibit distinct open chromatin loci that reflect the transformed cell of origin and suggest that open chromatin patterns may be leveraged as prognostic signatures in human AML.

  6. Prognostic value of histobiological factors (malignancy grading and AgNOR content) assessed at the invasive tumour front of oral squamous cell carcinomas.

    Science.gov (United States)

    Piffkò, J; Bànkfalvi, A; Ofner, D; Bryne, M; Rasch, D; Joos, U; Böcker, W; Schmid, K W

    1997-01-01

    Tumour cells at the invasive front of carcinomas have been found to differ substantially from the rest of tumour cells in a variety of human cancers. The present multivariate survival analysis of 94 oral squamous cell carcinomas (OSCCs) revealed that both the argyrophilic nucleolar organizer regions-associated protein (AgNOR) content of invading tumour cells and a multiparametric histopathological tumour front grade were significantly and independently associated with tumour-related death, irrespective of conventional Broders' grade and clinical stage of the tumours. High tumour front scores and AgNOR content at the invasive OSCC front thus seem to reflect increased malignant potential. Proliferative activity, assessed by standardized AgNOR analysis, most probably represents one of the biological features underlying the usefulness of evaluating the invasive tumour front.

  7. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting.

    Science.gov (United States)

    Reubi, Jean Claude; Waser, Beatrice

    2003-05-01

    Peptide receptors have been found to represent excellent targets for in vivo cancer diagnosis and therapy. Recent in vitro studies have shown that many cancers can overexpress not only one but several peptide receptors concomitantly. One of the challenges for nuclear medicine in this field in the coming decade will be to take advantage of the co-expression of peptide receptors for multireceptor tumour targeting. In vitro receptor studies can reveal which peptide receptor is overexpressed in which tumour and which receptors are co-expressed in an individual tumour; such knowledge is a prerequisite for successful in vivo development. One group of tumours of particular interest in this respect is the neuroendocrine tumours, which have previously been shown often to express peptide receptors. This review summarises our investigations of the concomitant expression of 13 different peptide receptors, in more than 100 neuroendocrine tumours of the human intestine, pancreas and lung, using in vitro receptor autoradiography with subtype-selective ligands. The incidence and density of the somatostatin receptors sst(1)-sst(5), the VIP receptors VPAC(1) and VPAC(2), the CCK(1) and CCK(2) receptors, the three bombesin receptor subtypes BB(1) (NMB receptor), BB(2) (GRP receptor) and BB(3), and GLP-1 receptors were evaluated. While the presence of VPAC(1) and sst(2) was detected in the majority of these neuroendocrine tumours, the other receptors, more differentially expressed, revealed a characteristic receptor pattern in several tumour types. Ileal carcinoids expressed sst(2) and VPAC(1) receptors in virtually all cases and had CCK(1), CCK(2), sst(1) or sst(5) in approximately half of the cases; they were the only tumours of this series to express NMB receptors. Insulinomas were characterised by a very high incidence of GLP-1, CCK(2) and VPAC(1) receptors, with the GLP-1 receptors expressed in a particularly high density; they expressed sst(2) in two-thirds and sst(1) in

  8. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting

    Energy Technology Data Exchange (ETDEWEB)

    Reubi, Jean Claude; Waser, Beatrice [Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, PO Box 62, 3010, Berne (Switzerland)

    2003-05-01

    Peptide receptors have been found to represent excellent targets for in vivo cancer diagnosis and therapy. Recent in vitro studies have shown that many cancers can overexpress not only one but several peptide receptors concomitantly. One of the challenges for nuclear medicine in this field in the coming decade will be to take advantage of the co-expression of peptide receptors for multireceptor tumour targeting. In vitro receptor studies can reveal which peptide receptor is overexpressed in which tumour and which receptors are co-expressed in an individual tumour; such knowledge is a prerequisite for successful in vivo development. One group of tumours of particular interest in this respect is the neuroendocrine tumours, which have previously been shown often to express peptide receptors. This review summarises our investigations of the concomitant expression of 13 different peptide receptors, in more than 100 neuroendocrine tumours of the human intestine, pancreas and lung, using in vitro receptor autoradiography with subtype-selective ligands. The incidence and density of the somatostatin receptors sst{sub 1}-sst{sub 5}, the VIP receptors VPAC{sub 1} and VPAC{sub 2}, the CCK{sub 1} and CCK{sub 2} receptors, the three bombesin receptor subtypes BB{sub 1} (NMB receptor), BB{sub 2} (GRP receptor) and BB{sub 3}, and GLP-1 receptors were evaluated. While the presence of VPAC{sub 1} and sst{sub 2} was detected in the majority of these neuroendocrine tumours, the other receptors, more differentially expressed, revealed a characteristic receptor pattern in several tumour types. Ileal carcinoids expressed sst{sub 2} and VPAC{sub 1} receptors in virtually all cases and had CCK{sub 1}, CCK{sub 2}, sst{sub 1} or sst{sub 5} in approximately half of the cases; they were the only tumours of this series to express NMB receptors. Insulinomas were characterised by a very high incidence of GLP-1, CCK{sub 2} and VPAC{sub 1} receptors, with the GLP-1 receptors expressed in a

  9. Spontaneous intracranial hypotension: use of unenhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Quinones Tapia, D.; Lopez-Ibor, L. [Dept. of Neuroradiology, Clinica de La Zarzuela, Aravaca, Madrid (Spain); Pardo, J.; Anciones, V. [Dept. of Neurology, Clinica de La Zarzuela, Aravaca, Madrid (Spain); Serrano, J.M. [Dept. of Ophthalmology, Fundacion Jimenez Diaz, Madrid (Spain)

    2000-07-01

    We report a case of spontaneous intracranial hypotension diagnosed with unenhanced cranial MRI, showing laminar subdural fluid and engorgement of the hypophysis and perisellar sinuses. Cerebrospinal fluid pressure was low. MRI was normal after resolution of symptoms. Prior reports emphasise the enhancing pachymeninges seen in this syndrome. We maintain that, when subdural collections and perisellar engorgement are detected on unenhanced MRI in the proper clinical setting, contrast enhancement may not be necessary for the diagnosis. (orig.)

  10. Minimally Invasive Diagnosis of Secondary Intracranial Lymphoma

    Directory of Open Access Journals (Sweden)

    A. P. McClement

    2016-01-01

    Full Text Available Diffuse large B cell lymphomas (DLBCL are an aggressive group of non-Hodgkin lymphoid malignancies which have diverse presentation and can have high mortality. Central nervous system relapse is rare but has poor survival. We present the diagnosis of primary mandibular DLBCL and a unique minimally invasive diagnosis of secondary intracranial recurrence. This case highlights the manifold radiological contributions to the diagnosis and management of lymphoma.

  11. 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.

  12. [Congenital medulloblastoma associated with intracranial arachnoid cyst].

    Science.gov (United States)

    Gelabert González, Miguel; Serramito-García, Ramón; Liñares Paz, Mercedes; Aran-Echabe, Eduardo; García-Allut, Alfredo

    2014-01-01

    Arachnoid cysts are very common lesions in paediatric patients, with treatment depending on their location and symptomatology. They are usually solitary cysts but may be associated with other central nervous system diseases such as tumours and congenital deformities. We describe the case of a neonate diagnosed with an arachnoid cyst of the quadrigeminal cistern treated by endoscopy. After the operation, the child's condition worsened; a CT scan revealed a midline posterior fossa tumour not visible in the preoperative neuroradiological tests. The tumour, a medulloblastoma, was partially removed. Given the child's age and the poor prognosis, oncological treatment was not undertaken. The association between medulloblastoma and arachnoid cyst is very rare, and we could find only one such case in the literature. Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  13. Tumour tissue selectivity in the uptake and retention of SN 28049, a new topoisomerase II-directed anticancer agent.

    Science.gov (United States)

    Lukka, Pradeep B; Chen, Ying Yi; Finlay, Graeme J; Joseph, Wayne R; Richardson, Emma; Paxton, James W; Baguley, Bruce C

    2013-11-01

    A variety of anticancer drugs, including doxorubicin and mitoxantrone, have structures in which a DNA-intercalating chromophore is linked to a positively charged side chain. These drugs generally inhibit tumour growth and survival by poisoning the enzyme DNA topoisomerase II. SN 28049, a benzonaphthyridine derivative with these properties, has curative activity against the Colon 38 tumour in mice. Previous pharmacokinetic studies have demonstrated tumour-selective retention with approximately 20-fold higher area under the concentration-time curve (AUC) for tumour tissue as compared to normal tissues. We have investigated here whether such retention is tumour specific. Plasma and tissue pharmacokinetics were assessed in the murine Lewis lung (LL3) tumour in C57 BL/6 mice and in xenografts of the NZM4, NZM10 and NZM52 human melanoma lines in Balb/c Rag-1 immunodeficient mice. The in vitro cellular localisation of SN 28049 in murine and human cell lines was studied by confocal fluorescence microscopy. A 260-fold variation, from 8.9 μM h (NZM4) to 2,334 μM h (Colon 38), was found among the different tumours. Only small variations were observed in the corresponding plasma AUC (2.9-5 μM h). Moreover, in vivo activity, as measured by tumour growth delay, varied from 1 day (NZM4) to curative (Colon 38), consistent with the tumour pharmacokinetic data. In cultured cell lines, SN 28049 was found in cytoplasmic bodies, suggesting that drug sequestration could contribute to tumour pharmacokinetics. SN 28049 shows dramatic differences in both tumour AUC and antitumour activity against different tumours. These differences point to the presence of a tumour-specific uptake and retention mechanism.

  14. Endovascular treatment for pediatric intracranial aneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Xianli; Jiang, Chuhan; Li, Youxiang; Yang, Xinjian; Wu, Zhongxue [Capital Medical University, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Beijing, Hebei (China)

    2009-11-15

    The purpose of this study is to report the characteristics and outcomes of pediatric patients with intracranial aneurysms. From 1998 to 2005, 25 pediatric patients (aged {<=}17 years) with intracranial aneurysm were treated at our institute. Eleven of 25 patients had subarachnoid hemorrhage. In ten patients, the aneurysm was an incidental finding. One patient presented with cranial nerves dysfunction and three with neurological deficits. The locations of the aneurysms were as follows: vertebral artery (VA; n = 9), middle cerebral artery (MCA; n = 5), posterior cerebral artery (PCA; n = 4), basilar artery (BA; n = 2), anterior communicating artery (n = 2), anterior cerebral artery (n = 2), and internal carotid artery (n = 1). Five patients were treated with selective embolization with coils. Sixteen patients were treated with parent vessel occlusion (PVO). Eight PVOs were performed with balloons and eight were performed with coils. One patient with a VA aneurysm was spontaneously thrombosed 4 days after the initial diagnostic angiogram. In three patients treated with stent alone or stent-assisted coiling, one with BA trunk aneurysm died. One aneurismal recurrence occurred and was retreated. At a mean follow-up duration of 23.5 months, 96% of patients had a Glasgow Outcome Scale score of 4 or 5. Pediatric intracranial aneurysms occur more commonly in male patients and have a predilection for the VA, PCA, and MCA. PVO is an effective and safe treatment for fusiform aneurysms. Basilar trunk fusiform aneurysms were difficult to treat and were associated with a high mortality rate. (orig.)

  15. The Technique of Endovascular Intracranial Revascularization

    Directory of Open Access Journals (Sweden)

    John J. Connors

    2014-11-01

    Full Text Available Intracranial atherosclerosis was traditionally believed to carry a risk of stroke of 8% to 22% per annum. The annualized stroke rate in the recent Stenting and Aggressive Medical Management for Preventing Stroke in Intracranial Stenosis trial medical management arm was 12.2%. This trial was halted due to excessive periprocedural events in the stent arm. This stroke rate Is still Unacceptably high and a treatment strategy is still needed. SAMMPRIS has no bearing on angioplasty alone. Angioplasty alone has always been our primary intervention for intracranial atherosclerosis and remains so to this day due to its relative simplicity, low complication rate, and efficacy. We have, however, made adjustments to our patient management regimen based on the results of SAMMPRIS. This paper outlines our current patient selection, procedural technique, and post-procedure management. The complications we have encountered while developing our technique are described along with how to avoid them and how to manage them. Our most recent results (since previous publications are also discussed.

  16. Spaceflight-Induced Intracranial Hypertension: An Overview

    Science.gov (United States)

    Traver, William J.

    2011-01-01

    This slide presentation is an overview of the some of the known results of spaceflight induced intracranial hypertension. Historical information from Gemini 5, Apollo, and the space shuttle programs indicated that some vision impairment was reported and a comparison between these historical missions and present missions is included. Optic Disc Edema, Globe Flattening, Choroidal Folds, Hyperopic Shifts and Raised Intracranial Pressure has occurred in Astronauts During and After Long Duration Space Flight. Views illustrate the occurrence of Optic Disc Edema, Globe Flattening, and Choroidal Folds. There are views of the Arachnoid Granulations and Venous return, and the question of spinal or venous compliance issues is discussed. The question of increased blood flow and its relation to increased Cerebrospinal fluid (CSF) is raised. Most observed on-orbit papilledema does not progress, and this might be a function of plateau homeostasis for the higher level of intracranial pressure. There are seven cases of astronauts experiencing in flight and post flight symptoms, which are summarized and follow-up is reviewed along with a comparison of the treatment options. The question is "is there other involvement besides vision," and other Clinical implications are raised,

  17. Idiopathic intracranial hypertension in pediatric patients

    Directory of Open Access Journals (Sweden)

    Nada Jirásková

    2008-11-01

    Full Text Available Nada Jirásková, Pavel RozsívalDepartment of Ophthalmology, University Hospital, Hradec Králové, Czech RepublicPurpose: To evaluate retrospectively the features, treatment, and outcome of idiopathic intracranial hypertension (IIH in children.Methods: Nine patients, 15 years and younger, diagnosed with IIH. Inclusion criteria were papilledema, normal brain computer tomography or magnetic resonance imaging, cerebrospinal fluid pressure greater than 250 mm H2O, normal cerebrospinal fluid content, and a nonfocal neurologic examination except for sixth nerve palsy.Results: Of the nine patients, eight were girls. Five girls were overweight and one boy was obese. The most common presenting symptom was headache (5 patients. Diplopia or strabismus did not occur in our group. Visual field abnormalities were present in all eyes, and severe visual loss resulting in light perception vision occurred in both eyes of one patient. Eight patients were treated medically with acetazolamide alone, and one girl needed a combination of acetazolamide and corticosteroids. This girl also required optic nerve sheath decompression surgery. Resolution of papilledema and recovery of visual function occurred in all patients.Conclusions: Idiopathic intracranial hypertension in prepubertal children is rather uncommon. Prompt diagnosis and management are important to prevent permanent visual loss.Keywords: idiopathic intracranial hypertension, pediatric, treatment

  18. Abciximab for thrombolysis during intracranial aneurysm coiling

    Energy Technology Data Exchange (ETDEWEB)

    Gralla, Jan [West Wing, John Radcliffe Hospital, Department of Neuroradiology, Oxford (United Kingdom); Inselspital-University of Bern, Department of Neuroradiology, Bern (Switzerland); Rennie, Adam T.M.; Corkill, Rufus A.; Lalloo, Shivendra T.; Molyneux, Andrew; Byrne, James V.; Kuker, Wilhem [West Wing, John Radcliffe Hospital, Department of Neuroradiology, Oxford (United Kingdom)

    2008-12-15

    Thrombotic events are a common and severe complication of endovascular aneurysm treatment with significant impact on patients' outcome. This study evaluates risk factors for thrombus formation and assesses the efficacy and safety of abciximab for clot dissolution. All patients treated with abciximab during (41 patients) or shortly after (22 patients) intracranial aneurysm coil embolisation were retrieved from the institutional database (2000 to 2007, 1,250 patients). Sixty-three patients (mean age, 55.3 years, {+-}12.8) had received either intra-arterial or intravenous abciximab. Risk factors for clot formation were assessed and the angiographic and clinical outcome evaluated. No aneurysm rupture occurred during or after abciximab application. The intra-procedural rate of total recanalisation was 68.3%. Thromboembolic complications were frequently found in aneurysms of the Acom complex and of the basilar artery, whilst internal carotid artery aneurysms were underrepresented. Two patients died of treatment-related intracranial haemorrhages into preexisting cerebral infarcts. Two patients developed a symptomatic groin haematoma. Abciximab is efficacious and safe for thrombolysis during and after endovascular intracranial aneurysm treatment in the absence of preexisting ischaemic stroke. (orig.)

  19. Intracranial aneurysms in patients with CREST syndrome.

    Science.gov (United States)

    Nakae, Ryuta; Idei, Masaru; Kumano, Kiyoshi; Okita, Shinji; Yamane, Kanji

    2009-09-01

    CREST syndrome is a variant of scleroderma characterized by calcinosis, Raynaud's phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia, and is a collagen vascular disease characterized by inflammation and fibrosis of multiple organs/tissues. Neurological and cerebrovascular abnormalities are uncommon in CREST syndrome. Here, we report two patients with CREST syndrome harboring intracranial aneurysms. A 53-year-old woman with a 6-month history of CREST syndrome had multiple intracranial aneurysms that arose from the right middle cerebral artery, the left middle cerebral artery, the choroidal segment of the left internal carotid artery, and the left anterior cerebral artery. A 64-year-old woman with a 2-year history of CREST syndrome had a fusiform aneurysm located on the insular segment of the left middle cerebral artery. These patients were treated surgically and good outcome was achieved in both cases. The pathogenesis of cerebral aneurysms associated with collagen diseases, including CREST syndrome, remains unclear. Early treatment of CREST syndrome and other collagen diseases may prevent arteritis from progressing to affect the intracranial arteries and thus reduce the occurrence of aneurysms. The prognosis for patients with collagen diseases after rupture of cerebral aneurysm seems to be poor because the multiplicity, atypical morphology, and atypical location of their aneurysms make treatment difficult. Thus, early detection and treatment are important to improve the prognosis.

  20. Idiopathic intracranial hypertension without papilledema in children: A case series

    Directory of Open Access Journals (Sweden)

    Kaliopy Matheos

    2015-05-01

    Full Text Available Papilledema has long been considered a hallmark of idiopathic intracranial hypertension, a disease defined by elevated intracranial pressure with indiscernible etiology. Papilledema is often seen in the pediatric population, and as such can lead to delays in diagnosis, and often misdiagnosis. Here, we describe three children who were confirmed to have idiopathic intracranial hypertension with raised intracranial pressure by repeated lumbar puncture or intracranial pressure monitoring, normal neuroimaging and absence of papilledema. All three cases had atypical clinical presentations with visual disturbances or photophobia. The patients had a normal body mass index. This case series demonstrates that idiopathic intracranial hypertension can manifest in the absence of clinically obvious papilledema, and has, as such, the potential to cause permanent visual loss if the diagnosis is missed.

  1. Changes in intracranial pressure associated with chest physiotherapy.

    Science.gov (United States)

    Olson, DaiWai M; Thoyre, Suzanne M; Turner, Dennis A; Bennett, Stacey; Graffagnino, Carmelo

    2007-01-01

    Management of intracranial hypertension is pivotal in the care of brain-injured patients. We report the case of a patient with both a closed head injury and anoxic encephalopathy, who subsequently experienced episodes of refractory intracranial hypertension. The patient's care was complicated by the development of a pneumonia, which required frequent turning of the patient and chest physiotherapy. Conventional wisdom suggests that these interventions may stimulate the patient and worsen intracranial pressure, and therefore should be avoided. Our observations on this patient, however, contradict this belief. This single-subject study presents data to support the use of chest physiotherapy in patients at risk for intracranial hypertension. Further, the evidence is compelling that a randomized-controlled trial is indicated to test the hypothesis that chest physiotherapy may actually result in short-term resolution of high intracranial pressure, and thus provide one more clinical tool in the management of elevated intracranial pressure.

  2. MET is required for the recruitment of anti-tumoural neutrophils.

    Science.gov (United States)

    Finisguerra, Veronica; Di Conza, Giusy; Di Matteo, Mario; Serneels, Jens; Costa, Sandra; Thompson, A A Roger; Wauters, Els; Walmsley, Sarah; Prenen, Hans; Granot, Zvi; Casazza, Andrea; Mazzone, Massimiliano

    2015-06-18

    Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-α or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential 'Achilles' heel' of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases.

  3. Intracranial hypertension as the first manifestation of primary Sjogren's syndrome.

    Science.gov (United States)

    Lim, Sung-Chul; Kim, Joong-Seok; Lee, Young-Hyun; Park, Kyung-Su; Shin, Sun Young

    2011-04-01

    Central nervous system involvement with primary Sjögren's syndrome (pSS) is rare, and often undiagnosed. Sjögren's syndrome and concomitant intracranial hypertension is a very rare event. We describe a patient with pSS who presented with intracranial hypertension as the initial symptom of the disease. This is the first case report of a patient with pSS that presented with intracranial hypertension only.

  4. Intracranial hypertension in 2 children with marfan syndrome.

    Science.gov (United States)

    Hilhorst-Hofstee, Yvonne; Kroft, Lucia J M; Pals, Gerard; van Vugt, Jeroen P P; Overweg-Plandsoen, Wouterina C G

    2008-08-01

    Two unrelated children with Marfan syndrome presented with recurrent intracranial hypertension. Both children complained of headache, nausea, and vomiting and one of them had papilledema. Both had increased cerebrospinal fluid pressure, and their complaints disappeared after lumbar puncture. Although severe headache has been reported in Marfan syndrome due to intracranial hypotension, this is to our knowledge the first report of intracranial hypertension in Marfan patients.

  5. Computerized tomographic evaluation of intracranial metastases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bo Yong; Lee, Mi Sook; Choi, Jin Ok; Jeon, Doo Sung; Kim, Hong Soo; Rhee, Hak Song [Presbyterian Medical Center, Chonju (Korea, Republic of)

    1986-12-15

    In a study of intracranial metastases, 46 cases having satisfactory clinical, operative and histological proofs were analyzed by computerized tomography at Presbyterian Medical Center from May, 1982 to February, 1986. The results were as follows: 1. The male to female ratio of intracranial metastases were 67:33. The 5th decade group (34.8%) was the most prevalent age group, followed by the 6th decade (21.7%) and 7th decade (21.7%). 2. The number of lesions was found be: single -25 cases (54.3%); multiple -21 cases (45.7%). 3. The source of intracranial metastases found to be: lung 15 cases (32.6%); unknown 12 cases (26.0%); chorioca 3 cases (6.5%); liver 3 cases (6.5%); stomach 2 cases (4.3%); parotid, breast, kidney, prostate, melanoma, rectal ca, rhabdomyosarcoma, nasal ca, lymphoma, testicular ca, cervix, each 1 case (2.2%). 4. The locations of the intracranial metastases were as follows: Cerebral hemisphere 37.7% in parietal region Cerebral hemisphere 15.9% in in frontal region Cerebral hemisphere 13.4% in occipital region Cerebral hemisphere 10.5% in temporal region Cerebellar hemisphere 3.2% Cerebellopontine angle 3.2% Intraventricular 4.8% Meninges 4.8% Skull vault 6.5% 5. Peritumor edema was found to be: Grade II-17 cases (37.0%): Grade III-14 cases (30.4%); Grade I-8 cases (17.4%); Grade 0-7 cases (15.2%) in that order. 6. The chief complaints of intracranial metastases on admission, were as follows: Headache 30 cases (65.2%); Vomiting 11 cases (23.9%); deteriorated mental state 10 cases (21.7%); Hemiplegia 7 cases (15.2%); visual disturbance 6 cases (13.0%); hemiparesis 4 cases (8.7%); seizure 4 cases (8.7%); other symptoms were less frequent. 7. On pre-contrast scan, hyperdense lesions were present in 18 cases (39.1%); hypodense lesions in 15 cases (32.6%); mixed density in 8 cases (17.4%); isodensity was present in 5 cases (10.9%). On post-contrast scan, ring enhancement was seen in 19 cases (41.3%); nodular enhancement in 17 cases (37%), mixed ring

  6. Analysis of Fascin-1 in Relation to Gleason Risk Classification and Nuclear ETS-Related Gene Status of Human Prostate Carcinomas: An Immunohistochemical Study of Clinically Annotated Tumours From the Wales Cancer Bank.

    Science.gov (United States)

    Jefferies, Matthew T; Pope, Christopher S; Kynaston, Howard G; Clarke, Alan R; Martin, Richard M; Adams, Josephine C

    2017-01-01

    Although prostate-specific antigen (PSA) testing can identify early-stage prostate cancers, additional biomarkers are needed for risk stratification. In one study, high levels of the actin-bundling protein, fascin-1, were correlated with lethal-phase, hormone-refractory prostate cancer. Analyses of independent samples are needed to establish the value of fascin-1 as a possible biomarker. We examined fascin-1 by immunohistochemistry in tumour specimens from the Wales Cancer Bank in comparison with nuclear-located ETS-related gene (ERG), an emerging marker for aggressive prostate cancer. Fascin-1 was elevated in focal areas of a minority of tumours, yet fascin-1-positivity did not differentiate tumours of low-, intermediate-, or high-risk Gleason scores and did not correlate with PSA status or biochemical relapse after surgery. Stromal fascin-1 correlated with high Gleason score. Nuclear ERG was upregulated in tumours but not in stroma. The complexities of fascin-1 status indicate that fascin-1 is unlikely to provide a suitable biomarker for prediction of aggressive prostate cancers.

  7. Idiopathic Intracranial Hypertension in Monozygotic Female Twins: Intracranial Pressure Dynamics and Treatment Outcome.

    Science.gov (United States)

    Polemikos, Manolis; Heissler, Hans E; Hermann, Elvis J; Krauss, Joachim K

    2017-05-01

    Familial cases of idiopathic intracranial hypertension (IIH) are exceedingly rare, and its occurrence in monozygotic twins has not been reported previously. We report monozygotic female twins who developed IIH, one at age 25 years and the other at age 28 years. Continuous intracranial pressure (ICP) monitoring confirmed elevated ICP as measured initially by lumbar puncture. In both cases, successful treatment with resolution of papilledema and symptoms relief was achieved after ventriculoperitoneal shunting. This report documents the first case of IIH in monozygotic twins and the associated changes in ICP dynamics. Interestingly, almost equivalent alterations in ICP dynamics were found in the 2 patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Tumour expression of bladder cancer-associated urinary proteins.

    Science.gov (United States)

    Lindén, Mårten; Segersten, Ulrika; Runeson, Marcus; Wester, Kenneth; Busch, Christer; Pettersson, Ulf; Lind, Sara Bergström; Malmström, Per-Uno

    2013-08-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The current basis for diagnosis and prognosis in urinary bladder cancer is based on the pathologists' assessment of a biopsy of the tumour. Urinary biomarkers are preferable as they can be non-invasively sampled. Urinary cytology is the only test with widespread use but is hampered by poor reproducibility and low sensitivity. By studying the protein expression in bladder tumour tissue samples of proteins previously found in elevated levels in the urine of patients with bladder cancer, we have been able to show that these proteins originate from the tumour. The immunoreactivity of three of the investigated proteins increased with higher stage. Also a serine peptidase inhibitor was found to be predictive of progression from non-muscle-invasive to muscle-invasive tumours. To analyse the expression of five bladder cancer-associated urinary proteins and investigate if expression is related to the malignant phenotype of the tumour. To explore the possible prognostic value of these proteins. Urine samples, 16 from patients with bladder cancer and 26 from controls, were used in Western Blotting experiments. Tissue microarrays with bladder tissue from 344 patients diagnosed with bladder cancer between 1984 and 2005 was used in immunohistochemistry experiments. The proteins apolipoprotein E (APOE), fibrinogen β chain precursor (FGB), leucine-rich α2-glycoprotein (LRG1), polymerase (RNA) I polypeptide E (POLR1E), α1-antitrypsin (SERPINA1) and topoisomerase 2A (TOP2A) were probed with antibodies validated by the Human Protein Atlas. Increased expressions of APOE, FGB and POLR1E were correlated with increased tumour stage (P SERPINA1 in Ta and T1 tumours was found to increase the risk of tumour progression (hazard ratio 2.57, 95% confidence interval 1.13-5.87; P = 0.025) CONCLUSIONS: All proteins previously detected in urine from patients with bladder cancer were also expressed in bladder cancer tissue. The

  9. [Prolonged hypothermia in refractory intracranial hypertension. Report of one case].

    Science.gov (United States)

    Rovegno, Maximiliano; Valenzuela, José Luis; Mellado, Patricio; Andresen, Max

    2012-02-01

    The use of hypothermia after cardiac arrest caused by ventricular fibrillation is a standard clinical practice, however its use for neuroprotection has been extended to other conditions. We report a 23-year-old male with intracranial hypertension secondary to a parenchymal hematoma associated to acute hydrocephalus. An arterial malformation was found and embolized. Due to persistent intracranial hypertension, moderate hypothermia with a target temperature of 33°C was started. After 12 hours of hypothermia, intracranial pressure was controlled. After 13 days of hypothermia a definitive control of intracranial pressure was achieved. The patient was discharged 40 days after admission, remains with a mild hemiparesia and is reassuming his university studies.

  10. Very Low Prevalence of Intracranial Hypertension in Trigonocephaly.

    Science.gov (United States)

    Cornelissen, Martijn J; Loudon, Sjoukje E; van Doorn, Frida E C; Muller, Rogier P M; van Veelen, Marie-Lise C; Mathijssen, Irene M J

    2017-01-01

    Trigonocephaly is caused by metopic suture synostosis. It is treated by fronto-orbital remodeling, not only to correct the deformity but also to prevent intracranial hypertension, the reported prevalence in trigonocephaly of which ranges from 0 to 33 percent. To support treatment analysis and the design of a treatment protocol for intracranial hypertension in these patients, the authors wished to more accurately quantify the prevalence of preoperative and postoperative intracranial hypertension in a large patient cohort. The authors included all trigonocephaly patients born between 2001 and 2013 who had all been operated on at a single center. During follow-up, the presence of intracranial hypertension was evaluated by funduscopy, and occipitofrontal head circumference was measured. The occipitofrontal head circumference curve was analyzed and its relation to intracranial hypertension assessed. In total, 262 patients with trigonocephaly were included. Before surgery, 1.9 percent of them had intracranial hypertension; after surgery, 1.5 percent did (mean age at last follow-up, 4.9 years). Sixteen of 176 patients (9 percent) had occipitofrontal head circumference curve stagnation, which was significantly related to intracranial hypertension (p = 0.001, Fisher's exact test). Intracranial hypertension occurs only sporadically in patients with metopic suture synostosis. Occipitofrontal head circumference measurement should take a prominent place in the postoperative follow-up of metopic suture synostosis patients; stagnation of the occipitofrontal head circumference requires additional screening for intracranial hypertension. Therapeutic, IV.

  11. Imaging and interventions in idiopathic intracranial hypertension: A pictorial essay.

    Science.gov (United States)

    Sivasankar, Rajeev; Pant, Rochan; Indrajit, Inna K; Negi, Raj S; Sahu, Samresh; Hashim, P I; D'Souza, John

    2015-01-01

    Intracranial hypertension is a syndrome of elevated intracranial pressure that can be primary or secondary. The primary form, now termed idiopathic intracranial hypertension (IIH), was in the past a disease of exclusion and imaging played a limited role of excluding organic causes of raised intracranial pressure. However imaging markers have been described with patients with IIH at the orbit, sella and cerebral venous system. We wish to reiterate the characteristic imaging features of this poorly understood disease and also emphasise that stenting of the transverse sinus in select cases of IIH is an efficacious option.

  12. A segmentation algorithm of intracranial hemorrhage CT image

    Science.gov (United States)

    Wang, Haibo; Chen, Zhiguo; Wang, Jianzhi

    2011-10-01

    To develop a computer aided detection (CAD) system that improves diagnostic accuracy of intracranial hemorrhage on cerebral CT. A method for CT image segmentation of brain is proposed, with which, several regions that are suspicious of hemorrhage can be segmented rapidly and effectively. Extracting intracranial area algorithm is introduced firstly to extract intracranial area. Secondly, FCM is employed twice, we named it with TFCM. FCM is first employed to identify areas of intracranial hemorrhage. Finally, FCM is employed to segment the lesions. Experimental results on real medical images demonstrate the efficiency and effectiveness.

  13. Imaging and interventions in idiopathic intracranial hypertension: A pictorial essay

    Directory of Open Access Journals (Sweden)

    Rajeev Sivasankar

    2015-01-01

    Full Text Available Intracranial hypertension is a syndrome of elevated intracranial pressure that can be primary or secondary. The primary form, now termed idiopathic intracranial hypertension (IIH, was in the past a disease of exclusion and imaging played a limited role of excluding organic causes of raised intracranial pressure. However imaging markers have been described with patients with IIH at the orbit, sella and cerebral venous system. We wish to reiterate the characteristic imaging features of this poorly understood disease and also emphasise that stenting of the transverse sinus in select cases of IIH is an efficacious option.

  14. Complications of invasive intracranial pressure monitoring devices in neurocritical care.

    Science.gov (United States)

    Tavakoli, Samon; Peitz, Geoffrey; Ares, William; Hafeez, Shaheryar; Grandhi, Ramesh

    2017-11-01

    Intracranial pressure monitoring devices have become the standard of care for the management of patients with pathologies associated with intracranial hypertension. Given the importance of invasive intracranial monitoring devices in the modern neurointensive care setting, gaining a thorough understanding of the potential complications related to device placement-and misplacement-is crucial. The increased prevalence of intracranial pressure monitoring as a management tool for neurosurgical patients has led to the publication of a plethora of papers regarding their indications and complications. The authors aim to provide a concise review of key contemporary articles in the literature concerning important complications with the hope of elucidating practices that improve outcomes for neurocritically ill patients.

  15. Targeted radiotherapy with {sup 177} Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, M. A de; Pedraza L, M. [Department of Nuclear Medicine, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico D.F. (Mexico); Rodriguez C, J. [Faculty of Medicine, UAEM, Toluca, Estado de Mexico (Mexico); Ferro F, G. [ININ, 52045 Estado de Mexico (Mexico); Murphy S, E. [Hospital Santelena, Mexico D.F. (Mexico)

    2006-07-01

    Malignant pancreas tumours induced in athymic mice are a good model for targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses and to evaluate {sup 177}Lu-DOTA-TATE as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells, which over-express somatostatin receptors, were injected in athymic mice and 20 days later the mean tumour size was 3.08 square cm (n=3). A mean of 86.3 MBq {sup 177}Lu-DOTA-TATE, was injected in a tail vein and 19 days after therapy the size of the tumours was 0.81 square cm. There was a partial relapse and after 16 days, when sacrificed, the mean tumour size was 8.28 cubic cm. An epithelial and sarcoma mixed tumour in the kidney of one treated mouse was found. The tumour of the control mouse was 8.61 cubic cm when sacrificed 14 days after tumour induction. Radiotherapy estimates to the tumours was 35.9-39.7 Gy and the tumours might have been completely reduced with a second therapy dose. These preliminary studies justify further therapeutic and dosimetry estimations to ensure that Lu-{sup 177}-DOTA-TATE will act as expected in man, considering kidney radiation. (Author)

  16. Pathohistological and immunohistochemical parameters significant for prognosis and therapy of tumours in cats and dogs

    Directory of Open Access Journals (Sweden)

    Aleksić-Kovačević Sanja

    2015-01-01

    Full Text Available The development of tumours implies a disproportion between proliferation, growth and differentiation, which is accompanied by significant genotypic and phenotypic variations in the diseased. The scenario of multiple oncogenic effects on the inhibition of cell growth, apoptosis and maturation, on the stimulation of proliferation, on cell migration and tissue invasion, is responsible for the occurrence of tumours both in humans and in animals. The qualitative and quantitative determination of biological prognostic factors in the tissue of affected cats and dogs directly indicates a possible tumour metastasizing, and consequently also the prognosis of neoplastic disease. Monitoring of clinical and biological prognostic factors is important for therapy and prediction of tumours in humans and animals. The determination of the proliferative potential of tumour cells by immunohistochemical detection of Ki-67 and PCNA is used in grading certain tumours in cats and dogs. It is also possible immunohistochemically to prove factors of angiogenesis and numerous activating and inhibiting proteins in the tumour tissue. In addition to other histological, clinical and biological parameters, they are significant for the further prognosis and therapy of neoplastic diseases.

  17. Development of intracranial hypertension after surgical management of intracranial arachnoid cyst: report of three cases and review of the literature.

    Science.gov (United States)

    Kaliaperumal, Chandrasekaran; O'Connor, Brendan; Marks, Charles

    2013-01-01

    To describe three cases of delayed development of intracranial hypertension (IH) after surgical treatment of intracranial arachnoid cyst, including the pathogenesis of IH and a review of the literature. A retrospective and prospective analysis of three male patients (two 18 years old and one 45 years old) was performed. All patients underwent surgical intervention for symptomatic intracranial arachnoid cyst in the form of fenestration of the cyst and a cystoperitoneal shunt. All three patients presented at a later stage with new-onset headaches after the initial management of arachnoid cyst. Magnetic resonance imaging and magnetic resonance venography ruled out any intracranial vascular pathology. Lumbar puncture and intracranial pressure monitoring showed increased intracranial pressure suggestive of idiopathic IH. To manage IH, intracranial pressure monitoring, cystoperitoneal shunt, ventriculoperitoneal shunt, and lumboperitoneal shunt were performed. The pathogenesis of delayed development of IH in this clinical setting is not clearly elucidated. When intracranial arachnoid cysts are treated, the possibility of future development of IH should be borne in mind. Delayed presentation with headaches in patients after treatment of intracranial arachnoid cysts should raise the possibility of IH. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Omega-3 fatty acid supplement prevents development of intracranial atherosclerosis.

    Science.gov (United States)

    Shen, Jiamei; Hafeez, Adam; Stevenson, James; Yang, Jianjie; Yin, Changbin; Li, Fengwu; Wang, Sainan; Du, Huishan; Ji, Xunming; Rafols, Jose A; Geng, Xiaokun; Ding, Yuchuan

    2016-10-15

    silent information regulator 1 (SIRT1) activation, thus increasing cholesterol efflux from macrophages to HDL. Long-term O3FA dietary supplementation prevents the development of intracranial atherosclerosis. This O3FA effect appears to be mediated by its prevention of macrophage infiltration into the vessel wall, therefore reducing inflammation and intimal thickening. While similar effects in humans need to be determined, O3FA dietary supplement shows promising results in the prevention of ICAS. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, B.B.; Aukema, T.S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vrancken Peeters, M.J.T.F.D.; Rutgers, E.J.T. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Wesseling, J.; Lips, E.H. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Pathology and Experimental Therapy, Amsterdam (Netherlands); Vogel, W.V.; Valdes Olmos, R.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Werkhoven, E. van [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, K.G.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

    2012-12-15

    The aim of this study was to evaluate the association of primary tumour {sup 18}F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake. PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUV{sub max}). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses. In 203 tumours (95 %) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUV{sub max} was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUV{sub max}. Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT. (orig.)

  20. Fertility sparing treatment in borderline ovarian tumours

    Science.gov (United States)

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  1. Pro-inflammatory cytokines: Useful markers for the diagnosis of canine mammary tumours?

    Science.gov (United States)

    Andaluz, Ana; Yeste, Marc; Rodríguez-Gil, Joan E; Rigau, Teresa; García, Félix; Rivera del Álamo, Maria Montserrat

    2016-04-01

    The aim of the present study was to analyse the expression of 60 pro-inflammatory cytokines as possible markers of malignancy in canine mammary tumours using a human cytokine antibody array. The cytokines were grouped into two different categories: (1) cytokines in which expression indicated the presence of a mammary tumour and (2) cytokines in which expression differentiated between simple mammary adenoma, tubulopapillary carcinoma or complex carcinoma. These data suggest that specific pro-inflammatory cytokines could be useful as tools for the diagnosis of canine mammary tumours. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Expression of tissue factor in canine mammary tumours and correlation with grade, stage and markers of haemostasis and inflammation

    DEFF Research Database (Denmark)

    Andreasen, Eva Bartholin; Nielsen, Ole Lerberg; Tranholm, M.

    2016-01-01

    Tissue factor (TF) expression in human cancers has been associated with a procoagulant state and facilitation of metastasis. This study was conducted in order to evaluate if TF was expressed in canine mammary tumours. Forty epithelial mammary tumours from 28 dogs were included. TF expression...... in a lymph node metastasis classified as anaplastic mammary carcinoma from a dog with concomitant disseminated intravascular coagulation (DIC)....

  3. An unusual presentation of a glomus tumour.

    LENUS (Irish Health Repository)

    Nugent, N

    2011-02-01

    Glomus tumours are benign, soft tissue tumours, usually of fingertips. Classically they present with severe pain, temperature sensitivity and localised tenderness. The diagnosis is often delayed due to sometimes non-specific symptoms and rarity of the disorder. While usually a clinical diagnosis, imaging may be necessary for diagnosis and localisation. We present a case of glomus tumour of the fingertip with an unusual history.

  4. Refractive index of carcinogen-induced rat mammary tumours

    Science.gov (United States)

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

    2006-05-01

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

  5. Utility of intracranial pressure monitoring for diagnosis of Idiopathic Intracranial Hypertension in the absence of papilledema.

    Science.gov (United States)

    Bridges, Kelly J; Raslan, Ahmed M

    2017-12-16

    Idiopathic intracranial hypertension (IIH) is characterized by headaches, visual obscurations, and papilledema, while diagnosis involves lumbar puncture (LP) with an elevated opening pressure (OP) ≥ 20cm H20. When papilledema is absent, diagnosis becomes less clear. Some physicians have argued that absence of papilledema rules out IIH, while others maintain that elevated OP is sufficient for diagnosis. The authors performed a single institution 4-year retrospective analysis of patients who underwent invasive intracranial pressure (ICP) monitoring for presumed IIH. A total of 22 patients were reviewed and 13 had classic symptoms of IIH, documented elevated OP and absence of papilledema, 5/13 (38%) patients had proven intracranial hypertension using invasive ICP monitoring, while 8/13 (62%) had normal ICP. Using current diagnostic algorithms of clinical presentation and elevated OP, over half of patients without papilledema in our series would be falsely diagnosed with IIH, which could result in unnecessary medical and surgical intervention. Thus, elevated OP as determined by LP is insufficient to diagnosis IIH. On the other hand, the absence of papilledema does not rule out intracranial hypertension. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Fluid Shifts Before, During and After Prolonged Space Flight and Their Association with Intracranial Pressure and Visual Impairment

    Science.gov (United States)

    Stenger, Michael; Hargens, Alan; Dulchavsky, Scott

    2014-01-01

    Future human space travel will primarily consist of long duration missions onboard the International Space Station or exploration class missions to Mars, its moons, or nearby asteroids. Current evidence suggests that long duration missions might increase risk of permanent ocular structural and functional changes, possibly due to increased intracranial pressure resulting from a spaceflight-induced cephalad (headward) fluid shift.

  7. Bilateral ovarian tumour in a young girl

    Directory of Open Access Journals (Sweden)

    Krishna Kumar Govindarajan

    2013-01-01

    Full Text Available Bilateral ovarian tumour in a girl presents the dilemma of conservative versus aggressive approach towards these tumours. When faced with suspicious tumour and complete replacement of the ovaries bilaterally, bilateral oophorectomy is a viable option, though the certain possibility of infertility and lifelong hormonal supplementation is unavoidable. We report a case of bilateral ovarian masses in a young girl, which on histopathological examination showed mature teratoma with aggregates of proliferating capillary and cavernous sized vessels in the tumour wall. Such associations are rare and must be differentiated from a vascular neoplasm.

  8. Tumour-targeted nanomedicines: principles and practice

    National Research Council Canada - National Science Library

    Lammers, T.G.G.M; Hennink, W.E; Storm, G

    2008-01-01

    .... Various different tumour-targeted nanomedicines have been evaluated over the years, and clear evidence is currently available for substantial improvement of the therapeutic index of anticancer agents...

  9. Elevated tumour marker: an indication for imaging?

    LENUS (Irish Health Repository)

    McMahon, Colm J

    2012-02-01

    INTRODUCTION: The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication. MATERIALS AND METHODS: Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and\\/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of \\'elevated tumour marker\\' in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated. RESULTS: Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41-91] y), were imaged to evaluate: \\'elevated tumour marker\\'. They underwent 29 imaging studies (mean [+\\/-standard deviation (SD)] per patient = 1.2 [+\\/-0.4]), and had 42 elevated tumour marker serology tests (mean [+\\/-SD] per patient = 1.7 [+\\/-0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker. CONCLUSION: The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of \\'elevated tumour marker\\'. \\'Elevated tumour marker\\

  10. Focused ultrasound for treatment of bone tumours.

    Science.gov (United States)

    Rodrigues, Dario B; Stauffer, Paul R; Vrba, David; Hurwitz, Mark D

    2015-05-01

    Focused ultrasound (FUS) is a modality with rapidly expanding applications across the field of medicine. Treatment of bone lesions with FUS including both benign and malignant tumours has been an active area of investigation. Recently, as a result of a successful phase III trial, magnetic resonance-guided FUS is now a standardised option for treatment of painful bone metastases. This report reviews the clinical applications amenable to treatment with FUS and provides background on FUS and image guidance techniques, results of clinical studies, and future directions. A comprehensive literature search and review of abstracts presented at the recently completed fourth International Focused Ultrasound Symposium was performed. Case reports and older publications revisited in more recent studies were excluded. For clinical studies that extend beyond bone tumours, only the data regarding bone tumours are presented. Fifteen studies assessing the use of focused ultrasound in treatment of primary benign bone tumours, primary malignant tumours, and metastatic tumours meeting the search criteria were identified. For these clinical studies the responders group varied within 91-100%, 85-87% and 64-94%, respectively. Major complications were reported in the ranges 0%, 0-28% and 0-4% for primary benign, malignant and metastatic tumours, respectively. Image-guided FUS is both safe and effective in the treatment of primary and secondary tumours. Additional phase III trials are warranted to more fully define the role of FUS in treatment of both benign and malignant bone tumours.

  11. Flurbiprofen and hypertension but not hydroxyethyl starch are associated with post-craniotomy intracranial haematoma requiring surgery.

    Science.gov (United States)

    Jian, M; Li, X; Wang, A; Zhang, L; Han, R; Gelb, A W

    2014-11-01

    Post-craniotomy intracranial haematoma is one of the most serious complications after neurosurgery. We examined whether post-craniotomy intracranial haematoma requiring surgery is associated with the non-steroidal anti-inflammatory drugs flurbiprofen, hypertension, or hydroxyethyl starch (HES). A case-control study was conducted among 42 359 patients who underwent elective craniotomy procedures at Beijing Tiantan Hospital between January 2006 and December 2011. A one-to-one control group without post-craniotomy intracranial haematoma was selected matched by age, pathologic diagnosis, tumour location, and surgeon. Perioperative blood pressure records up to the diagnosis of haematoma, the use of flurbiprofen and HES were examined. The incidence of post-craniotomy intracranial haematoma and the odds ratios for the risk factors were determined. A total of 202 patients suffered post-craniotomy intracranial haematoma during the study period, for an incidence of 0.48% (95% CI=0.41-0.55). Haematoma requiring surgery was associated with an intraoperative systolic blood pressure of >160 mm Hg (OR=2.618, 95% CI=2.084-2.723, P=0.007), an intraoperative mean blood pressure of >110 mm Hg (OR=2.600, 95% CI=2.312-3.098, P=0.037), a postoperative systolic blood pressure of >160 mm Hg (OR=2.060, 95% CI= 1.763-2.642, P=0.022), a postoperative mean blood pressure of >110 mm Hg (OR=3.600, 95% CI= 3.226-4.057, P=0.001), and the use of flurbiprofen during but not after the surgery (OR=2.256, 95% CI=2.004-2.598, P=0.005). The intraoperative infusion of HES showed no significant difference between patients who had a haematoma and those who did not. Intraoperative and postoperative hypertension and the use of flurbiprofen during surgery are risk factors for post-craniotomy intracranial haematoma requiring surgery. The intraoperative infusion of HES was not associated with a higher incidence of haematoma. © The Author 2014. Published by Oxford University Press on behalf of the British

  12. Supratentorial cystic intracranial lesions: MR imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Joo; Son, Young Bo; Choi, Kyu Ho; Chun, Kyung Ah; Kim, Sung Hoon; Park, Seog Hee; Shinn, Kyung Sub [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    1997-01-01

    To describe MR findings and differential points of supratentorial cystic intracranial lesions. We retrospectively reviewed and analyzed the MR findings of 59 patients with supratentorial cystic intracranial lesions, and classified them as follows : tumor-associated cyst, infectious cyst, ex-vacuo type cyst, and congentital/developmental cyst. Among 59 patients, 47 tumor-associated cysts were seen in 17, 42 infectious cysts in 13, 17 ex-vacuo type cysts in 10, and 19 congenital/developmental cysts in 19. In 44 of 47 tumor-associate cysts, increased or inhomogeneous internal signal intensity was seen on T1-weighted image, 37 of 47 showed thick uneven walls ; 37 of 47 had enhancing solid components and there was variable perifocal edema and mass effect. Infectious cysts were multiple (11 of 13). In cases of brain abscess, increased internal signal intensity on T1-weighted image, low signal intensity of abscess wall on T2-weighted image, thick even enhancing wall, and marked perifocal edema (4 of 4) were seen in all four cases. Cysts in cysticercosis were variable in appearance depending on the stage, but were smaller than other cystic lesions. Ex vacuo type cysts were of uniform CSF signal intensity in all pulse sequences and there was no identifiable wall or enhancement associated with enlarged adjacent ventricle and encephalomalacia (17 of 17). Congenital/developmental cysts showed a single lesion (19 of 19), a signal intensity similar to CSF in all pulse sequences (15 of 19), no identifiable wall (16 of 19), no enhancement (17 of 19), and no perifocal edema (19 of 19). MR was used to categorize supratentorial cystic intracranial lesions into four groups on the basis of their number, size, internal homogeneity of signal intensity on T1-weighted image, enhancing pattern, perifocal edema and mass effect, thereby improving diagnostic specificity and patient management.

  13. Case Report - Bilateral synchronous testicular germ cell tumours in ...

    African Journals Online (AJOL)

    Bilateral testicular tumours are rare, and 80% of bilateral tumours are metachronous. The incidence of testicular tumours is high in cryptorchidism. Synchronous bilateral testicular tumours are rare, and bilateral synchronous testicular tumours in bilateral cryptorchidism extremely rare, probably not reported previously.

  14. Characterization of Endocrine Cells and Tumours in the Stomach

    OpenAIRE

    Tsolakis, Apostolos V.

    2008-01-01

    Enterochromaffin-like (ECL) and ghrelin cells, in the human gastric mucosa and in gastric endocrine tumours (GETs), were subclassified with respect to immunohistochemical reaction vs. vesicular monoamine transporter 2 (VMAT-2), ghrelin/obestatin, and histidine decarboxylase (HDC). The immunohistochemical expression of ghrelin/obestatin and HDC in GETs was related/correlated to plasma ghrelin/obestatin and urinary methyl imidazole acetic acid (U-MeImAA) excretion respectively, with the intenti...

  15. Tumour Cell Heterogeneity [version 1; referees: 5 approved

    Directory of Open Access Journals (Sweden)

    Laura Gay

    2016-02-01

    Full Text Available The population of cells that make up a cancer are manifestly heterogeneous at the genetic, epigenetic, and phenotypic levels. In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the ramifications and opportunities that ITH presents for cancer prognostication and treatment.

  16. Intracranial Extramedullary Hematopoiesis in Beta-Thalassemia

    Energy Technology Data Exchange (ETDEWEB)

    Karki, Bivek; Xu, Yi Kai; Wu, Yuan Kui [Nan fang Hospital, Southern Medical University, Guangzhou (China); Tamrakar, Karuna [Zhujiang Hospital, Southern Medical University, Guangzhou (China)

    2012-03-15

    Extramedullary hematopoiesis (EMH) represents tumor-like proliferation of hemopoietic tissue which complicates chronic hemoglobinopathy. Intracranial EMH is an extremely rare occurrence. Magnetic resonance imaging (MRI) offers a precise diagnosis. It is essential to distinguish EMH from other extradural central nervous system tumors, because treatment and prognosis are totally different. Herein, we report the imaging findings of beta-thalassemia in a 13-year-old boy complaining of weakness of left side of the body and gait disturbance; CT and MRI revealed an extradural mass in the right temporoparietal region.

  17. Secondary Intracranial Hypotension: A Case Report

    Directory of Open Access Journals (Sweden)

    Pinar Gundogan Bozdag

    2014-04-01

    Full Text Available Intracranial hypotension is a clinical condition that characterized by postural (orthostatic headache and low pressure. It apperas with cerebrospinal fluid leak which occurs spontaneous or depending on the secondary attempts. 31 years old female patient which has diagnosis of acute appendicitis and underwent appendectomy under spinal anesthesia. postoperative 5.day she admitted with a postural headache, diplopia. Patient was treated with conservative methods after diagnosed with magnetic resonance imaging. We aim to asses an encountered complication after spinal anesthesia which widely applied for surgical procedures with imaging findings and literature.

  18. Imaging features of unusual intracranial cystic meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    Demir, M.K. [Trakya Univ. School of Medicine, Dept. of Radiology, Edirne (Turkey); Haydarpasa Numune Education and Research Hospital, Dept. of Radiology, Istanbul (Turkey)]. E-mail: demirkemal@superonline.com; Musluman, M. [Sisli Etfal Education and Research Hospital, Dept. of Neurosurgery, Istanbul (Turkey); Kilicoglu, G. [Haydarpasa Numune Education and Research Hospital, Dept. of Radiology, Istanbul (Turkey); Hakan, T. [Haydarpasa Numune Education and Research Hospital, Dept. of Neurosurgery, Istanbul (Turkey); Aker, F.V. [Haydarpasa Numune Education and Research Hospital, Dept. of Pathology, Istanbul (Turkey)

    2007-04-15

    To describe the imaging features of unusual intracranial cystic meningiomas in infants and adults. We retrospectively reviewed the magnetic resonance and computed tomography findings for 2 female patients and 3 male patients, ranging in age from 1 to 73 years (median 41 years), with histopathologically proven cystic meningioma. Although cystic meningiomas usually appear as solid and cystic masses, they may present as a mainly multicystic lesion. The wall of a cystic part of the meningioma may include both enhancing and unenhancing areas at imaging. The cystic portion of a meningioma is hypointense on diffusion-weighted images and markedly hyperintense on corresponding apparent diffusion coefficient maps. (author)

  19. Idiopathic intracranial hypertension and transverse sinus stenoses

    DEFF Research Database (Denmark)

    Skyrman, Simon; Fytagoridis, Anders; Andresen, Morten

    2013-01-01

    An 18-year-old woman was diagnosed with idiopathic intracranial hypertension (IIH) and bilateral transverse sinus stenoses (TSS), after presenting with papilledema and decreased visual acuity. Lumbar puncture revealed an opening pressure of >60 cm H2O. MRI showed bilateral TSS believed to be asso...... was inserted since the patient had improved with CSF diversion. MRI verified reopening of the venous sinuses after shunt placement, and the patient remains asymptomatic with no signs of relapse after 3 years of follow-up....

  20. A case of intracranial malignant fibrous histiocytoma

    Directory of Open Access Journals (Sweden)

    Amir Hossein Sarrami

    2011-01-01

    Full Text Available We describe a case of intracranial malignant fibrous histiocytoma which had infiltrated pons, cerebellum and basal surface of left temporal lobe without any visible mass. The patient presented with a sudden loss of consciousness and vomiting. Clinical findings, laboratory tests, imaging and examination of the cerebrospinal fluid tended to establish the diagnosis of an infectious condition than a malignancy. Without any response to the antibiotics and with a progressive deterioration of neurologic and mental condition, the patient died after 20 days. In the autopsy, histological and immunohistochemical study of the brain revealed the diagnosis of malignant fibrous histiocytoma (MFH.