Despite aggressive surgery, radiotherapy and chemotherapy, malignant gliomas remain uniformly fatal. To progress, these tumours stimulate the formation of new blood vessels through processes driven primarily by vascular endothelial growth factor (VEGF). However, the resulting vessels are structurally and functionally abnormal, and contribute to a hostile microenvironment (low oxygen tension and high interstitial fluid pressure) that selects for a more
Emmanuelle di Tomaso; Dan G. Duda; Jay S. Loeffler; A. Gregory Sorensen; Tracy T. Batchelor; Rakesh K. Jain
Tissue texture is known to exhibit a heterogeneous or non-stationary nature; therefore using a single resolution approach for optimum classification might not suffice. A clinical decision support system that exploits the subbands' textural fractal characteristics for best bases selection of meningioma brain histopathological image classification is proposed. Each subband is analysed using its fractal dimension instead of energy, which has the advantage of being less sensitive to image intensity and abrupt changes in tissue texture. The most significant subband that best identifies texture discontinuities will be chosen for further decomposition, and its fractal characteristics would represent the optimal feature vector for classification. The performance was tested using the support vector machine (SVM), Bayesian and k-nearest neighbour (kNN) classifiers and a leave-one-patient-out method was employed for validation. Our method outperformed the classical energy based selection approaches, achieving for SVM, Bayesian and kNN classifiers an overall classification accuracy of 94.12%, 92.50% and 79.70%, as compared to 86.31%, 83.19% and 51.63% for the co-occurrence matrix, and 76.01%, 73.50% and 50.69% for the energy texture signatures; respectively. These results indicate the potential usefulness as a decision support system that could complement radiologists' diagnostic capability to discriminate higher order statistical textural information; for which it would be otherwise difficult via ordinary human vision. PMID:24962336
Al-Kadi, Omar S
Using the term odontome for any tumour arising from the dental formative tissues, Broca suggested a classification of odontogenic tumours (OTs) in 1869. From 1888 to 1914, Bland-Sutton and Gabell, James and Payne modified tumour terminology, while maintaining Broca's odontome concept. Thoma and Goldman's classification (1946) divided the OTs into tumours of ectodermal, mesodermal and mixed origin and abolished the general term odontome. The Pindborg and Clausen classification (1958) based on the idea that the reciprocal epithelial-mesenchymal tissue interactions were also operating in the pathogenesis of OTs. In 1966, WHO established a Collaborating Centre for the Histological Classification of Odontogenic Tumours and Allied Lesions (including jaw cysts) headed by Dr Jens Pindborg. In 1971, the first authoritative WHO guide to the classification of OTs and cysts appeared followed in 1992 by a second edition. In 2002, Philipsen and Reichart produced a revision of the 1992-edition and in 2003, the editors of the WHO Blue Book series: 'WHO Classification of Tumours' decided to produce a volume on the Head and Neck Tumours including a chapter on Odontogenic Tumours and Bone Related Lesions. In July of 2005 this volume was published by IARC, Lyon. PMID:16968232
Philipsen, Hans Peter; Reichart, Peter A
Three patients are described in whom irradiation of 2750 rad or more was used in the management of primary brain tumours, and 21 years or more later a second brain tumour of a different type occurred. One of the new tumours was a meningioma and the other two were cerebral astrocytomas. There is evidence to show that moderate doses of ionising radiations given in childhood for tinea capitis are associated with a late risk of developing a meningioma. Higher doses of radiation used for tumours in childhood are followed also by a late hazard of meningioma. There is insufficient evidence to implicate ionising radiations in the aetiology of gliomas. The oncogenic hazards of radiotherapy to the brain do not outweigh its therapeutic value in brain tumour. Images PMID:213536
Robinson, R G
The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem
Sheila K. Singh; Cynthia Hawkins; Ian D. Clarke; Jeremy A. Squire; Jane Bayani; Takuichiro Hide; R. Mark Henkelman; Michael D. Cusimano; Peter B. Dirks
Background Although rare, brain tumours represent one of the relatively larger groups of congenital neoplasias. Most studies on congenital neoplastic disease deal with several types of neoplasms and are dominated by leukaemias, retinoblastomas and systemic solid tumours. Few studies are dedicated to congenital brain tumours. We present nine newborns (four boys and five girls) who were diagnosed with congenital brain tumours
Henrik Carstensen; Marianne Juhler; Lars Bøgeskov; Henning Laursen
The last decade has witnessed unprecedented developments in the genetic and epigenetic analyses of solid tumours. Transcriptional and DNA copy-number studies have improved our understanding and classification of solid tumours and highlighted the patterns of genomic aberrations associated with outcome. The identification of altered transcriptional and translational silencing by microRNAs and epigenetic modification by methylation in tumours has showed a
C Swanton; C Caldas
Background: The purpose of this study is to evaluate the relationship between brain tumour location and core areas of cognitive and behavioural functioning for paediatric brain tumour survivors. The extant literature both supports and refutes an association between paediatric brain tumour location and neurocognitive outcomes. We examined…
Patel, S. K.; Mullins, W. A.; O'Neil, S. H.; Wilson, K.
A survey of brain tumours that had been diagnosed prenatally by foetal sonography yielded 89 cases. The most commonly found\\u000a tumour entities were teratomas (53.9%), glioblastomas (14.6%), lipomas (9.0%), plexus papillomas (7.9%) and craniopharyngiomas\\u000a (5.6%). The mean gestational age at ultrasound diagnosis was 30.0 weeks, ranging between 25.4 weeks in craniopharyngiomas\\u000a and 35.3 weeks in lipomas. Girls were more frequently
Christian H. Rickert
The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO ‘Blue Book’, the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide. PMID:17618441
Louis, David N.; Ohgaki, Hiroko; Wiestler, Otmar D.; Cavenee, Webster K.; Burger, Peter C.; Jouvet, Anne; Scheithauer, Bernd W.
Cognitive function, with survival and response on brain imaging, is increasingly regarded as an important outcome measure in patients with brain tumours. This measure provides us with information on a patient's clinical situation and adverse treatment effects. Radiotherapy has been regarded as the main cause of cognitive decline in these patients, because children with brain tumours can develop intellectual deterioration
Martin JB Taphoorn; Martin Klein
The normal gross and histological anatomy of the equine nasal and paranasal sinuses are reviewed and the relationships between the local anatomy, the occurrence of different tumour types, and of tumour spread are examined. The histological classification of the more common equine sinonasal tumours and tumour-like lesions are discussed. Clinical and pathological descriptions of 50 more recently recorded such tumours are separately tabulated. The literature shows that equine sinonasal tumours, both endemic and sporadic, are relatively uncommon in horses, with non-neoplastic growths such as maxillary (sinus) cysts, progressive ethmoid haematoma and inflammatory nasal polyps more commonly recorded. The equine paranasal sinuses, especially the caudal maxillary sinus, are the most common sites for sinonasal tumours and, in contrast to other species, primary nasal tumours are uncommon. The more common tumour types include squamous cell carcinoma that, in some cases, arise in the oral cavity and spread to the maxillary sinuses; adenocarcinomas; bone and dental tumours; fibrosarcomas and haemangiosarcomas. Except for some benign bone tumours, there are few records of successful treatment of equine sinonasal tumours. PMID:10328838
Head, K W; Dixon, P M
Brain MRI Classification using the Expectation Maximization made a brain magnetic resonance image (MRI) classification algorithm that uses a twostage applied to a set of normal brain MR images for further testing. We accomplished a working
The lifetime risk of patients with brain tumours to have focal epileptic seizures is 20?-?80?%. Based on current evidence the management of tumour-related seizures does not differ substantially from that applied to epilepsies from other aetiologies. Therefore, the choice of an anticonvulsant is based, above all, on tolerability and pharmacokinetic interactions with chemotherapeutic drugs. Levetiracetam is recommended by many authors as first-line therapy in brain tumour-related epilepsy; this corresponds with the recommendation of the German guidelines on the treatment of focal seizures of any aetiology. Based on current evidence, the prophylactic prescription of long-term antiepileptic drugs in brain tumour patients who have not presented with seizures is not justified. Because of the high risk of recurrence, however, antiepileptic treatment should be strongly considered after a single brain tumour-related seizure. PMID:25489755
Fröscher, W; Kirschstein, T; Rösche, J
Hepatic tumours in dogs have recently been re-classified to follow a revised human classification system that takes account of identified hepatic progenitor cells. This study investigated the presence and relative frequency of morphological types of feline primary hepatic neoplasms and aimed to determine whether a similar new classification scheme could be applied in cats. Feline primary liver tumours (n?=?61) were examined histologically and with a series of immunohistochemical markers. Six cases of nodular hyperplasia and 21 tumours of hepatocellular origin were diagnosed. The latter were subdivided into hepatocellular tumours that were well differentiated and had no evidence of metastases (n?=?18) and tumours that showed poorly differentiated areas with marked cellular and nuclear pleomorphism and had intrahepatic and, or, distant metastases (n?=?3). These malignant feline hepatocellular tumours maintained their hepatocellular characteristics (HepPar-1, MRP2, pCEA positive) and were negative, or only <5% positive, for K19. Twenty-five cholangiocellular tumours were diagnosed and all had intrahepatic and, or, distant metastases. Eight NSE positive small cell carcinomas (carcinoids) were diagnosed and subdivided into small cell carcinomas with HPC characteristics (K19 positive) and neuroendocrine carcinomas (K19 negative). In addition, one squamous cell carcinoma originating from the distal part of the choledochal duct was recognised. Feline primary hepatic neoplasms can be sub-divided into benign and malignant hepatocellular tumours, cholangiocellular carcinomas, small cell carcinomas with HPC characteristics, neuroendocrine carcinomas and squamous cell carcinomas. The marked species difference justifies a specific classification for feline primary hepatic neoplasms. PMID:25439443
van Sprundel, Renee G H M; van den Ingh, Ted S G A M; Guscetti, Franco; Kershaw, Olivia; van Wolferen, Monique E; Rothuizen, Jan; Spee, Bart
A survey of tumours derived from each of the four cell types of nasal epithelium is presented. Criticism is levelled at the adoption of additional terms for tissue types such as lympho-epithelium and transitional cell epithelium and tumours said to be derived from them. Electron microscopy is of assistance in classification particularly in the detection of evidence of keratin synthesis. The proposed classification of tumours of the nasal epithelium is: (1) Pseudostratified columnar epithelium: (a) papillary adenoma, (b) papillary carcinoma. (2) Squamous epithelium: (a) everted squamous papilloma, (b) inverted papilloma, (c) squamous carcinoma of any grade of differentiation from well differentiated to undifferentiated. (3) Melanocyte: malignant melanoma. (4) Olfactory neuroepithelium: olfactory neuroblastoma. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15Fig. 16Fig. 17Fig. 18Fig. 19Fig. 21Fig. 20 PMID:1197175
Michaels, L.; Hyams, V. J.
In a clinical pilot study radiofrequency echograms were acquired during routine echography of intraocular tumours. The data acquisition was performed with an "add-on" device, which was developed at our laboratory. The acquired data were pre-processed to remove the effects due to equipment performance and beam characteristics. The analysis was performed in the frequency domain (acoustospectrography) and acoustic tissue parameters like the attentuation coefficient and backscatter cross section estimated. In addition the gray level statistics of B-mode images were analysed. A set of parameters was thus obtained which was subjected to a discriminant analysis, based on a classification of the tumours by histology (i.e. after removal of the eyes). The results show a significant discriminability between different tumours and even between histological types of the same tumour (choroidal melanoma).
Romijn, R. L.; Thijssen, Johan M.
High-grade gliomas represent rapidly growing malignant brain tumours. Early diagnostics of this decease and immediately applied treatment entails better life prognosis for the patient. The goal of this work is to initialize the development of an automated tumour recognition method based on computed tomography images processing. The resulting method is aimed at early glioma diagnostics support by distinguishing between the
Z. Mÿeÿr ´ õnsky; A. Prochazka
During glioblastoma surgery, delineation of the brain tumour margins remains difficult especially since infiltrated and normal tissues have the same visual appearance. This problematic constitutes our research interest. We developed a fibre-optical fluorescence probe for spectroscopic and time domain measurements. First measurements of endogenous tissue fluorescence were performed on fresh and fixed rat tumour brain slices. Spectral characteristics, fluorescence redox ratios and fluorescence lifetime measurements were analysed. Fluorescence information collected from both, lifetime and spectroscopic experiments, appeared promising for tumour tissue discrimination. Two photon measurements were performed on the same fixed tissue. Different wavelengths are used to acquire two-photon excitation-fluorescence of tumorous and healthy sites.
Abi Haidar, D.; Leh, B.; Allaoua, K.; Genoux, A.; Siebert, R.; Steffenhagen, M.; Peyrot, D.; Sandeau, N.; Vever-Bizet, C.; Bourg-Heckly, G.; Chebbi, I.; Collado-Hilly, M.
Background Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective To investigate the long-term effect of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort. Methods During 1993–1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced residential addresses from 1 January 1971 until 31 December 2009 and calculated radon concentrations at each address using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and 95% confidence intervals (CI) for the risk of primary brain tumours associated with residential radon exposure with adjustment for age, sex, occupation, fruit and vegetable consumption and traffic-related air pollution. Effect modification by air pollution was assessed. Results Median estimated radon was 40.5 Bq/m3. The adjusted IRR for primary brain tumour associated with each 100 Bq/m3 increment in average residential radon levels was 1.96 (95% CI: 1.07; 3.58) and this was exposure-dependently higher over the four radon exposure quartiles. This association was not modified by air pollution. Conclusions We found significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies. PMID:24066143
Bräuner, Elvira V.; Andersen, Zorana J.; Andersen, Claus E.; Pedersen, Camilla; Gravesen, Peter; Ulbak, Kaare; Hertel, Ole; Loft, Steffen; Raaschou-Nielsen, Ole
Iodine-125 brachytherapy has been applied to brain tumours since 1979. Even though the physical and biological characteristics make these implants particularly attractive for minimal invasive treatment, the place for stereotactic brachytherapy is still poorly defined. An extensive review of the literature has been performed, especially concerning indications, results and complications. Iodine-125 seeds have been implanted in astrocytomas I-III, glioblastomas, metastases and several other tumour entities. Outcome data given in the literature are summarized. Complications are rare in carefully selected patients. All in all, for highly selected patients with newly diagnosed or recurrent primary or metastatic tumours, this method provides encouraging survival rates with relatively low complication rates and a good quality of life. PMID:22394548
Solitary fibrous tumour (SFT) is a mesenchymal neoplasm of subendothelial origin that can be found in all anatomical locations, but rarely in the lungs. A 71-year old female was referred to our hospital because of the increase in size of a solitary pulmonary mass. Chest contrast-enhanced dynamic computed tomography showed a well-circumscribed lobulated mass measuring 3.1×1.6 cm in the posterior segment of the right upper lobe of the lung. Positron emission tomography with 18F-fluorodeoxyglucose (FDG) demonstrated that the mass had high FDG uptake. A right upper lobectomy of the lung and mediastinal lymphadenectomy were performed. The tumour was pathologically diagnosed as an SFT. Seven months later, the patient was found to have brain metastases of the tumour, which led to dizziness. A craniotomy and successive radiosurgery with a gamma knife were performed for the metastatic tumours. She is still alive without evidence of disease 12 months after the treatment of the metastases. Pulmonary SFT seldom behaves aggressively, and only two previous cases of primary pulmonary SFT with brain metastases have been reported. Local therapy including surgery and radiotherapy against metastases from SFT could help improve the survival of such patients. PMID:23711464
Ozeki, Naoki; Kawaguchi, Koji; Taniguchi, Tetsuo; Yokoi, Kohei
We review six cases of primary brain tumours with an initial manifestation of symptoms during pregnancy. Three patients presented with epileptic seizures, two with progressive motor disturbance, and one with visual disturbance. Three patients were diagnosed as harbouring brain tumours at 20–25 weeks of pregnancy, while the remaining three were diagnosed at 36–38 weeks of pregnancy. The tumours consisted of
Shunji Nishio; Takato Morioka; Satoshi Suzuki; Iwao Takeshita; Kiyonobu Ikezaki; Masashi Fukui; Hitoo Nakano
ASHRAF ELSAYED et al.: MRI BRAIN SCAN CLASSIFICATION 1 MRI Brain Scan Classification According Magnetic Resonance Image (MRI) brain scans ac- cording to the nature of the corpus callosum are described. The first mechanism adopts an approach founded on the concept of graph mining whereby MRI scans
OBJECTIVES—Brain tumours cause considerable concern due to a high mortality and there are increasing efforts to provide adequate care, sometimes outside hospitals. Health care utilisation, direct costs of care, and the indirect social cost of morbidity and early mortality caused by brain tumours in Sweden in the year 1996 was analysed.?METHODS—Quantification of ambulatory care, care in hospital, long term and palliative/terminal care, drug consumption, temporary as well as long term morbidity, and mortality from comprehensive national data sources. Direct costs were calculated using 1996charges. Indirect costs were calculated by sex and age specific salaries. A sensitivity analysis considered the impact of alternative estimates of each item.?RESULTS—Indirect costs were 75% of the total and were caused mainly by early mortality. Direct costs were predominantly for care in hospital, long term care, and home health care. Among direct costs, astrocytomas III-IV and meningiomas accounted for 42% and 30% respectively.?CONCLUSIONS—The cost of illness from brain tumours reflects the characteristics of these malignancies. Despite their low incidence rate, the economic impact caused by high mortality among young persons is a predominant trait. Costs of acute hospital care and also long term care and home care are considerable.?? PMID:11080235
Blomqvist, P; Lycke, J; Strang, P; Tornqvist, H; Ekbom, A
The brain is highly vulnerable to neurotoxic agents during the prime learning period of a child's life. Paediatric patients with brain tumours who are treated with cranial radiation therapy (CRT) often go on to develop neurocognitive deficits, which are reflected in poor academic achievement and impaired memory, attention and processing speed. The extent of these delayed effects varies with radiation dose, brain volume irradiated, and age at treatment, and might also be influenced by genetic factors and individual susceptibility. CRT-induced impairment involves axonal damage and disruption of white matter growth, and can affect brain structures implicated in memory function and neurogenesis, such as the hippocampus. In this article, we review the underlying mechanisms and clinical consequences of CRT-induced neurocognitive damage in survivors of paediatric brain tumours. We discuss the recent application of neuroimaging technologies to identify white matter injury following CRT, and highlight new radiation techniques, pharmacological and neurological interventions, as well as rehabilitation programmes that have potential to minimize neurocognitive impairment following CRT. PMID:22964509
Padovani, Laetitia; André, Nicolas; Constine, Louis S; Muracciole, Xavier
Pituitary tumours, the most frequent intracranial tumour, are historically considered benign. However, various pieces of clinical evidence and recent advances in pathological and molecular analyses suggest the need to consider these tumours as more than an endocrinological disease, despite the low incidence of metastasis. Recently, we proposed a new prognostic clinicopathological classification of these pituitary tumours, according to the tumour size (micro, macro and giant), type (prolactin, GH, FSH/LH, ACTH and TSH) and grade (grade 1a, non-invasive; 1b, non-invasive and proliferative; 2a, invasive; 2b, invasive and proliferative and 3, metastatic). In addition to this classification, numerous molecular prognostic markers have been identified, allowing a better characterisation of tumour behaviour and prognosis. Moreover, clinical and preclinical studies have demonstrated that pituitary tumours could be treated by some chemotherapeutic drugs or new targeted therapies. Our improved classification of these tumours should now allow the identification of prognosis markers and help the clinician to propose personalised therapies to selected patients presenting tumours with a high risk of recurrence. PMID:24431196
Raverot, Gerald; Jouanneau, Emmanuel; Trouillas, Jacqueline
TUMOUR progression is a fundamental feature of the biology of cancer1. Cancers do not arise de novo in their final form, but begin as small, indolent growths, which gradually acquire characteristics associated with malignancy. In the brain, for example, low-grade tumours (astrocytomas) evolve into faster growing, more dysplastic and invasive high-grade tumours (glioblastomas)2,3. To define the genetic events underlying brain
David Sidransky; Tom Mikkelsen; Karl Schwechheimer; Mark L. Rosenblum; Web Cavanee; Bert Vogelstein
Aldehyde dehydrogenase (ALDH) has been identified in stem cells from both normal and cancerous tissues. This study aimed to evaluate the potential of ALDH as a universal brain tumour initiating cell (BTIC) marker applicable to primary brain tumours and their biological role in maintaining stem cell status. Cells from various primary brain tumours (24paediatric and 6 adult brain tumours) were stained with Aldefluor and sorted by flow cytometry. We investigated the impact of ALDH expression on BTIC characteristics in vitro and on tumourigenic potential in vivo. Primary brain tumours showed universal expression of ALDH, with 0.3-28.9% of the cells in various tumours identified as ALDH(+). The proportion of CD133(+) cells within ALDH(+) is higher than ALDH cells. ALDH(+) cells generate neurospheres with high proliferative potential, express neural stem cell markers and differentiate into multiple nervous system lineages. ALDH(+) cells tend to show high expression of induced pluripotent stem cell-related genes. Notably, targeted knockdown of ALDH1 by shRNA interference in BTICs potently disturbed their self-renewing ability. After 3months, ALDH(+) cells gave rise to tumours in 93% of mice whereas ALDH cells did not. The characteristic pathology of mice brain tumours from ALDH(+) cells was similar to that of human brain tumours, and these cells are highly proliferative in vivo. Our data suggest that primary brain tumours contain distinct subpopulations of cells that have high expression levels of ALDH and BTIC characteristics. ALDH might be a potential therapeutic target applicable to primary brain tumours. PMID:24103144
Choi, Seung Ah; Lee, Ji Yeoun; Phi, Ji Hoon; Wang, Kyu-Chang; Park, Chul-Kee; Park, Sung-Hye; Kim, Seung-Ki
This article presents a dosimetric investigation of boron neutron capture therapy (BNCT) combined with (252)Cf brachytherapy for brain tumour control. The study was conducted through computational simulation in MCNP5 code, using a precise and discrete voxel model of a human head, in which a hypothetical brain tumour was incorporated. A boron concentration ratio of 1:5 for healthy-tissue: tumour was considered. Absorbed and biologically weighted dose rates and neutron fluency in the voxel model were evaluated. The absorbed dose rate results were exported to SISCODES software, which generates the isodose surfaces on the brain. Analyses were performed to clarify the relevance of boron concentrations in occult infiltrations far from the target tumour, with boron concentration ratios of 1:1 up to 1:50 for healthy-tissue:infiltrations and healthy-tissue:tumour. The average biologically weighted dose rates at tumour area exceed up to 40 times the surrounding healthy tissue dose rates. In addition, the biologically weighted dose rates from boron have the main contribution at the infiltrations, especially far from primary tumour. In conclusion, BNCT combined with (252)Cf brachytherapy is an alternative technique for brain tumour treatment because it intensifies dose deposition at the tumour and at infiltrations, sparing healthy brain tissue. PMID:21705767
Brandão, Sâmia F; Campos, Tarcísio P R
The 4(th) edition of the WHO Classification of Tumours of the Nervous System (WHO 2007) introduces changes that reflect both the recognition of new brain tumour types and a better understanding of neoplastic behavior. Three new tumours, angiocentric glioma (AG), pilomyxoid astrocytoma (PMA), and pituicytoma are added to the section on gliomas. AG is a slowly growing cerebral tumour that typically presents with seizures in children and young adults. It is characterized by monomorphous, bipolar tumour cells with a striking perivascular growth pattern. Although the 'cell of origin' of AG is not clear, ultrastructural evidence points to an ependymal derivation. Typically, AG can be cured by total resection, and is designated WHO grade I. PMA is a solid, circumscribed tumour occurring mainly in the hypothalamic region of young children. It is composed of a monomorphous population of bipolar tumour cells within a rich myxoid background, with a conspicuous anglocentric arrangement. While PMA is considered a more aggressive variant of pilocytic astrocytoma, this relationship awaits further clarification. The PMA has been designated WHO grade II. The pituicytoma, involves the posterior pituitary and/or its stalk and affects adults. It is solid in architecture, composed of spindle cells and presumably derived from pituicytes. Pituicytomas are indolent tumours, and are designated WHO grade I. PMID:17598825
Brat, Daniel J; Scheithauer, Bernd W; Fuller, Gregory N; Tihan, Tarik
Clinical experience suggests that application of the fundamental principles of rehabilitation medicine can improve the care of patients with cancer. Despite the high incidence of neurological and functional deficits in patients affected by brain tumours (BTs), rehabilitation treatment of this population is not as well established as it is for patients with other neurological conditions. To assess functional outcome in brain tumour inpatients who underwent early rehabilitation after surgery. 75 patients who had undergone neurosurgery for primary BTs and 75 patients affected by stroke were enrolled in a case-control study. All patients were evaluated by means of a core set of clinical scales (Functional Independence Measure, Sitting Balance score, Standing Balance score, Hauser Index, Massachusetts General Hospital Functional Ambulation Classification). Patients were evaluated before the beginning (T0) and at the end (T1) of rehabilitation treatment. The neurorehabilitation programme consisted of individual 60-min sessions of treatment, administered once a day, six days a week, for four consecutive weeks. Speech therapy was included when aphasia was diagnosed. All the measures of outcome were indicative of substantial improvements for neuro-oncological and for stroke patients (P = 0.000). Analysis of subgroups showed that patients affected by meningioma achieved better results (in efficiency terms) as regards independence in activities of daily living (P = 0.02) and mobility (P = 0.04) compared with patients affected by glioblastoma or stroke. Rehabilitation after surgery can improve functional outcome, justifying the delivery of rehabilitation services, even during the acute phase, to BTs inpatients, irrespective of tumour type. PMID:22124725
Bartolo, Michelangelo; Zucchella, Chiara; Pace, Andrea; Lanzetta, Gaetano; Vecchione, Carmine; Bartolo, Marcello; Grillea, Giovanni; Serrao, Mariano; Tassorelli, Cristina; Sandrini, Giorgio; Pierelli, Francesco
A young person presents with a highly malignant brain tumour with hemiparesis and limited prognosis after resection. She then suffers an iatrogenic cardiac and respiratory arrest that results in profound anoxic encephalopathy. A difference in opinion between the treatment team and the parent is based on a question of futile therapy. Opinions from five intensivists from around the world explore the differences in ethical and legal issues. A Physician-ethicist comments on the various approaches. PMID:15312199
Gunn, Scott; Hashimoto, Satoru; Karakozov, Michael; Marx, Thomas; Tan, Ian KS; Thompson, Dan R; Vincent, Jean-Louis
Random Forest Classification for Training a Brain Computer Interface (BCI) Abstract1 Brain brain activity. Most3 existing BCIs detect specific mental activity in a so-called synchronous4 paradigm extraction7 followed by a classification scheme to detect intentions from the brain8 signal. In this paper
de Freitas, Nando
OBJECTIVE—To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours.?METHODS—Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation—that is, movements of the paretic hand activated predominately the ipsilateral cortex. Brain activation was achieved with a flexion extension of the fingers. Statistical parametric activation was obtained using a t test and a threshold of p<0.001. These patients, candidates for tumour resection, also underwent cortical intraoperative stimulation that was correlated to the fMRI spatial data using three dimensional reconstructions of the brain. Three patients also had postoperative control fMRI.?RESULTS—The absence of fMRI activation of the primary sensorimotor cortex normally innervating the paretic hand for the threshold chosen, was correlated with completely negative cortical responses of the cortical hand area during the operation. The preoperative fMRI activation of these patients predominantly found in the ipsilateral frontal and primary sensorimotor cortices could be related to the residual ipsilateral hand function. Postoperatively, the fMRI activation returned to more classic patterns of activation, reflecting the consequences of therapy.?CONCLUSION—In paretic patients with brain tumours, ipsilateral control could be implicated in the residual hand function, when the normal primary pathways are impaired. The possibility that functional tissue still remains in the peritumorous sensorimotor cortex even when the preoperative fMRI and the cortical intraoperative stimulations are negative, should be taken into account when planning the tumour resection and during the operation.?? PMID:10990503
Roux, F; Boulanouar, K; Ibarrola, D; Tremoulet, M; Chollet, F; Berry, I
Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants.
Jain, Anjana; Betancur, Martha; Patel, Gaurangkumar D.; Valmikinathan, Chandra M.; Mukhatyar, Vivek J.; Vakharia, Ajit; Pai, S. Balakrishna; Brahma, Barunashish; MacDonald, Tobey J.; Bellamkonda, Ravi V.
Young children with malignant brain tumours have particularly poor survival and manifest severe sequelae of radiation therapy. A multi-institutional pilot study of post-operative primary chemotherapy for children under 3 years with primitive neuroectodermal tumours (PNET) or ependymoma was initiated in 1987. The chemotherapy protocol comprised earboplatin, vincristine and the “eight drugs in 1 day” regimen. Radiation was recommended only if
Les White; Heather Johnston; Robert Jones; Hedy Mameghan; Vim Nayanar; William McWhirter; Stuart Kellie; Keith Waters; Ian Toogood
Adaptive Multi-class classification for Brain Computer Interfaces 1 . A. Llera, V. GÂ´omez, H. J. email@example.com Keywords: Brain computer interfaces, adaptive classification, unsupervised data from different subjects. 1 Introduction Brain computer interfaces (BCI) (Vidal, 1973) aim
Background and objectives: Brain tumours responsible for longstanding partial epilepsy are characterised by a high prevalence of dysembryoplastic neuroepithelial tumour (DNT), whose natural evolution is much more benign than that of gliomas. The preoperative diagnosis of DNT, which is not yet feasible on the basis of available clinical and imaging data, would help optimise the therapeutic strategy for this type of tumour. This study tested whether [11C]-methionine positron emission tomography (MET-PET) could help to distinguish DNTs from other epileptogenic brain tumours. Methods: Prospective study of 27 patients with partial epilepsy of at least six months duration related to a non-rapidly progressing brain tumour on magnetic resonance imaging (MRI). A structured visual analysis, which distinguished between normal, moderately abnormal, or markedly abnormal tumour methionine uptake, as well as various regions of interest and semiquantitative measurements were conducted. Results: Pathological results showed 11 DNTs (41%), 5 gangliogliomas (18%), and 11 gliomas (41%). MET-PET visual findings significantly differed between the various tumour types (p<0.0002), regardless of gadolinium enhancement on MRI, and were confirmed by semiquantitative analysis (p<0.001 for all calculated ratios). All gliomas and gangliogliomas were associated with moderately or markedly increased tumour methionine uptake, whereas 7/11 DNTs had a normal methionine uptake, including all six located in the mesiotemporal structures. No DNT presented with a marked MET-PET abnormality. Conclusion: Normal MET-PET findings in patient with an epileptogenic and non-rapidly progressing brain tumour are suggestive of DNT, whereas a markedly increased tumour methionine uptake makes this diagnosis unlikely. PMID:16291894
Rosenberg, D; Demarquay, G; Jouvet, A; Le Bars, D; Streichenberger, N; Sindou, M; Kopp, N; Mauguiere, F; Ryvlin, P
The most common initial treatment received by patients with a brain tumour is surgical removal of the growth. Precise histopathological diagnosis of brain tumours is to some extent subjective. Furthermore, currently available diagnostic imaging techniques to delineate the excision border during cytoreductive surgery lack the required spatial precision to aid surgeons. We set out to determine whether infrared (IR) and/or Raman spectroscopy combined with multivariate analysis could be applied to discriminate between normal brain tissue and different tumour types (meningioma, glioma and brain metastasis) based on the unique spectral “fingerprints” of their biochemical composition. Formalin-fixed paraffin-embedded tissue blocks of normal brain and different brain tumours were de-waxed, mounted on low-E slides and desiccated before being analyzed using attenuated total reflection Fourier-transform IR (ATR-FTIR) and Raman spectroscopy. ATR-FTIR spectroscopy showed a clear segregation between normal and different tumour subtypes. Discrimination of tumour classes was also apparent with Raman spectroscopy. Further analysis of spectral data revealed changes in brain biochemical structure associated with different tumours. Decreased tentatively-assigned lipid-to-protein ratio was associated with increased tumour progression. Alteration in cholesterol esters-to-phenylalanine ratio was evident in grade IV glioma and metastatic tumours. The current study indicates that IR and/or Raman spectroscopy have the potential to provide a novel diagnostic approach in the accurate diagnosis of brain tumours and have potential for application in intra-operative diagnosis. PMID:24098310
Gajjar, Ketan; Heppenstall, Lara D.; Pang, Weiyi; Ashton, Katherine M.; Trevisan, Júlio; Patel, Imran I.; Llabjani, Valon; Stringfellow, Helen F.; Martin-Hirsch, Pierre L.; Dawson, Timothy; Martin, Francis L.
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. PMID:25268364
Libard, Sylwia; Popova, Svetlana N.; Amini, Rose-Marie; Kärjä, Vesa; Pietiläinen, Timo; Hämäläinen, Kirsi M.; Sundström, Christer; Hesselager, Göran; Bergqvist, Michael; Ekman, Simon; Zetterling, Maria; Smits, Anja; Nilsson, Pelle; Pfeifer, Susan; de Ståhl, Teresita Diaz; Enblad, Gunilla; Ponten, Fredrik; Alafuzoff, Irina
The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named ‘Immunoscore’ has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune). © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:24122236
Galon, Jérôme; Mlecnik, Bernhard; Bindea, Gabriela; Angell, Helen K; Berger, Anne; Lagorce, Christine; Lugli, Alessandro; Zlobec, Inti; Hartmann, Arndt; Bifulco, Carlo; Nagtegaal, Iris D; Palmqvist, Richard; Masucci, Giuseppe V; Botti, Gerardo; Tatangelo, Fabiana; Delrio, Paolo; Maio, Michele; Laghi, Luigi; Grizzi, Fabio; Asslaber, Martin; D'Arrigo, Corrado; Vidal-Vanaclocha, Fernando; Zavadova, Eva; Chouchane, Lotfi; Ohashi, Pamela S; Hafezi-Bakhtiari, Sara; Wouters, Bradly G; Roehrl, Michael; Nguyen, Linh; Kawakami, Yutaka; Hazama, Shoichi; Okuno, Kiyotaka; Ogino, Shuji; Gibbs, Peter; Waring, Paul; Sato, Noriyuki; Torigoe, Toshihiko; Itoh, Kyogo; Patel, Prabhu S; Shukla, Shilin N; Wang, Yili; Kopetz, Scott; Sinicrope, Frank A; Scripcariu, Viorel; Ascierto, Paolo A; Marincola, Francesco M; Fox, Bernard A; Pagès, Franck
Transformed, oncogenic precursors, possessing both defining neural-stem-cell properties and the ability to initiate intracerebral tumours, have been identified in human brain cancers. Here we report that bone morphogenetic proteins (BMPs), amongst which BMP4 elicits the strongest effect, trigger a significant reduction in the stem-like, tumour-initiating precursors of human glioblastomas (GBMs). Transient in vitro exposure to BMP4 abolishes the capacity of
S. G. M. Piccirillo; B. A. Reynolds; N. Zanetti; G. Lamorte; E. Binda; G. Broggi; H. Brem; A. Olivi; F. Dimeco; A. L. Vescovi
Lactate, a by-product of glycolysis, is an indicator of poor tissue perfusion and is a useful biomarker with prognostic value in risk-stratifying patients in several diseases. Furthermore, elevated lactate production is observed in tumour glycolysis, also known as the Warburg effect, and is essential in promoting tumour cell invasion, metastasis, and immune system evasion, promoting resistance to cell death. However, there are no studies of elevated serum lactate in brain tumour patients as a potential biomarker, to our knowledge. The aim of this study is to determine possible correlations between the malignancy of tumours and pre- and intraoperative serum lactate elevation in patients undergoing craniotomy for tumour resection. We provide initial evidence that a rise in serum lactate can be used as a non-invasive biomarker that correlates with brain tumour grade. The results from this study and future prospective studies may allow for determination of tumour progression and response to therapy using serum lactate as a biomarker. PMID:25172017
Mariappan, Ramamani; Venkatraghavan, Lashmi; Vertanian, Alenoush; Agnihotri, Sameer; Cynthia, Shalini; Reyhani, Sareh; Tung, Takyee; Khan, Osaama H; Zadeh, Gelareh
Objectives Comparison of redox conditions in malignant and benign tumours is essential for understanding the role of reactive oxygen species in the pathophysiology of aggressive cancer profiles. Here we compare antioxidative systems in highly malignant brain tumour - glioblastoma multiforme (GBM), and in meningioma, a benign brain tumour. Methods Tumour tissues and blood of 67 GBM patients (mean age: 52.9 ± 11.5 years) and 67 meningioma patients (59.2 ± 10.2 years), and blood of 30 control subjects (50.8 ± 12.79 years) were analysed via biochemical assays. Results Components of glutathione system, which is responsible for H2O2 removal, showed lower activity/level in GBM: glutathione peroxidase (GBM: 9.90 ± 0.22; meningioma: 11.78 ± 0.23 U/mg of proteins; P < 0.001), glutathione reductase (GBM: 3.83 ± 0.13; meningioma: 4.67 ± 0.11 U/mg of proteins; P < 0.001), and glutathione (GBM: 6.70 ± 0.12; meningioma: 7.58 ± 0.14 ?mol/g of tissue; P < 0.001). In contrast, the rank order of glutathione reductase activity and glutathione level in erythrocytes was: GBM > meningioma > control. Superoxide dismutase and catalase activities were lower in the blood of cancer patients compared to controls. Discussion Cells of malignant brain tumour show down-regulated antioxidative system which might result in increased levels of H2O2 compared to benign tumour tissue. PMID:25247681
Bogosavljevi?, Vojislav; Baj?eti?, Milica; Spasojevi?, Ivan
Objective To describe the use of temozolomide (tmz) in Canadian children treated for brain tumours and to evaluate survival and predictors of survival for children treated with this agent. Methods A survey was conducted within the Canadian Paediatric Brain Tumour Consortium (cpbtc), a group of tertiary care centres in pediatric neuro-oncology (n = 16) in Canada that are involved in the treatment of children with central nervous system tumours. Results In 10 of the 16 participating pediatric oncology centres of the cpbtc, 137 children with brain tumours were treated with tmz between January 2000 and March 2006. Although 33% of the children were enrolled into a clinical trial, 67% were treated outside open studies. Most patients (72%) received tmz treatment on recurrence of their brain tumour (first or subsequent). The most commonly administered regimen was single-agent tmz 150–200 mg/m2 administered on 5 consecutive days every 28 days. The median duration of tmz treatment was 141 days (range: 4–1102 days). Response data were provided for 127 of the 137 patients, of whom 6 showed a complete response. Sixteen patients experienced a minor or partial response, 53 had stable disease, and 52 had progressive disease. Of 32 patients alive at last follow-up, 19 had a diagnosis of low-grade glioma. Conclusions Temozolomide is used in a variety of pediatric brain tumours, often at the time of recurrence. The lack of insight into clear indications for this agent in pediatric brain tumours—used either alone or in combination therapy—may be a result of suboptimal design of phase i and ii studies and a lack of phase iii trials in the pediatric brain tumour population. PMID:21331268
Bartels, U.; Baruchel, S.; Carret, A.S.; Crooks, B.; Hukin, J.; Johnston, D.; Silva, M.; Strother, D.; Wilson, B.; Zelcer, S.; Eisenstat, D.; Sung, L.; Bouffet, E.
In this paper a novel framework for brain classification is proposed in the context of mental health research. A learning by example method is introduced by combining local measurements with non linear Support Vector Machine. Instead of considering a voxel-by-voxel comparison between patients and controls, we focus on landmark points which are characterized by local region descriptors, namely Scale Invariance Feature Transform (SIFT). Then, matching is obtained by introducing the local kernel for which the samples are represented by unordered set of features. Moreover, a new weighting approach is proposed to take into account the discriminative relevance of the detected groups of features. Experiments have been performed including a set of 54 patients with schizophrenia and 54 normal controls on which region of interest (ROI) have been manually traced by experts. Preliminary results on Dorso-lateral PreFrontal Cortex (DLPFC) region are promising since up to 75% of successful classification rate has been obtained with this technique and the performance has improved up to 85% when the subjects have been stratified by sex.
Castellani, U.; Rossato, E.; Murino, V.; Bellani, M.; Rambaldelli, G.; Tansella, M.; Brambilla, P.
The inference of transcriptional networks that regulate transitions into physiological or pathological cellular states remains a central challenge in systems biology. A mesenchymal phenotype is the hallmark of tumour aggressiveness in human malignant glioma, but the regulatory programs responsible for implementing the associated molecular signature are largely unknown. Here we show that reverse-engineering and an unbiased interrogation of a glioma-specific
Maria Stella Carro; Wei Keat Lim; Mariano Javier Alvarez; Robert J. Bollo; Xudong Zhao; Evan Y. Snyder; Erik P. Sulman; Sandrine L. Anne; Fiona Doetsch; Howard Colman; Anna Lasorella; Ken Aldape; Andrea Califano; Antonio Iavarone
ADAPTIVE CLASSIFICATION OF MENTAL STATES FOR ASYNCHRONOUS BRAIN COMPUTER INTERFACES Jean Le Pavec.Clerc@sophia.inria.fr ABSTRACT Brain Computers Interfaces (BCI) are emerging as a new means of communication, aiming to make by a subject using support vector machines (SVM). KEYWORDS brain computer interfaces, electroencephalography
Paris-Sud XI, UniversitÃ© de
Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants. PMID:24531400
Jain, Anjana; Betancur, Martha; Patel, Gaurangkumar D; Valmikinathan, Chandra M; Mukhatyar, Vivek J; Vakharia, Ajit; Pai, S Balakrishna; Brahma, Barunashish; MacDonald, Tobey J; Bellamkonda, Ravi V
Diet and lifestyle produce major effects on tumour incidence, prevalence, and natural history. Moderate dietary restriction has long been recognised as a natural therapy that improves health, promotes longevity, and reduces both the incidence and growth of many tumour types. Dietary restriction differs from fasting or starvation by reducing total food and caloric intake without causing nutritional deficiencies. No prior studies have evaluated the responsiveness of malignant brain cancer to dietary restriction. We found that a moderate dietary restriction of 30–40% significantly inhibited the intracerebral growth of the CT-2A syngeneic malignant mouse astrocytoma by almost 80%. The total dietary intake for the ad libitum control group (n=9) and the dietary restriction experimental group (n=10) was about 20 and 13?Kcal?day?1, respectively. Overall health and vitality was better in the dietary restriction-fed mice than in the ad libitum-fed mice. Tumour microvessel density (Factor VIII immunostaining) was two-fold less in the dietary restriction mice than in the ad libitum mice, whereas the tumour apoptotic index (TUNEL assay) was three-fold greater in the dietary restriction mice than in the ad libitum mice. CT-2A tumour cell-induced vascularity was also less in the dietary restriction mice than in the ad libitum mice in the in vivo Matrigel plug assay. These findings indicate that dietary restriction inhibited CT-2A growth by reducing angiogenesis and by enhancing apoptosis. Dietary restriction may shift the tumour microenvironment from a proangiogenic to an antiangiogenic state through multiple effects on the tumour cells and the tumour-associated host cells. Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers. British Journal of Cancer (2002) 86, 1615–1621. DOI: 10.1038/sj/bjc/6600298 www.bjcancer.com © 2002 Cancer Research UK PMID:12085212
Mukherjee, P; El-Abbadi, M M; Kasperzyk, J L; Ranes, M K; Seyfried, T N
Objective: To investigate verbally administered Barthel Index asa measure of functional status in patients withhigh grade gliomas. Background: Barthel Index (BI) isa performance score of activities of daily livingwhich has been validated in patients with neurologicaldisability. While any assessment of quality of lifein brain tumour patients should include all theaspects of CNS function we concentrated on measurementof physical performance status
L. Brazil; R. Thomas; R. Laing; F. Hines; D. Guerrero; S. Ashley; M. Brada
Microbeam radiation therapy (MRT) is an experimental radiotherapy concept that has been primarily developed for the treatment of malignant brain tumours. MRT uses high flux synchrotron x-rays delivered as an array of parallel microbeams in high doses of irradiation in fractions of seconds. The aims of this study were to 1) investigate the induction of bystander effects after normal and
The inference of transcriptional networks that regulate transitions into physiological or pathological cellular states remains a central challenge in systems biology. A mesenchymal phenotype is the hallmark of tumour aggressiveness in human malignant glioma, but the regulatory programs responsible for implementing the associated molecular signature are largely unknown. Here we show that reverse-engineering and an unbiased interrogation of a glioma-specific regulatory network reveal the transcriptional module that activates expression of mesenchymal genes in malignant glioma. Two transcription factors (C/EBPbeta and STAT3) emerge as synergistic initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBPbeta and STAT3 reprograms neural stem cells along the aberrant mesenchymal lineage, whereas elimination of the two factors in glioma cells leads to collapse of the mesenchymal signature and reduces tumour aggressiveness. In human glioma, expression of C/EBPbeta and STAT3 correlates with mesenchymal differentiation and predicts poor clinical outcome. These results show that the activation of a small regulatory module is necessary and sufficient to initiate and maintain an aberrant phenotypic state in cancer cells. PMID:20032975
Carro, Maria Stella; Lim, Wei Keat; Alvarez, Mariano Javier; Bollo, Robert J; Zhao, Xudong; Snyder, Evan Y; Sulman, Erik P; Anne, Sandrine L; Doetsch, Fiona; Colman, Howard; Lasorella, Anna; Aldape, Ken; Califano, Andrea; Iavarone, Antonio
Objects Radiation-induced cerebral tumours constitute a significant risk for subjects undergoing radiotherapy for the management of\\u000a cerebral neoplasms. Age-related cerebral vulnerability could be a specific factor in the genesis of these complications.\\u000a \\u000a \\u000a \\u000a Methods The pertinent literature of both paediatric and adult series has been reviewed. Three personal cases were added.\\u000a \\u000a \\u000a \\u000a Results One hundred forty-two paediatric second brain tumours were evaluated. Out of them,
Benedetta Ludovica Pettorini; Young-Soo Park; Massimo Caldarelli; Luca Massimi; Gianpiero Tamburrini; Concezio Di Rocco
The applicability and limitations of a photodynamic threshold model, used to describe quantitatively the in vivo response of tissues to photodynamic therapy, are currently being investigated in a variety of normal and malignant tumour tissues. The model states that tissue necrosis occurs when the number of photons absorbed by the photosensitiser per unit tissue volume exceeds a threshold. New Zealand White rabbits were sensitised with porphyrin-based photosensitisers. Normal brain or intracranially implanted VX2 tumours were illuminated via an optical fibre placed into the tissue at craniotomy. The light fluence distribution in the tissue was measured by multiple interstitial optical fibre detectors. The tissue concentration of the photosensitiser was determined post mortem by absorption spectroscopy. The derived photodynamic threshold values for normal brain are significantly lower than for VX2 tumour for all photosensitisers examined. Neuronal damage is evident beyond the zone of frank necrosis. For Photofrin the threshold decreases with time delay between photosensitiser administration and light treatment. No significant difference in threshold is found between Photofrin and haematoporphyrin derivative. The threshold in normal brain (grey matter) is lowest for sensitisation by 5 delta-aminolaevulinic acid. The results confirm the very high sensitivity of normal brain to porphyrin photodynamic therapy and show the importance of in situ light fluence monitoring during photodynamic irradiation. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8562339
Lilge, L.; Olivo, M. C.; Schatz, S. W.; MaGuire, J. A.; Patterson, M. S.; Wilson, B. C.
Brain connectivity network has been used for diagnosis and classification of neurodegenerative diseases, such as Alzheimer's disease (AD) as well as its early stage, i.e., mild cognitive impairment (MCI). However, conventional connectivity network is usually constructed based on the pairwise correlation among brain regions and thus ignores the higher-order relationship among them. Such information loss is unexpected because the brain itself is a complex network and the higher-order interaction may contain useful information for classification. Accordingly, in this paper, we propose a new brain connectivity hyper-network based method for MCI classification. Here, the connectivity hyper-network denotes a network where an edge can connect more than two brain regions, which can be naturally represented with a hyper-graph. Specifically, we first construct connectivity hyper-networks from the resting-state fMRI time series using sparse representation modeling. Then, we extract three sets of the brain-region specific features from the connectivity hyper-networks, and exploit a manifold regularized multi-task feature selection method to jointly select the most discriminative features. Finally, we use multi-kernel support vector machine (SVM) for classification. The experimental results demonstrate the efficacy of our proposed method for MCI classification with comparison to the conventional connectivity network based methods. PMID:25485444
Jie, Biao; Shen, Dinggang; Zhang, Daoqiang
The survival outcome of patients suffering from gliomas is directly linked to the complete surgical resection of the tumour. To help the surgeons to delineate precisely the boundaries of the tumour, we developed an intraoperative positron probe with background noise rejection capability. The probe was designed to be directly coupled to the excision tool such that detection and removal of the radiolabelled tumours could be simultaneous. The device consists of two exchangeable detection heads composed of clear and plastic scintillating fibres. Each head is coupled to an optic fibre bundle that exports the scintillating light to a photodetection and processing electronic module placed outside the operative wound. The background rejection method is based on a real-time subtraction technique. The measured probe sensitivity for 18F was 1.1 cps kBq-1 ml-1 for the small head and 3.4 cps kBq-1 ml-1 for the large head. The mean spatial resolution was 1.6 mm FWHM on the detector surface. The ?-ray rejection efficiency measured by realistic brain phantom modelling of the surgical cavity was 99.4%. This phantom also demonstrated the ability of the probe to detect tumour discs as small as 5 mm in diameter (20 mg) for tumour-to-background ratios higher than 3:1 and with an acquisition time around 4 s at each scanning step. These results indicate that our detector could be a useful complement to existing techniques for the accurate excision of brain tumour tissue and more generally to improve the efficiency of radio-guided cancer surgery.
Bogalhas, F.; Charon, Y.; Duval, M.-A.; Lefebvre, F.; Palfi, S.; Pinot, L.; Siebert, R.; Ménard, L.
We propose a simple, well grounded classification technique which is suited for group classification on brain fMRI data sets that have high dimensionality, small number of subjects, high noise level, high subject variability, imperfect registration and capture subtle cognitive effects. We propose threshold-split region as a new feature selection method and majority voteas the classification technique. Our method does not require a predefined set of regions of interest. We use average acros ssessions, only one feature perexperimental condition, feature independence assumption, and simple classifiers. The seeming counter-intuitive approach of using a simple design is supported by signal processing and statistical theory. Experimental results in two block design data sets that capture brain function under distinct monetary rewards for cocaine addicted and control subjects, show that our method exhibits increased generalization accuracy compared to commonly used feature selection and classification techniques.
Honorio, J.; Goldstein, R.; Honorio, J.; Samaras, D.; Tomasi, D.; Goldstein, R.Z.
The promyelocytic leukaemia (PML) protein controls multiple tumour suppressive functions and is downregulated in diverse types of human cancers through incompletely characterized post-translational mechanisms. Here we identify USP11 as a PML regulator by RNAi screening. USP11 deubiquitinates and stabilizes PML, thereby counteracting the functions of PML ubiquitin ligases RNF4 and the KLHL20-Cul3 (Cullin 3)-Roc1 complex. We find that USP11 is transcriptionally repressed through a Notch/Hey1-dependent mechanism, leading to PML destabilization. In human glioma, Hey1 upregulation correlates with USP11 and PML downregulation and with high-grade malignancy. The Notch/Hey1-induced downregulation of USP11 and PML not only confers multiple malignant characteristics of aggressive glioma, including proliferation, invasiveness and tumour growth in an orthotopic mouse model, but also potentiates self-renewal, tumour-forming capacity and therapeutic resistance of patient-derived glioma-initiating cells. Our study uncovers a PML degradation mechanism through Notch/Hey1-induced repression of the PML deubiquitinase USP11 and suggests an important role for this pathway in brain tumour pathogenesis. PMID:24487962
Wu, Hsin-Chieh; Lin, Yu-Ching; Liu, Cheng-Hsin; Chung, Hsiang-Ching; Wang, Ya-Ting; Lin, Ya-Wen; Ma, Hsin-I; Tu, Pang-Hsien; Lawler, Sean E; Chen, Ruey-Hwa
In recent years, it became clear that a better understanding of the interactions among the main elements involved in the cancer network is necessary for the treatment of cancer and the suppression of cancer growth. In this work we propose a system of coupled differential equations that model brain tumour under treatment by chemotherapy, which considers interactions among the glial cells, the glioma, the neurons, and the chemotherapeutic agents. We study the conditions for the glioma growth to be eliminated, and identify values of the parameters for which the inhibition of the glioma growth is obtained with a minimal loss of healthy cells. PMID:25596516
Iarosz, Kelly C; Borges, Fernando S; Batista, Antonio M; Baptista, Murilo S; Siqueira, Regiane A N; Viana, Ricardo L; Lopes, Sergio R
Abstract The heterogeneity of traumatic brain injury (TBI) is considered one of the most significant barriers to finding effective therapeutic interventions. In October, 2007, the National Institute of Neurological Disorders and Stroke, with support from the Brain Injury Association of America, the Defense and Veterans Brain Injury Center, and the National Institute of Disability and Rehabilitation Research, convened a workshop to outline the steps needed to develop a reliable, efficient and valid classification system for TBI that could be used to link specific patterns of brain and neurovascular injury with appropriate therapeutic interventions. Currently, the Glasgow Coma Scale (GCS) is the primary selection criterion for inclusion in most TBI clinical trials. While the GCS is extremely useful in the clinical management and prognosis of TBI, it does not provide specific information about the pathophysiologic mechanisms which are responsible for neurological deficits and targeted by interventions. On the premise that brain injuries with similar pathoanatomic features are likely to share common pathophysiologic mechanisms, participants proposed that a new, multidimensional classification system should be developed for TBI clinical trials. It was agreed that preclinical models were vital in establishing pathophysiologic mechanisms relevant to specific pathoanatomic types of TBI and verifying that a given therapeutic approach improves outcome in these targeted TBI types. In a clinical trial, patients with the targeted pathoanatomic injury type would be selected using an initial diagnostic entry criterion, including their severity of injury. Coexisting brain injury types would be identified and multivariate prognostic modeling used for refinement of inclusion/exclusion criteria and patient stratification. Outcome assessment would utilize endpoints relevant to the targeted injury type. Advantages and disadvantages of currently available diagnostic, monitoring, and assessment tools were discussed. Recommendations were made for enhancing the utility of available or emerging tools in order to facilitate implementation of a pathoanatomic classification approach for clinical trials. PMID:18627252
Saatman, Kathryn E.; Duhaime, Ann-Christine; Bullock, Ross; Maas, Andrew I.R.; Valadka, Alex
Microbeam radiation therapy (MRT) is a promising experimental and preclinical radiotherapy method for cancer treatment. Synchrotron based MRT experiments have shown that spatially fractionated microbeam radiation has the unique capability of preferentially eradicating tumour cells while sparing normal tissue in brain tumour bearing animal models. We recently demonstrated the feasibility of generating orthovoltage microbeam radiation with an adjustable microbeam width using a carbon nanotube based x-ray source array. Here we report the preliminary results from our efforts in developing an image guidance procedure for the targeted delivery of the narrow microbeams to the small tumour region in the mouse brain. Magnetic resonance imaging was used for tumour identification, and on-board x-ray radiography was used for imaging of landmarks without contrast agents. The two images were aligned using 2D rigid body image registration to determine the relative position of the tumour with respect to a landmark. The targeting accuracy and consistency were evaluated by first irradiating a group of mice inoculated with U87 human glioma brain tumours using the present protocol and then determining the locations of the microbeam radiation tracks using ?-H2AX immunofluorescence staining. The histology results showed that among 14 mice irradiated, 11 received the prescribed number of microbeams on the targeted tumour, with an average localization accuracy of 454 µm measured directly from the histology (537 µm if measured from the registered histological images). Two mice received one of the three prescribed microbeams on the tumour site. One mouse was excluded from the analysis due to tissue staining errors.
Zhang, Lei; Yuan, Hong; Burk, Laurel M.; Inscoe, Christy R.; Hadsell, Michael J.; Chtcheprov, Pavel; Lee, Yueh Z.; Lu, Jianping; Chang, Sha; Zhou, Otto
Microbeam radiation therapy (MRT) is a promising experimental and preclinical radiotherapy method for cancer treatment. Synchrotron based MRT experiments have shown that spatially fractionated microbeam radiation has the unique capability of preferentially eradicating tumour cells while sparing normal tissue in brain tumour bearing animal models. We recently demonstrated the feasibility of generating orthovoltage microbeam radiation with an adjustable microbeam width using a carbon nanotube based x-ray source array. Here we report the preliminary results from our efforts in developing an image guidance procedure for the targeted delivery of the narrow microbeams to the small tumour region in the mouse brain. Magnetic resonance imaging was used for tumour identification, and on-board x-ray radiography was used for imaging of landmarks without contrast agents. The two images were aligned using 2D rigid body image registration to determine the relative position of the tumour with respect to a landmark. The targeting accuracy and consistency were evaluated by first irradiating a group of mice inoculated with U87 human glioma brain tumours using the present protocol and then determining the locations of the microbeam radiation tracks using ?-H2AX immunofluorescence staining. The histology results showed that among 14 mice irradiated, 11 received the prescribed number of microbeams on the targeted tumour, with an average localization accuracy of 454 µm measured directly from the histology (537 µm if measured from the registered histological images). Two mice received one of the three prescribed microbeams on the tumour site. One mouse was excluded from the analysis due to tissue staining errors. PMID:24556798
Zhang, Lei; Yuan, Hong; Burk, Laurel M; Inscoe, Christy R; Hadsell, Michael J; Chtcheprov, Pavel; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto
Though clinical trials demonstrated effectiveness of the anti-VEGF antibody bevacizumab (Avastin) in adjuvant therapies for some solid tumours, there are rather few experimental data about cellular effects of bevacizumab on tumour cells and tumour associated endothelial cells. Recent reports demonstrate resistance mechanisms and secondary re-angiogenesis after a transient normalization of tumour vessels. Therefore we investigated the influence of bevacizumab on human glioma cells and human brain derived as well as tumour derived endothelial cells focussing on the role of VEGF-C and -D as potential alternative pro-angiogenic factors. Bevacizumab treatment showed no influence on proliferation after short term exposure (1-5 days) but slowed down endothelial cell proliferation by 25-30% after 14 days treatment. There was no significant induction of apoptosis after short or long term exposure. Tube formation capabilities were significantly impaired by bevacizumab with a continuing effect after 14 days of treatment even after omitting the antibody. VEGF-C and -D had no effect on endothelial cells in untreated or short term treatment groups. However, cells developed responsiveness to these factors in terms of increased proliferation and tube formation after 14 days bevacizumab treatment. Furthermore, bevacizumab induced expression of VEGF-C and -D in glioma cells. Treatment with bevacizumab may induce alterations in human brain and tumour endothelial cells leading to escape mechanisms from anti-VEGF therapy. VEGF-C and -D thus might act as alternative pro-angiogenic factors during anti-VEGF therapy. PMID:21308397
Grau, S; Thorsteinsdottir, J; von Baumgarten, L; Winkler, F; Tonn, J-C; Schichor, C
Aims To investigate the relationship between extremely low frequency magnetic field (ELF?MF) exposure and mortality from leukaemia and brain tumour in a cohort of Swiss railway workers. Methods 20?141 Swiss railway employees with 464?129 person?years of follow?up between 1972 and 2002 were studied. Mortality rates for leukaemia and brain tumour of highly exposed train drivers (21??T average annual exposure) were compared with medium and low exposed occupational groups (i.e. station masters with an average exposure of 1??T). In addition, individual cumulative exposure was calculated from on?site measurements and modelling of past exposures. Results The hazard ratio (HR) for leukaemia mortality of train drivers was 1.43 (95% CI 0.74 to 2.77) compared with station masters. For myeloid leukaemia the HR of train drivers was 4.74 (95% CI 1.04 to 21.60) and for Hodgkin's disease 3.29 (95% CI 0.69 to 15.63). Lymphoid leukaemia, non?Hodgkin's disease and brain tumour mortality were not associated with magnetic field exposure. Concordant results were obtained from analyses based on individual cumulative exposure. Conclusions Some evidence of an exposure–response association was found for myeloid leukaemia and Hodgkin's disease, but not for other haematopoietic and lymphatic malignancies and brain tumours. PMID:17525094
Röösli, Martin; Lörtscher, Manfred; Egger, Matthias; Pfluger, Dominik; Schreier, Nadja; Lörtscher, Emanuel; Locher, Peter; Spoerri, Adrian; Minder, Christoph
Radioisotopic scanning of brain, liver, lungs and the skeleton is briefly reviewed with a survey of recent developments of clinical significance. In brain scanning neoplasm detection rates of greater than 90% are claimed. The true figure is probably 70-80%. Autopsy data shows a number of false negatives, particularly with vascular lesions. Attempts to make scanning more specific in differentiating neoplasm from vascular lesions by rapid sequence blood flow studies are reviewed. In liver scanning by means of colloids again high success rate is claimed but small metastases are frequently missed and the false negative scan rate is probably quite high. Lung scanning still has its main place in investigating pulmonary embolic disease. Ventilation studies using Xenon 133 are useful, particularly combined with perfusion studies. The various radiopharmaceuticals for use in bone scanning are reviewed. The appearance of technetium labelled phosphate compounds will probably allow much wider use of total skeletal scanning. Research into tumour localizing agents continues, the most recent and interesting being Gallium citrate and labelled bleomycin. Neither agent is predictable however although Gallium may have a place in Hodgkins disease and bronchogenic neoplasm and both may have a place in the detection of cerebral tumours. ImagesFig. 1Fig. 2Fig. 3p452-bFig. 3bFig. 4Fig. 5Fig. 5bFig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 12c & 12dFig. 13Fig. 13 b,c,dFig. 14Fig. 14bFig. 15Fig. 15bFig. 16Fig. 17Fig. 18 PMID:4602127
Lavender, J. P.
, tensor, higher order discriminant analysis (HODA), electroencephalography (EEG), event-related potentials of brain signals . Feature extraction and classification of electroencephalography (EEG) signals
Being diagnosed with a metastatic brain tumour can be devastating as it is characterized by very low cure rates, as well as significant morbidity and mortality. Given the poor life expectancy and progressive disability that ensues, patients and family members experience much turmoil, which includes losses that bring about changes to family roles, routines and relationships. Crisis and conflict are common during such major disruptions to a family system, as individual members attempt to make sense of the illness experience based on cultural and spiritual beliefs, past experiences and personal philosophies. It is imperative health care providers strive towards increased awareness and knowledge of how culture affects the overall experience of illness and death in order to help create a mutually satisfactory care plan. Providing culturally-competent care entails the use of proper communication skills to facilitate the exploration of patient and family perspectives and allows for mutual decision making. A case study will illustrate the challenges encountered in providing culturally-competent care to a woman with brain cancer and her family. As the patient's health declined, the family entered into a state of crisis where communication between family members and health care professionals was strained; leading to conflict and sub-optimal outcomes. This paper will address the ethical dilemma of providing culturally-competent care when a patient's safety is at risk, and the nursing implications of upholding best practices in the context of differing beliefs and priorities. PMID:25265763
Longo, Lianne; Slater, Serena
Primary brain tumours are among the most lethal of all cancers, largely as a result of their lack of responsiveness to current therapy. Numerous new therapies hold great promise for the treatment of patients with brain cancer, but the main challenge is to determine which treatment is most likely to benefit an individual patient. DNA-microarray-based technologies, which allow simultaneous analysis
Timothy F. Cloughesy; Stanley F. Nelson; Paul S. Mischel
Although intrinsic tumours of the brain seldom metastasize to distant sites, their diffuse, infiltrative-invasive growth within the brain generally precludes successful surgical and adjuvant therapy. Hence, attention has now focused on novel therapeutic approaches to combat brain tumours that include the use of anti-invasive and anti-proliferative agents. The effect of four anti-invasive agents, swainsonine (a locoweed alkaloid), captopril (an anti-hypertensive drug), tangeretin and nobiletin (both citrus flavonoids), were investigated on various parameters of brain tumour invasion such as matrix metalloproteinase (MMP) secretion, migration, invasion and adhesion. A standard cytotoxicity assay was used to optimize working concentrations of the drugs on seven human brain tumour-derived cell lines of various histological type and grade of malignancy. A qualitative assessment by gelatin zymography revealed that the effect of these agents varied between the seven cell lines such that the low grade pilocytic astrocytoma was unaffected by three of the agents. In contrast, downregulation of the two gelatinases, MMP-2 and MMP-9 was seen in the grade 3 astrocytoma irrespective of which agent was used. Generally, swainsonine was the least effective whereas the citrus flavonoids, particularly nobiletin, showed the greatest downregulation of secretion of the MMPs. Furthermore, captopril and nobiletin were most efficient at inhibiting invasion, migration and adhesion in four representative cell lines (an ependymoma, a grade II oligoastrocytoma, an anaplastic astrocytoma and a glioblastoma multiforme). Yet again, the effects of the four agents varied between the four cell lines. Nobiletin was, nevertheless, the most effective agent used in these assays. In conclusion, the differential effects seen on the various parameters studied by these putative anti-invasive agents may be the result of interference with MMPs and other mechanisms underlying the invasive phenotype. From these pilot studies, it is possible that these agents, especially the citrus flavonoids, could be of future therapeutic value. However, further work is needed to validate this in a larger study. PMID:11299000
Rooprai, H K; Kandanearatchi, A; Maidment, S L; Christidou, M; Trillo-Pazos, G; Dexter, D T; Rucklidge, G J; Widmer, W; Pilkington, G J
Brain regions in the mammalian cerebral cortex are linked by a complex network of fiber bundles. These inter-regional networks have previously been analyzed in terms of their node degree, structural motif, path length and clustering coefficient distributions. In this paper we focus on the identification and classification of hub regions, which are thought to play pivotal roles in the coordination of information flow. We identify hubs and characterize their network contributions by examining motif fingerprints and centrality indices for all regions within the cerebral cortices of both the cat and the macaque. Motif fingerprints capture the statistics of local connection patterns, while measures of centrality identify regions that lie on many of the shortest paths between parts of the network. Within both cat and macaque networks, we find that a combination of degree, motif participation, betweenness centrality and closeness centrality allows for reliable identification of hub regions, many of which have previously been functionally classified as polysensory or multimodal. We then classify hubs as either provincial (intra-cluster) hubs or connector (inter-cluster) hubs, and proceed to show that lesioning hubs of each type from the network produces opposite effects on the small-world index. Our study presents an approach to the identification and classification of putative hub regions in brain networks on the basis of multiple network attributes and charts potential links between the structural embedding of such regions and their functional roles. PMID:17940613
Sporns, Olaf; Honey, Christopher J.; Kötter, Rolf
We propose a method to adaptively select an optimal cortical segmentation for brain connectivity analysis that maximizes feature-based disease classification performance. In standard structural connectivity analysis, the cortex is typically subdivided (parcellated) into N anatomical regions. White matter fiber pathways from tractography are used to compute an N × N matrix, which represents the pairwise connectivity between those regions. We optimize this representation by sampling over the space of possible region combinations and represent each configuration as a set partition of the N anatomical regions. Each partition is assigned a score using accuracy from a support vector machine (SVM) classifier of connectivity matrices in a group of patients and controls. We then define a high-dimensional optimization problem using simulated annealing to identify an optimal partition for maximum classification accuracy. We evaluate the results separately on test data using cross-validation. Specifically, we demonstrate results on the ADNI-2 dataset, where we optimally parcellate the cortex to yield an 85% classification accuracy using connectivity information alone. We refer to our method as evolving partitions to improve connectomics (EPIC). PMID:25405000
Prasad, Gautam; Joshi, Shantanu H; Thompson, Paul M
Double-labelling immunohistochemistry for MGMT and a “cocktail” of non-tumourous elements is a reliable, quick and easy technique for inferring methylation status in glioblastomas and other primary brain tumours
Background Our aim was to develop a new protocol for MGMT immunohistochemistry with good agreement between observers and good correlation with molecular genetic tests of tumour methylation. We examined 40 primary brain tumours (30 glioblastomas and 10 oligodendroglial tumours) with our new technique, namely double-labelling immunohistochemistry for MGMT and a "cocktail" of non-tumour antigens (CD34, CD45 and CD68). We compared the results with single-labelling immunohistochemistry for MGMT and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA, a recognised molecular genetic technique which we applied as the gold-standard for the methylation status). Results Double-labelling immunohistochemistry for MGMT produced a visual separation of tumourous and non-tumourous elements on the same histological slide, making it quick and easy to determine whether tumour cell nuclei were MGMT-positive or MGMT-negative (and thereby infer the methylation status of the tumour). We found good agreement between observers (kappa 0.76) and within observer (kappa 0.84). Furthermore, double-labelling showed good specificity (80%), sensitivity (73.33%), positive predictive value (PPV, 83.33%) and negative predictive value (NPV, 68.75%) compared to MS-MLPA. Double-labelling was quicker and easier to assess than single-labelling and it outperformed quantitative computerised image analysis of MGMT single-labelling in terms of sensitivity, specificity, PPV and NPV. Conclusions Double-labelling immunohistochemistry for MGMT and a cocktail of non-tumourous elements provides a "one look" method for determining whether tumour cell nuclei are MGMT-positive or MGMT-negative. This can be used to infer the methylation status of the tumour. There is good observer agreement and good specificity, sensitivity, PPV and NPV compared to a molecular gold-standard. PMID:24252243
FAST TRAUMATIC BRAIN INJURY CT SLICE INDEXING VIA ANATOMICAL FEATURE CLASSIFICATION Ruizhe Liu for Infocomm Research ABSTRACT Computed tomography (CT) is used widely in traumatic brain injury diagnosis. One diagnosis components. Specifically, computed tomography (CT) is used widely in traumatic brain injury (TBI
Tan, Chew Lim
Classification of evoked potentials by Pearson's correlation in a Brain-Computer Interface F learn- ing technique for use in a brain-computer interface. Electroencephalogram (EEG) signals ac collected from eight individuals. Keywords: Brain-computer interface; BCI; linear classifier; evoked
Paris-Sud XI, UniversitÃ© de
The field of application of magnetic resonance spectroscopy (MRS) in biomedical research is expanding all the time and providing opportunities to investigate tissue metabolism and function. The data derived can be integrated with the information on tissue structure gained from conventional and non-conventional magnetic resonance imaging (MRI) techniques. Clinical MRS is also strongly expected to play an important role as a diagnostic tool. Essential for the future success of MRS as a clinical and research tool in biomedical sciences, both in vivo and in vitro, is the development of an accurate, biochemically relevant and physically consistent and reliable data analysis standard. Stable and well established analysis algorithms, in both the time and the frequency domain, are already available, as is free commercial software for implementing them. In this study, we propose an automatic algorithm that takes into account anatomical localisation, relative concentrations of white matter, grey matter, cerebrospinal fluid and signal abnormalities and inter-scan patient movement. The endpoint is the collection of a series of covariates that could be implemented in a multivariate analysis of covariance (MANCOVA) of the MRS data, as a tool for dealing with differences that may be ascribed to the anatomical variability of the subjects, to inaccuracies in the localisation of the voxel or slab, or to movement, rather than to the pathology under investigation. The aim was to develop an analysis procedure that can be consistently and reliably applied in the follow up of brain tumour. In this study, we demonstrate that the inclusion of such variables in the data analysis of quantitative MRS is fundamentally important (especially in view of the reduced accuracy typical of MRS measures compared to other MRI techniques), reducing the occurrence of false positives. PMID:19331784
Poloni, Guy; Bastianello, S; Vultaggio, Angela; Pozzi, S; Maccabelli, Gloria; Germani, Giancarlo; Chiarati, Patrizia; Pichiecchio, Anna
Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and BrdU using anti-PCNA and anti-BrdU monoclonal antibodies, respectively, was performed in 16 human brain tumours, including 3 glioblastomas multiforme, 2 anaplastic astrocytomas, 1 cerebellar astrocytoma, 2 recurrent meningiomas, 4 non-recurrent meningiomas, 3 neurinomas and 1 medulloblastoma. Patients with brain tumours received an injection of bromodeoxyuridine (BrdU) intravenously during surgery, and tumour specimens were fixed in 70% ethanol and embedded in paraffin. The percentage of positive cells for PCNA was compared with a BrdU labelling index using adjacent paraffin-embedded sections. The percentage of PCNA-positive cells was correlated with the BrdU labelling index and the histological malignancy of the brain tumours. The correlation coefficient was 0.84. This suggests that the immunohistochemical staining for PCNA in paraffin sections is a good alternative to the BrdU labelling index. PMID:1357920
Sasaki, A; Naganuma, H; Kimura, R; Isoe, S; Nakano, S; Nukui, H; Suzuki, K; Kawaoi, A
We compare a variety of different anatomic connectivity measures, including several novel ones, that may help in distinguishing Alzheimer's disease (AD) patients from controls. We studied diffusion-weighted magnetic resonance imaging from 200 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative. We first evaluated measures derived from connectivity matrices based on whole-brain tractography; next, we studied additional network measures based on a novel flow-based measure of brain connectivity, computed on a dense 3-dimensional lattice. Based on these 2 kinds of connectivity matrices, we computed a variety of network measures. We evaluated the measures' ability to discriminate disease with a repeated, stratified 10-fold cross-validated classifier, using support vector machines, a supervised learning algorithm. We tested the relative importance of different combinations of features based on the accuracy, sensitivity, specificity, and feature ranking of the classification of 200 people into normal healthy controls and people with early or late mild cognitive impairment or AD. PMID:25264345
Prasad, Gautam; Joshi, Shantanu H; Nir, Talia M; Toga, Arthur W; Thompson, Paul M
The purpose of this study was to compare functional magnetic resonance (MR) imaging of the motor cortex in healthy volunteers and patients with brain tumours. Functional MR imaging was performed in 14 healthy volunteers and 14 patients with tumours in or near the primary motor cortex with groups being matched for age, sex, and handedness. Functional images were acquired during motion of the right and left hand. Time courses of signal intensity within the contralateral, ipsilateral, and supplementary motor cortex as well as z-maps were calculated, their quality being assessed visually. Mean signal increase between activation and rest were evaluated within the contralateral, ipsilateral, and supplementary motor cortex, the activated area in those regions of interest was measured using z-maps. The quality of functional MR experiments was generally lower in patients than in volunteers. The quantitative results showed a trend towards increased ipsilateral activation in volunteers during left hand compared to right hand motion and in patients during motion of the affected compared to the non-affected hand. Considering quantitative and qualitative results, significantly increased ipsilateral activation was found in patients compared to healthy volunteers. In conclusion, functional MR imaging quality was significantly reduced in patient studies compared to healthy volunteers, even if influences of age, sex, and handedness were excluded. Increased ipsilateral activation was found in patients with brain tumours which can be interpreted by an improved connectivity between both hemispheres. PMID:10321113
Fellner, C; Schlaier, J; Fellner, F; Held, P; Blank, M; Schwerdtner, J; Brawanski, A; Kalender, W A
Machine learning techniques have been widely used to detect morphological abnormalities from structural brain magnetic resonance imaging data and to support the diagnosis of neurological diseases such as dementia. In this paper, we propose to use a multiple instance learning (MIL) method in an application for the detection of Alzheimer's disease (AD) and its prodromal stage mild cognitive impairment (MCI). In our work, local intensity patches are extracted as features. However, not all the patches extracted from patients with dementia are equally affected by the disease and some of them may not be characteristic of morphology associated with the disease. Therefore, there is some ambiguity in assigning disease labels to these patches. The problem of the ambiguous training labels can be addressed by weakly supervised learning techniques such as MIL. A graph is built for each image to exploit the relationships among the patches and then to solve the MIL problem. The constructed graphs contain information about the appearances of patches and the relationships among them, which can reflect the inherent structures of images and aids the classification. Using the baseline MR images of 834 subjects from the ADNI study, the proposed method can achieve a classification accuracy of 89% between AD patients and healthy controls, and 70% between patients defined as stable MCI and progressive MCI in a leave-one-out cross validation. Compared with two state-of-the-art methods using the same dataset, the proposed method can achieve similar or improved results, providing an alternative framework for the detection and prediction of neurodegenerative diseases. PMID:24858570
Tong, Tong; Wolz, Robin; Gao, Qinquan; Guerrero, Ricardo; Hajnal, Joseph V; Rueckert, Daniel
Lymph node metastasis in dogs with mast cell tumour has been reported as a negative prognostic indicator; however, no standardized histological criteria exist to define metastatic disease. The primary aim of this study was to determine whether different histological patterns of node-associated mast cells correlate with clinical outcome in dogs with mast cell tumour. A secondary goal was to propose a criteria-defined classification system for histological evaluation of lymph node metastasis. The Colorado State University Diagnostic Medicine Center database was searched for cases of canine mast cell tumours with reported lymph node metastasis or evidence of node-associated mast cells. Additional cases were obtained from a clinical trial involving sentinel lymph node mapping and node extirpation in dogs with mast cell neoplasia. Forty-one cases were identified for inclusion in the study. Demographic data, treatment and clinical outcome were collected for each case. Lymph nodes were classified according to a novel classification system (HN0-HN3) based on the number of, distribution of, and architectural disruption by, nodal mast cells. The findings of this study indicate that characterization of nodal mast cells as proposed by this novel classification system correlates with, and is prognostic for, clinical outcome in dogs with mast cell tumours. PMID:25172053
Weishaar, K M; Thamm, D H; Worley, D R; Kamstock, D A
Introduction: Perfusion computed tomography (PCT) allows to quantitatively assess haemodynamic characteristics of brain tissue. We investigated if different brain tumor types can be distinguished from each other using Patlak analysis of PCT data. Methods: PCT data from 43 patients with brain tumours were analysed with a commercial implementation of the Patlak method. Four patients had low-grade glioma (WHO II), 31 patients had glioblastoma (WHO IV) and eight patients had intracerebral lymphoma. Tumour regions of interest (ROIs) were drawn in a morphological image and automatically transferred to maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and permeability (KTrans). Mean values were calculated, group differences were tested using Wilcoxon and Mann Whitney U-tests. Results: In comparison with normal parenchyma, low-grade gliomas showed no significant difference of perfusion parameters (p?>?0.05) , whereas high-grade gliomas demonstrated significantly higher values (p?0.0001 for KTrans, p?0.0001 for CBV and p?=?0.0002 for CBF). Lymphomas displayed significantly increased mean KTrans values compared with unaffected cerebral parenchyma (p?=?0.0078) but no elevation of CBV. High-grade gliomas show significant higher CBV values than lymphomas (p?=?0.0078). Discussion: PCT allows to reliably classify gliomas and lymphomas based on quantitative measurements of CBV and KTrans. PMID:20495977
Xyda, Argyro; Klotz, Ernst; Tronnier, Volker; Knauth, Michael; Hartmann, Marius
In this paper we review classification algorithms used to design brain-computer interface (BCI) systems based on electroencephalography (EEG). We briefly present the commonly employed algorithms and describe their critical properties. Based on the literature, we compare them in terms of performance and provide guidelines to choose the suitable classification algorithm(s) for a specific BCI.
F. Lotte; M. Congedo; A. Lécuyer; F. Lamarche; B. Arnaldi
3-D MRI Brain Scan Feature Classification Using an Oct-tree Representation Akadej Udomchaiporn1 of spe- cific 3-D features in Magnetic Resonance Imaging (MRI) brain scan vol- umes. The main of interest from MRI volumes, (ii) an oct-tree technique to represent the extracted sub-volumes and (iii
BRAIN AND COGNITION 10, 256-295 (1989) Patient Classification in Neuropsychological Research ALFONSO CARAMAZZA AND WILLIAM BADECKER Cognitive Neuropsychology Laboratory, Cognitive Science Center to the cognitive system that are introduced by brain damage. We have argued that in such cases very restrictive
The INTEROCC project is a multi-centre case-control study investigating the risk of developing brain cancer due to occupational chemical and electromagnetic field exposures. To estimate chemical exposures, the Finnish Job Exposure Matrix (FINJEM) was modified to improve its performance in the INTEROCC study and to address some of its limitations, resulting in the development of the INTEROCC JEM. An international team of occupational hygienists developed a crosswalk between the Finnish occupational codes used in FINJEM and the International Standard Classification of Occupations 1968 (ISCO68). For ISCO68 codes linked to multiple Finnish codes, weighted means of the exposure estimates were calculated. Similarly, multiple ISCO68 codes linked to a single Finnish code with evidence of heterogeneous exposure were refined. One of the key time periods in FINJEM (1960-1984) was split into two periods (1960-1974 and 1975-1984). Benzene exposure estimates in early periods were modified upwards. The internal consistency of hydrocarbon exposures and exposures to engine exhaust fumes was improved. Finally, exposure to polycyclic aromatic hydrocarbon and benzo(a)pyrene was modified to include the contribution from second-hand smoke. The crosswalk ensured that the FINJEM exposure estimates could be applied to the INTEROCC study subjects. The modifications generally resulted in an increased prevalence of exposure to chemical agents. This increased prevalence of exposure was not restricted to the lowest categories of cumulative exposure, but was seen across all levels for some agents. Although this work has produced a JEM with important improvements compared to FINJEM, further improvements are possible with the expansion of agents and additional external data. PMID:23467593
van Tongeren, Martie; Kincl, Laurel; Richardson, Lesley; Benke, Geza; Figuerola, Jordi; Kauppinen, Timo; Lakhani, Ramzan; Lavoué, Jérôme; McLean, Dave; Plato, Nils; Cardis, Elisabeth
Functional MR imaging (fMRI) enables to detect different activated brain areas according to the performed tasks. However, data are usually evaluated after the experiment, which prohibits intra-experiment optimization or more sophisticated applications such as biofeedback experiments. Using a human-brain-interface (HBI), subjects are able to communicate with external programs, e.g. to navigate through virtual scenes, or to experience and modify their own brain activation. These applications require the real-time analysis and classification of activated brain areas. Our paper presents first results of different strategies for real-time pattern analysis and classification realized within a flexible experiment control system that enables the volunteers to move through a 3D virtual scene in real-time using finger tapping tasks, and alternatively only thought-based tasks.
Moench, Tobias; Hollmann, Maurice; Grzeschik, Ramona; Mueller, Charles; Luetzkendorf, Ralf; Baecke, Sebastian; Luchtmann, Michael; Wagegg, Daniela; Bernarding, Johannes
A brain tumour-associated marker, urokinase (UK), was investigated using rabbit anti-UK polyclonal and murine anti-UK monoclonal antibodies, which were prepared by immunization with low molecular weight UK (LMW-UK) and high molecular weight urokinase (HMW-UK) synthetic peptide respectively. The polyclonal antibody cross-reacted with both LMW-UK and HMW-UK, whereas the murine MAbs were specific for HMW-UK. These immunological probes were used to study urokinase in glioma extracts, tissues, sera and cell lines that had been prepared from primary cultures of freshly dissected gliomas. Radioimmunoassays showed that glioma extracts had much higher level (5- to 44-fold) of UK than normal human brain extracts. This result was confirmed by immunoblotting of electrophoresis gels of glioma and human brain extracts. Immunohistochemical study using anti-UK MAb demonstrated much higher levels of UK in glioma tissue than normal brain tissue. Immunohistochemical study using anti-UK MAbs localized UK on the cell surface of glioma cells. Anti-UK MAbs inhibited the proliferation of AA cell lines and GB cell lines (50% to > 90%) and exerted minor effects (< or = 20%) on normal human liver, intestine and lymphocyte cell lines. Taken together, these results suggest that anti-UK MAbs may have therapeutic potential for human gliomas and cancer metastasis. Images Figure 2 Figure 3 PMID:9862567
Abaza, M. S.; Shaban, F. A.; Narayan, R. K.; Atassi, M. Z.
Brain tumor segmentation is an important procedure for early tumor diagnosis and radiotherapy planning. Although numerous brain tumor segmentation methods have been presented, enhancing tumor segmentation methods is still challenging because brain tumor MRI images exhibit complex characteristics, such as high diversity in tumor appearance and ambiguous tumor boundaries. To address this problem, we propose a novel automatic tumor segmentation method for MRI images. This method treats tumor segmentation as a classification problem. Additionally, the local independent projection-based classification (LIPC) method is used to classify each voxel into different classes. A novel classification framework is derived by introducing the local independent projection into the classical classification model. Locality is important in the calculation of local independent projections for LIPC. Locality is also considered in determining whether local anchor embedding is more applicable in solving linear projection weights compared with other coding methods. Moreover, LIPC considers the data distribution of different classes by learning a softmax regression model, which can further improve classification performance. In this study, 80 brain tumor MRI images with ground truth data are used as training data and 40 images without ground truth data are used as testing data. The segmentation results of testing data are evaluated by an online evaluation tool. The average dice similarities of the proposed method for segmenting complete tumor, tumor core, and contrast-enhancing tumor on real patient data are 0.84, 0.685, and 0.585, respectively. These results are comparable to other state-of-the-art methods. PMID:24860022
Huang, Meiyan; Yang, Wei; Wu, Yao; Jiang, Jun; Chen, Wufan; Feng, Qianjin
A known-groups design was used to determine the classification accuracy of 12 Booklet Category Test variables in the detection of malingered neurocognitive dysfunction (MND) in traumatic brain injury (TBI). Participants were 206 TBI and 60 general clinical patients seen for neuropsychological evaluation. Slick, Sherman, and Iverson's (1999) criteria were used to classify the TBI patients into non-malingering, suspect, and MND
Kevin W. Greve; Kevin J. Bianchini; Triche Roberson
On the effect of data set size on bias and variance in classification learning Damien Brain with large data sets. However, most machine learning research has been conducted in the context of learning from very small data sets. To date most approaches to scaling up machine learning to large data sets
The accurate prediction of general neuropsychiatric disorders, on an individual basis, using resting-state functional magnetic resonance imaging (fMRI) is a challenging task of great clinical significance. Despite the progress to chart the differences between the healthy controls and patients at the group level, the pattern classification of functional brain networks across individuals is still less developed. In this paper we
Jie Zhang; Wei Cheng; ZhengGe Wang; ZhiQiang Zhang; WenLian Lu; GuangMing Lu; Jianfeng Feng
Schizophrenia Classification Using Regions of Interest in Brain MRI D. S. Cheng1 , M. Bicego1 , U by schizophrenia and other mental illnesses traditionally diagnosed by self-reports and behavioral observations encouraging agreements with previous medical studies in schizophrenia research. 1 Introduction Computational
Multiple stages classification of Alzheimers disease based on structural brain networks using for a progressing disease such as Alzheimers dis- ease is a key issue for the disease prevention and treatment networks in the progression of the Alzheimers disease. Here we developed a framework to utilize generalized
Though clinical trials demonstrated effectiveness of the anti-VEGF antibody bevacizumab (Avastin) in adjuvant therapies for\\u000a some solid tumours, there are rather few experimental data about cellular effects of bevacizumab on tumour cells and tumour\\u000a associated endothelial cells. Recent reports demonstrate resistance mechanisms and secondary re-angiogenesis after a transient\\u000a normalization of tumour vessels. Therefore we investigated the influence of bevacizumab on
S. Grau; J. Thorsteinsdottir; L. von Baumgarten; F. Winkler; J.-C. Tonn; C. Schichor
In structural Magnetic Resonance Imaging (MRI), neurodegenerative diseases generally present complex brain patterns that can be correlated with di erent clinical onsets of this pathologies. An objective method that aims to determine both global and local changes is not usually available in clinical practice, thus the interpretation of these images is strongly dependent on the radiologist's skills. In this paper, we propose a strategy which interprets the brain structure using a framework that highlights discriminant brain patterns for neurodegenerative diseases. This is accomplished by combining a probabilistic learning technique, which identi es and groups regions with similar visual features, with a visual saliency method that exposes relevant information within each region. The association of such patterns with a speci c disease is herein evaluated in a classi cation task, using a dataset including 80 Alzheimer's disease (AD) patients and 76 healthy subjects (NC). Preliminary results show that the proposed method reaches a maximum classi cation accuracy of 81.39%.
Pulido, Andrea; Rueda, Andrea; Romero, Eduardo
and Communication Technology (ICT) to assist clinicians during the decision making for the diagnosis and treatment in the acquisition and analysis of biomedical data in major health problems such like brain tumors. The quick and easy access to the most recent ICT developments will provide translational results for clinical
Abstract. Brain tumors are one of the leading causes of death in adults with cancer; however proportion of deaths in older adults (1). According to the US Central Brain Tumor Registry, between 2000 and a robust classification strategy. We used ~2 mg of tissue at -8Â°C from each of 55 brain biopsies
Machine learning techniques have been widely used to support the diagnosis of neurological diseases such as dementia. Recent approaches utilize local intensity patterns within patches to derive voxelwise grading measures of disease. However, the relationships among these patches are usually ignored. In addition, there is some ambiguity in assigning disease labels to the extracted patches. Not all of the patches extracted from patients with dementia are characteristic of morphology associated with disease. In this paper, we propose to use a multiple instance learning method to address the problem of assigning training labels to the patches. In addition, a graph is built for each image to exploit the relationships among these patches, which aids the classification work. We illustrate the proposed approach in an application for the detection of Alzheimer's disease (AD): Using the baseline MR images of 834 subjects from the ADNI study, the proposed method can achieve a classification accuracy of 88.8% between AD patients and healthy controls, and 69.6% between patients with stable Mild Cognitive Impairment (MCI) and progressive MCI. These results compare favourably with state-of-the-art classification methods. PMID:24579190
Tong, Tong; Wolz, Robin; Gao, Qinquan; Hajnal, Joseph V; Rueckert, Daniel
Objective. The paper investigates the presence of autism using the functional brain connectivity measures derived from electro-encephalogram (EEG) of children during face perception tasks. Approach. Phase synchronized patterns from 128-channel EEG signals are obtained for typical children and children with autism spectrum disorder (ASD). The phase synchronized states or synchrostates temporally switch amongst themselves as an underlying process for the completion of a particular cognitive task. We used 12 subjects in each group (ASD and typical) for analyzing their EEG while processing fearful, happy and neutral faces. The minimal and maximally occurring synchrostates for each subject are chosen for extraction of brain connectivity features, which are used for classification between these two groups of subjects. Among different supervised learning techniques, we here explored the discriminant analysis and support vector machine both with polynomial kernels for the classification task. Main results. The leave one out cross-validation of the classification algorithm gives 94.7% accuracy as the best performance with corresponding sensitivity and specificity values as 85.7% and 100% respectively. Significance. The proposed method gives high classification accuracies and outperforms other contemporary research results. The effectiveness of the proposed method for classification of autistic and typical children suggests the possibility of using it on a larger population to validate it for clinical practice.
Jamal, Wasifa; Das, Saptarshi; Oprescu, Ioana-Anastasia; Maharatna, Koushik; Apicella, Fabio; Sicca, Federico
The E-cadherin adhesive profile expressed by a tumour is a characterization of the intracellular and intercellular protein interactions that control cell-cell adhesion. Within the intracellular proteins that determine the tumour adhesive profile, Src and PI3 are two essentials to initiate the formation of the E-cadherin adhesion complex. On the other hand, Src has also the capability of disrupting the ?-catenin-E-cadherin complex and down-regulating cell-cell adhesion. In this paper, using a multi-scale mathematical model, we study the role of each of these proteins in the adhesive profile and invasive properties of the tumour. To do this, we create three versions of an intracellular model that explains the interplay between the proteins E-cadherin, ?-catenin, Src and PI3; and we couple them to the strength of the cell-cell adhesion forces within an individual-cell-based model. The simulation results show how the tumour profile and its aggressive potential may change depending on the intrinsic characteristics of the protein pathways, and how these pathways may influence the early stages of cancer invasion. Our major findings may be summarized as follows. (1) Intermediate levels of Src synthesis rates generate the least invasive tumour phenotype. (2) Conclusions drawn from findings obtained from the intracellular molecular dynamics (here cadherin-catenin binding complexes) to the multi-cellular invasive potential of a tumour may be misleading or erroneous. The conclusions should be validated in a multi-cellular context on timescales relevant for population growth. (3) Monoclonal populations of more cohesive cells with otherwise equal properties tend to grow slower. (4) Less cohesive cells tend to outcompete more cohesive cells. (5) Less cohesive cells have a larger probability of invasion as migration forces can more easily outbalance cohesive forces.
Ramis-Conde, Ignacio; Drasdo, Dirk
Accurate diagnosis of Alzheimer's disease (AD) from structural Magnetic Resonance (MR) images is difficult due to the complex alteration of patterns in brain anatomy that could indicate the presence or absence of the pathology. Currently, an effective approach that allows to interpret the disease in terms of global and local changes is not available in the clinical practice. In this paper, we propose an approach for classification of brain MR images, based on finding pathology-related patterns through the identification of regional structural changes. The approach combines a probabilistic Latent Semantic Analysis (pLSA) technique, which allows to identify image regions through latent topics inferred from the brain MR slices, with a bottom-up Graph-Based Visual Saliency (GBVS) model, which calculates maps of relevant information per region. Regional saliency maps are finally combined into a single map on each slice, obtaining a master saliency map of each brain volume. The proposed approach includes a one-to-one comparison of the saliency maps which feeds a Support Vector Machine (SVM) classifier, to group test subjects into normal or probable AD subjects. A set of 156 brain MR images from healthy (76) and pathological (80) subjects, splitted into a training set (10 non-demented and 10 demented subjects) and one testing set (136 subjects), was used to evaluate the performance of the proposed approach. Preliminary results show that the proposed method reaches a maximum classification accuracy of 87.21%.
Pulido, Andrea; Rueda, Andrea; Romero, Eduardo
Reported studies describing normal and abnormal aging based on anatomical MRI analysis do not consider morphological brain changes, but only volumetric measures to distinguish among these processes. This work presents a classification scheme, based both on size and shape features extracted from brain volumes, to determine different aging stages: healthy control (HC) adults, mild cognitive impairment (MCI), and Alzheimer's disease (AD). Three support vector machines were optimized and validated for the pair-wise separation of these three classes, using selected features from a set of 3D discrete compactness measures and normalized volumes of several global and local anatomical structures. Our analysis show classification rates of up to 98.3% between HC and AD; of 85% between HC and MCI and of 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indexes to classify different aging stages.
Perez-Gonzalez, J. L.; Yanez-Suarez, O.; Medina-Bañuelos, V.
A known-groups design was used to determine the classification accuracy of verbal fluency variables in detecting Malingered Neurocognitive Dysfunction (MND) in traumatic brain injury (TBI). Participants were 204 TBI and 488 general clinical patients. The Slick et al. (1999) criteria were used to classify the TBI patients into non-MND and MND groups. An educationally corrected FAS Total Correct word T-score
Kelly L. Curtis; Laura K. Thompson; Kevin W. Greve; Kevin J. Bianchini
Objectives Autism spectrum disorders (ASD) are diagnosed based on early-manifesting clinical symptoms, including markedly impaired social communication. We assessed the viability of resting-state functional MRI (rs-fMRI) connectivity measures as diagnostic biomarkers for ASD and investigated which connectivity features are predictive of a diagnosis. Methods Rs-fMRI scans from 59 high functioning males with ASD and 59 age- and IQ-matched typically developing (TD) males were used to build a series of machine learning classifiers. Classification features were obtained using 3 sets of brain regions. Another set of classifiers was built from participants' scores on behavioral metrics. An additional age and IQ-matched cohort of 178 individuals (89 ASD; 89 TD) from the Autism Brain Imaging Data Exchange (ABIDE) open-access dataset (http://fcon_1000.projects.nitrc.org/indi/abide/) were included for replication. Results High classification accuracy was achieved through several rs-fMRI methods (peak accuracy 76.67%). However, classification via behavioral measures consistently surpassed rs-fMRI classifiers (peak accuracy 95.19%). The class probability estimates, P(ASD|fMRI data), from brain-based classifiers significantly correlated with scores on a measure of social functioning, the Social Responsiveness Scale (SRS), as did the most informative features from 2 of the 3 sets of brain-based features. The most informative connections predominantly originated from regions strongly associated with social functioning. Conclusions While individuals can be classified as having ASD with statistically significant accuracy from their rs-fMRI scans alone, this method falls short of biomarker standards. Classification methods provided further evidence that ASD functional connectivity is characterized by dysfunction of large-scale functional networks, particularly those involved in social information processing.
Plitt, Mark; Barnes, Kelly Anne; Martin, Alex
We report a pilot study of performing classification of motor imagery for brain-computer interface applications, by means of source analysis of scalp-recorded EEGs. Independent component analysis (ICA) was used as a spatio-temporal filter extracting signal components relevant to left or right motor imagery (MI) tasks. Source analysis methods including equivalent dipole analysis and cortical current density imaging were applied to
Lei Qin; Lei Ding; Bin He
Controversy surrounds the classification of posttraumatic stress disorder (PTSD), particularly in children and adolescents with traumatic brain injury (TBI). In these populations, it is difficult to differentiate TBI-related organic memory loss from dissociative amnesia. Several alternative PTSD classification algorithms have been proposed for use with children. This paper investigates DSM-IV-TR and alternative PTSD classification algorithms, including and excluding the dissociative
Greg Iselin; Robyne Le Brocque; Justin Kenardy; Vicki Anderson; Lynne McKinlay
A brain-machine interface (BMI) links a user's brain activity directly to an external device. It enables a person to control devices using only thought. Hence, it has gained significant interest in the design of assistive devices and systems for people with disabilities. In addition, BMI has also been proposed to replace humans with robots in the performance of dangerous tasks like explosives handling/diffusing, hazardous materials handling, fire fighting etc. There are mainly two types of BMI based on the measurement method of brain activity; invasive and non-invasive. Invasive BMI can provide pristine signals but it is expensive and surgery may lead to undesirable side effects. Recent advances in non-invasive BMI have opened the possibility of generating robust control signals from noisy brain activity signals like EEG and EOG. A practical implementation of a non-invasive BMI such as robot control requires: acquisition of brain signals with a robust wearable unit, noise filtering and signal processing, identification and extraction of relevant brain wave features and finally, an algorithm to determine control signals based on the wave features. In this work, we developed a wireless brain-machine interface with a small platform and established a BMI that can be used to control the movement of a robot by using the extracted features of the EEG and EOG signals. The system records and classifies EEG as alpha, beta, delta, and theta waves. The classified brain waves are then used to define the level of attention. The acceleration and deceleration or stopping of the robot is controlled based on the attention level of the wearer. In addition, the left and right movements of eye ball control the direction of the robot.
Oh, Sechang; Kumar, Prashanth S.; Kwon, Hyeokjun; Varadan, Vijay K.
We present a cluster spatial analysis method using nanoscopic dSTORM images to determine changes in protein cluster distributions within brain tissue. Such methods are suitable to investigate human brain tissue and will help to achieve a deeper understanding of brain disease along with aiding drug development. Human brain tissue samples are usually treated postmortem via standard fixation protocols, which are established in clinical laboratories. Therefore, our localization microscopy-based method was adapted to characterize protein density and protein cluster localization in samples fixed using different protocols followed by common fluorescent immunohistochemistry techniques. The localization microscopy allows nanoscopic mapping of serotonin 5-HT1A receptor groups within a two-dimensional image of a brain tissue slice. These nanoscopically mapped proteins can be confined to clusters by applying the proposed statistical spatial analysis. Selected features of such clusters were subsequently used to characterize and classify the tissue. Samples were obtained from different types of patients, fixed with different preparation methods, and finally stored in a human tissue bank. To verify the proposed method, samples of a cryopreserved healthy brain have been compared with epitope-retrieved and paraffin-fixed tissues. Furthermore, samples of healthy brain tissues were compared with data obtained from patients suffering from mental illnesses (e.g., major depressive disorder). Our work demonstrates the applicability of localization microscopy and image analysis methods for comparison and classification of human brain tissues at a nanoscopic level. Furthermore, the presented workflow marks a unique technological advance in the characterization of protein distributions in brain tissue sections.
Sams, Michael; Silye, Rene; Göhring, Janett; Muresan, Leila; Schilcher, Kurt; Jacak, Jaroslaw
Adaptive Classification for Brain Computer Interfaces Julie Blumberg, JÂ¨orn Rickert, Stephan the performance of a new adaptive classifier for the use within a Brain Computer- Interface (BCI). The classifier Computer Interfaces (BCIs) infer the movement in- tentions of subjects by analyzing electrophysiological
Abstract More than 70 benign and malignant sinonasal tumours and tumour-like conditions have been described. However, sinonasal tumours are rare, and sinonasal cancers comprise only 3% of all head and neck cancers and 1% of all malignancies, with a peak incidence in the 5th to 7th decades and with a male preponderance. The early symptoms and imaging findings of sinonasal tumours are similar to rhinosinusitis with runny and stuffy nose, lacrimation and epistaxis and therefore neglected both by the patients and doctors. When late symptoms such as anosmia, visual disturbances, cranial neuropathy (Cn II, IV, V, VI) or facial swelling appear, the patient is referred to sinonasal endoscopy or imaging. At the time of correct diagnosis more than half of the tumours have reached an advanced stage with a poor prognostic outcome. Even if imaging is performed in the early stages, a radiologist inexperienced with sinonasal anatomy and tumour features may easily interpret early signs of a malignant tumour as rhinosinusitis or a lesion that does not require follow-up. This article presents the imaging findings in some of the most common benign and malignant sinonasal tumours, and the TNM classification and staging of sinonasal carcinomas. PMID:22571851
The availability of combined MR-PET scanners opens new opportunities for the characterisation of tumour environment. In this study, water content and relaxation properties of glioblastoma were investigated in five patients using advanced MRI. The region containing metabolically active tumour tissue was defined by simultaneously measured FET-PET uptake. The mean value of water content in tumour tissue - obtained noninvasively with high precision and accuracy for the first time - amounted to 84.5%, similar to the value for normal grey matter. Constancy of water content contrasted with a large variability of T2* values in tumour tissue, qualitatively related to the magnetic inhomogeneity of tissue created by blood vessels and/or microbleeds. The quantitative MRI protocol takes 71/2 > min of measurement time and is proposed for extended clinical use.
Oros-Peusquens, A.-M.; Keil, F.; Langen, K. J.; Herzog, H.; Stoffels, G.; Weiss, C.; Shah, N. J.
We investigate the use of a recent technique for shape analysis of brain substructures in identifying learning disabilities in third-grade children. This Riemannian technique provides a quantification of differences in shapes of parameterized surfaces, using a distance that is invariant to rigid motions and re-parameterizations. Additionally, it provides an optimal registration across surfaces for improved matching and comparisons. We utilize an efficient gradient based method to obtain the optimal re-parameterizations of surfaces. In this study we consider 20 different substructures in the human brain and correlate the differences in their shapes with abnormalities manifested in deficiency of mathematical skills in 106 subjects. The selection of these structures is motivated in part by the past links between their shapes and cognitive skills, albeit in broader contexts. We have studied the use of both individual substructures and multiple structures jointly for disease classification. Using a leave-one-out nearest neighbor classifier, we obtained a 62.3% classification rate based on the shape of the left hippocampus. The use of multiple structures resulted in an improved classification rate of 71.4%.
Kurtek, Sebastian; Klassen, Eric; Gore, John C.; Ding, Zhaohua; Srivastava, Anuj
Purpose This study was conducted to assess the possibility of identifying precise white matter tracts situated in proximity to intracranial\\u000a tumours, to define the anatomical and topographical relations between the same white matter tracts and the tumour, to verify\\u000a the possibility of integrating tractographic images in the context of a package of three-dimensional anatomical images to\\u000a send to the neuronavigation system,
A. Romano; M. Ferrante; V. Cipriani; F. Fasoli; L. Ferrante; G. D’Andrea; L. M. Fantozzi; A. Bozzao
We present an algorithm that automatically segments and classifies the brain structures in a set of magnetic resonance (MR) brain images using expert information contained in a small subset of the image set. The algorithm is intended to do the segmentation and classification tasks mimicking the way a human expert would reason. The algorithm uses a knowledge base taken from a small subset of semiautomatically classified images that is combined with a set of fuzzy indexes that capture the experience and expectation a human expert uses during recognition tasks. The fuzzy indexes are tissue specific and spatial specific, in order to consider the biological variations in the tissues and the acquisition inhomogeneities through the image set. The brain structures are segmented and classified one at a time. For each brain structure the algorithm needs one semiautomatically classified image and makes one pass through the image set. The algorithm uses low-level image processing techniques on a pixel basis for the segmentations, then validates or corrects the segmentations, and makes the final classification decision using higher level criteria measured by the set of fuzzy indexes. We use single-echo MR images because of their high volumetric resolution; but even though we are working with only one image per brain slice, we have multiple sources of information on each pixel: absolute and relative positions in the image, gray level value, statistics of the pixel and its three-dimensional neighborhood and relation to its counterpart pixels in adjacent images. We have validated our algorithm for ease of use and precision both with clinical experts and with measurable error indexes over a Brainweb simulated MR set. PMID:15376508
Algorri, Maria-Elena; Flores-Mangas, Fernando
Motor imagery is the task most commonly used to induce changes in electroencephalographic (EEG) signals for mental imagery-based brain computer interfacing (BCI). In this study, we investigated EEG patterns that were induced by seven different mental tasks (i.e. mental rotation, word association, auditory imagery, mental subtraction, spatial navigation, imagery of familiar faces and motor imagery) and evaluated the binary classification performance. The aim was to provide a broad range of reliable and user-appropriate tasks to make individual optimization of BCI control strategies possible. Nine users participated in four sessions of multi-channel EEG recordings. Mental tasks resulting most frequently in good binary classification performance include mental subtraction, word association, motor imagery and mental rotation. Our results indicate that a combination of 'brain-teasers' - tasks that require problem specific mental work (e.g. mental subtraction, word association) - and dynamic imagery tasks (e.g. motor imagery) result in highly distinguishable brain patterns that lead to an increased performance. PMID:22289414
Friedrich, Elisabeth V C; Scherer, Reinhold; Neuper, Christa
Recent research has shown that social anxiety disorder (SAD) is accompanied by abnormalities in brain functional connections. However, these findings are based on group comparisons, and, therefore, little is known about whether functional connections could be used in the diagnosis of an individual patient with SAD. Here, we explored the potential of the functional connectivity to be used for SAD diagnosis. Twenty patients with SAD and 20 healthy controls were scanned using resting-state functional magnetic resonance imaging. The whole brain was divided into 116 regions based on automated anatomical labeling atlas. The functional connectivity between each pair of regions was computed using Pearson's correlation coefficient and used as classification feature. Multivariate pattern analysis was then used to classify patients from healthy controls. The pattern classifier was designed using linear support vector machine. Experimental results showed a correct classification rate of 82.5 % (p < 0.001) with sensitivity of 85.0 % and specificity of 80.0 %, using a leave-one-out cross-validation method. It was found that the consensus connections used to distinguish SAD were largely located within or across the default mode network, visual network, sensory-motor network, affective network, and cerebellar regions. Specifically, the right orbitofrontal region exhibited the highest weight in classification. The current study demonstrated that functional connectivity had good diagnostic potential for SAD, thus providing evidence for the possible use of whole brain functional connectivity as a complementary tool in clinical diagnosis. In addition, this study confirmed previous work and described novel pathophysiological mechanisms of SAD. PMID:24072164
Liu, Feng; Guo, Wenbin; Fouche, Jean-Paul; Wang, Yifeng; Wang, Wenqin; Ding, Jurong; Zeng, Ling; Qiu, Changjian; Gong, Qiyong; Zhang, Wei; Chen, Huafu
This paper presents a knowledge based approach to automatic classification and tissue labeling of 2D magnetic resonance (MR) images of human brain. The system consists of two components: an unsupervised clustering algorithm and an expert system. MR brain data is initially segmented by the unsupervised algorithm, then, the expert system locates a focus-of- attention tissue or cluster and analyzes it by matching it with a model or searching in it for an expected feature. The focus-of-attention tissue location and its analysis are repeated until a tumor is found or all tissues are labeled. Abnormal slices are labeled by reclustering regions of interest with knowledge accumulated from previous analysis. The domain knowledge contains tissue distribution in feature space acquired with a clustering algorithm, and tissue models. Default reasoning is used to match a qualitative model with its instances. The system has been tested with fifty-three slices acquired at different times by two different scanners.
Li, ChunLin; Hall, Lawrence O.; Goldgof, Dmitry B.
Previous studies have shown a consistent association between long-term use of mobile and cordless phones and glioma and acoustic neuroma, but not for meningioma. When used these phones emit radiofrequency electromagnetic fields (RF-EMFs) and the brain is the main target organ for the hand-held phone. The International Agency for Research on Cancer (IARC) classified in May, 2011 RF-EMF as a group 2B, i.e. a ‘possible’ human carcinogen. The aim of this study was to further explore the relationship between especially long-term (>10 years) use of wireless phones and the development of malignant brain tumours. We conducted a new case-control study of brain tumour cases of both genders aged 18–75 years and diagnosed during 2007–2009. One population-based control matched on gender and age (within 5 years) was used to each case. Here, we report on malignant cases including all available controls. Exposures on e.g. use of mobile phones and cordless phones were assessed by a self-administered questionnaire. Unconditional logistic regression analysis was performed, adjusting for age, gender, year of diagnosis and socio-economic index using the whole control sample. Of the cases with a malignant brain tumour, 87% (n=593) participated, and 85% (n=1,368) of controls in the whole study answered the questionnaire. The odds ratio (OR) for mobile phone use of the analogue type was 1.8, 95% confidence interval (CI)=1.04–3.3, increasing with >25 years of latency (time since first exposure) to an OR=3.3, 95% CI=1.6–6.9. Digital 2G mobile phone use rendered an OR=1.6, 95% CI=0.996–2.7, increasing with latency >15–20 years to an OR=2.1, 95% CI=1.2–3.6. The results for cordless phone use were OR=1.7, 95% CI=1.1–2.9, and, for latency of 15–20 years, the OR=2.1, 95% CI=1.2–3.8. Few participants had used a cordless phone for >20–25 years. Digital type of wireless phones (2G and 3G mobile phones, cordless phones) gave increased risk with latency >1–5 years, then a lower risk in the following latency groups, but again increasing risk with latency >15–20 years. Ipsilateral use resulted in a higher risk than contralateral mobile and cordless phone use. Higher ORs were calculated for tumours in the temporal and overlapping lobes. Using the meningioma cases in the same study as reference entity gave somewhat higher ORs indicating that the results were unlikely to be explained by recall or observational bias. This study confirmed previous results of an association between mobile and cordless phone use and malignant brain tumours. These findings provide support for the hypothesis that RF-EMFs play a role both in the initiation and promotion stages of carcinogenesis. PMID:24064953
HARDELL, LENNART; CARLBERG, MICHAEL; SÖDERQVIST, FREDRIK; MILD, KJELL HANSSON
Fibroepithelioma of Pinkus is a rare cutaneous tumour. Its classification is controversial and is considered as a variant of either basal cell carcinoma or trichoblastoma. Its presentation as a multiple tumour is rare. We are reporting such a case occurring in a 55-year-old man presenting with multiple seborrheic keratosis-like lesions corresponding histologically to Pinkus tumours. The clinical diagnosis of Pinkus tumour represents a challenge. Histological examination is extremely useful in aiding in the diagnosis of difficult cases. PMID:24466765
Sehli Attafi, S; Jones, M; Fazaa, B; Zermani, R; Rommany, S R
We have developed a novel approach using source analysis for classifying motor imagery tasks. Two-equivalent-dipoles analysis was proposed to aid classification of motor imagery tasks for brain-computer interface (BCI) applications. By solving the electroencephalography (EEG) inverse problem of single trial data, it is found that the source analysis approach can aid classification of motor imagination of left- or right-hand movement
Baharan Kamousi; Zhongming Liu; Bin He
One major hallmark of the Alzheimer's disease (AD) is the loss of neurons in the brain. In many cases, medical experts use magnetic resonance imaging (MRI) to qualitatively measure the neuronal loss by the shrinkage or enlargement of the structures-of-interest. Brain ventricle is one of the popular choices. It is easily detectable in clinical MR images due to the high contrast of the cerebro-spinal fluid (CSF) with the rest of the parenchyma. Moreover, atrophy in any periventricular structure will directly lead to ventricle enlargement. For quantitative analysis, volume is the common choice. However, volume is a gross measure and it cannot capture the entire complexity of the anatomical shape. Since most existing shape descriptors are complex and difficult-to-reproduce, more straightforward and robust ways to extract ventricle shape features are preferred in the diagnosis. In this paper, a novel ventricle shape based classification method for Alzheimer's disease has been proposed. Training process is carried out to generate two probability maps for two training classes: healthy controls (HC) and AD patients. By subtracting the HC probability map from the AD probability map, we get a 3D ventricle discriminant map. Then a matching coefficient has been calculated between each training subject and the discriminant map. An adjustable cut-off point of the matching coefficients has been drawn for the two classes. Generally, the higher the cut-off point that has been drawn, the higher specificity can be achieved. However, it will result in relatively lower sensitivity and vice versa. The benchmarked results against volume based classification show that the area under the ROC curves for our proposed method is as high as 0.86 compared with only 0.71 for volume based classification method.
Wang, Jingnan; de Haan, Gerard; Unay, Devrim; Soldea, Octavian; Ekin, Ahmet
OBJECTIVE—To investigate whether risk of brain tumour is related to occupational exposure to magnetic fields.?METHODS—The mortality experienced by a cohort of 83 997 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1973-97. All workers were employed for at least 6 months with some employment in the period 1973-82. Computerised work histories were available for 79 972 study subjects for the period 1971-93. Detailed calculations had been performed by others to enable a novel assessment to be made of exposures to magnetic fields. Two analytical approaches were used, indirect standardisation (n=83 997) and Poisson regression (n=79 972).?RESULTS—Based on serial mortalities for England and Wales, deaths from brain cancer were close to expectation (observed 158, expected 146.4). No significant positive trends were shown for risks of brain tumours either with lifetime cumulative exposure to magnetic fields or with such exposures received in the most recent 5 years.?CONCLUSIONS—There are no discernible excess risks of brain tumours as a consequence of occupational exposure to magnetic fields in United Kingdom electricity generation and transmission workers.???Keywords: magnetic fields; brain tumours; electricity generation and transmission; cohort mortality study PMID:11555682
Sorahan, T; Nichols, L; van Tongeren, M; Harrington, J
The ADHD-200 Global Competition provides an excellent opportunity for building diagnostic classifiers of Attention-Deficit/Hyperactivity Disorder (ADHD) based on resting-state functional MRI (rs-fMRI) and structural MRI data. Here, we introduce a simple method to classify ADHD based on morphological information without using functional data. Our test results show that the accuracy of this approach is competitive with methods based on rs-fMRI data. We used isotropic local binary patterns on three orthogonal planes (LBP-TOP) to extract features from MR brain images. Subsequently, support vector machines (SVM) were used to develop classification models based on the extracted features. In this study, a total of 436 male subjects (210 with ADHD and 226 controls) were analyzed to show the discriminative power of the method. To analyze the properties of this approach, we tested disparate LBP-TOP features from various parcellations and different image resolutions. Additionally, morphological information using a single brain tissue type (i.e., gray matter (GM), white matter (WM), and CSF) was tested. The highest accuracy we achieved was 0.6995. The LBP-TOP was found to provide better discriminative power using whole-brain data as the input. Datasets with higher resolution can train models with increased accuracy. The information from GM plays a more important role than that of other tissue types. These results and the properties of LBP-TOP suggest that most of the disparate feature distribution comes from different patterns of cortical folding. Using LBP-TOP, we provide an ADHD classification model based only on anatomical information, which is easier to obtain in the clinical environment and which is simpler to preprocess compared with rs-fMRI data. PMID:23024630
Chang, Che-Wei; Ho, Chien-Chang; Chen, Jyh-Horng
Objective. Brain-machine interface systems translate recorded neural signals into command signals for assistive technology. In individuals with upper limb amputation or cervical spinal cord injury, the restoration of a useful hand grasp could significantly improve daily function. We sought to determine if electrocorticographic (ECoG) signals contain sufficient information to select among multiple hand postures for a prosthetic hand, orthotic, or functional electrical stimulation system.Approach. We recorded ECoG signals from subdural macro- and microelectrodes implanted in motor areas of three participants who were undergoing inpatient monitoring for diagnosis and treatment of intractable epilepsy. Participants performed five distinct isometric hand postures, as well as four distinct finger movements. Several control experiments were attempted in order to remove sensory information from the classification results. Online experiments were performed with two participants. Main results. Classification rates were 68%, 84% and 81% for correct identification of 5 isometric hand postures offline. Using 3 potential controls for removing sensory signals, error rates were approximately doubled on average (2.1×). A similar increase in errors (2.6×) was noted when the participant was asked to make simultaneous wrist movements along with the hand postures. In online experiments, fist versus rest was successfully classified on 97% of trials; the classification output drove a prosthetic hand. Online classification performance for a larger number of hand postures remained above chance, but substantially below offline performance. In addition, the long integration windows used would preclude the use of decoded signals for control of a BCI system. Significance. These results suggest that ECoG is a plausible source of command signals for prosthetic grasp selection. Overall, avenues remain for improvement through better electrode designs and placement, better participant training, and characterization of non-stationarities such that ECoG could be a viable signal source for grasp control for amputees or individuals with paralysis.
Chestek, Cynthia A.; Gilja, Vikash; Blabe, Christine H.; Foster, Brett L.; Shenoy, Krishna V.; Parvizi, Josef; Henderson, Jaimie M.
Objective Brain machine interface systems translate recorded neural signals into command signals for assistive technology. In individuals with upper limb amputation or cervical spinal cord injury, the restoration of a useful hand grasp could significantly improve daily function. We sought to determine if electrocorticographic (ECoG) signals contain sufficient information to select among multiple hand postures for a prosthetic hand, orthotic, or functional electrical stimulation system. Approach We recorded ECoG signals from subdural macro- and microelectrodes implanted in motor areas of three participants who were undergoing inpatient monitoring for diagnosis and treatment of intractable epilepsy. Participants performed 5 distinct isometric hand postures, as well as 4 distinct finger movements. Several control experiments were attempted in order to remove sensory information from the classification results. Online experiments were performed with 2 participants. Main Results Classification rates were 68%, 84%, and 81% for correct identification of 5 isometric hand postures offline. Using 3 potential controls for removing sensory signals, error rates were approximately doubled on average (2.1×). A similar increase in errors (2.6×) was noted when the participant was asked to make simultaneous wrist movements along with the hand postures. In online experiments, fist versus rest was successfully classified on 97% of trials; the classification output drove a prosthetic hand. Online classification performance for a larger number of hand postures remained above chance, but substantially below offline performance. In addition, the long integration windows used would preclude the use of decoded signals for control of a BCI system. Significance These results suggest that ECoG is a plausible source of command signals for prosthetic grasp selection. Overall, avenues remain for improvement through better electrode designs and placement, better participant training, and characterization of non-stationarities such that ECoG could be a viable signal source for grasp control for amputees or individuals with paralysis. PMID:23369953
Chestek, Cynthia A.; Gilja, Vikash; Blabe, Christine H.; Foster, Brett L.; Shenoy, Krishna V.; Parvizi, Josef; Henderson, Jaimie M.
The study deals with the challenging task of automatic segmentation of MR brain images with multiple sclerosis lesions (MSL). Multi-Channel data is used, including "fast fluid attenuated inversion recovery" (fast FLAIR or FF), and statistical modeling tools are developed, in order to improve cerebrospinal fluid (CSF) classification and to detect MSL. Two new concepts are proposed for use within an EM framework. The first concept is the integration of prior knowledge as it relates to tissue behavior in different MRI modalities, with special attention given to the FF modality. The second concept deals with running the algorithm on a subset of the input that is most likely to be noise- and artifact-free data. This enables a more reliable learning of the Gaussian mixture model (GMM) parameters for brain tissue statistics. The proposed method focuses on the problematic CSF intensity distribution, which is a key to improved overall segmentation and lesion detection. A level-set based active contour stage is performed for lesion delineation, using gradient and shape properties combined with previously learned region intensity statistics. In the proposed scheme there is no need for preregistration of an atlas, a common characteristic in brain segmentation schemes. Experimental results on real data are presented.
Wolff, Yulian; Miron, Shmuel; Achiron, Anat; Greenspan, Hayit
Classifiers based on statistical pattern recognition analysis of MRSI data are becoming important tools for the non-invasive diagnosis of human brain tumors. Here we investigate the potential interest of perturbation-enhanced MRSI (PE-MRSI), in this case acute hyperglycemia, for improving the discrimination between mouse brain MRS patterns of glioblastoma multiforme (GBM), oligodendroglioma (ODG), and non-tumor brain parenchyma (NT). Six GBM-bearing mice and three ODG-bearing mice were scanned at 7 Tesla by PRESS-MRSI with 12 and 136 ms echo-time, during euglycemia (Eug) and also during induced acute hyperglycemia (Hyp), generating altogether four datasets per animal (echo time + glycemic condition): 12Eug, 136Eug, 12Hyp, and 136Hyp. For classifier development all spectral vectors (spv) selected from the MRSI matrix were unit length normalized (UL2) and used either as a training set (76 GBM spv, four mice; 70 ODG spv, two mice; 54 NT spv) or as an independent testing set (61 GBM spv, two mice; 31 ODG, one mouse; 23 NT spv). All Fisher's LDA classifiers obtained were evaluated as far as their descriptive performance-correctly classified cases of the training set (bootstrapping)-and predictive accuracy-balanced error rate of independent testing set classification. MRSI-based classifiers at 12Hyp were consistently more efficient in separating GBM, ODG, and NT regions, with overall accuracies always >80% and up to 95-96%; remaining classifiers were within the 48-85% range. This was also confirmed by user-independent selection of training and testing sets, using leave-one-out (LOO). This highlights the potential interest of perturbation-enhanced MRSI protocols for improving the non-invasive characterization of preclinical brain tumors. PMID:22193155
Simões, Rui Vasco; Ortega-Martorell, Sandra; Delgado-Goñi, Teresa; Le Fur, Yann; Pumarola, Martí; Candiota, Ana Paula; Martín, Juana; Stoyanova, Radka; Cozzone, Patrick J; Julià-Sapé, Margarida; Arús, Carles
Background Childhood obesity has reached epidemic proportions and is impacting children's health globally. In adults, obesity is associated with chronic low-grade inflammation that leads to insulin resistance, which is one of the important mechanisms through which dysregulation of metabolism occurs. There is limited information available about the contribution of inflammation to metabolic health in obese children, and how individual and lifestyle factors impact this risk. One of the paediatric groups at risk of higher rates of obesity includes the survivors of childhood brain tumours. The aim of this study was to evaluate the mechanisms that contribute to inflammation in obese survivors of childhood brain tumours. Methods and analysis This is a prospective cohort study. We will recruit lean and obese survivors of childhood brain tumours, and a control group composed of lean and obese children with no history of tumours. We will measure circulating and urinary cytokine levels and cytokine gene expression in monocytes. In addition, the methylation patterns of cytokine genes and that of toll-like receptor genes will be evaluated. These will be correlated with individual and lifestyle factors including age, sex, ethnicity, puberty, body mass index, fasting lipid levels, insulin sensitivity, diet, exercise, sleep, stress and built environment. The sample size calculation showed that we need 25 participants per arm Ethics and dissemination This study has received ethics approval from the institutional review board. Once completed, we will publish this work in peer-reviewed journals and share the findings in presentations and posters in meetings. Discussion This study will permit the interrogation of inflammation as a contributor to obesity and its complications in obese survivors of childhood brain tumours and compare them with lean survivors and lean and obese controls with no history of tumours, which may help identify therapeutic and preventative interventions to combat the rising tide of obesity. PMID:23794554
Samaan, M Constantine; Thabane, Lehana; Burrow, Sarah; Dillenburg, Rejane F; Scheinemann, Katrin
A known-groups design was used to determine the classification accuracy of Wechsler Adult Intelligence Scale-III (WAIS-III) variables in detecting malingered neurocognitive dysfunction (MND) in traumatic brain injury (TBI). TBI patients were classified into the following groups: (a) mild TBI not-MND (n = 26), (b) mild TBI MND (n = 31), and (c)…
Curtis, Kelly L.; Greve, Kevin W.; Bianchini, Kevin J.
Parcellation, one of several brain analysis methods, is a procedure popular for subdividing the regions identified by segmentation into smaller topographically defined units. The fuzzy clustering algorithm is mainly used to preprocess parcellation into several segmentation methods, because it is very appropriate for the characteristics of magnetic resonance imaging (MRI), such as partial volume effect and intensity inhomogeneity. However, some gray matter, such as basal ganglia and thalamus, may be misclassified into the white matter class using the conventional fuzzy C-Means (FCM) algorithm. Parcellation has been nearly achieved through manual drawing, but it is a tedious and time-consuming process. We propose improved classification using successive fuzzy clustering and implementing the parcellation module with the modified graphic user interface (GUI) for the convenience of users. PMID:11442112
Yoon, U C; Kim, J S; Kim, J S; Kim, I Y; Kim, S I
A classification concealed information test (CIT) used the "brain fingerprinting" method of applying P300 event-related potential (ERP) in detecting information that is (1) acquired in real life and (2) unique to US Navy experts in military medicine. Military medicine experts and non-experts were asked to push buttons in response to three types of text stimuli. Targets contain known information relevant to military medicine, are identified to subjects as relevant, and require pushing one button. Subjects are told to push another button to all other stimuli. Probes contain concealed information relevant to military medicine, and are not identified to subjects. Irrelevants contain equally plausible, but incorrect/irrelevant information. Error rate was 0%. Median and mean statistical confidences for individual determinations were 99.9% with no indeterminates (results lacking sufficiently high statistical confidence to be classified). We compared error rate and statistical confidence for determinations of both information present and information absent produced by classification CIT (Is a probe ERP more similar to a target or to an irrelevant ERP?) vs. comparison CIT (Does a probe produce a larger ERP than an irrelevant?) using P300 plus the late negative component (LNP; together, P300-MERMER). Comparison CIT produced a significantly higher error rate (20%) and lower statistical confidences: mean 67%; information-absent mean was 28.9%, less than chance (50%). We compared analysis using P300 alone with the P300 + LNP. P300 alone produced the same 0% error rate but significantly lower statistical confidences. These findings add to the evidence that the brain fingerprinting methods as described here provide sufficient conditions to produce less than 1% error rate and greater than 95% median statistical confidence in a CIT on information obtained in the course of real life that is characteristic of individuals with specific training, expertise, or organizational affiliation. PMID:25565941
Farwell, Lawrence A; Richardson, Drew C; Richardson, Graham M; Furedy, John J
A classification concealed information test (CIT) used the “brain fingerprinting” method of applying P300 event-related potential (ERP) in detecting information that is (1) acquired in real life and (2) unique to US Navy experts in military medicine. Military medicine experts and non-experts were asked to push buttons in response to three types of text stimuli. Targets contain known information relevant to military medicine, are identified to subjects as relevant, and require pushing one button. Subjects are told to push another button to all other stimuli. Probes contain concealed information relevant to military medicine, and are not identified to subjects. Irrelevants contain equally plausible, but incorrect/irrelevant information. Error rate was 0%. Median and mean statistical confidences for individual determinations were 99.9% with no indeterminates (results lacking sufficiently high statistical confidence to be classified). We compared error rate and statistical confidence for determinations of both information present and information absent produced by classification CIT (Is a probe ERP more similar to a target or to an irrelevant ERP?) vs. comparison CIT (Does a probe produce a larger ERP than an irrelevant?) using P300 plus the late negative component (LNP; together, P300-MERMER). Comparison CIT produced a significantly higher error rate (20%) and lower statistical confidences: mean 67%; information-absent mean was 28.9%, less than chance (50%). We compared analysis using P300 alone with the P300 + LNP. P300 alone produced the same 0% error rate but significantly lower statistical confidences. These findings add to the evidence that the brain fingerprinting methods as described here provide sufficient conditions to produce less than 1% error rate and greater than 95% median statistical confidence in a CIT on information obtained in the course of real life that is characteristic of individuals with specific training, expertise, or organizational affiliation. PMID:25565941
Farwell, Lawrence A.; Richardson, Drew C.; Richardson, Graham M.; Furedy, John J.
This paper presents a method for robust volumetric texture classification. It also proposes 2D and 3D gradient calculation methods designed to be robust to imaging effects and artifacts. Using the proposed 2D method, the gradient information is extracted on the XYZ orthogonal planes at each voxel and used to form a local coordinate system. The local coordinate system and the local 3D gradient computed by the proposed 3D gradient calculator are then used to define volumetric texture features. It is shown that the presented gradient calculation methods can be efficiently implemented by convolving with 2D and 3D kernels. The experimental results demonstrate that the proposed gradient operators and the texture features are robust to imaging effects and artifacts, such as blurriness and noise in 2D and 3D images. The proposed method is compared with three state-of- the-art volumetric texture classification methods the 3D gray level cooccurance matrix, 3D local binary patterns, and second orientation pyramid on magnetic resonance imaging data of the brain. The experimental results show the superiority of the proposed method in accuracy, robustness, and speed. PMID:25167550
Maani, Rouzbeh; Kalra, Sanjay; Yang, Yee-Hong
Graph theory is increasingly used in the field of neuroscience to understand the large-scale network structure of the human brain. There is also considerable interest in applying machine learning techniques in clinical settings, for example, to make diagnoses or predict treatment outcomes. Here we used support-vector machines (SVMs), in conjunction with whole-brain tractography, to identify graph metrics that best differentiate individuals with Major Depressive Disorder (MDD) from nondepressed controls. To do this, we applied a novel feature-scoring procedure that incorporates iterative classifier performance to assess feature robustness. We found that small-worldness, a measure of the balance between global integration and local specialization, most reliably differentiated MDD from nondepressed individuals. Post-hoc regional analyses suggested that heightened connectivity of the subcallosal cingulate gyrus (SCG) in MDDs contributes to these differences. The current study provides a novel way to assess the robustness of classification features and reveals anomalies in large-scale neural networks in MDD.
Sacchet, Matthew D.; Prasad, Gautam; Foland-Ross, Lara C.; Thompson, Paul M.; Gotlib, Ian H.
Patients affected by brain tumours may show behavioural and emotional regulation deficits, sometimes showing flattened affect and sometimes experiencing a true 'change' in personality. However, little evidence is available to the surgeon as to what changes are likely to occur with damage at specific sites, as previous studies have either relied on single cases or provided only limited anatomical specificity, mostly reporting associations rather than dissociations of symptoms. We investigated these aspects in patients undergoing surgery for the removal of cerebral tumours. We argued that many of the problems described can be ascribed to the onset of difficulties in one or more of the different levels of the process of mentalizing (i.e. abstracting and reflecting upon) emotion and intentions, which impacts on everyday behaviour. These were investigated in terms of (i) emotion recognition; (ii) Theory of Mind; (iii) alexithymia; and (iv) self-maturity (personality disorder). We hypothesized that temporo/limbic areas would be critical for processing emotion and intentions at a more perceptual level, while frontal lobe structures would be more critical when higher levels of mentalization/abstraction are required. We administered four different tasks, Task 1: emotion recognition of Ekman faces; Task 2: the Eyes Test (Theory of Mind); Task 3: Toronto Alexithymia Scale; and Task 4: Temperament and Character Inventory (a personality inventory), both immediately before and few days after the operation for the removal of brain tumours in a series of 71 patients (age range: 18-75 years; 33 female) with lesions located in the left or right frontal, temporal and parietal lobes. Lobe-based and voxel-based analysis confirmed that tasks requiring interpretation of emotions and intentions at more basic (less mentalized) levels (Tasks 1 and 2) were more affected by temporo/insular lesions, with emotion recognition (Task 1) being maximally impaired by anterior temporal and amygdala lesions and Task 2 (found to be a 'basic' Theory of Mind task involving only limited mentalization) being mostly impaired by posterior temporoparietal lesions. Tasks relying on higher-level mentalization (Tasks 3 and 4) were maximally affected by prefrontal lesions, with the alexithymia scale (Task 3) being mostly associated with anterior/medial lesions and the self-maturity measure (Task 4) with lateral prefrontal ones. PMID:25027503
Campanella, Fabio; Shallice, Tim; Ius, Tamara; Fabbro, Franco; Skrap, Miran
There is a recent increase in the use of multivariate analysis and pattern classification in prediction and real-time feedback of brain states from functional imaging signals and mapping of spatio-temporal patterns of brain activity. Here we present MANAS, a generalized software toolbox for performing online and offline classification of fMRI signals. MANAS has been developed using MATLAB, LIBSVM, and SVMlight packages to achieve a cross-platform environment. MANAS is targeted for neuroscience investigations and brain rehabilitation applications, based on neurofeedback and brain-computer interface (BCI) paradigms. MANAS provides two different approaches for real-time classification: subject dependent and subject independent classification. In this article, we present the methodology of real-time subject dependent and subject independent pattern classification of fMRI signals; the MANAS software architecture and subsystems; and finally demonstrate the use of the system with experimental results. PMID:24151454
Rana, Mohit; Gupta, Nalin; Dalboni Da Rocha, Josue L.; Lee, Sangkyun; Sitaram, Ranganatha
There is a recent increase in the use of multivariate analysis and pattern classification in prediction and real-time feedback of brain states from functional imaging signals and mapping of spatio-temporal patterns of brain activity. Here we present MANAS, a generalized software toolbox for performing online and offline classification of fMRI signals. MANAS has been developed using MATLAB, LIBSVM, and SVMlight packages to achieve a cross-platform environment. MANAS is targeted for neuroscience investigations and brain rehabilitation applications, based on neurofeedback and brain-computer interface (BCI) paradigms. MANAS provides two different approaches for real-time classification: subject dependent and subject independent classification. In this article, we present the methodology of real-time subject dependent and subject independent pattern classification of fMRI signals; the MANAS software architecture and subsystems; and finally demonstrate the use of the system with experimental results. PMID:24151454
Rana, Mohit; Gupta, Nalin; Dalboni Da Rocha, Josue L; Lee, Sangkyun; Sitaram, Ranganatha
The Na +-independent L-type LAT1 amino acid transport system for large and neutral amino acids has been shown to be expressed higher in tumour tissue relative to normal tissue and has been regarded as a key point for the development of new amino acid based tumour tracers for molecular imaging. We developed a new fluorinated phenylalanine analogue, 2-[ 18F]fluoromethyl- L-phenylalanine, considering that the spatial volume of FCH 3 is comparable with that of the iodine atom in 2-I- L-phenylalanine, of which we have proven that it is taken up excellently in tumours by the LAT1 system. The substrate molecule for radiolabeling, Boc-2-bromomethyl- L-phenylalanine- tButylester, was prepared by radical bromination of Boc-2-methyl- L-phenylalanine- tButylester. [ 18F -] for bromine exchange is performed within 3 min in conditions comparable to the [ 18F]FDG synthesis with a radiochemical yield of at least 85%. After deprotection and semi-preparative HPLC purification, the 2-[ 18F]fluoromethyl- L-phenylalanine is recovered n.c.a. (57%) with a high purity and 3.7 MBq were injected into R1M rhabdomyosarcoma tumour-bearing rats. Imaging was performed with a human PET camera from 5 to 45 min p.i. The tumour/background and tumour/blood ratios obtained from PET acquisition were at least 2.5. DUR values for the tumours were at least about 5. Furthermore, a small tumour implanted near a kidney could be well visualized completely separated from this kidney. Moreover in all tumours the "active" tumour tissue can clearly be differentiated from less active tumour tissue. This proves that 2-[ 18F]fluoromethyl- L-phenylalanine has a great potential as a new tracer for specific tumour diagnosis with PET.
Kersemans, Ken; Bauwens, Matthias; Lahoutte, Tony; Bossuyt, Axel; Mertens, John
Introduction. Among brain tumours, those arising from the deep brain are rare. In many cases they are low-grade astrocytomas. But primitive neuroectodermal tumours, ganglion cell tumours, oligodendrogliomas, lymphomas, and germinal neoplasms can also grow up from the basal ganglia and thalamic region. In other occasions peripheral neoplasms developing in neighbouring structures like the cerebral lobes, the ventricular walls, choroidal plexus,
José M. García-Santos; Silvia Torres del Río; Ana Sánchez; Juan F. Martínez-Lage
Objectives To compare assignment of occupational pesticide and solvent exposure using self?reported data collected by a computer assisted personal interview (CAPI) with exposure based on expert assessment of job codes. To discuss the advantages and disadvantages of using a CAPI to collect individual occupational exposure data. Methods Between 2001 and 2004, 1495 participants were interviewed using a CAPI for a case?control study of adult brain tumours and acoustic neuromas. Two types of occupational data were collected: (1) a full history, including job title from which a job code was assigned from the Standard Occupational Classification; and (2) specific details on pesticide and solvent exposure reported by participants. Study members' experiences of using the CAPI were recorded and advantages and disadvantages summarised. Results Of 7192 jobs recorded, the prevalence of self?reported exposure was 1.3% for pesticides and 11.5% for solvents. Comparing this with exposure expertly assessed from job titles showed 53.6% and 45.8% concordance for pesticides and solvents respectively. Advantages of the CAPI include no data entry stage, automatic input validation, and a reduction in interviewer bias. Disadvantages include an adverse effect on study implementation as a consequence of resources required for programming and difficulties encountered with data management prior to analysis. Conclusions Different methods of exposure assessment derive different exposure levels for pesticide and solvent exposure at work. Agreement between self?reported and expert assessment of exposure was greater for pesticides compared to solvents. The advantages of using a CAPI for the collection of complex data outweigh the disadvantages for interviewers and data quality but using such a method requires extra resources at the study outset. PMID:16556747
Hepworth, S J; Bolton, A; Parslow, R C; van Tongeren, M; Muir, K R; McKinney, P A
We improved the performance of a functional near-infrared spectroscopy (fNIRS)-based brain-computer interface based on relatively short task duration and multiclass classification. A custom-built eight-channel fNIRS system was used over the motor cortex areas in both hemispheres to measure the hemodynamic responses evoked by four different motor tasks (overt execution of arm lifting and knee extension for both sides) instead of finger tapping. The hemodynamic responses were classified using the naive Bayes classifier. Among the mean, max, slope, variance, and median of the signal amplitude and the time lag of the signal, several signal features are chosen to obtain highest classification accuracy. Ten runs of threefold cross-validation were conducted, which yielded classification accuracies of 87.1%±2.4% to 95.5%±2.4%, 77.5%±1.9% to 92.4%±3.2%, and 73.8%±3.5% to 91.5%±1.4% for the binary, ternary, and quaternary classifications, respectively. Eight seconds of task duration for obtaining sufficient quaternary classification accuracy was suggested. The bit transfer rate per minute (BPM) based on the quaternary classification accuracy was investigated. A BPM can be achieved from 2.81 to 5.40 bits/min. PMID:24967916
Shin, Jaeyoung; Jeong, Jichai
Objective This study proposes an automated diagnostic method to classify patients with Alzheimer's disease (AD) of degenerative etiology using magnetic resonance imaging (MRI) markers. Methods Twenty-seven patients with subjective memory impairment (SMI), 18 patients with mild cognitive impairment (MCI), and 27 patients with AD participated. MRI protocols included three dimensional brain structural imaging and diffusion tensor imaging to assess the cortical thickness, subcortical volume and white matter integrity. Recursive feature elimination based on support vector machine (SVM) was conducted to determine the most relevant features for classifying abnormal regions and imaging parameters, and then a factor analysis for the top-ranked factors was performed. Subjects were classified using nonlinear SVM. Results Medial temporal regions in AD patients were dominantly detected with cortical thinning and volume atrophy compared with SMI and MCI patients. Damage to white matter integrity was also accredited with decreased fractional anisotropy and increased mean diffusivity (MD) across the three groups. The microscopic damage in the subcortical gray matter was reflected in increased MD. Classification accuracy between pairs of groups (SMI vs. MCI, MCI vs. AD, SMI vs. AD) and among all three groups were 84.4% (±13.8), 86.9% (±10.5), 96.3% (±4.6), and 70.5% (±11.5), respectively. Conclusion This proposed method may be a potential tool to diagnose AD pathology with the current clinical criteria.
Jung, Won Beom; Lee, Young Min; Kim, Young Hoon
This article describes a classification and imaging diagnosis of intracranial midline cystic malformations based on neuroembryologic analysis. Midline cystic malformations are classified into two categories from an embryologic point of view. In one category, the cyst represents expansion of the roof plate of the brain vesicle, and in the other the cyst consists of extraaxial structures such as an arachnoid membrane or migrating ependymal cells. Infratentorial cysts, such as the Dandy-Walker cyst or Blake's pouch cyst, and supratentorial cysts, such as a communicating interhemispheric cyst with callosal agenesis or a dorsal cyst with holoprosencephaly, are included in the first category. Infratentorial arachnoid cavities, such as the arachnoid cyst, arachnoid pouch, and mega cisterna magna, are in the second category. Noncommunicating interhemispheric cysts, such as interhemispheric arachnoid cyst or ependymal cyst, with callosal agenesis are also in the second category. A careful review of embryologic development is essential for understanding these midline cysts and for making a more accurate radiologic diagnosis. PMID:16958432
Utsunomiya, Hidetsuna; Yamashita, Shinichi; Takano, Koichi; Ueda, Yukiyo; Fujii, Akira
In this study, subsets of MR slices were examined to assess their ability to optimally predict the total cerebral volume of gray matter, white matter and CSF. Patients underwent a clinical imaging protocol consisting of T1-, T2-, PD-, and FLAIR-weighted images after obtaining informed consent. MR imaging sets were registered, RF-corrected, and then analyzed with a hybrid neural network segmentation and classification algorithm to identify normal brain parenchyma. After processing the data, the correlation between the image subsets and the total cerebral volumes of gray matter, white matter and CSF were examined. The 29 subjects (18F, 11M) assessed in this study were 1.7 ? 18.7 (median = 5.2) years of age. The five subsets accounted for 5%, 15%, 24%, 56%, and 79% of the total cerebral volume. The predictive correlation for gray matter, white matter, and CSF in each of these subsets were: 5% (R= 0.94, 0.92, 0.91), 15% (R= 0.93, 0.95, 0.94), 24% (R= 0.92, 0.95, 0.94), 56% (R= 0.75, 0.95, 0.89), and 79% (R= 0.89, 0.98, 0.99) respectively. All subsets of slices examined were significantly correlated (p<0.001) with the total cerebral volume of gray matter, white matter, and CSF.
Glass, John O.; Reddick, Wilburn E.; Ji, Qing; Glas, Lauren S.
Parcellation of the cortex has received a great deal of attention in magnetic resonance (MR) image analysis, but its usefulness has been limited by time-consuming algorithms that require manual labeling. An automatic labeling scheme is necessary to accurately and consistently parcellate a large number of brains. The large variation of cortical folding patterns makes automatic labeling a challenging problem, which cannot be solved by deformable atlas registration alone. In this work, an automated classification scheme that consists of a mix of both atlas driven and data driven methods is proposed to label the sulcal regions, which are defined as the gray matter regions of the cortical surface surrounding each sulcus. The premise for this algorithm is that sulcal regions can be classified according to the pattern of anatomical features (e.g. supramarginal gyrus, cuneus, etc.) associated with each region. Using a nearest-neighbor approach, a sulcal region is classified as being in the same class as the sulcus from a set of training data which has the nearest pattern of anatomical features. Using just one subject as training data, the algorithm correctly labeled 83% of the regions that make up the main sulci of the cortex.
Behnke, Kirsten J.; Rettmann, Maryam E.; Pham, Dzung L.; Shen, Dinggang; Resnick, Susan M.; Davatzikos, Christos; Prince, Jerry L.
Project Overview: Classification is grouping similar objects together. When you go into a grocery store, you see fresh fruits and vegetables, frozen food, cereal, and pet suplies in different aisles. Imagine how difficult life would be if you went into a store, and the aisles were not labeled to tell you where to find the items! You don't have to be a scientist to use classification! You use classification when you group your IPOD music into different genres and when you divide your dark colored clothing from light colors to do laundry. You might even use it to sort Halloween candy into 4 groups: chocolate candy, hard candy, chewy candy, and gum. The science of classification is called taxonomy. Taxonomy classifies organisms based on evolutionary relationships and describes and names organisms with a two-part name: genus and species. Scientists use taxonomy to identify unknown organisms by using books called field guides or by using taxonomic keys (also called dichomotous keys). Project Objective: As a class,you will be previewing and answering some questions about some classification resources to learn how to use a dichotomous key, how to key a specimen, and to help you write your own dichotomous key for school items. Project: Get a sheet of notebook paper and pencil and refer to the websites to find the answers to the questions. One way to classify objects is to create a "tree" to group similar objects together.Open hierarchical classfication of objects to the second page and find the diagram of common household objects. See how all the ...
N-terminal brain natriuretic peptide is a more powerful predictor of mortality than endothelin-1, adrenomedullin and tumour necrosis factor-a in patients referred for consideration of cardiac transplantation
Background: The selection of patients for cardiac transplantation is notoriously difficult. We have demonstrated that N-terminal brain natriuretic peptide (NT-proBNP) is a powerful predictor of mortality in advanced heart failure and is superior to the traditional markers of chronic heart failure (CHF) severity. However, the comparative prognostic power of endothelin-1 (Et-1), adrenomedullin (Adm) and tumour necrosis factor-alpha (TNF-a) in this
Roy S. Gardner; Victor Chong; Iain Morton; Theresa A. McDonagh
Two main issues for event-related potential (ERP) classification in brain-computer interface (BCI) application are curse-of-dimensionality and bias-variance tradeoff, which may deteriorate classification performance, especially with insufficient training samples resulted from limited calibration time. This study introduces an aggregation of sparse linear discriminant analyses (ASLDA) to overcome these problems. In the ASLDA, multiple sparse discriminant vectors are learned from differently l1-regularized least-squares regressions by exploiting the equivalence between LDA and least-squares regression, and are subsequently aggregated to form an ensemble classifier, which could not only implement automatic feature selection for dimensionality reduction to alleviate curse-of-dimensionality, but also decrease the variance to improve generalization capacity for new test samples. Extensive investigation and comparison are carried out among the ASLDA, the ordinary LDA and other competing ERP classification algorithms, based on different three ERP datasets. Experimental results indicate that the ASLDA yields better overall performance for single-trial ERP classification when insufficient training samples are available. This suggests the proposed ASLDA is promising for ERP classification in small sample size scenario to improve the practicability of BCI. PMID:24344691
Zhang, Yu; Zhou, Guoxu; Jin, Jing; Zhao, Qibin; Wang, Xingyu; Cichocki, Andrzej
Functional MR imaging (fMRI) enables to detect different activated brain areas according to the performed tasks. However, data are usually evaluated after the experiment, which prohibits intra-experiment optimization or more sophisticated applications such as biofeedback experiments. Using a human-brain-interface (HBI), subjects are able to communicate with external programs, e.g. to navigate through virtual scenes, or to experience and modify their
Tobias Moench; Maurice Hollmann; Ramona Grzeschik; Charles Mueller; Ralf Luetzkendorf; Sebastian Baecke; Michael Luchtmann; Daniela Wagegg; Johannes Bernarding
Traumatic Brain Injuries Tianxia Gong, Nengli Lim, Li Cheng, Hwee Kuan Lee Bioinformatics Institute Agency of traumatic brain injury (TBI) patients with hematomas. Hematoma caused by blood vessel rupture is the major diagnosis have become popular research topics. For traumatic brain injury (TBI), head computed tomography
Tan, Chew Lim
Functional near infrared spectroscopy (fNIRS) is an emerging technique for the in-vivo assessment of functional activity of the cerebral cortex as well as in the field of brain-computer-interface (BCI) research. A common challenge for the utilization of fNIRS for BCIs is a stable and reliable single trial classification of the recorded spatio-temporal hemodynamic patterns. Many different classification methods are available, but up to now, not more than two different classifiers were evaluated and compared on one data set. In this work, we overcome this issue by comparing five different classification methods on mental arithmetic fNIRS data: linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), support vector machines (SVM), analytic shrinkage regularized LDA (sLDA), and analytic shrinkage regularized QDA (sQDA). Depending on the used method and feature type (oxy-Hb or deoxy-Hb), achieved classification results vary between 56.1 % (deoxy-Hb/QDA) and 86.6% (oxy-Hb/SVM). We demonstrated that regularized classifiers perform significantly better than non-regularized ones. Considering simplicity and computational effort, we recommend the use of sLDA for fNIRS-based BCIs. PMID:25570376
Bauernfeind, Gunther; Steyrl, David; Brunner, Clemens; Muller-Putz, Gernot R
Controversy surrounds the classification of posttraumatic stress disorder (PTSD), particularly in children and adolescents with traumatic brain injury (TBI). In these populations, it is difficult to differentiate TBI-related organic memory loss from dissociative amnesia. Several alternative PTSD classification algorithms have been proposed for use with children. This paper investigates DSM-IV-TR and alternative PTSD classification algorithms, including and excluding the dissociative amnesia item, in terms of their ability to predict psychosocial function following pediatric TBI. A sample of 184 children aged 6-14 years were recruited following emergency department presentation and/or hospital admission for TBI. PTSD was assessed via semi-structured clinical interview (CAPS-CA) with the child at 3 months post-injury. Psychosocial function was assessed using the parent report CHQ-PF50. Two alternative classification algorithms, the PTSD-AA and 2 of 3 algorithms, reached statistical significance. While the inclusion of the dissociative amnesia item increased prevalence rates across algorithms, it generally resulted in weaker associations with psychosocial function. The PTSD-AA algorithm appears to have the strongest association with psychosocial function following TBI in children and adolescents. Removing the dissociative amnesia item from the diagnostic algorithm generally results in improved validity. PMID:20541906
Iselin, Greg; Le Brocque, Robyne; Kenardy, Justin; Anderson, Vicki; McKinlay, Lynne
This off-line study aims to assess the performance of five classifiers commonly used in the brain-computer interface (BCI) community, when applied to a gaze-independent P300-based BCI. In particular, we compared the results of four linear classifiers and one nonlinear: Fisher's linear discriminant analysis (LDA), stepwise linear discriminant analysis (SWLDA), Bayesian linear discriminant analysis (BLDA), linear support vector machine (LSVM) and Gaussian supported vector machine (GSVM). Moreover, different values for the decimation of the training dataset were tested. The results were evaluated both in terms of accuracy and written symbol rate with the data of 19 healthy subjects. No significant differences among the considered classifiers were found. The optimal decimation factor spanned a range from 3 to 24 (12 to 94 ms long bins). Nevertheless, performance on individually optimized classification parameters is not significantly different from a classification with general parameters (i.e. using an LDA classifier, about 48 ms long bins).
Aloise, F.; Schettini, F.; Aricò, P.; Salinari, S.; Babiloni, F.; Cincotti, F.
The automatic segmentation of brain tissues in magnetic resonance (MR) is usually performed on T1-weighted images, due to their high spatial resolution. T1w sequence, however, has some major downsides when brain lesions are present: the altered appearance of diseased tissues causes errors in tissues classification. In order to overcome these drawbacks, we employed two different MR sequences: fluid attenuated inversion recovery (FLAIR) and double inversion recovery (DIR). The former highlights both gray matter (GM) and white matter (WM), the latter highlights GM alone. We propose here a supervised classification scheme that does not require any anatomical a priori information to identify the 3 classes, "GM", "WM", and "background". Features are extracted by means of a local multi-scale texture analysis, computed for each pixel of the DIR and FLAIR sequences. The 9 textures considered are average, standard deviation, kurtosis, entropy, contrast, correlation, energy, homogeneity, and skewness, evaluated on a neighborhood of 3x3, 5x5, and 7x7 pixels. Hence, the total number of features associated to a pixel is 56 (9 textures x3 scales x2 sequences +2 original pixel values). The classifier employed is a Support Vector Machine with Radial Basis Function as kernel. From each of the 4 brain volumes evaluated, a DIR and a FLAIR slice have been selected and manually segmented by 2 expert neurologists, providing 1st and 2nd human reference observations which agree with an average accuracy of 99.03%. SVM performances have been assessed with a 4-fold cross-validation, yielding an average classification accuracy of 98.79%.
Poletti, Enea; Veronese, Elisa; Calabrese, Massimiliano; Bertoldo, Alessandra; Grisan, Enrico
Angiogenesis, the formation of new blood vessels, is required for the growth and expansion of tumours. Gliomas, the most common brain tumours, are particularly highly vascularized and, therefore, serve as a model to elucidate the process of tumour angiogenesis and to investigate new anti-angiogenic therapies. This review describes the role of angiogenic factors in glioma angiogenesis and new strategies to
Rolf Mentlein; Janka Held-Feindt
Structural brain imaging is playing a vital role in identification of changes that occur in brain associated with Alzheimer's disease. This paper proposes an automated image processing based approach for the identification of AD from MRI of the brain. The proposed approach is novel in a sense that it has higher specificity/accuracy values despite the use of smaller feature set as compared to existing approaches. Moreover, the proposed approach is capable of identifying AD patients in early stages. The dataset selected consists of 85 age and gender matched individuals from OASIS database. The features selected are volume of GM, WM, and CSF and size of hippocampus. Three different classification models (SVM, MLP, and J48) are used for identification of patients and controls. In addition, an ensemble of classifiers, based on majority voting, is adopted to overcome the error caused by an independent base classifier. Ten-fold cross validation strategy is applied for the evaluation of our scheme. Moreover, to evaluate the performance of proposed approach, individual features and combination of features are fed to individual classifiers and ensemble based classifier. Using size of left hippocampus as feature, the accuracy achieved with ensemble of classifiers is 93.75%, with 100% specificity and 87.5% sensitivity. PMID:25276224
Farhan, Saima; Tauseef, Huma
Quantitative analysis of magnetic resonance (MR) brain images are facilitated by the development of automated segmentation algorithms. A single image voxel may contain of several types of tissues due to the finite spatial resolution of the imaging device. This phenomenon, termed partial volume effect (PVE), complicates the segmentation process, and, due to the complexity of human brain anatomy, the PVE is an important factor for accurate brain structure quantification. Partial volume estimation refers to a generalized segmentation task where the amount of each tissue type within each voxel is solved. This review aims to provide a systematic, tutorial-like overview and categorization of methods for partial volume estimation in brain MRI. The review concentrates on the statistically based approaches for partial volume estimation and also explains differences to other, similar image segmentation approaches. PMID:25431640
parameter of the tissue . With MR imaging, acquisition parameters, or 'pulse sequences', can be tailored to differentially weight the contribution of three variables affecting signal intensity: proton density (PD), spin-lattice relax- ation time (Tl... computer . " Neural network models, simulations, and architectures are often greatly simplified because of the complexity of the human brain  . The human brain is a complex structure composed of billions of nerve cells, neurons , [40...
Kischell, Eric Robert
) classifiers. Classification accuracy was assessed using a stratified random sampling scheme. The results. Feature extraction tech- niques such as peak integration, including also the automated quantitation method integration feature extraction method. I. INTRODUCTION Ex-vivo high resolution magic angle spinning (HR
The paper describes work on the brain--computer interface (BCI). The BCI is designed to help patients with severe motor impairment (e.g. amyotropic lateral sclerosis) to communicate with their environment through wilful modification of their EEG. To establish such a communication channel, two major prerequisites have to be fulfilled: features that reliably describe several distinctive brain states have to be available, and these features must be classified on-line, i.e. on a single-trial basis. The prototype Graz BCI II, which is based on the distinction of three different types of EEG pattern, is described, and results of online and offline classification performance of four subjects are reported. The online results suggest that, in the best case, a classification accuracy of about 60% is reached after only three training sessions. The online results show how selection of specific frequency bands influences the classification performance in single-trial data. PMID:8945865
Kalcher, J; Flotzinger, D; Neuper, C; Gölly, S; Pfurtscheller, G
pathologies (e.g. Alzheimer's disease). The study of RSNs in fMRI data is a typical blind source separationMRI signals and because they have been shown to differ between the normal and diseased brain in some and pro- cessing time. Although the co-localisation of RSNs and regions affected by physiological (PHY
Objective: To test the hypothesis that a combination of magnetic resonance imaging (MRI) brain measures obtained during early childhood distinguish children with autism spectrum disorders (ASD) from typically developing children and is associated with functional outcome. Method: Quantitative MRI technology was used to measure gray and white matter…
Akshoomoff, Natacha; Lord, Catherine; Lincoln, Alan J.; Courchesne, Rachel Y.; Carper, Ruth A.; Townsend, Jeanne; Courchesne, Eric
The present study determined specificity and sensitivity to malingered neurocognitive dysfunction (MND) in traumatic brain injury (TBI) for several Wechsler Adult Intelligence Scale (WAIS) Digit Span scores. TBI patients (n = 344) were categorized into one of five groups: no incentive, incentive only, suspect, probable MND, and definite MND.…
Heinly, Matthew T.; Greve, Kevin W.; Bianchini, Kevin J.; Love, Jeffrey M.; Brennan, Adrianne
Parametric modeling strategies are explored in conjunction with linear discriminant analysis for use in an electroencephalogram (EEG)-based brain-computer interface (BCI). A left\\/right self-paced typing exercise is analyzed by extending the usual autoregressive (AR) model for EEG feature extraction with an AR with exogenous input (ARX) model for combined filtering and feature extraction. The ensemble averaged Bereitschaftspotential (an event related potential
Dave P. Burke; Simon P. Kelly; Philip de Chazal; Richard B. Reilly; Ciarán Finucane
A new technique is presented to create nosologic images of the brain based on magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI). A nosologic image summarizes the presence of different tissues and lesions in a single image by color coding each voxel or pixel according to the histopathological class it is assigned to. The proposed technique applies advanced methods from image processing as well as pattern recognition to segment and classify brain tumors. First, a registered brain atlas and a subject-specific abnormal tissue prior, obtained from MRSI data, are used for the segmentation. Next, the detected abnormal tissue is classified based on supervised pattern recognition methods. Class probabilities are also calculated for the segmented abnormal region. Compared to previous approaches, the new framework is more flexible and able to better exploit spatial information leading to improved nosologic images. The combined scheme offers a new way to produce high-resolution nosologic images, representing tumor heterogeneity and class probabilities, which may help clinicians in decision making. PMID:19105242
Luts, Jan; Laudadio, Teresa; Idema, Albert J; Simonetti, Arjan W; Heerschap, Arend; Vandermeulen, Dirk; Suykens, Johan A K; Van Huffel, Sabine
Although classification of astrocytic tumors is standardized by the WHO grading system, which is mainly based on microscopy-derived, histomorphological features, there is great interobserver variability. The main causes are thought to be the complexity of morphological details varying from tumor to tumor and from patient to patient, variations in the technical histopathological procedures like staining protocols, and finally the individual experience of the diagnosing pathologist. Thus, to raise astrocytoma grading to a more objective standard, this paper proposes a methodology based on atomic force microscopy (AFM) derived images made from histopathological samples in combination with data mining techniques. By comparing AFM images with corresponding light microscopy images of the same area, the progressive formation of cavities due to cell necrosis was identified as a typical morphological marker for a computer-assisted analysis. Using genetic programming as a tool for feature analysis, a best model was created that achieved 94.74% classification accuracy in distinguishing grade II tumors from grade IV ones. While utilizing modern image analysis techniques, AFM may become an important tool in astrocytic tumor diagnosis. By this way patients suffering from grade II tumors are identified unambiguously, having a less risk for malignant transformation. They would benefit from early adjuvant therapies. PMID:24062997
Huml, Marlene; Silye, René; Zauner, Gerald
Characterization and quantification of magnetic resonance perfusion images is important for clinical interpretation, though this calls for a reproducible and accurate method of analysis and a robust healthy reference. The few studies which have examined the perfusion of the healthy brain using dynamic susceptibility contrast (DSC) imaging were largely limited to manual definition of the regions of interest (ROI) and results were dependent on the location of the ROI. The current study aimed to develop a methodology for DSC data analysis and to obtain reference values of healthy subjects. Twenty three healthy volunteers underwent DSC. An unsupervised multiparametric clustering method was applied to four perfusion parameters. Three clusters were defined and identified as: dura-blood-vessels, gray matter and white matter and their vascular characteristics were obtained. Additionally, regional perfusion differences were studied and revealed a prolonged mean transient time and a trend for higher vascularity in the posterior compared with the anterior and middle cerebral vascular territories. While additional studies are required to confirm our findings, this result may have important clinical implications. The proposed unsupervised multiparametric method enabled accurate tissue differentiation, is easy replicable and has a wide range of applications in both pathological and healthy brains. PMID:21419230
Artzi, M; Aizenstein, O; Hendler, T; Ben Bashat, D
Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are rare tumours that present many clinical features. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects. In 2000 the WHO developed a new classification which gives a better description of the characteristics and biological behaviour of the tumour. Surgical
Marialuisa Appetecchia; Roberto Baldelli
Oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development, but its investigation has so far been restricted to cultured cells that have been manipulated to overexpress an oncogene. Here we analyse tumours initiated by an endogenous oncogene, ras, and show that senescent cells exist in premalignant tumours but not in malignant ones. Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer.
Collado, Manuel; Gil, Jesús; Efeyan, Alejo; Guerra, Carmen; Schuhmacher, Alberto J.; Barradas, Marta; Benguría, Alberto; Zaballos, Angel; Flores, Juana M.; Barbacid, Mariano; Beach, David; Serrano, Manuel
Purpose: To explore whether gender and race influence survival in non-small-cell lung cancer (NSCLC) in patients with brain metastases, using our large single-institution brain tumor database and the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) brain metastases classification. Methods and materials: A retrospective review of a single-institution brain metastasis database for the interval January 1982 to September 2004 yielded 835 NSCLC patients with brain metastases for analysis. Patient subsets based on combinations of gender, race, and RPA class were then analyzed for survival differences. Results: Median follow-up was 5.4 months (range, 0-122.9 months). There were 485 male patients (M) (58.4%) and 346 female patients (F) (41.6%). Of the 828 evaluable patients (99%), 143 (17%) were black/African American (B) and 685 (83%) were white/Caucasian (W). Median survival time (MST) from time of brain metastasis diagnosis for all patients was 5.8 months. Median survival time by gender (F vs. M) and race (W vs. B) was 6.3 months vs. 5.5 months (p = 0.013) and 6.0 months vs. 5.2 months (p = 0.08), respectively. For patients stratified by RPA class, gender, and race, MST significantly favored BFs over BMs in Class II: 11.2 months vs. 4.6 months (p = 0.021). On multivariable analysis, significant variables were gender (p = 0.041, relative risk [RR] 0.83) and RPA class (p < 0.0001, RR 0.28 for I vs. III; p < 0.0001, RR 0.51 for II vs. III) but not race. Conclusions: Gender significantly influences NSCLC brain metastasis survival. Race trended to significance in overall survival but was not significant on multivariable analysis. Multivariable analysis identified gender and RPA classification as significant variables with respect to survival.
Videtic, Gregory M.M., E-mail: firstname.lastname@example.org [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Reddy, Chandana A. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Chao, Samuel T. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Brain Tumor and NeuroOncology Center, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Rice, Thomas W. [Department of Thoracic and Cardiovascular Surgery, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Adelstein, David J. [Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Barnett, Gene H. [Brain Tumor and NeuroOncology Center, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Department of Neurosurgery, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Mekhail, Tarek M. [Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Vogelbaum, Michael A. [Brain Tumor and NeuroOncology Center, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Department of Neurosurgery, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Suh, John H. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States); Brain Tumor and NeuroOncology Center, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH (United States)
We employed a multi-scale clustering methodology known as "data cloud geometry" to extract functional connectivity patterns derived from functional magnetic resonance imaging (fMRI) protocol. The method was applied to correlation matrices of 106 regions of interest (ROIs) in 29 individuals with autism spectrum disorders (ASD), and 29 individuals with typical development (TD) while they completed a cognitive control task. Connectivity clustering geometry was examined at both "fine" and "coarse" scales. At the coarse scale, the connectivity clustering geometry produced 10 valid clusters with a coherent relationship to neural anatomy. A supervised learning algorithm employed fine scale information about clustering motif configurations and prevalence, and coarse scale information about intra- and inter-regional connectivity; the algorithm correctly classified ASD and TD participants with sensitivity of 82.8% and specificity of 82.8%. Most of the predictive power of the logistic regression model resided at the level of the fine-scale clustering geometry, suggesting that cellular versus systems level disturbances are more prominent in individuals with ASD. This article provides validation for this multi-scale geometric approach to extracting brain functional connectivity pattern information and for its use in classification of ASD. PMID:23056205
Wang, Hui; Chen, Chen; Fushing, Hsieh
Fluorescence molecular tomography (FMT) systems coupled to conventional imaging modalities such as magnetic resonance imaging (MRI) and computed tomography provide unique opportunities to combine data sets and improve image quality and content. Yet, the ideal approach to combine these complementary data is still not obvious. This preclinical study compares several methods for incorporating MRI spatial prior information into FMT imaging algorithms in the context of in vivo tissue diagnosis. Populations of mice inoculated with brain tumors that expressed either high or low levels of epidermal growth factor receptor (EGFR) were imaged using an EGF-bound near-infrared dye and a spectrometer-based MRI-FMT scanner. All data were spectrally unmixed to extract the dye fluorescence from the tissue autofluorescence. Methods to combine the two data sets were compared using student's t-tests and receiver operating characteristic analysis. Bulk fluorescence measurements that made up the optical imaging data set were also considered in the comparison. While most techniques were able to distinguish EGFR(+) tumors from EGFR(-) tumors and control animals, with area-under-the-curve values=1, only a handful were able to distinguish EGFR(-) tumors from controls. Bulk fluorescence spectroscopy techniques performed as well as most imaging techniques, suggesting that complex imaging algorithms may be unnecessary to diagnose EGFR status in these tissue volumes.
Davis, Scott C.; Samkoe, Kimberley S.; O'Hara, Julia A.; Gibbs-Strauss, Summer L.; Paulsen, Keith D.; Pogue, Brian W.
Oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development, but its investigation has so far been restricted to cultured cells that have been manipulated to overexpress an oncogene. Here we analyse tumours initiated by an endogenous oncogene, ras, and show that senescent cells exist in premalignant tumours but not in malignant ones. Senescence is
Manuel Collado; Jesús Gil; Alejo Efeyan; Carmen Guerra; Alberto J. Schuhmacher; Marta Barradas; Alberto Benguría; Angel Zaballos; Juana M. Flores; Mariano Barbacid; David Beach; Manuel Serrano
RECORDINGS IN A BRAIN COMPUTER INTERFACE TASK N. Firat INCE1,2 , Sami ARICA2 , Ahmed H. TEWFIK1,2 Department oscillations induced by motor imagery in a Brain Computer Interface task. The proposed method requires no prior has gained significant interest in the last several years. The Brain Computer Interface (BCI
Minnesota, University of
The members of the French Society of Pediatric Oncology treated, between January 1985 and June 1989, 67 cases of non-metastatic, non-seminomatous malignant germ cell tumours (nSGCT) in sites other than the brain. They used a clinical pre- and postsurgical TNM-type classification in order to standardize the treatment regardless of tumour site. The intensity of the treatment was decreased in comparison with the previous regimen (elimination of adriamycin, reduction in the length of treatment). The actuarial 2-year disease-free survival rate is 80%; results are excellent for patients with clinical stage I and II tumours and permit cure with moderate chemotherapy, avoiding undesirable late effects. On the other hand it is inadequate for patients with stage III suggesting that the initial chemotherapy should be intensified for these latter patients in future protocols. PMID:8390599
Baranzelli, M C; Flamant, F; De Lumley, L; Le Gall, E; Lejars, O
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 schwannomas. Measuring concentrations of various proteins [albumin, immunoglobulin G (IgG), IgA, alpha 2-macroglobulin and IgM] in cyst fluid, CSF and blood plasma provides insight into the state of the semipermeability of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier. Peritumoral cysts accompanying intra-axial brain tumours are the end result of disruption of the BBB and oedema formation. Unlike intra-axial tumours which lie embedded within nervous tissue, extra-axial tumours tend to be separated from nervous tissue by arachnoid and pia mater. High concentrations of proteins were measured in the cyst fluid, approaching blood plasma levels, suggesting a local barrier disruption, and passage across the arachnoid, pia mater and cortical/medullary layer into the CNS parenchyma, leaving the protein concentrations of CSF practically unchanged. We confirmed that very high concentrations of protein are to be found in tumour cysts, plasma proteins forming almost 90% of the total protein in the cyst. We review current hypotheses on the pathogenesis of cysts accompanying neoplasms, particularly meningiomas and schwannomas, and conclude that the majority of proteins in cyst fluid in extra-axial, intradural meningiomas and schwannomas are plasma proteins. This provides a strong argument for pathogenesis of extra-axial intradural tumour cysts in favour of leakage of plasma proteins out of the tumour vessels into the nervous tissue. PMID:9987761
Lohle, P N; Wurzer, H A; Seelen, P J; Kingma, L M; Go, K G
All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves, notochord remnants, etc.) can give rise to benign\\u000a or malignant tumours. Bone metastases and intraosseous sites of haematological malignancies, lymphoma and multiple myeloma\\u000a are the most frequent aetiologies, while primary bone tumours and meningeal or nerve tumours are less common. Some histological\\u000a types have a predilection for the sacrum,
S. Gerber; L. Ollivier; J. Leclère; D. Vanel; G. Missenard; H. Brisse; G. de Pinieux; S. Neuenschwander
The morphometric differences between the urothelial cells (wet-fixed Papanicolaoustained) in the voided urine of 2 patients with low grade and high grade bladder tumours were measured. The morphometrical data of this learning set resulted in a cytomorphometrical classification rule, which was applied to a test set of 21 cases with low grade and high grade bladder tumours. The results of the cytomorphometrical classification rule correspond very well with the histomorphometrical classification and the histological grade of the parent tumours. The results indicate that it is feasible to classify bladder tumours using the cytomorphometrical data of the exfoliated urothelial cells alone. PMID:7130416
Ooms, E C; Kurver, P J; Boon, M E
Monitoring response to treatment of tumours is an increasingly important aspect of cancer radiology for several reasons. Firstly, the incidence of cancer is increasing and, furthermore, there have been major advances in treatment which have resulted in a larger number of patients surviving with treated tumours. Equally important is that there have been enormous advances in imaging over the past
J. E. Husband
It is now accepted that the growth of solid tumours is dependent on their capacity to acquire a blood supply, and much effort has been directed towards the development of agents (known as anti-angiogenics) that disrupt this process. More recently, it has become apparent that targeted destruction of the established tumour vasculature is another avenue for exciting therapeutic opportunities. In
Dario Neri; Roy Bicknell
The completeness and accuracy of registration of primary intracranial tumours in the Scottish Cancer Registry was compared with a detailed incidence study performed over a two year period (1989-90). Of 228 patients with any primary intracranial tumour in the incidence study, 124 (54%) were identified as intracranial tumours in the cancer registry. The registry excluded benign tumours (although this was not consistent) and so the sensitivity of the registry varied with tumour type (84% for neuroepithelial tumours, 22% meningeal, 29% sellar, 0% cranial nerve). Of the 31 malignant tumours not found in the registry on our initial search, nine were found to have been included between 1989-90 but using different International Classification of Diseases-9th revision (ICD-9) codes or postcodes, and seven were found registered after 1990.Eleven per cent of cases (18/170) identified in the cancer registry were excluded from the incidence study: 11 had evidence of an intracranial tumour before 1989 whereas four definitely did not have an intracranial tumour. The cancer registry therefore significantly underestimated the incidence of all primary intracranial tumours, and of malignant intracranial tumours. Incidence studies must use additional methods to identify all primary tumours. Cancer registries should consider registering all primary intracranial tumours and may improve case ascertainment by screening neuroradiology data.?? PMID:9221974
Counsell, C.; Collie, D.; Grant, R.
Background Brain computer interface (BCI) is an emerging technology for paralyzed patients to communicate with external environments. Among current BCIs, the steady-state visual evoked potential (SSVEP)-based BCI has drawn great attention due to its characteristics of easy preparation, high information transfer rate (ITR), high accuracy, and low cost. However, electroencephalogram (EEG) signals are electrophysiological responses reflecting the underlying neural activities which are dependent upon subject’s physiological states (e.g., emotion, attention, etc.) and usually variant among different individuals. The development of classification approaches to account for each individual’s difference in SSVEP is needed but was seldom reported. Methods This paper presents a multiclass support vector machine (SVM)-based classification approach for gaze-target detections in a phase-tagged SSVEP-based BCI. In the training steps, the amplitude and phase features of SSVEP from off-line recordings were used to train a multiclass SVM for each subject. In the on-line application study, effective epochs which contained sufficient SSVEP information of gaze targets were first determined using Kolmogorov-Smirnov (K-S) test, and the amplitude and phase features of effective epochs were subsequently inputted to the multiclass SVM to recognize user’s gaze targets. Results The on-line performance using the proposed approach has achieved high accuracy (89.88?±?4.76%), fast responding time (effective epoch length?=?1.13?±?0.02 s), and the information transfer rate (ITR) was 50.91?±?8.70 bits/min. Conclusions The multiclass SVM-based classification approach has been successfully implemented to improve the classification accuracy in a phase-tagged SSVEP-based BCI. The present study has shown the multiclass SVM can be effectively adapted to each subject’s SSVEPs to discriminate SSVEP phase information from gazing at different gazed targets. PMID:23692974
Recruitment feasibility to a cohort study of endocrine and metabolic health among survivors of childhood brain tumours: a report from the Canadian study of Determinants of Endometabolic Health in ChIlDrEn (CanDECIDE)
Objectives The aim of this study was to test the feasibility of recruitment and performance of study procedures of the Canadian Study of Determinants of Endometabolic Health in ChIlDrEn (CanDECIDE) study, which was designed to assess the determinants of endocrine and metabolic health in survivors of childhood brain tumours. Setting A single paediatric tertiary care centre in Hamilton, Ontario, Canada. Participants We included boys and girls, aged 5?years and older, who were lean (body mass index (BMI) below 85th centile for age and gender) or overweight/obese (BMI 85th centile or above for age and gender). We excluded children on steroids or immunosuppressant therapy, smokers and those who had an active infection for the 2?weeks prior to participation. Outcomes Feasibility targets included recruitment rate of at least 50%, the consenting of 80% of participants to provide biological samples, 90% questionnaire completion rate and the ability to process biological samples from at least 80% of participants. Results We approached 210 potential participants, and of the 112 (53%) who agreed to participate, 30 (26.8%) completed the study visit over 7?months. All participants agreed to fast, provide biological samples and complete the questionnaires. Sample collection was successful in 97% (29/30) of participants and laboratory procedures were feasible in 100% of collected samples. We also tested resources required for the conduct of the full study including personnel, space, laboratory equipment and procedures and determined that they are all feasible. Conclusions Recruitment and consenting of patients for the CanDECIDE study may be feasible. However, we are considering prolonging recruitment duration and collaboration with other centres to meet recruitment targets due to lower than expected recruitment rate. Completion of questionnaires and implementation of sample processing protocols are feasible. PMID:24969784
Samaan, M Constantine; Scheinemann, Katrin; Burrow, Sarah; Dillenburg, Rejane F; Barr, Ronald D; Wang, Kuan-Wen; Valencia, Marlie; Thabane, Lehana
Analysis of electroencephalogram (EEG) requires a framework that facilitates handling the uncertainties associated with the varying brain dynamics and the presence of noise. Recently, the type-2 fuzzy logic systems (T2 FLSs) have been found effective in modeling uncertain data. This paper examines the potential of the T2 FLS methodology in devising an EEG-based brain-computer interface (BCI). In particular, a T2
P. Herman; G. Prasad; T. M. McGinnity
The purpose of individual 3D region-of-interest atlas extraction is to automatically define anatomically meaningful regions in 3D MRI images for quantification of functional parameters (PET, SPECT: rMRGlu, rCBF). The first step of atlas extraction is to automatically classify brain tissue types into gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), scalp/bone (SB) and background (BG). A feed-forward neural network with back-propagation training algorithm is used and compared to other numerical classifiers. It can be trained by a sample from the individual patient data set in question. Classification is done by a 'winner takes all' decision. Automatic extraction of a user-specified number of training points is done in a cross-sectional slice. Background separation is done by simple region growing. The most homogeneous voxels define the region for WM training point extraction (TPE). Non-white-matter and nonbackground regions are analyzed for GM and CSF training points. For SB TPE, the distance from the BG region is one feature. For each class, spatially uniformly distributed training points are extracted by a random generator from these regions. Simulated and real 3D MRI images are analyzed and error rates for TPE and classification calculated. The resulting class images can be analyzed for extraction of anatomical ROIs.
Wagenknecht, Gudrun; Kaiser, Hans-Juergen; Obladen, Thorsten; Sabri, Osama; Buell, Udalrich
There has been an increase in research interest for brain–computer interface (BCI) technology as an alternate mode of communication and environmental control for the disabled, such as patients suffering from amyotrophic lateral sclerosis (ALS), brainstem stroke and spinal cord injury. Disabled patients with appropriate physical care and cognitive ability to communicate with their social environment continue to live with a
Ranganatha Sitaram; Haihong Zhang; Cuntai Guan; Manoj Thulasidas; Yoko Hoshi; Akihiro Ishikawa; Koji Shimizu; Niels Birbaumer
During the last years interest has been growing to find an effective communication channel which translates human intentions into control signals for a computer, the so called brain-computer interface (BCI). One main goal of research is to help patients with severe neuromuscular disabilities by substituting normal motor outputs. Various cortical processes were identified which are suitable for implementing such a
Guido Dornhege; Benjamin Blankertz; Gabriel Curio
Response prediction is an important emerging concept in oncologic imaging, with tailored, individualized treatment regimens increasingly becoming the standard of care. This review aims to define tumour response and illustrate the ways in which imaging techniques can demonstrate tumour biological characteristics that provide information on the likely benefit to be received by treatment. Two imaging approaches are described: identification of therapeutic targets and depiction of the treatment-resistant phenotype. The former approach is exemplified by the use of radionuclide imaging to confirm target expression before radionuclide therapy but with angiogenesis imaging and imaging correlates for genetic response predictors also demonstrating potential utility. Techniques to assess the treatment-resistant phenotype include demonstration of hypoperfusion with dynamic contrast-enhanced computed tomography and magnetic resonance imaging (MRI), depiction of necrosis with diffusion-weighted MRI, imaging of hypoxia and tumour adaption to hypoxia, and 99mTc-MIBI imaging of P-glycoprotein mediated drug resistance. To date, introduction of these techniques into clinical practice has often been constrained by inadequate cross-validation of predictive criteria and lack of verification against appropriate response end points such as survival. With further refinement, imaging predictors of response could play an important role in oncology, contributing to individualization of therapy based on the specific tumour phenotype. This ability to predict tumour response will have implications for improving efficacy of treatment, cost-effectiveness and omission of futile therapy. PMID:24061161
Kyle, Samuel D; Law, W Phillip; Miles, Kenneth A
Background. A group of 27 patients with brain injury were treated by electroencephalographic (EEG) NeuroBioFeedback under drug-free conditions. They were studied for distribution in classes of major syndromes for evaluation of treatment efficiency and rehabilitation rates with respect to associated EEG and other physiological changes.Methods. A total of 48 clinical symptoms were listed, each present in at least one patient.
Michel Bounias; Rima E. Laibow; A. Bonaly; Albert N. Stubblebine
Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312
Siddle, Hannah V; Kaufman, Jim
Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312
Siddle, Hannah V; Kaufman, Jim
Ocular tumours present a therapeutic challenge because of the sensitive tissues involved and the necessity to destroy the tumour while minimising visual loss. Radiotherapy (RT) is one of several modalites used apart from surgery, laser, cryotherapy, and chemotherapy. Both external beam RT (EBRT) and brachytherapy are used. Tumours of the bulbar conjunctiva, squamous carcinoma and malignant melanoma, can be treated with a radioactive plaque: strontium-90, ruthenium-106 (Ru-106), or iodine-125 (I-125), after excision. If the tumour involves the fornix or tarsal conjunctiva, proton therapy can treat the conjunctiva and spare most of the eye. Alternatively, an I-125 interstitial implant can be used with shielding of the cornea and lens. Conjunctival mucosal-associated lymphoid tissue lymphoma can be treated with an anterior electron field with lens shielding and 25–30 Gray (Gy) in 2?Gy fractions. Discrete retinoblastoma (RB), too large for cryotherapy or thermolaser, or recurrent after these modalities, can be treated with plaque therapy, I-125, or Ru-106. For large RB, multiple tumours, or vitreous seeds the whole eye can be treated with an I-125 applicator, sparing the bony orbit, or with EBRT, under anaesthetic, using X-rays or proton therapy with vacuum contact lenses to fix the eyes in the required position. Post-enucleated orbits at risk for recurrent RB can be treated with an I-125 implant with shielding to reduce the dose to the bony orbit. Uveal malignant melanomas can be treated with plaque or proton therapy with excellent local control. Preservation of vision will depend on the initial size and location of the tumour. PMID:23174750
Stannard, C; Sauerwein, W; Maree, G; Lecuona, K
Brain tumour is the third leading cause of death in children and adolescents younger than 16 years of age. The increasing survival rate of these patients makes their follow-up and quality of life assessment an important task. This study evaluated the gait pathology of the patients after the combined treatment for central nervous system (CNS) tumours. It assessed if the
Ma?gorzata Syczewska; Bo?ena Dembowska-Bagi?ska; Marta Perek-Polnik; Ma?gorzata Kalinowska; Danuta Perek
Adenomatoid odontogenic tumour (AOT) is a benign non-invasive odontogenic tumour, having mostly a slow and sustained growth pattern. AOT is an uncommon lesion of odontogenic origin, which affects young individuals, with a female predilection and mostly occurring in the second decade. In the literature, it has been considered as a hamartoma rather than a true neoplasm because of its limited size, minimal growth potential and the lack of recurrence. We present an extrafollicular central variant of AOT with a occurrence rate of 30%, adjacent to the incisors. PMID:23814209
Prakasam, Michael; Tiwari, Saba; Satpathy, Mrinal; Banda, Vanaja Reddy
Brain activity can be recorded by means of EEG (Electroencephalogram) electrodes placed on the scalp of the patient. The EEG reflects the activity of groups of neurons located in the head, and the fundamental problem in neurophysiology is the identification of the sources responsible of brain activity, especially if a seizure occurs and in this case it is important to identify it. The studies conducted in order to formalize the relationship between the electromagnetic activity in the head and the recording of the generated external field allow to know pattern of brain activity. The inverse problem, that is given the sampling field at different electrodes the underlying asset must be determined, is more difficult because the problem may not have a unique solution, or the search for the solution is made difficult by a low spatial resolution which may not allow to distinguish between activities involving sources close to each other. Thus, sources of interest may be obscured or not detected and known method in source localization problem as MUSIC (MUltiple SIgnal Classification) could fail. Many advanced source localization techniques achieve a best resolution by exploiting sparsity: if the number of sources is small as a result, the neural power vs. location is sparse. In this work a solution based on the spatial sparsity of the field signal is presented and analyzed to improve MUSIC method. For this purpose, it is necessary to set a priori information of the sparsity in the signal. The problem is formulated and solved using a regularization method as Tikhonov, which calculates a solution that is the better compromise between two cost functions to minimize, one related to the fitting of the data, and another concerning the maintenance of the sparsity of the signal. At the first, the method is tested on simulated EEG signals obtained by the solution of the forward problem. Relatively to the model considered for the head and brain sources, the result obtained allows to have a significant improvement compared to the classical MUSIC method, with a small margin of uncertainty about the exact location of the sources. In fact, the constraints of the spatial sparsity on the signal field allow to concentrate power in the directions of active sources, and consequently it is possible to calculate the position of the sources within the considered volume conductor. Later, the method is tested on the real EEG data too. The result is in accordance with the clinical report even if improvements are necessary to have further accurate estimates of the positions of the sources.
Vergallo, P.; Lay-Ekuakille, A.
Ion beams represent a promising radiotherapy modality for the treatment of deep seated tumours. Compared to conventional photon beams, in particular beams of heavier ions like e.g. carbon show several advantages which are related to their different physical and radiobiological properties:•The dose increases with penetration depth and shows a sharp distal fall off at the end of the particle range,
Background and Purpose Clinical and radiological findings of intracranial abscesses may mimic the findings of brain tumours and vice versa. However, the discrimination is of great clinical importance in planning treatment and in following prognosis and response to therapy. This study evaluates the Computed Tomography (CT) perfusion parameters, especially the permeability index, with the aim of evaluating the usefulness of dynamic CT perfusion imaging as an alternative tool to differentiate necrotic brain tumours and intracerebral abscesses. Materials and Methods A total of 21 patients underwent perfusion CT study and were divided into 2 groups: Group 1, patients with necrotic brain tumours (n=13); and Group 2, patients with cerebral abscesses (n=8). The mean perfusion parameters were obtained from the enhancing part of the lesion. The relative ratios were then calculated by using the results from mirrored regions within the contralateral hemisphere as reference. Results The results of this study showed that there was significant difference in the relative permeability surface values between necrotic brain tumours and cerebral abscesses (p=0.005). By applying the ROC curve, a value of 25.1 for rPS was found to be the best estimate to distinguish necrotic brain tumours from cerebral abscesses with a specificity of 88 % and sensitivity of 70 %. Conclusion CT perfusion, especially permeability surface, may allow for better differentiation of cerebral abscesses from brain tumours, making it a strong additional imaging modality in the early diagnosis of these two entities. PMID:21611026
Ramli, N; Rahmat, K; Mah, E; Waran, V; Tan, LK; Chong, HT
Abstract Anterior mediastinal tumours include primary and secondary tumours. Patients may be asymptomatic or present with symptoms related to local tumour invasion or systemic symptoms due to release of hormones/cytokines or antibodies. The most common symptoms at presentation include chest pain, dyspnoea, cough, fever and chills. Despite rapid developments in imaging techniques, accurate staging of anterior mediastinal tumours remains a diagnostic quandary. Multimodality imaging plays an important role in determining surgical resectability and/or impact on subsequent management. This article briefly discusses the epidemiology and incidence of anterior mediastinal tumours and describes the role of imaging in tumour characterization and staging in detail. We focus on the more commonly encountered anterior mediastinal tumours. PMID:23131900
Ching Ong, Ching
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.
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
The spleen has been considered a ‘forgotten organ’ even if it is included and well demonstrated on every CT and MRI of the abdomen. Tumours of the spleen are rare; however, radiologists need to be aware of the main tumoral features and patterns in order to try to distinguish between benign and malignant masses often discovered incidentally. The principal tumoral masses, benign (cysts, haemangiomas, litteral cell angioma, lymphangioma) and malignant (lymphoma, metastases haemagiosarcoma), are described. PMID:16154823
Giovagnoni, Andrea; Giorgi, Chiara; Goteri, Gaia
This special article aims to summarise the current knowledge regarding the two groups of tumours with their origin in the adrenal gland: 1) adrenocortical tumours, derived from the cortex of the adrenal gland and 2) phaeochromocytomas and paragangliomas, neuroendocrine tumours derived from nodes of neural crest derived cells symmetrically distributed at both sides of the entire spine (paragangliomas [PG]). These PGs can be functioning tumors that secrete catecholamines, which confers their typical dark colour after staining with chromium salts (chromaffin tumors). Among these, the term phaeochromocytoma (PC) is restricted to those PGs derived from the chromaffin cells in the adrenal medulla (intra-adrenal PGs), whereas the term PG is used for those sympathetic or parasympathetic ones in an extra-adrenal location. We analyse the state of the art of their pathogenic and genetic bases, as well as their clinical signs and symptoms, the tests currently available for performing their diagnosis (biochemical, hormonal, imaging and molecular studies) and management (surgery, pre- and post-surgical medical treatment), considering the current and developing strategies in chemo- and radiotherapy. PMID:23796614
Martos-Moreno, G A; Pozo-Román, J; Argente, J
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
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
Maspin is a protein that belongs to serin protease inhibitor (serpin) superfamily. The purpose of this study was to review the literature concerning the expression of maspin in salivary gland tumours. A literature search was done using MEDLINE, accessed via the National Library of Medicine PubMed interface. Statistical analysis was not done because only seven studies were available in literature, the collected data were different and the results could not be compared. Expression of maspin was down regulated in more aggressive salivary gland tumours. Maspin may function as a tumour suppressor in salivary gland tumours.
Ashok, Nipun; Sheirawan, Mohammad Kinan; Altamimi, Mohammed Alsakran; Alenzi, Faris; Azzeghaiby, Saleh Nasser; Baroudi, Kusai; Nassani, Mohammad Zakaria
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.
Milotti, E.; Vyshemirsky, V.; Sega, M.; Stella, S.; Chignola, R.
Primary mesenteric gastrointestinal stromal tumours (GISTs) are rare tumours and can be included as a differential for an expanding intraabdominal mass. We present the case, in our institution, of a 72-year-old male who presented with non-specific symptoms and was diagnosed with a primary mesenteric GIST following resection. We report his follow-up and discuss the current theories as to the origins of these rare tumours and current treatment modalities. PMID:24876518
Kirby, R.; Rajasagaram, N.; Ghusn, M.
Vascular tumours and malformations, fibrous and fibrohistiocytic tumours and pseudotumours are the most common benign soft-tissue\\u000a masses observed in children, and can be treated conservatively. Rhabdomyosarcomas are the most frequent malignant tumours,\\u000a accounting for about half of soft tissue sarcomas. A child referred for a soft-tissue mass should ideally be managed by a\\u000a multidisciplinary team and primary excision should be
Hervé J. Brisse; Daniel Orbach; Jerzy Klijanienko
The function of vascular endothelial growth factor (VEGF) in cancer is not limited to angiogenesis and vascular permeability. VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumour initiation. In addition to VEGF receptor tyrosine kinases, the neuropilins are crucial for mediating the effects of VEGF on tumour cells, primarily because of their ability to regulate the function and the trafficking of growth factor receptors and integrins. This has important implications for our understanding of tumour biology and for the development of more effective therapeutic approaches. PMID:24263190
Goel, Hira Lal; Mercurio, Arthur M.
Objective. Some patients suffering from severe neuromuscular diseases have difficulty controlling not only their bodies but also their eyes. Since these patients have difficulty gazing at specific visual stimuli or keeping their eyes open for a long time, they are unable to use the typical steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) systems. In this study, we introduce a new paradigm for SSVEP-based BCI, which can be potentially suitable for disabled individuals with impaired oculomotor function. Approach. The proposed electroencephalography (EEG)-based BCI system allows users to express their binary intentions without needing to open their eyes. A pair of glasses with two light emitting diodes flickering at different frequencies was used to present visual stimuli to participants with their eyes closed, and we classified the recorded EEG patterns in the online experiments conducted with five healthy participants and one patient with severe amyotrophic lateral sclerosis (ALS). Main results. Through offline experiments performed with 11 participants, we confirmed that human SSVEP could be modulated by visual selective attention to a specific light stimulus penetrating through the eyelids. Furthermore, the recorded EEG patterns could be classified with accuracy high enough for use in a practical BCI system. After customizing the parameters of the proposed SSVEP-based BCI paradigm based on the offline analysis results, binary intentions of five healthy participants were classified in real time. The average information transfer rate of our online experiments reached 10.83 bits min-1. A preliminary online experiment conducted with an ALS patient showed a classification accuracy of 80%. Significance. The results of our offline and online experiments demonstrated the feasibility of our proposed SSVEP-based BCI paradigm. It is expected that our ‘eyes-closed’ SSVEP-based BCI system can be potentially used for communication of disabled individuals with impaired oculomotor function.
Lim, Jeong-Hwan; Hwang, Han-Jeong; Han, Chang-Hee; Jung, Ki-Young; Im, Chang-Hwan
We present a case of radiation-associated angiosarcoma. A 67-year-old Thai woman was diagnosed with endometrium carcinoma stage IC and was treated with surgery and radiations. Ten years later, she presented with a gradually enlarging mass on the pubic area, in the shape of a pair of panties. Skin biopsy of lesions confirmed angiosarcoma. The diagnosis was radiation-associated angiosarcoma. She was treated with chemotherapy due to unresectable tumour. The chemotherapy was started with paclitaxel 70 mg/m2 every 2 weeks. After completing the fifth cycle of paclitaxel, the lesion was markedly decreased in size and the symptoms previously described were also completely resolved. PMID:25566052
Kanokrungsee, Silada; Vachiramon, Vasanop; Sirithanabadeekul, Punyaphat
Two hundred and four cases of breast carcinoma were classified according to cytological features, and these were related to prognosis. A disease free interval of seven years was 95% for patients with grade I, 70% for those with grade II, and 45% for those with grade III tumours. The risk of recurrence was also related to tumour size and the presence or absence of steroid receptors in the tumour. Cytological classification of breast carcinoma based on fine needle aspiration provides valuable information concerning the prognosis of patients, which is relevant to their clinical management. Images PMID:3722403
Mouriquand, J; Gozlan-Fior, M; Villemain, D; Bouchet, Y; Sage, J C; Mermet, M A; Bolla, M
Tumour samples from 150 patients with squamous cell carcinoma of the oesophagus were investigated immunohistochemically with the monoclonal antibody MIB-1, which recognises proliferating cells. Using light microscopy, the number of MIB-1-positive tumour cells was counted in the areas with the highest proliferative activity. The MIB-1 index was determined as the proportion of MIB-1-positive and MIB-1-negative tumour cells. A considerable variation of the MIB-1 indices was found between the different tumours with a minimum of 6% and a maximum of 95% (median, 33%). The MIB-1 index correlated significantly with the mitotic activity in the tumour tissue (r = 0.33; P = 0.0001) and with the proportion of apoptotic tumour cells (r = 0.25; P = 0.0017). No significant correlation was found between the MIB-1 index and various other prognostic parameters including pT classification, pN classification, tumour grade, blood vessel invasion and lymphatic vessel invasion. In the univariate survival analysis no significant difference was found between tumours with low (< or = 33%) and high MIB-1 index (> 33%) 5-year survival rate: low MIB-1 index, 19.2%; high MIB-1 index, 22.2%). In a Cox proportional hazard regression analysis only the parameters lymphatic vessel invasion (P = 0.0001), pT classification (P = 0.0034) and pN classification (P = 0.0256), but not the MIB-1 index, could be verified as independent prognostic variables. In conclusion, evaluation of the MIB-1 index does not provide prognostic information for oesophageal cancer patients. PMID:8855967
Sarbia, M; Bittinger, F; Porschen, R; Dutkowski, P; Torzewski, M; Willers, R; Gabbert, H E
Tumour samples from 150 patients with squamous cell carcinoma of the oesophagus were investigated immunohistochemically with the monoclonal antibody MIB-1, which recognises proliferating cells. Using light microscopy, the number of MIB-1-positive tumour cells was counted in the areas with the highest proliferative activity. The MIB-1 index was determined as the proportion of MIB-1-positive and MIB-1-negative tumour cells. A considerable variation of the MIB-1 indices was found between the different tumours with a minimum of 6% and a maximum of 95% (median, 33%). The MIB-1 index correlated significantly with the mitotic activity in the tumour tissue (r = 0.33; P = 0.0001) and with the proportion of apoptotic tumour cells (r = 0.25; P = 0.0017). No significant correlation was found between the MIB-1 index and various other prognostic parameters including pT classification, pN classification, tumour grade, blood vessel invasion and lymphatic vessel invasion. In the univariate survival analysis no significant difference was found between tumours with low (< or = 33%) and high MIB-1 index (> 33%) 5-year survival rate: low MIB-1 index, 19.2%; high MIB-1 index, 22.2%). In a Cox proportional hazard regression analysis only the parameters lymphatic vessel invasion (P = 0.0001), pT classification (P = 0.0034) and pN classification (P = 0.0256), but not the MIB-1 index, could be verified as independent prognostic variables. In conclusion, evaluation of the MIB-1 index does not provide prognostic information for oesophageal cancer patients. Images Figure 1 PMID:8855967
Sarbia, M.; Bittinger, F.; Porschen, R.; Dutkowski, P.; Torzewski, M.; Willers, R.; Gabbert, H. E.
We report a case of temporal lobe epilepsy and incomplete Brown-Sequard syndrome of the thoracic cord. Computed tomography and magnetic resonance (MR) imaging showed multiple supratentorial masses with the classical radiological appearances of multifocal dysembryoplastic neuroepithelial tumour (DNET). Spinal MR imaging revealed intradural lipomas, not previously reported in association with multifocal DNET. Presentation and imaging findings are discussed along with classification and natural history of the tumour. PMID:22606558
White, Richard D.; Kanodia, Avinash K.; Sammler, Esther M.; Brunton, John N.; Heath, Craig A.
The diagnosis of germ-cell tumour is based on the histological examination of the inguinal orchiectomy specimen. The histological classification allows discriminating seminoma and non seminomatous tumours. Non seminomatous tumours are heterogeneous, different sub-groups are described: embryonal carcinoma, teratoma, choriocarcinoma, yolk sac tumours, but components are often mixed. Serum tumour markers, human chorionic gonadotropin hormone and alpha-foetoprotein, are important as well in the initial diagnosis, the prognosis, and follow-up of the disease. The staging procedure is strict and the prognostic factors allow defining the optimal treatment according to well established guidelines. Complete information of the patient is mandatory. All consequences of the disease and treatment must be managed, the most important being sperm conservation. PMID:17455738
Mottet, Nicolas; Berger, Nicole; Droz, Jean-Pierre
Here we provide compelling evidence that next-generation sequencing will revolutionize diagnostics. We reappraised a case from 1991, published in 1993, describing the unique occurrence of an ovarian immature teratoma arising in a young woman and a clonally distinct intracerebral immature teratoma developing in her daughter. We conducted whole-exome sequencing on constitutional DNA from the mother and her daughter and identified a previously unreported nonsense mutation (c.3533G>A; p.Trp1178*) in the chromatin remodelling gene, SMARCA4, that was present in both individuals and was subject to nonsense-mediated decay. Tumour analysis by Sanger sequencing revealed a somatic SMARCA4 mutation in both the mother (c.2438+1G>T) and her daughter (c.3229C>T; p.Arg1077*), which are predicted to be truncating. As immature teratomas are classified as germ cell tumours, we performed a comprehensive mutation survey of 106 apparently sporadic germ cell tumours, but did not find any other clearly deleterious SMARCA4 mutations. Recently, inactivating mutations in SMARCA4 have been found in two cases of rhabdoid tumour predisposition syndrome type 2. In the light of these findings, renewed efforts to locate previously unobtainable tumour samples were successfully undertaken. Histopathological and immunohistochemical re-analysis of the daughter's tumour revealed that it was indeed a rhabdoid tumour (atypical teratoid/rhabdoid tumour). In this context, the original pathology report of the mother's ovarian tumour was re-interpreted as describing a malignant rhabdoid tumour of the ovary. This report raises the question as to whether molecular genetic analysis should be included in tumour classification, alongside more traditional microscopy-based methods. The use of new sequencing technologies, particularly when applied to archived samples, will lead to many more 'molecular rediagnoses'. This is the earliest known case of rhabdoid tumour predisposition syndrome type 2 and the first described case with an autosomal dominant pattern of inheritance, only discovered through an exome sequencing project. PMID:23775540
Witkowski, Leora; Lalonde, Emilie; Zhang, Jian; Albrecht, Steffen; Hamel, Nancy; Cavallone, Luca; May, Sandra Thompson; Nicholson, James C; Coleman, Nicholas; Murray, Matthew J; Tauber, Peter F; Huntsman, David G; Schönberger, Stefan; Yandell, David; Hasselblatt, Martin; Tischkowitz, Marc D; Majewski, Jacek; Foulkes, William D
Melanotic neuroectodermal tumour of infancy is an extremely rare neoplasm arising in newborns and young children, typically involving the face or cranium. A case arising from the maxilla, requiring extensive resection with a near-total maxillectomy, is presented. A thorough review of the literature on this unusual tumour is provided, with emphasis on prognostic factors and appropriate treatment. PMID:19554164
Hamilton, Scott; MacRae, Duncan; Agrawal, Sumit; Matic, Damir
Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.
Peres, Elodie A.; Valable, Samuel [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France)] [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Guillamo, Jean-Sebastien [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France) [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Departement de Neurologie, CHU de Caen (France); Marteau, Lena [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France)] [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Bernaudin, Jean-Francois [Service d'Histologie-Biologie Tumorale, ER2UPMC, Universite Paris 6, Hopital Tenon, Paris (France)] [Service d'Histologie-Biologie Tumorale, ER2UPMC, Universite Paris 6, Hopital Tenon, Paris (France); Roussel, Simon [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France)] [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Lechapt-Zalcman, Emmanuele [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France) [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Service d'Anatomie Pathologique, CHU de Caen (France); Bernaudin, Myriam [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France)] [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Petit, Edwige, E-mail: email@example.com [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France)] [CERVOxy team 'Hypoxia and cerebrovascular pathophysiology', UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France)
Peripheral nerve sheath tumors are common neoplasms in daily practice. Diagnosis and classification of most conventional peripheral nerve sheath tumors are relatively straightforward for the experienced observer; but on occasion, they are diagnostically challenging (especially with locally aggressive and malignant tumors). This article aims to provide an update of the data (clinical, histological, immunohistochemistry and genomic) of benign, intermediate and malignant peripheral nerve sheath tumors, thanks to the latest WHO "Classification of Tumors of Soft Tissue and Bone", published in 2013, which includes a new chapter on "Nerve Sheath Tumors". Advances in molecular biology have provided new insights into the nature of the various peripheral nerve sheath tumors, and have begun to suggest novel targeted therapeutic approaches. PMID:25541115
Le Guellec, Sophie
Accurate identification of the primary tumour in cancer of unknown primary (CUP) is required for effective treatment selection and improved patient outcomes. The aim of this study was to develop and validate a gene expression tumour classifier and integrate it with histopathology to identify the likely site of origin in CUP.RNA was extracted from 450 formalin fixed, paraffin embedded samples of known origin comprising 18 tumour groups. Whole genome expression analysis was performed using a bead-based array. Classification of the tumours made use of a binary support vector machine, together with recursive feature elimination. A hierarchical tumour classifier was developed and incorporated with conventional histopathology to identify the origins of metastatic tumours.The classifier demonstrated an accuracy of 88% for correctly predicting the tumour type on a validation set of known tumours (n?=?94). For CUP samples (n?=?49) having a final clinical diagnosis, the classifier improved the accuracy of histology alone for both single and multiple predictions. Furthermore, where histology alone could not suggest any specific diagnosis, the classifier was able to correctly predict the primary site of origin.We demonstrate the integration of gene expression profiling with conventional histopathology to aid the investigation of CUP. PMID:25485653
Tothill, Richard W; Shi, Fan; Paiman, Lisa; Bedo, Justin; Kowalczyk, Adam; Mileshkin, Linda; Buela, Evangeline; Klupacs, Robert; Bowtell, David; Byron, Keith
Isolated central nervous system (CNS) tuberculoma is a rare disease. This disease is associated with high morbidity and mortality, despite modern methods of detection and treatment. CNS tuberculosis can present as meningitis, arachnoiditis, tuberculomas or the uncommon form of tuberculous subdural empyema and brain abscess. We present the clinical, radiological and pathological findings of cerebellar tuberculoma in an Iranian immunocompetent patient mimicking a malignant tumour. PMID:23966456
Binesh, Fariba; Zahir, Shokouh Taghipour; Bovanlu, Taghi Roshan
Six primary duodenal tumours were diagnosed in our 300 bed institute during a period of 10 years. Two patients had benign tumours (leiomyoma and carcinoid) and four had malignant tumours (adenocarcinoma). The most common manifestation was severe iron deficiency anemia. Diagnosis was usually delayed (with a mean time of 7.7 months from initial complaints), endoscopy being the most common and useful diagnostic tool. A curative procedure was performed in two patients. Patients with unexplained chronic iron deficiency anaemia should undergo thorough gastrointestinal evaluation, including the small intestine, as a curable disease may be found to be the source of the complaint. Images Figure 1 PMID:8506195
Kaminski, N.; Shaham, D.; Eliakim, R.
Copper stimulates the proliferation and migration of endothelial cells and is required for the secretion of several angiogenic factors by tumour cells. Copper chelation decreases the secretion of many of these factors. Serum copper levels are upregulated in many human tumours and correlate with tumour burden and prognosis. Copper chelators reduce tumour growth and microvascular density in animal models. New
Sarah A. Lowndes; Adrian L. Harris
Abstract Heterogeneity is a key feature of malignancy associated with adverse tumour biology. Quantifying heterogeneity could provide a useful non-invasive imaging biomarker. Heterogeneity on computed tomography (CT) can be quantified using texture analysis which extracts spatial information from CT images (unenhanced, contrast-enhanced and derived images such as CT perfusion) that may not be perceptible to the naked eye. The main components of texture analysis can be categorized into image transformation and quantification. Image transformation filters the conventional image into its basic components (spatial, frequency, etc.) to produce derived subimages. Texture quantification techniques include structural-, model- (fractal dimensions), statistical- and frequency-based methods. The underlying tumour biology that CT texture analysis may reflect includes (but is not limited to) tumour hypoxia and angiogenesis. Emerging studies show that CT texture analysis has the potential to be a useful adjunct in clinical oncologic imaging, providing important information about tumour characterization, prognosis and treatment prediction and response. PMID:23545171
Miles, Kenneth A.
Glomus tumours (GTs) resemble the normal glomus body and have a predilection for skin and subcutaneous tissue. Although the majority of glomus tumours are small, benign neoplasms that occur in the dermis or subcutis of the extremities and cases of atypical or malignant variants have been reported. We report a case of a man who presented with a 1-year history of subcutaneous nodule in the right scapular area which was mildly tender. The nodule measured 2?cm. Microscopic examination showed features of glomus tumour with increased mitotic activity. These features, by current definition, would suggest glomus tumour of uncertain malignant potential. Three months later, he presented with recurrence. During his metastasis work-up, we noticed bilateral pulmonary metastasis. Metastasising GTs are rare. The patient underwent wide local excision and received chemotherapy. PMID:23291816
Binesh, Fariba; Akhavan, Ali; Zahir, Shokouh Taghipour; Bovanlu, Taghi Roshan
This lesson shows students that living things can be sorted into groups in many ways using various features to decide which things belong to which group and that classification schemes will vary with purpose. It is the first of a two-part series on classification. At this grade level, students should have the opportunity to learn about an increasing variety of living organisms, both the familiar and the exotic, and should become more precise in identifying similarities and differences among them. Firsthand observation of the living environment is essential for students to gain an understanding of the differences among organisms. This lesson is intended to supplement direct investigations made by students by using the Internet to expose them to a variety of living organisms, as well as encourage them to start developing classification schemes of their own.
Intracranial germ cell tumours (IGCTs) are a group of rare heterogeneous brain tumours that are clinically and histologically similar to the more common gonadal GCTs. IGCTs show great variation in their geographical and gender distribution, histological composition and treatment outcomes. The incidence of IGCTs is historically five- to eightfold greater in Japan and other East Asian countries than in Western countries, with peak incidence near the time of puberty. About half of the tumours are located in the pineal region. The male-to-female incidence ratio is approximately 3-4:1 overall, but is even higher for tumours located in the pineal region. Owing to the scarcity of tumour specimens available for research, little is currently known about this rare disease. Here we report the analysis of 62 cases by next-generation sequencing, single nucleotide polymorphism array and expression array. We find the KIT/RAS signalling pathway frequently mutated in more than 50% of IGCTs, including novel recurrent somatic mutations in KIT, its downstream mediators KRAS and NRAS, and its negative regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy number gains of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding upregulation of AKT1 expression. We identified loss-of-function mutations in BCORL1, a transcriptional co-repressor and tumour suppressor. We report significant enrichment of novel and rare germline variants in JMJD1C, which codes for a histone demethylase and is a coactivator of the androgen receptor, among Japanese IGCT patients. This study establishes a molecular foundation for understanding the biology of IGCTs and suggests potentially promising therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway. PMID:24896186
Wang, Linghua; Yamaguchi, Shigeru; Burstein, Matthew D; Terashima, Keita; Chang, Kyle; Ng, Ho-Keung; Nakamura, Hideo; He, Zongxiao; Doddapaneni, Harshavardhan; Lewis, Lora; Wang, Mark; Suzuki, Tomonari; Nishikawa, Ryo; Natsume, Atsushi; Terasaka, Shunsuke; Dauser, Robert; Whitehead, William; Adekunle, Adesina; Sun, Jiayi; Qiao, Yi; Marth, Gábor; Muzny, Donna M; Gibbs, Richard A; Leal, Suzanne M; Wheeler, David A; Lau, Ching C
The paper describes work on the brain-computer interface (BCI). The BCI is designed to help patients with severe motor impairment\\u000a (e.g. amyotropic lateral sclerosis) to communicate with their environment through wilful modification of their EEG. To establish\\u000a such a communication channel, two major prerequisites have to be fulfilled: features that reliably describe several distinctive\\u000a brain states have to be available,
J. Kalcher; D. Flotzinger; Ch. Neuper; S. Gölly; G. Pfurtscheller
In a recent study of cervical carcinoma, 13 cases with a marked eosinophil infiltrate around the tumour were found. The histological appearance of the tumours was distinctive and suggested a specific response, similar to the lymphocyte infiltration in medullary carcinoma of the breast and seminoma. A review of published reports shows that tumour-associated tissue eosinophilia (TATE) and tumour-associated blood eosinophilia (TABE) may be seen in tumours of different histological types from different anatomical sites, and may occur together or separately. Tumours with TATE alone appear to have a better prognosis that those without, while TABE is associated with tumor spread and a poor prognosis. Images PMID:7035499
Lowe, D; Jorizzo, J; Hutt, M S
Solid pseudopapillary tumour of pancreas (SPT) is an extremely rare pancreatic tumour, which has a low malignant potential and occurs mainly in young women. Pathologic and imaging findings include a well defined encapsulated pancreatic mass with cystic and solid components with evidence of haemorrhage. This is a case of a 16 years old girl who presented with upper abdominal pain of long duration and epigastric mass on palpation. Computed Tomography (CT) scan demonstrated a large well defined heterogenous attenuation mass of solid enhancing and cystic non enhancing areas, arising from the head of the pancreas. Radiologically it was diagnosed as a case of pancreatic neoplasm. Fine needle aspiration cytology (FNAC) and histopathology of the biopsy material diagnosed as solid pseudopapillary tumour of pancreas. PMID:24858174
Bose, B; Majumder, S; Khan, A U
Mucoepidermoid tumours of the bronchial tree are uncommon neoplasms, which are believed to arise from terminal ducts of the proximal tracheobronchial tree. The first case of a peripheral mucoepidermoid tumour of the lung is reported. Images PMID:1871698
Green, L. K.; Gallion, T. L.; Gyorkey, F.
An 8-year-old boy with an 18 month history of left limb hemi-dystonia due to a right lenticular nucleus astrocytoma originating in the putamen is reported. Subsequent neuropathological study demonstrated that the tumour was mainly localised to the right lenticular nucleus, with cystic necrosis in the infero-lateral putamen. Solid tumour also infiltrated the right hypothalamus, the anterior commisure and the optic chiasm, and there was perivascular spread into the globus pallidus, internal capsule and roof of the right lateral ventricle. This case, and the few other published reports of symptomatic dystonia due to focal brain lesions verified pathologically, indicate that damage to the lenticular nucleus, and to the putamen in particular, can cause limb dystonia in man. Images PMID:6747646
Narbona, J; Obeso, J A; Tuñon, T; Martinez-Lage, J M; Marsden, C D
The purpose of this resource is to develop a classification system for a set of objects and learn about hierarchical classification systems. Any set of objects, such as insects or rocks, may be used as well.
The GLOBE Program, University Corporation for Atmospheric Research (UCAR)
Taxonomic classification of astronomically observed stellar objects is described in terms of spectral properties. Stars receive a classification containing a letter, number, and a Roman numeral, which relates the star to other stars of higher or lower Roman numerals. The citation indicates the stellar chromatic emission in relation to the wavelengths of other stars. Standards are chosen from the available objects detected. Various classification schemes such as the MK, HD, and the Barbier-Chalonge-Divan systems are defined, including examples of indexing differences. Details delineating the separations between classifications are discussed with reference to the information content in spectral and in photometric classification schemes. The parameters usually used for classification include the temperature, luminosity, reddening, binarity, rotation, magnetic field, and elemental abundance or composition. The inclusion of recently discovered extended wavelength characteristics in nominal classifications is outlined, together with techniques involved in automated classification.
Surgical resection of hepatic tumours is not always possible. Alternative techniques consist in locally using chemical or physical agents to destroy the tumour and this may be performed percutaneously. It requires a precise localisation of the tumour placement during ablation. Computer-assisted surgery tools may be used in conjunction to these new ablation techniques to improve the therapeutic efficiency whilst benefiting from minimal invasiveness. This communication introduces the principles of a system for computer-assisted hepatic tumour ablation.
Voirin, D; Amavizca, M; Leroy, A; Letoublon, C; Troccaz, J; Voirin, David; Payan, Yohan; Amavizca, Miriam; Leroy, Antoine; Letoublon, Christian; Troccaz, Jocelyne
An atypical case of the malignant carcinoid syndrome, associated with multiple peptic ulcers, is described. The tumour cells were argyrophil but not argentaffin, and the tumour was found to contain 5-hydroxytryptophan (5-H.T.P.) but not 5-hydroxytryptamine (5-H.T.). This aberrant biochemical behaviour was associated with the virtual absence of 5-H.T.P.-decarboxylase from the tumour tissue. The tumour contained notable quantities of histamine. PMID:14018107
Campbell, A. C. P.; Gowenlock, A. H.; Platt, D. S.; Snow, P. J. D.
The experience with magnetic resonance imaging (MRI) of 81 patients with primary bone tumours and tumour-like lesions is reported. MRI proved to be a sensitive method of detecting primary bone tumours. Intramedullary and extraosseous parts of bone tumours were, delineated better than by plain films and computed tomography (CT). Surgical clips and Harrington rods did not appreciably limit the estimation
K. Bohndorf; M. Reiser; B. Lochner; W. Féaux de Lacroix; W. Steinbrich
Sporadic multiple endocrine neoplasia type 1 (MEN1) is defined as the occurrence of tumours in two of three main endocrine tissue types: parathyroid, pituitary and pancreaticoduodenal. A prolactinoma variant or Burin variant of MEN1 was found to occur in three large kindreds, with more prolactinomas and fewer gastrinomas than typical MEN1. MEN1 tumours differ from common tumours by showing features from the MEN1 gene (e.g. larger pituitary tumours). They also show various expressions of tumour multiplicity; however, pituitary tumour in MEN1 is usually solitary. Diagnosis in MEN1 carriers during childhood is not directed at cancers but at benign morbid tumours. Morbid prolactinoma occurred at the age of 5 years in one MEN1 individual; hence, this is the earliest age at which to recommend tumour surveillance in carriers. The MEN1 gene shows biallelic inactivation in 30% of some types of common variety endocrine tumours (e.g. parathyroid adenoma, gastrinoma, insulinoma and bronchial carcinoid), but in only 1-5% of common pituitary tumours. Heterozygous knockout of MEN1 in mice provides a robust model of MEN1 and has been found to support further research on anti-angiogenesis therapy for pituitary tumours. The rarity of MEN1 mutations in some MEN1-like states aids the identification of other mutated genes, such as AIP, HRPT2 and p27(Kip1). We present recent clinical and basic findings about the MEN1 gene, particularly concerning hereditary vs. common variety pituitary tumours. PMID:19407509
Agarwal, Sunita K; Ozawa, Atsushi; Mateo, Carmen M; Marx, Stephen J
A variety of lifestyle factors, including physical activity, artificial sweeteners, alcohol consumption and smoking, have been reported to contribute to the risk of developing urological malignancies. A great number of epidemiological studies suggest that sports and physical activity may have a preventive influence on genitourinary tumours, especially on the incidence of prostate cancer. Smoking appears to be the most relevant
Frank Sommer; Theo Klotz; Bernd J. Schmitz-Dräger
The present study used criterion groups validation to determine the ability of the Millon Clinical Multiaxial Inventory–III (MCMI–III) modifier indices to detect malingering in traumatic brain injury (TBI). Patients with TBI who met criteria for malingered neurocognitive dysfunction (MND) were compared to those who showed no indications of malingering. Data were collected from 108 TBI patients referred for neuropsychological evaluation.
Luis E. Aguerrevere; Kevin W. Greve; Kevin J. Bianchini; Jonathan S. Ord
Objective: The Thought Translation Device (TTD) for brain–computer interaction was developed to enable totally paralyzed patients to communicate. Patients learn to regulate slow cortical potentials (SCPs) voluntarily with feedback training to select letters. This study reports the comparison of different methods of electroencephalographic (EEG) analysis to improve spelling accuracy with the TTD on a data set of 6650 trials of
Thilo Hinterberger; Andrea Kübler; Jochen Kaiser; Nicola Neumann; Niels Birbaumer
Parallel to the role that normal stem cells play in organogenesis, cancer stem cells are thought to be crucial for tumorigenesis. Understanding normal development might therefore lead to better treatments of cancer. We review recent data that stem cells of glioblastoma, a highly malignant brain tumour, seem to be dependent on cues from aberrant vascular niches that mimic the normal
Richard J. Gilbertson; Jeremy N. Rich
In the present study, we investigated the potential anti-angiogenic mechanism and anti-tumour activity of beta-eudesmol using in vitro and in vivo experimental models. Proliferation of human umbilical vein endothelial cells (HUVEC) stimulated with vascular endothelial growth factor (VEGF, 30 ng/ml) and basic fibroblast growth factor (bFGF, 30 ng/ml) was significantly inhibited by beta-eudesmol (50-100 microM). Beta-eudesmol (100 microM) also blocked the phosphorylation of cAMP response element binding protein (CREB) induced by VEGF (30 ng/ml) in HUVEC. Beta-eudesmol (10-100 microM) inhibited proliferation of HeLa, SGC-7901, and BEL-7402 tumour cells in a time- and dose-dependent manner. Moreover, beta-eudesmol treatment (2.5-5 mg/kg) significantly inhibited growth of H(22) and S(180) mouse tumour in vivo. These results indicated that beta-eudesmol inhibited angiogenesis by suppressing CREB activation in growth factor signalling pathway. This is the first study to demonstrate that beta-eudesmol is an inhibitor of tumour growth. PMID:18253884
Ma, En-Long; Li, Yan-Chun; Tsuneki, Hiroshi; Xiao, Jin-Fang; Xia, Ming-Yu; Wang, Min-Wei; Kimura, Ikuko
After withdrawal of bevacizumab in patients with recurrent high-grade glioma, we have observed a rapid tumour re-growth or\\u000a “rebound” radiographic phenomenon with accelerated clinical decline. We retrospectively reviewed 11 patients treated at the\\u000a Henry Ford Hermelin Brain Tumor Center with recurrent high-grade glioma who demonstrated a rebound progression pattern after\\u000a the discontinuation of bevacizumab. The original tumour area-of-enhancement increased by
Richard M. ZunigaRoy; Roy Torcuator; Rajan Jain; John Anderson; Thomas Doyle; Lonni Schultz; Tom Mikkelsen
Somatic gene mutations constitute key events in the malignant transformation of human cells. Somatic mutation can either actively speed up the growth of tumour cells or relax the growth constraints normally imposed upon them, thereby conferring a selective (proliferative) advantage at the cellular level. Neurofibromatosis type-1 (NF1) affects 1/3,000-4,000 individuals worldwide and is caused by the inactivation of the NF1 tumour suppressor gene, which encodes the protein neurofibromin. Consistent with Knudson's two-hit hypothesis, NF1 patients harbouring a heterozygous germline NF1 mutation develop neurofibromas upon somatic mutation of the second, wild-type, NF1 allele. While the identification of somatic mutations in NF1 patients has always been problematic on account of the extensive cellular heterogeneity manifested by neurofibromas, the classification of NF1 somatic mutations is a prerequisite for understanding the complex molecular mechanisms underlying NF1 tumorigenesis. Here, the known somatic mutational spectrum for the NF1 gene in a range of NF1-associated neoplasms --including peripheral nerve sheath tumours (neurofibromas), malignant peripheral nerve sheath tumours, gastrointestinal stromal tumours, gastric carcinoid, juvenile myelomonocytic leukaemia, glomus tumours, astrocytomas and phaeochromocytomas -- have been collated and analysed. PMID:22155606
Background Whether or not there is a relationship between use of mobile phones (analogue and digital cellulars, and cordless) and head tumour risk (brain tumours, acoustic neuromas, and salivary gland tumours) is still a matter of debate; progress requires a critical analysis of the methodological elements necessary for an impartial evaluation of contradictory studies. Methods A close examination of the protocols and results from all case-control and cohort studies, pooled- and meta-analyses on head tumour risk for mobile phone users was carried out, and for each study the elements necessary for evaluating its reliability were identified. In addition, new meta-analyses of the literature data were undertaken. These were limited to subjects with mobile phone latency time compatible with the progression of the examined tumours, and with analysis of the laterality of head tumour localisation corresponding to the habitual laterality of mobile phone use. Results Blind protocols, free from errors, bias, and financial conditioning factors, give positive results that reveal a cause-effect relationship between long-term mobile phone use or latency and statistically significant increase of ipsilateral head tumour risk, with biological plausibility. Non-blind protocols, which instead are affected by errors, bias, and financial conditioning factors, give negative results with systematic underestimate of such risk. However, also in these studies a statistically significant increase in risk of ipsilateral head tumours is quite common after more than 10 years of mobile phone use or latency. The meta-analyses, our included, examining only data on ipsilateral tumours in subjects using mobile phones since or for at least 10 years, show large and statistically significant increases in risk of ipsilateral brain gliomas and acoustic neuromas. Conclusions Our analysis of the literature studies and of the results from meta-analyses of the significant data alone shows an almost doubling of the risk of head tumours induced by long-term mobile phone use or latency. PMID:21679472
It is now well known that most malignant tumours contain a significant amount of leucocytic infiltrates the presence of which has, on many occasions, been linked to poor patient prognosis. These leucocyte populations are recruited to tumours by chemotactic factors released by either viable or necrotic tumour cells, or by cells within the tumour stroma. In recent times, most studies have analysed the role that tumour-associated macrophages (TAM) have on tumour progression. However, there is now increasing evidence to show that neutrophils also actively participate in this process. Whilst there are some data to suggest that neutrophil-derived factors can promote genetic mutations leading to tumourigenesis, or secrete factors that promote tumour cell proliferation; there is now substantial evidence to show that neutrophils, like TAM, significantly affect tumour angiogenesis. In this review, we discuss the likely mechanisms by which neutrophils are recruited into the tumour and then elaborate on how these cells may induce tumour vascularization by the secretion of powerful pro-angiogenic factors. We also discuss possible future chemotherapeutic strategies that are aimed at limiting tumour angiogenesis by inhibiting neutrophil recruitment. PMID:19563607
Tazzyman, Simon; Lewis, Claire E; Murdoch, Craig
Abstract The objective of the current study was to determine the classification accuracy of serum S100B and apolipoprotein (apoA-I) for mild traumatic brain injury (mTBI) and abnormal initial head computed tomography (CT) scan, and to identify ethnic, racial, age, and sex variation in classification accuracy. We performed a prospective, multi-centered study of 787 patients with mTBI who presented to the emergency department within 6?h of injury and 467 controls who presented to the outpatient laboratory for routine blood work. Serum was analyzed for S100B and apoA-I. The outcomes were disease status (mTBI or control) and initial head CT scan. At cutoff values defined by 90% of controls, the specificity for mTBI using S100B (0.899 [95% confidence interval (CI): 0.78–0.92]) was similar to that using apoA-I (0.902 [0.87–0.93]), and the sensitivity using S100B (0.252 [0.22–0.28]) was similar to that using apoA-I (0.249 [0.22–0.28]). The area under the receiver operating characteristic curve (AUC) for the combination of S100B and apoA-I (0.738, 95% CI: 0.71, 0.77), however, was significantly higher than the AUC for S100B alone (0.709, 95% CI: 0.68, 0.74, p=0.001) and higher than the AUC for apoA-I alone (0.645, 95% CI: 0.61, 0.68, p<0.0001). The AUC for prediction of abnormal initial head CT scan using S100B was 0.694 (95%CI: 0.62, 0.77) and not significant for apoA-I. At a S100B cutoff of <0.060??g/L, the sensitivity for abnormal head CT was 98%, and 22.9% of CT scans could have been avoided. There was significant age and race-related variation in the accuracy of S100B for the diagnosis of mTBI. The combined use of serum S100B and apoA-I maximizes classification accuracy for mTBI, but only S100B is needed to classify abnormal head CT scan. Because of significant subgroup variation in classification accuracy, age and race need to be considered when using S100B to classify subjects for mTBI. PMID:23758329
Blyth, Brian J.; He, Hua; Mookerjee, Sohug; Jones, Courtney; Kiechle, Karin; Moynihan, Ryan; Wojcik, Susan M.; Grant, William D.; Secreti, LaLainia M.; Triner, Wayne; Moscati, Ronald; Leinhart, August; Ellis, George L.; Khan, Jawwad
Despite aggressive therapy, the majority of primary and metastatic brain tumour patients have a poor prognosis with brief survival periods. This is because of the different pharmacokinetic parameters of systemically administered chemotherapeutic agents between the brain and the rest of the body. Specifically, before systemically administered drugs can distribute into the CNS, they must cross two membrane barriers, the blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier (BCB). To some extent, these structures function to exclude xenobiotics, such as anticancer drugs, from the brain. An understanding of these unique barriers is essential to predict when and how systemically administered drugs will be transported to the brain. Specifically, factors such as physiological variables (e.g. blood flow), physicochemical properties of the drug (e.g. molecular weight), as well as influx and efflux transporter expression at the BBB and BCB (e.g. adenosine triphosphate-binding cassette transporters) determine what compounds reach the CNS. A large body of preclinical and clinical research exists regarding brain penetration of anticancer agents. In most cases, a surrogate endpoint (i.e. CSF to plasma area under the concentration-time curve [AUC] ratio) is used to describe how effectively agents can be transported into the CNS. Some agents, such as the topoisomerase I inhibitor, topotecan, have high CSF to plasma AUC ratios, making them valid therapeutic options for primary and metastatic brain tumours. In contrast, other agents like the oral tyrosine kinase inhibitor, imatinib, have a low CSF to plasma AUC ratio. Knowledge of these data can have important clinical implications. For example, it is now known that chronic myelogenous leukaemia patients treated with imatinib might need additional CNS prophylaxis. Since most anticancer agents have limited brain penetration, new pharmacological approaches are needed to enhance delivery into the brain. BBB disruption, regional administration of chemotherapy and transporter modulation are all currently being evaluated in an effort to improve therapeutic outcomes. Additionally, since many chemotherapeutic agents are metabolised by the cytochrome P450 3A enzyme system, minimising drug interactions by avoiding concomitant drug therapies that are also metabolised through this system may potentially enhance outcomes. Specifically, the use of non-enzyme-inducing antiepileptic drugs and curtailing nonessential corticosteroid use may have an impact. PMID:16928151
Motl, Susannah; Zhuang, Yanli; Waters, Christopher M; Stewart, Clinton F
Most tumours arise from a single normal cell through a sequential evolutionary process of mutation and selection. Tumours are initiated by escaping non-immune surveillance, which includes defective DNA repair, epigenetic gene alternation, resistance to apoptosis and loss of intercellular contact inhibition. Tumour cells harbour mutations in a number of critical genes that provide selective advantages at various stages during the evolution of the tumour. The tumour cells that circumvent the tumour suppressor mechanisms of the non-immune surveillance process are edited by the immune system, resulting in the selection of a resistant tumour variant. The selection of the tumour cell is further shaped by its interactions with cells and other factors in its microenvironment. Tumour evolution is thought to adhere to Darwinian principles by escaping both non-immune (intrinsic) and immune (extrinsic) responses against self-altered tumour cells. At end-stage, tumours have escaped both non-immune and immune surveillance with increased threshold of apoptosis. Combination therapy has been proposed, by exploring the non-immune and immune suppressive nature of the tumour, and has been found to have a therapeutic efficiency on tumour regression as compared with monotherapies. The combination of immunotherapy and other different modalities, especially vaccines, with conventional anticancer therapies with optimized dosage and scheduling can offer synergistic antitumour effects. Here, we focus on the mechanism of tumour evolution and its implication in combination therapy. PMID:20384587
Bhutia, Sujit K; Mallick, Sanjaya K; Maiti, Tapas K
Photons are exponentially attenuated in matter producing high doses close to the surface. Therefore they are not well suited for the treatment of deep seated tumours. Charged particles, in contrast, exhibit a sharp increase of ionisation density close to the end of their range, the so-called Bragg-peak. The depth of the Bragg-peak can be adjusted by varying the particle's energy. In parallel with the large energy deposit the increase in biological effectiveness for cell killing at the end of the range provides an ideal scalpel for the surgeon effectively without touching the surface tissue. Consequently proton therapy has gained a lot of ground for treating well localized tumours. Even superior still are heavy ions, where the ionisation pattern is increased by the square of their charge.
Tumours of cutaneous sweat glands are uncommon, with a wide histological spectrum, complex classification and many different terms often used to describe the same tumour. Furthermore, many eccrine/apocrine lesions coexist within hamartomas or within lesions with composite/mixed differentiation. In addition to the eccrine and apocrine glands, two other skin sweat glands have recently been described: the apoeccrine and the mammary?like glands of the anogenital area. In this review (the second of two articles on skin adnexal neoplasms), common as well as important benign and malignant lesions of cutaneous sweat glands are described, and a summary for differentiating primary adnexal neoplasms from metastatic carcinoma is outlined, striving to maintain a common and acceptable terminology in this complex subject. Composite/mixed adnexal tumours are also discussed briefly. PMID:16882695
Obaidat, Nidal A; Alsaad, Khaled O; Ghazarian, Danny
Medulloblastoma and neuroblastoma are malignant embryonal childhood tumours of the central and peripheral nervous systems,\\u000a respectively, which often show poor clinical prognosis due to resistance to current chemotherapy. Both these tumours have\\u000a deficient apoptotic machineries adopted from their respective progenitor cells. This review focuses on the specific background\\u000a for tumour development, and highlights biological pathways that present potential targets for
John Inge Johnsen; Per Kogner; Ami Albihn; Marie Arsenian Henriksson
In testicular germ cell tumour (GCT), imaging plays a central role in assessment of tumour bulk, sites of metastases, monitoring response to therapy, surgical planning and accurate assessment of disease at relapse. The primary modality used for imaging patients with GCT is computed tomography (CT) but plain film radiography, ultrasound, magnetic resonance imaging (MRI) and positron emission tomography (PET) may all have roles to play. This article reviews the role of imaging of testicular germ cell tumours. PMID:16966068
Dalal, P U; Sohaib, S A; Huddart, R
The various types of primary tumour that may affect the bones are reviewed. No attempt is made to cover so wide a field in detail, but the more important clinical, radiological, and histological features of each type of tumour are emphasized and its management outlined. Mention is also made of a number of lesions which, while not strictly tumours, may resemble them radiologically. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:4594301
Taxonomic classification of astronomically observed stellar objects is described in terms of spectral properties. Stars receive a classification containing a letter, number, and a Roman numeral, which relates the star to other stars of higher or lower Roman numerals. The citation indicates the stellar chromatic emission in relation to the wavelengths of other stars. Standards are chosen from the available
A fingerprint classification algorithm is presented in this paper. Fingerprints are classified into five categories: arch, tented arch, left loop, right loop and whorl. The algorithm extracts singular points (cores and deltas) in a fingerprint image and performs classification based on the number and locations of the detected singular points. The classifier is invariant to rotation, translation and small amounts
Kalle Karu; Anil K. Jain
A classification scheme for galaxies, devised in its original form in 1925 by Edwin P Hubble (1889-1953), and still widely used today. The Hubble classification recognizes four principal types of galaxy---elliptical, spiral, barred spiral and irregular---and arranges these in a sequence that is called the tuning-fork diagram....
Standfirst Supramolecular structures composed of inorganic nanoparticles and DNA strands can efficiently target tumours and then be disassembled in order to ease elimination from the body. PMID:24463360
Choi, Hak Soo
Two patients presented with hypophosphataemic osteomalacia and were subsequently found to have small tumours unusual histopathology and location causing the osteomalacia. Each tumour was found after an intensive search for occult masses. Studies of vitamin D metabolism and renal tubular function before and after surgery yielded further insight into the pathophysiology of oncogenic osteomalacia. These cases demonstrate that microscopic quantities of tumour are capable of causing the syndrome and further illustrate the high index of suspicion often necessary to locate causative tumours in patients with hypophosphataemic osteomalacia. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:4022870
Weiss, D.; Bar, R. S.; Weidner, N.; Wener, M.; Lee, F.
Nowadays, the incidence of endometrial cancer is rising, especially of high-grade endometrial tumours. Recently, the FIGO classification of endometrial cancer has changed worldwide. Besides that, treatment strategies are changing. The purpose of this study was to analyse the adherence to the national guidelines of cancer treatment and to analyse patterns of disease relapse and survival. We focused on a group of patients (n = 191) with endometrial cancer, in a time period in which new treatment strategies are not yet completely implemented. Because of multiple upcoming changes in patient characteristics, tumour classification, as well as treatment regimens, a more heterogeneous cohort of patients diagnosed with endometrial cancer will appear. From now on, all those changes will have their effects on the followup of conventional endometrial cancer treatment. In our opinion, it is, therefore, valuable to have the current, more homogenous, cohort clearly described. PMID:22229100
Tournois, F. K. L.; Mertens, H. J. M. M.
Major Depressive Disorder (MDD) has been associated with biased processing and abnormal regulation of negative and positive information, which may result from compromised coordinated activity of prefrontal and subcortical brain regions involved in evaluating emotional information. We tested whether patients with MDD show distributed changes in functional connectivity with a set of independently derived brain networks that have shown high correspondence with different task demands, including stimulus salience and emotional processing. We further explored if connectivity during emotional word processing related to the tendency to engage in positive or negative emotional states. In this study, 25 medication-free MDD patients without current or past comorbidity and matched controls (n = 25) performed an emotional word-evaluation task during functional MRI. Using a dual regression approach, individual spatial connectivity maps representing each subject's connectivity with each standard network were used to evaluate between-group differences and effects of positive and negative emotionality (extraversion and neuroticism, respectively, as measured with the NEO-FFI). Results showed decreased functional connectivity of the medial prefrontal cortex, ventrolateral prefrontal cortex, and ventral striatum with the fronto-opercular salience network in MDD patients compared to controls. In patients, abnormal connectivity was related to extraversion, but not neuroticism. These results confirm the hypothesis of a relative (para)limbic-cortical decoupling that may explain dysregulated affect in MDD. As connectivity of these regions with the salience network was related to extraversion, but not to general depression severity or negative emotionality, dysfunction of this network may be responsible for the failure to sustain engagement in rewarding behavior. PMID:24179829
van Tol, Marie-José; Veer, Ilya M; van der Wee, Nic J A; Aleman, André; van Buchem, Mark A; Rombouts, Serge A R B; Zitman, Frans G; Veltman, Dick J; Johnstone, Tom
This is a case report of prostate carcinoma metastasising to a renal oncocytoma. The report demonstrates the unusual presentation of metastases from a common cancer to a common benign tumour, and reviews the rare phenomenon of tumour-to-tumour metastases. PMID:23307454
Petts, Gemma; Rashid, Tina; Hrouda, David; Ngo, Nye-Thane
Resveratrol administration to rats inoculated with a fast growing tumour (the Yoshida AH-130 ascites hepatoma) caused a very significant decrease (25%) in the tumour cell content. The effects of this diphenol were associated with an increase in the number of cells in the G2\\/M cell cycle phase. Interestingly, flow cytometric analysis of the tumour cell population revealed the existence of
Neus Carbó; Paola Costelli; Francesco M. Baccino; Francisco J. López-Soriano; Josep M. Argilés
]. Platinum-based chemo- therapy is a curative therapy for most testicular cancer patients and cisplatin-small cell lung cancers. How- ever, the tumours can become refractory to chemo- therapy after the initial on cells in vitro, experimental tumours in vivo and in treatment of cutaneous tumour nodules in cancer
Ljubljana, University of
Concern has recently been expressed in Australia, both in the media and at the federal government level, over possible links between screen-based computer use and cancer, brain tumour in particular. The screen emissions assumed to be the sources of the putative hazard are the magnetic fields responsible for horizontal and vertical scanning of the display. Time-varying fluctuations in these magnetic fields induce electrical current flows in exposed tissues. This paper estimates that the induced current densities in the brain of the computer user are up to 1 mA/m2 (due to the vertical flyback). Corresponding values for other electrical appliances or installations are in general much less than this. The epidemiological literature shows no obvious signs of a sudden increase in brain tumour incidence, but the widespread use of computers is a relatively recent phenomenon. The occupational use of other equipment based on cathode ray tubes (such as TV repair) has a much longer history and has been statistically linked to brain tumour in some studies. A number of factors make this an unreliable indicator of the risk from computer screens, however. PMID:8867387
Wood, A W
The aim of this study was to present the clinical and functional results of revision surgery after failed hip endoprostheses\\u000a using the Modular Universal Tumour And Revision System (MUTARS®). Functional results of the hip endoprostheses were recorded\\u000a by applying the Harris hip score. The extent of the presurgical radiological bone defect was measured according to the classification\\u000a system of the
Carsten Gebert; Martin Wessling; Christian Götze; Georg Gosheger; Jendrik Hardes
Until recently induced gamma-band activity (GBA) was considered a neural marker of cortical object representation. However, induced GBA in the electroencephalogram (EEG) is susceptible to artifacts caused by miniature fixational saccades. Recent studies have demonstrated that fixational saccades also reflect high-level representational processes. Do high-level as opposed to low-level factors influence fixational saccades? What is the effect of these factors on artifact-free GBA? To investigate this, we conducted separate eye tracking and EEG experiments using identical designs. Participants classified line drawings as objects or non-objects. To introduce low-level differences, contours were defined along different directions in cardinal color space: S-cone-isolating, intermediate isoluminant, or a full-color stimulus, the latter containing an additional achromatic component. Prior to the classification task, object discrimination thresholds were measured and stimuli were scaled to matching suprathreshold levels for each participant. In both experiments, behavioral performance was best for full-color stimuli and worst for S-cone isolating stimuli. Saccade rates 200–700 ms after stimulus onset were modulated independently by low and high-level factors, being higher for full-color stimuli than for S-cone isolating stimuli and higher for objects. Low-amplitude evoked GBA and total GBA were observed in very few conditions, showing that paradigms with isoluminant stimuli may not be ideal for eliciting such responses. We conclude that cortical loops involved in the processing of objects are preferentially excited by stimuli that contain achromatic information. Their activation can lead to relatively early exploratory eye movements even for foveally-presented stimuli. PMID:24391611
Kosilo, Maciej; Wuerger, Sophie M.; Craddock, Matt; Jennings, Ben J.; Hunt, Amelia R.; Martinovic, Jasna
Eighteen cases of cerebral tumour composed partly or totally of primitive embryonal cells are reported. These lesions comprise 2.8% of all primary cerebral hemisphere tumours in the histopathology files of The Royal Marsden Hospital between 1971 and 1980 inclusive. Most exhibited some degree of differentiation towards neuronal or glial elements and, as more than one type of differentiation was often
CC Gaffney; JP Sloane; NJ Bradley; HJG Bloom
Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-d-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting. PMID:18509637
Van de Wiele, Christophe
Three cases of CSF rhinorrhoea due to pituitary tumours are reported and the literature reviewed. The treatment of choice appears to be trans-sphenoidal exploration of the pituitary fossa with insertion of a free muscle graft followed by radiotherapy. The probability of the tumour being a prolactin-secreting adenoma is discussed. PMID:7017123
Cole, I E; Keene, Malcolm
This lesson focuses on understanding the classification system intowhich herbicides are organized. Terms of classification, classificationhierachy, examples of classification and a brief overview of the eightmodes of action are all discussed in this lesson. Once this isunderstood it is much easier to grasp similar herbicides and know whythey may exhibit certain symptoms to weeds and plants alike.Objectives:1.Understand how herbicides are classified and why it is important for managing herbicide resistance2.Understand the Importance of classification and herbicides by mode of action rather than chemical family3.Be able to tell the difference between mode of action and site of action4.Be able to differentiate between herbicide families, modes of action, and sites of action5.Understand common name, trade names and sites of absorption
The term phyllodes tumour includes lesions ranging from completely benign tumours to malignant sarcomas. Clinically phyllodes tumours are smooth, rounded, and usually painless multinodular lesions indistinguishable from fibroadenomas. Percentage of phyllodes tumour classified as malignant ranges from 23% to 50%. We report a case of second largest phyllodes tumour in a 35-year-old lady who presented with swelling of right breast since 6 months, initially small in size, that progressed gradually to present size. Examination revealed mass in the right breast measuring 36×32?cms with lobulated firm surface and weighing 10?kgs. Fine needle aspiration cytology was reported as borderline phyllodes; however core biopsy examination showed biphasic neoplasm with malignant stromal component. Simple mastectomy was done and specimen was sent for histopathological examination which confirmed the core biopsy report. Postoperatively the patient received chemotherapy and radiotherapy. The patient is on follow-up for a year and has not shown any evidence of metastasis or recurrence. PMID:25548696
Krishnamoorthy, Ramakrishnan; Savasere, Thejas; Prabhuswamy, Vinod Kumar; Babu, Rajashekhara; Shivaswamy, Sadashivaiah
Recent advances in sequencing technologies have revealed extensive intratumour heterogeneity (ITH) both within individual tumours and between primary and metastatic tumours for different cancer types. Such genetic diversity may have clinical implications for both cancer diagnosis and treatment with increasing evidence linking ITH and therapeutic resistance. Nonetheless, whilst limiting the activity of targeted agents, tumour genetic heterogeneity may provide a new therapeutic opportunity through generation of neo-antigens that could be recognised and targeted by the patient's own immune system in response to immune-modulatory therapies. Longitudinal genomic studies assessing tumour clonal architecture and its correlation with the underlying immune response to cancer in each particular patient are needed to follow tumour evolutionary dynamics over time and through therapy, in order to further understand the mechanisms behind drug resistance and to inform the development of new combinatorial therapeutic strategies. PMID:23664091
Jamal-Hanjani, Mariam; Thanopoulou, Eirini; Peggs, Karl S; Quezada, Sergio A; Swanton, Charles
Neutron therapy has two branches: Fast Neutron Therapy (FNT) and Boron Neutron Capture Therapy (BNCT). The mean neutron energies used for FNT range from 2 MeV to 25 MeV whereas the maximum energy for BNCT is about 10 keV. Neutron generators for FNT have been cyclotrons, accelerators and reactors, whereas BNCT is so far bound to reactors. Both therapies use the effects of high-LET radiation (secondary recoil protons and alpha particles, respectively) and can attack otherwise radioresistant tumours, however, with the hazard of adverse effects for irradiated healthy tissue. FNT has been administered to about 30,000 patients world-wide. From formerly 40 facilities, only eight are operational or stand-by today. The reasons for this development have been, on the one hand, related to technical and economical conditions; on the other hand, strong side effects and insufficient proof of clinical results in the early years as well as increasing competition with new clinical methods have reduced patient numbers. In fact, strict observations of indications, appropriate therapy-planning including low-LET radiation, and consequent treatment of side effects have lead to remarkable results in the meantime. BNCT initially was developed for the treatment of extremely aggressive forms of brain tumour, taking advantage of the action of the blood-brain-barrier which allows for a boronated compound to be selectively enriched in tumour cells. Meanwhile, also malignant melanoma (MM) and Head-and-Neck (H&T) tumours are treated because of their relative radioresistance. At present, epithermal beams with sufficient flux are available only at two facilities. Existing research reactors were indispensable in the development of BNCT, but are to be replaced by hospital-based epithermal neutron sources. Clinical results indicate significantly increased survival times, but the number of patients ever treated is still below 1,000. 3D-dose calculation systems have been developed at several facilities and guarantee a high safety for both therapies, FNT and BNCT.
Wagner, F. M.; Loeper-Kabasakal, B.; Breitkreutz, H.
Summary Esthesioneuroblastoma is an uncommon tumour. Due to its low incidence, this neoplasm is difficult to evaluate and its treatment remains a matter of debate. Although the role of post-operative radiation is relatively well-defined, little is reported regarding the role of radiotherapy as the only treatment modality. A retrospective analysis of the literature has been conducted. With reference to the treatment of esthesioneuroblastoma, 55 patients submitted only to radiotherapy have been selected from publications of internationally indexed literature between 1979 and 2006. According to the Kadish classification, 6 patients were in stage A, 12 in stage B, and 37 in stage C. Response to therapy for each stage was assessed. There was no evidence of disease in: 6/6 stage A patients with a median follow-up period of 103.6 months, 7/12 stage B patients with a median follow-up period of 120 months, and 7/37 stage C patients with a median follow-up period of 77.3 months. A total of 27 patients died due to tumour-related causes and 5 due to intercurrent disease, while 3 patients were alive with disease (local recurrence and cervical lymph node metastasis). In conclusion, esthesioneuroblastoma is a malignant tumour which grows both locoregionally and distantly. For this reason, despite the satisfying results regarding response to radiotherapy alone in stage A patients, irradiation should be used only in early lesions arising below the cribriform plate, whereas all other cases require aggressive and multimodal therapy. PMID:19205593
Benfari, G; Fusconi, M; Ciofalo, A; Gallo, A; Altissimi, G; Celani, T; De Vincentiis, M
Macrophages have an important role in the maintenance of tissue homeostasis. To perform this function, macrophages must have the capacity to monitor the functional states of their 'client cells': namely, the parenchymal cells in the various tissues in which macrophages reside. Tumours exhibit many features of abnormally developed organs, including tissue architecture and cellular composition. Similarly to macrophages in normal tissues and organs, macrophages in tumours (tumour-associated macrophages) perform some key homeostatic functions that allow tumour maintenance and growth. However, the signals involved in communication between tumours and macrophages are poorly defined. Here we show that lactic acid produced by tumour cells, as a by-product of aerobic or anaerobic glycolysis, has a critical function in signalling, through inducing the expression of vascular endothelial growth factor and the M2-like polarization of tumour-associated macrophages. Furthermore, we demonstrate that this effect of lactic acid is mediated by hypoxia-inducible factor 1? (HIF1?). Finally, we show that the lactate-induced expression of arginase 1 by macrophages has an important role in tumour growth. Collectively, these findings identify a mechanism of communication between macrophages and their client cells, including tumour cells. This communication most probably evolved to promote homeostasis in normal tissues but can also be engaged in tumours to promote their growth. PMID:25043024
Colegio, Oscar R; Chu, Ngoc-Quynh; Szabo, Alison L; Chu, Thach; Rhebergen, Anne Marie; Jairam, Vikram; Cyrus, Nika; Brokowski, Carolyn E; Eisenbarth, Stephanie C; Phillips, Gillian M; Cline, Gary W; Phillips, Andrew J; Medzhitov, Ruslan
Optimising the delivery of antiangiogenic drugs requires the development of drug-disease models of vascular tumour growth that incorporate histological data indicative of cytostatic action. In this study, we formulated a model to analyse the dynamics of tumour progression in nude mice xenografted with HT29 or HCT116 colorectal cancer cells. In 30 mice, tumour size was periodically measured, and percentages of hypoxic and necrotic tissue were assessed using immunohistochemistry techniques on tumour samples after euthanasia. The simultaneous analysis of histological data together with longitudinal tumour size data prompted the development of a semi-mechanistic model integrating random effects of parameters. In this model, the peripheral non-hypoxic tissue proliferates according to a generalised-logistic equation where the maximal tumour size is represented by a variable called 'carrying capacity'. The ratio of the whole tumour size to the carrying capacity was used to define the hypoxic stress. As this stress increases, non-hypoxic tissue turns hypoxic. Hypoxic tissue does not stop proliferating, but hypoxia constitutes a transient stage before the tissue becomes necrotic. As the tumour grows, the carrying capacity increases owing to the process of angiogenesis. The model is shown to correctly predict tumour growth dynamics as well as percentages of necrotic and hypoxic tissues within the tumour. We show how the model can be used as a theoretical tool to investigate the effects of antiangiogenic treatments on tumour growth. This model provides a tool to analyse tumour size data in combination with histological biomarkers such as the percentages of hypoxic and necrotic tissue and is shown to be useful for gaining insight into the effects of antiangiogenic drugs on tumour growth and composition. PMID:21074409
Ribba, Benjamin; Watkin, Emmanuel; Tod, Michel; Girard, Pascal; Grenier, Emmanuel; You, Benoît; Giraudo, Enrico; Freyer, Gilles
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. PMID:25368033
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
Adenocarcinoma, neuroendocrine tumours, sarcomas and lymphomas are the four most common malignant tumours arising in the small intestine, although over forty different histological subtypes are described. Collectively these account for only 2% of cancers of the digestive system. The incidence of small bowel cancer has increased in recent decades with a four-fold increase in carcinoid tumours. Risk factors for small bowel tumours include coeliac disease, inflammatory bowel disease and a number of genetic abnormalities. The non-specific nature of their symptoms and the difficulty in visualising these tumours with normal endoscopic techniques often results in late diagnosis. Furthermore the paucity of literature on this topic has made it difficult to standardise management. There has however been marked improvement in imaging methods resulting in earlier diagnosis in many cases. As expected, early detection of localised, well differentiated tumours followed by surgical resection with negative margins offers the best chance of long term survival. Better adjuvant treatment, notably for gastrointestinal stromal tumours, has improved 5-year survival rates significantly. Development of surveillance guidelines for at risk populations may be a valuable way of improving early diagnosis of this challenging group of conditions. PMID:24637026
Reynolds, Ian; Healy, Paul; Mcnamara, Deborah A
The covalent binding of a carotene moiety to one phenyl ring and meso-tetraphenyl-substituted porphyrins (see Figure 1) efficiently quenches the photosensitising activity of the porphyrin while a relatively large yield of fluorescence emission around 650 nm is retained. Pharmacokinetic studies performed with two carotenoporphyrins (CPs) and the corresponding porphyrins (Ps) in Balb/c mice bearing an MS-2 fibrosarcoma show that the two Ps give a high selectivity of tumour localisation (tumour/peritumoral tissue ratios of dye concentration ranging between c. 30 and 90 at 24 h after injection of 4.2-8.4 mumol kg-1 in a Cremophor emulsion) and photosensitive tumour necrosis upon red light irradiation. For the same injected doses, the two CPs show no tumour-photosensitising activity even though they localise in the tumour in concentrations of the order of 10-40 micrograms g-1 at 24 h with tumour/peritumoral ratios larger than 10. Thus, the fluorescence emitted by these CPs in the tumour can be used for photodiagnostic purposes with no risk of skin photosensitisation. However, this approach is presently limited by the large accumulation and prolonged retention of the CPs in the liver and spleen. PMID:8286208
Reddi, E.; Segalla, A.; Jori, G.; Kerrigan, P. K.; Liddell, P. A.; Moore, A. L.; Moore, T. A.; Gust, D.
Receptor tyrosine kinases expressed in endothelial cells are potential targets for therapy with specific tyrosine kinase inhibitors. Endothelial cell KIT expression has not been systematically evaluated in human cancer. In the present study, endothelial cell KIT expression was assessed in 345 tumours consisting of 34 different histological types using a tissue microarray technique. Marked KIT expression occurred in the tumour endothelial cells only in primary glioblastomas in the microarray. Moderate to strong KIT and phosphorylated KIT expression was detected in the tumour endothelial cells in six (16%) and seven (19%) of the 37 primary glioblastomas examined, respectively. In whole tissue sections, KIT and phosphorylated KIT were expressed in tumour endothelial cells in 13 (59%) and 11 (50%) of the 22 glioblastomas examined, respectively. RNA in situ hybridization showed KIT mRNA expression in most glioblastomas both in tumour vessel endothelial cells and in perinecrotic palisading glioblastoma cells, whereas little KIT mRNA was found in the endothelial cells of colon or pancreatic carcinomas. Phosphorylated KIT, its ligand stem cell factor, and the downstream signalling molecules phosphorylated Akt and mTOR were often expressed in glioblastoma cells located in the perinecrotic tumour areas that often also contained abundant HIF-1alpha. It is concluded that marked KIT and phosphorylated KIT expression is frequently present in the endothelial cells of glioblastomas, which are known to harbour florid microvascular proliferation with characteristic morphological features. Glioblastomas also express phosphorylated KIT and its activated downstream signalling molecules in the tumour cells. Lower levels of KIT and phosphorylated KIT are present in endothelial cells of other tumour types and in normal tissues. Endothelial cell and tumour cell expression of activated KIT might explain in part the responsiveness of glioblastomas to the combination of imatinib (an inhibitor of KIT) and hydroxyurea. PMID:17294421
Sihto, H; Tynninen, O; Bützow, R; Saarialho-Kere, U; Joensuu, H
A retrospective analysis of surgical procedures for ovarian tumours, performed in the Department of General and Oncological Gynaecology at the Military Medical Academy (Sofia, Bulgaria) specified 81% of the tumour cases as benignant ones, 15.6% as malignant ones, and 3.4% as borderline ovarian tumours (BOT). The histological type of BOT was assessed as serous in 62% and as mucinous in 38%. The incidence of BOT was found to increase with increasing age. Most patients with BOT were parous (60%). Serum levels of CA 125 were within normal values in all patients with BOT. PMID:24283059
Nacheva, A; Atanasova, V; Miloshov, V; Ganovska, A; Simeonova, C
Extrarenal malignant rhabdoid tumour (EMRT) is very rare and aggresive childhood neoplasm with a rapid progression. The prognosis is still very poor with 80 % mortality rate. We report a case of a newborn baby with extrarenal malignant rhabdoid tumour of an upper eyelid. An EMRT was diagnosed based on the histological examination. This case report highlights the clinical presentation, radiological features and difficulty in diagnosis. The purpose is to underline the importance of its inclusion in the differential diagnosis of any aggresive lesion in a child. Key words: malignant rhabdoid tumour, childhood, diagnostic process. PMID:25030315
Prívarová, E; Griš?íková, L; Lokaj, M; Vokurková, J; Mazánek, P; Autrata, R
Introduction Germline mutations in the BRCA1 and BRCA2 genes account for a considerable fraction of familial predisposition to breast cancer. Somatic mutations in BRCA1 and BRCA2 have not been found and the involvement of these genes in sporadic tumour development therefore remains unclear. Methods The study group consisted of 67 primary breast tumours with and without BRCA1 or BRCA2 abnormalities. Genomic alterations were profiled by high-resolution (~7 kbp) comparative genome hybridisation (CGH) microarrays. Tumour phenotypes were analysed by immunohistochemistry on tissue microarrays using selected biomarkers (ER, PR, HER-2, EGFR, CK5/6, CK8, CK18). Results Classification of genomic profiles through cluster analysis revealed four subgroups, three of which displayed high genomic instability indices (GII). Two of these GII-high subgroups were enriched with either BRCA1- or BRCA2-related tumours whereas the third was not BRCA-related. The BRCA1-related subgroup mostly displayed non-luminal phenotypes, of which basal-like were most prominent, whereas the other two genomic instability subgroups BRCA2- and GII-high-III (non-BRCA), were almost entirely of luminal phenotype. Analysis of genome architecture patterns revealed similarities between the BRCA1- and BRCA2 subgroups, with long deletions being prominent. This contrasts with the third instability subgroup, not BRCA-related, where small gains were more prominent. Conclusions The results suggest that BRCA1- and BRCA2-related tumours develop largely through distinct genetic pathways in terms of the regions altered while also displaying distinct phenotypes. Importantly, we show that the development of a subset of sporadic tumours is similar to that of either familial BRCA1- or BRCA2 tumours. Despite their differences, we observed clear similarities between the BRCA1- and BRCA2-related subgroups reflected in the type of genomic alterations acquired with deletions of long DNA segments being prominent. This suggests similarities in the mechanisms promoting genomic instability for BRCA1- and BRCA2-associated tumours, possibly relating to deficiency in DNA repair through homologous recombination. Indeed, this feature characterized both familial and sporadic tumours displaying BRCA1- or BRCA2-like spectrums of genomic alterations. The importance of these findings lies in the potential benefit from targeted therapy, through the use of agents leading to DNA double-strand breaks such as PARP inhibitors (olaparib) and cisplatin, for a much larger group of patients than the few BRCA1 and BRCA2 germline mutation carriers. PMID:19589159
Stefansson, Olafur Andri; Jonasson, Jon Gunnlaugur; Johannsson, Oskar Thor; Olafsdottir, Kristrun; Steinarsdottir, Margret; Valgeirsdottir, Sigridur; Eyfjord, Jorunn Erla
Ninety-one patients with extradural spinal tumours were examined by magnetic resonance imaging. There were 76 metastases (6 from unknown primary tumours). Seven patients had primary spinal tumours and 8 had multiple myeloma. Sixteen had bulging, diseased vertebral bodies compressing the subarachnoid space and 67 had extradural tumour compressing the spinal cord. Sixty patients had paravertebral involvement. Intraspinal involvement did not
M. H. Li; S. Holtås; E. M. Larsson
The knowledge of the incidence of pineal tumours is important not only for diagnostic care but also for its therapeutic programme. We reviewed the incidence of pineal tumours reported in literature in an attempt to establish if a difference existed between pineal gland tumours and the pineal region tumours as different authors use both expressions to indicate the same thing. The rate of frequency of these tumours is useful to guide the therapeutic choice for patients as the decisional tree is completely different for either germ cell tumours, pineal gland tumours or pineal gliomas and eventually papillary tumours of the pineal region. According to the French Register of pineal tumours, true pineal tumours represent: 27% pineal parenchymal tumours (PPT), 27% germ cell tumours, 17% gliomas, 8% papillary tumours. True pineal gland tumours are represented by: pineocytomas - (13%), pineal parenchymal tumours with intermediary differentiation PTT-ID - (66%) and pinealoblastomas - (21%). There was no statistical difference found between the French register and the Lyon series concerning histological diagnosis. It seemed to us important to discover its true incidence by comparing the data published in the literature and to stress the utility of the French Register for these uncommon tumours not only for recording new histological cases but also to document clinical symptomatology, therapeutic programmes, length of follow-up and clinical results for each patient treated. A better understanding of their natural history and improved evaluation of different treatments and their complications should contribute to improve clinical results. PMID:25113513
Mottolese, C; Szathmari, A; Beuriat, P-A
Tumour ablation is clinically applied mainly for non-operable liver tumours, with increasing application to other organ sites like kidney, lung, adrenal gland and bone. Most current devices use radiofrequency (RF) current to heat tumour tissue surrounding the applicator, which is introduced into the tumour under imaging guidance. Tissue temperatures in excess of 1008C are achieved, with cell death due to
D. Haemmerich; P. F. Laeseke
Patients with pancreatic cancer usually lack signs and symptoms in the early course of the disease. Even when malignancy is suspected, differential diagnosis between benign and malignant pancreatic disorders may be difficult with current methods. An increasing interest has been focused on the utility of immunological tumour markers. CEA has been widely used since the early seventies, but the results in diagnosis of pancreatic cancer have been disappointing. Tumour marker tests for CA 19-9 and CA 50 are based on monoclonal antibodies to colonic carcinoma cell lines. CA 19-9 and CA 50 are strongly expressed in most tissue specimens from pancreatic carcinomas, but are also found in normal pancreas and benign pancreatic diseases. The CA 19-9 and CA 50 antigens are shed or released into the circulation, and are found in increased concentrations in 70-80% of patients with pancreatic cancer. Also 50-65% of patients with small resectable carcinomas have elevated CA 19-9 and CA 50 levels, although very high serum concentrations usually indicate advanced disease. Slightly elevated serum CA 19-9 and CA 50 levels are seen in some patients with benign pancreatic diseases, more often in acute than in chronic pancreatitis. Elevated values are often observed in patients with benign obstruction of the common bile duct, particularly in patients with cholangitis. In patients with jaundice of hepatocellular origin, the CA 19-9 and CA 50 levels are lower than in extrahepatic cholestasis. CA 19-9 and CA 50 have better diagnostic accuracy for pancreatic cancer than CEA, CA 125, DU-PAN-2, TPA and PSTI/TATI. However, the sensitivities and specificities of CA 19-9 and CA 50 are too low for screening of an asymptomatic population. Nevertheless, CA 19-9 and CA 50 have in our experience shown to be useful complements to other diagnostic methods in symptomatic patients with suspicion of pancreatic cancer. Combinations of different markers improve the sensitivity only slightly compared to the use of CA 19-9 or CA 50 alone. Follow-up using CA 19-9 and CA 50 is a simple and sensitive way of monitoring the postoperative course of patients with pancreatic cancer, and may give a lead time of several months for a recurrence compared to conventional methods. PMID:2667448
Haglund, C; Kuusela, P; Roberts, P J
Outline Stellar Populations Classification Surface photometry STRUCTURE OF GALAXIES 2. Stellar Populations, classification, surface photometry Piet van der Kruit Kapteyn Astronomical Institute University Populations, classification, surface photometry #12;Outline Stellar Populations Classification Surface
Kruit, Piet van der
Giant cell tumour (GCT) or osteoclastoma is a benign locally aggressive tumour with a tendency for local recurrence. 85-90% of cases occur in long bones; the sites most commonly affected being lower end of femur, upper end of tibia, lower end of radius and proximal humerus in descending order of frequency. Only 2% of GCT occurs in hand. GCT of bone accounts for 5% of all primary bone tumour. 80% of patients are above the age of 18 years, and it occurs commonly in adults between ages of 20 and 40 years. The authors report a case of GCT of first metacarpal which is very rare site for such tumour and only few cases reported in literature so far. PMID:22701064
Shahid, Mohammad; Varshney, Manoranjan; Maheshwari, Veena; Mubeen, Aysha; Gaur, Kavita; Siddiqui, Mohammad
Mediastinal neurogenic tumours generally arise as single benign lesions and their typical location is the costovertebral sulcus. In about 10% of cases mediastinal neurogenic tumours may extend to the spinal canal; occasionally they may extend to the cervical region and, more rarely, may be multiple or associated with other synchronous mediastinal lesions. The treatment of choice is surgical resection. This report describes three cases of unusual presentation of mediastinal benign schwannomas successfully treated at our Hospital. In the first case multiple simultaneous paravertebral lesions were resected through a posterior approach. In the second case a tumour of the posterior mediastinum extending to the cervical region was excised through a one-stage combined supraclavicular incision followed by left mini-invasive video-assisted thoracoscopic surgical techniques. The third case describes a patient with a posterior neurogenic mediastinal tumour with a synchronous parathyroid adenoma of the anterior mediastinum, which were both successfully resected by video-assisted thoracoscopic surgery. PMID:23738180
Negri, Giampiero; Bandiera, Alessandro; Carretta, Angelo; Puglisi, Armando; Mandelli, Carlo; Ciriaco, Paola; Zannini, Piero
One hundred and sixteen patients with proved cancer of the breast were followed up for five years to detect circulating tumour cells. Such cells were found in 61 patients, but, irrespective of the stage of the disease, the five-year survival rate in these was not significantly different from those in whom no tumour cells were found. The higher incidence of patients without circulating tumour cells in Stage I was not sufficient to influence the survival rate of the whole group. While the validity of the identification of these cells is questionable, the results of this study indicate that the presence or absence of tumour cells in the blood is of no prognostic significance. PMID:6017697
Webster, D. R.; Sabbadini, E.
The craniopharyngioma is a rare dysontogenetic tumour that originates from either scattered cells of the craniopharyngeal duct or from metaplastically mutated anterior pituitary parenchyma cells. Despite being classified as a WHO-Class-I tumour, the histologically benign craniopharyngioma may display an aggressive behaviour. Like other congenital tumours, it usually becomes manifest within the first two decades of life. Patients typically complain of headache and a chiasma syndrome with bitemporal hemianopsy may develop depending on tumour localisation. In children, anterior pituitary insufficiency often manifests as growth restriction. Additionally, diabetes insipidus and other hormonal disturbances may develop. Therapeutically either radical total removal or subtotal resection in combination with postoperative radiation is recommended. In cystic tumors, stereotactic cyst drainage and adjuvant radiation may be a possible alternative. The prognosis is best in patients who are diagnosed early. PMID:20715005
Stienen, M N; Cadosch, D; Bilz, S; Hildebrandt, G; Gautschi, Oliver P
Resveratrol administration to rats inoculated with a fast growing tumour (the Yoshida AH-130 ascites hepatoma) caused a very significant decrease (25%) in the tumour cell content. The effects of this diphenol were associated with an increase in the number of cells in the G2/M cell cycle phase. Interestingly, flow cytometric analysis of the tumour cell population revealed the existence of an aneuploid peak (representing 28% of total), which suggests that resveratrol causes apoptosis in the tumour cell population resulting in a decreased cell number. PMID:9920811
Carbó, N; Costelli, P; Baccino, F M; López-Soriano, F J; Argilés, J M
Primary peritoneal serous borderline tumour (PPSBT) is a rare epithelial neoplasm which is histologically identical to serous borderline tumour of the ovary. PPSBT is distinguishable from primary peritoneal serous carcinoma because the tumour cells do not invade the underlying tissue and affected patients have a good prognosis. We report the CT findings of surgically proven PPSBT in which multiple peritoneal cysts were seen. Although rare, PPSBT should be considered in the differential diagnosis of primary peritoneal tumours. Since the prognosis of the disease is good, conservation of the uterus and ovaries should be a consideration in young female patients during surgery. PMID:22190758
Go, H S; Hong, H S; Kim, J W; Woo, J Y
Background: Skin adnexal tumours (SATs) are a large and diverse group of benign and malignant neoplasms. They are uncommon. They can be single or multiple, sporadic or familial and they might be markers for syndromes associated with internal malignancies. Benign adnexal tumours are more common and malignant SATs are rare and are locally aggressive and have the potential for nodal involvement and distant metastasis with a poor clinical outcome.Therefore recognition of SATs and establishing a diagnosis of malignancy in SATs is important for therapeutic and prognostic reasons. Aims and Objectives: SATs are rare benign and malignant neoplasms. They are not commonly encountered in the routine surgical pathology practice.Hence this study aims at finding the frequency, clinical presentation and the histopathological appearances of SATS, and the differentiating features between benign and malignant tumours. Materials and Methods: This is partly a retrospective and partly a prospective study done in a tertiary care hospital over a period of four years .All the SATs reported during this period are analysed for their clinical features, age, sex incidence and their gross and histopathological features. Results: In the four years period 1,64,220 patients attended the hospital. The total number of SATS reported during this period were 21 cases (0.0128 %) Benign tumours were 19 (90.48%). Malignant tumours were 2(9.52%) The mean age for males 36.9 years and for females 35. Two years. There were 11 male patients and 10 female patients. Tumours of hair follicular differentiation were 7 (33.33%). Tumour like lesion of sebaceous origin was 1 (4.76%). Tumours of sweat gland origin were 11 (52.38%). Malignant tumours of eccrine origin were 2 (9.52%). Conclusion: SATs are not common. Their incidence in our study is only 0.0128 % of all cases. Eventhough benign SATs are more common than the malignant tumours, malignant SATs can occur both in young and elderly patients and they are aggressive and the SATs should be excised with wide tumour free margins. PMID:25386438
Selvakumar, Sathish; Rajeswari, K.; Meenakshisundaram, K.; G, Veena; Ramachandran, Padmini
Executive Summary Objective The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer’s disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson’s disease (PD). Clinical Need: Target Population and Condition Alzheimer’s disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006. In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging. Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci. Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000 people. Parkinson’s disease is the most prevalent movement disorder; it affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes, and response to therapy. The Technology Being Reviewed Functional Brain Imaging Functional brain imaging technologies measure blood flow and metabolism. The results of these tests are often used in conjunction with structural imaging (e.g., MRI or CT). Positron emission tomography and MRS identify abnormalities in brain tissues. The former measures abnormalities through uptake of radiotracers in the brain, while the latter measures chemical shifts in metabolite ratios to identify abnormalities. The potential role of functional MRI (fMRI) is to identify the areas of the brain responsible for language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. Magnetoencephalography measures magnetic fields of the electric currents in the brain, identifying aberrant activity. Magnetoencephalography may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex and auditory cortex. In terms of regulatory status, MEG and PET are licensed by Health Canada. Both MRS and fMRI use a MRI platform; thus, they do not have a separate licence from Health Canada. The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application. Review Strategy The literature published up to September 2006 was searched in the following databases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and International Network of Agencies for H
In this exercise, students get experience with image classification. Images are an increasingly important source of information about land cover and land use over time because comparisons of historic and current images can provide an estimate of change in the landscape.
In order to achieve a better understanding of factors involved in drug penetration into poorly vascularized tumour tissue, the penetration of some model substaces was studied in vitro. Multicellular human tumour spheroids were used as model system. The test substances were [3H]thymidine and [14C]glucose, both of which are capable of passing easily through cell membranes, and [3H]thymidine-5'-triphosphate, [3H]sucrose and [3H]inulin,
Thore Nederman; Jörgen Carlsson; Kerstin Kuoppa
Objectives The aim of this review is to evaluate the principal clinical and conventional radiographic features of non-syndromic keratocystic odontogenic tumour (KCOT) by systematic review (SR), and to compare the frequencies between four global groups. Methods The databases searched were the PubMed interface of Medline and LILACS. Only those reports of KCOTs that occurred in a series of consecutive cases, in the reporting authors' caseload, were considered. Results 51 reports, of 49 series of cases, were included in the SR. 11 SR-included series were in languages other than English. KCOTs affected males more frequently and were three times more prevalent in the mandible. Although the mean age at first presentation was 37 years, the largest proportion of cases first presented in the third decade. The main symptom was swelling. Over a third were found incidentally. Nearly two-thirds displayed buccolingual expansion. Over a quarter of cases recurred. Only a quarter of all SR-included reported series of cases included details of at least one radiological feature. The East Asian global group presented significantly as well-defined, even corticated, multilocular radiolucencies with buccolingual expansion. The KCOTs affecting the Western global group significantly displayed an association with unerupted teeth. Conclusions Long-term follow-up of large series that would have revealed detailed radiographic description and long-term outcomes of non-syndromic KCOT was lacking. PMID:21159911
MacDonald-Jankowski, D S
WILMS' tumour is an embryonic kidney tumour thought to arise through aberrant mesenchymal stem cell differentiation1 and to result from loss of function of a 'tumour suppressor' gene(s)2. Both sporadic and syndrome-associated Wilms' tumours are accompanied by an increased frequency of abnormalities of the urinary tract and genitalia3. Deletional analysis of individuals with the WAGR syndrome4-8 (for, Wilms' tumour, aniridia,
Kathryn Pritchard-Jones; Stewart Fleming; Duncan Davidson; Wendy Bickmore; David Porteous; Christine Gosden; Jonathan Bard; Alan Buckler; Jerry Pelletier; David Housman; Veronica van Heyningen; Nicholas Hastie
Solitary fibrous tumour is an uncommon neoplasm that arises predominantly from within the pleura. Extrapleural manifestation of solitary fibrous tumour, particularly in the head and neck area, is extremely rare. Here, we report a solitary fibrous tumour of the face in a 40-year old woman. The tumour was removed with a radiological combined approach, with embolisation of tumour blood vessels prior to excision. Eight months following surgery, the patient is well and free of disease. PMID:19527945
Profyris, Christos; Soilleux, Elizabeth; Corkill, Rufus; Birch, Jeremy
The differential diagnosis of renal and supra-renal masses firstly depends on the age of the child. Neuroblastoma (NBL) may be seen antenatally or in the newborn period; this tumour has a good prognosis unlike NBL seen in older children (particularly NBL in those aged 2–4 years). Benign renal masses predominate in early infancy but beyond the first year of life Wilms' tumour is the most common renal malignancy, until adolescence when renal cell carcinoma has similar or increased frequency as children get older. Adrenal adenomas and carcinomas also occur in childhood; these tumours are indistinguishable on imaging but criteria for the diagnosis of adrenal carcinoma include size larger than 5?cm, a tendency to invade the inferior vena cava and to metastasise. The most topical dilemmas in the radiological assessment of renal and adrenal tumours are presented. Topics covered include a proposed revision to the staging of NBL, the problems inherent in distinguishing nephrogenic rests from Wilms' tumour and the current recently altered approach regarding small lung nodules in children with Wilms' tumour. PMID:17339140
Background: Glomus tumours are rare vascular tumours arising subungually in fingernails. Surgical excision provides histopathologic diagnosis and rapid resolution of symptoms. Objective: Present study was aimed at delineating common presentations and long-term treatment outcome of this rare subungual tumour. Patients and Methods: The clinical features and imaging results for 10 patients with subungual glomus tumours were recorded. All were treated with transungual excision. Per-operative findings and, treatment outcomes were recorded and analysed. Results: Females outnumbered males with average age being 33.3 ± 7.55 years. Presenting symptoms were severe pain (100%); nail-plate discoloration and onycholysis. X-ray was normal in 70%, though a magnetic resonance imaging done for five, helped visualise the lesion in three patients. The tumour involved nail bed in five cases and matrix in five, with an average size being 6.1 ± 2.13 mm (range 3-11 mm). An average follow-up of 16.8 months (range 8-24 months) was largely uneventful with longitudinal ridging in two cases and recurrence in two (both attributed to a sister lesion). Conclusion: Subungual glomus tumours have characteristic clinical presentation. Imaging is helpful pre-operatively but has a low success rate. Transungual surgical excision is safe and effective, allowing better visualisation, easy exploration and minimal long-term complications. PMID:24470715
Grover, Chander; Khurana, Ananta; Jain, Rajat; Rathi, Vinita
EEG classification using Learning Vector Quantization (LVQ) is introduced on the basis of a Brain-Computer Interface (BCI) built in Graz, where a subject controlled a cursor in one dimension on a monitor using potentials recorded from the intact scalp. The method of classification with LVQ is described in detail along with first results on a subject who participated in four on-line cursor control sessions. Using this data, extensive off-line experiments were performed to show the influence of the various parameters of the classifier and the extracted features of the EEG on the classification results. PMID:1286147
Flotzinger, D; Kalcher, J; Pfurtscheller, G
BackgroundTumour-to-tumour metastasis (TTM) occurs when one tumour metastasises to a separate tumour within the same individual. TTM is observed frequently in breast cancer but has not been described in male breast cancer. In addition reports describing solitary fibrous tumours (SFT) of the pleura hosting other neoplasms¿ metastases are limited. We report an exceptional case of male breast cancer metastasising to an extrapleural SFT, occurring in the subcutaneous tissue of the back of a 68-year old Caucasian patient.Case presentationA 68-year old male was diagnosed with a metastasising ductal breast cancer. He was treated by mastectomy of the right breast and axillary lymph-adenectomy. Further staging revealed an increasing subcutaneous expansion located on the patient¿s back. Excision biopsy confirmed a SFT hosting a breast cancer metastasis. The patient received palliative chemotherapy but died of disease seven years after initial diagnosis.ConclusionsThe abundance of blood vessels within these lesions might predispose SFTs for an involvement in TTM. This case describes the possibility of concurrent rare occurrences and reminds clinicians, as well as pathologists, to be open-minded and fastidious about their differential diagnoses, sampling and examination of histological specimens.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_203. PMID:25420931
Scheipl, Susanne; Moinfar, Farid; Leithner, Andreas; Sadoghi, Patrick; Jorgensen, Mette; Rinner, Beate; Liegl, Bernadette
The clinical relevance of circulating tumour cells (CTC) in peripheral blood of patients with colorectal cancer (CRC) has been described as an independent prognostic factor useful to monitor drug effects and clinical status. The aim of the present study was to compare the epidermal growth factor receptor (EGFR) status of primary tumour, related metastases and CTC of patients with CRC. Therefore, in addition to EGFR, the tumour-associated transcripts gastrointestinal tumour-associated antigen 733-2 (GA733-2) and carcinoembryonic antigen (CEA) were analyzed in a multiplex RT-PCR to characterize CTC. 55% patients were positive for CTC. EGFR expression was detected in 18% of these patients. EGFR was expressed more frequently in metastatic and primary tumour tissues as revealed by immunohistochemistry. Besides, detailed expression profiling of EGFR variants in various colorectal and glioma cell lines has been performed to generate positive controls, resulting in the discovery of two new transcript deletion variations (cEX12_15del, cEX12_14del) located on the extracellular domain of the EGFR. PMID:18936523
Lankiewicz, Silke; Rother, Eva; Zimmermann, Silke; Hollmann, Christiane; Korangy, Firouzeh; Greten, Tim F
The aim of this clinical study was to determine the tumour control rate, clinical outcome and complication rate following gamma knife treatment for glomus jugulare tumours. Between May 1992 and May 1998, 13 patients with glomus tumours underwent stereotactic radiosurgical treatment in our department. The age of these patients ranged from 21 to 80 years. The male:female ratio was 2:11. Six patients had primary open surgery for partial removal or recurrent growth and subsequent radiosurgical therapy. Radiosurgery was performed as primary treatment in 7 cases. The median tumour volume was 6.4 cm3 (range: 4.6-13.7 cm3). The median marginal dose applied to an average isodose volume of 50% (30-50%) was 13.5 Gy (12-20 Gy). In 10 patients, a total of 48 MRI and CT follow-up scans were available. The remaining three patients have been excluded from the postradiosurgical evaluation since the observation time (t < 12 months) was too short or patients were lost to follow up. The median interval from Gamma Knife treatment to the last radiological follow-up was 37.6 months (5-68 months). In 4 patients (40%) decreased tumour volumes were observed and in 6 cases (60%) the tumour size remained unchanged. Neurological follow-up examinations revealed improved clinical status in 5 patients (50%), a stable neurological status in 5 patients (50%) and no complications occurred. According to our preliminary experience Gamma Knife radiosurgery represents an effective treatment option for glomus jugulare tumours. PMID:10536716
Eustacchio, S; Leber, K; Trummer, M; Unger, F; Pendl, G
In Germany in about 50,000 patients lung cancer is diagnosed per year - actually it is the tumour most likely to result in death. Furthermore, the lung is the second most common site of distant metastases of extrathoracic tumours. In recent years image-guided thermo-ablative techniques are increasingly being used in patients unable to undergo surgery. Radiofrequency ablation (RFA) is the most frequently used technique, cryoablation, microwave-ablation and laser-induced thermoablation are new and promising techniques. Actually there is only a small evidence base, only retrospective and prospective case series have been published as yet. Randomised controlled trials have not been conducted up to now. RFA results in a local control of tumour growth in about 90?%. Long-term results indicate 5-year survival rates of 20-61?% in patients with lung cancer or lung metastases. Pneumothorax is the most common morbidity - requiring drainage in about 10?% after the intervention. In the long term no loss of pulmonary function results after the ablation of peripheral lesions. Peripherally localised tumours 3?cm in diameter are the most promising targets, the treatment of centrally localised tumours is subtle due to the "heat-loss" effect. The current evidence is insufficient to develop a procedure for differential indication of ablative techniques versus stereotactic radiotherapy. Tumour ablation always should be indicated on the basis of interdisciplinary consensus (including pulmonologists, oncologists, thoracic surgeons, radiotherapists). Inoperability should be assigned by the thoracic surgeon himself. Actually it cannot be considered an alternative to surgery for the treatment of malignant lung tumours with curative intent, however thermal ablation broadens the range of treatment options for patients being no candidates for surgery. PMID:25329865
In this lesson students learn how classification of organisms is based on evolutionary relationships. They will also learn how primates are categorized, and how they are related. Students transfer examples (names) of primates from their location in an outline hierarchy of primate groups into a set of nested boxes reflecting that same hierarchy. A cladogram can then be drawn illustrating how these groups are related in an evolutionary way.
Tumour proliferation is promoted by an intratumoral metabolic symbiosis in which lactate from stromal cells fuels energy generation in the oxygenated domain of the tumour. Furthermore, empirical data show that tumour cells adopt an intermediate metabolic state between lactate respiration and glycolysis. This study models the metabolic symbiosis in the tumour through the formalism of evolutionary game theory. Our game model of metabolic symbiosis in cancer considers two types of tumour cells, hypoxic and oxygenated, while glucose and lactate are considered as the two main sources of energy within the tumour. The model confirms the presence of multiple intermediate stable states and hybrid energy strategies in the tumour. It predicts that nonlinear interaction between two subpopulations leads to tumour metabolic critical transitions and that tumours can obtain different intermediate states between glycolysis and respiration which can be regulated by the genomic mutation rate. The model can apply in the epithelial-stromal metabolic decoupling therapy. PMID:25097747
Kianercy, Ardeshir; Veltri, Robert; Pienta, Kenneth J
Tumour proliferation is promoted by an intratumoral metabolic symbiosis in which lactate from stromal cells fuels energy generation in the oxygenated domain of the tumour. Furthermore, empirical data show that tumour cells adopt an intermediate metabolic state between lactate respiration and glycolysis. This study models the metabolic symbiosis in the tumour through the formalism of evolutionary game theory. Our game model of metabolic symbiosis in cancer considers two types of tumour cells, hypoxic and oxygenated, while glucose and lactate are considered as the two main sources of energy within the tumour. The model confirms the presence of multiple intermediate stable states and hybrid energy strategies in the tumour. It predicts that nonlinear interaction between two subpopulations leads to tumour metabolic critical transitions and that tumours can obtain different intermediate states between glycolysis and respiration which can be regulated by the genomic mutation rate. The model can apply in the epithelial–stromal metabolic decoupling therapy. PMID:25097747
Kianercy, Ardeshir; Veltri, Robert; Pienta, Kenneth J.
Classification of brain images obtained through functional magnetic resonance imaging (fMRI) poses a serious challenge to pattern recognition and machine learning due to the extremely large feature-to-instance ratio. This calls for revision and adaptation of the current state-of-the-art classification methods. We investigate the suitability of the random subspace (RS) ensemble method for fMRI classification. RS samples from the original feature
Ludmila I. Kuncheva; Juan José Rodríguez Diez; Catrin O. Plumpton; David E. J. Linden; Stephen J. Johnston
A rare case of a thymoma metastatic to brain is reported. This tumor was localized intraoperatively with the use of transdural ultrasound imaging, and gross total resection was accomplished. Radiation therapy was administered to both brain and mediastinum. The growth characteristics, classification, and treatment of thymomas are discussed. PMID:3553984
Dewes, W; Chandler, W F; Gormanns, R; Ebhardt, G
Somatic mutations in the POLE gene encoding the catalytic subunit of DNA polymerase ? have been found in sporadic colorectal cancers (CRCs) and are most likely of importance in tumour development and/or progression. Recently, families with dominantly inherited colorectal adenomas and colorectal cancer were shown to have a causative heterozygous germline mutation in the proofreading exonuclease domain of POLE. The highly penetrant mutation was associated with predisposition to CRC only and no extra-colonic tumours were observed. We have identified a mutation in a large family in which the carriers not only developed CRC, they also demonstrate a highly penetrant predisposition to extra-intestinal tumours such as ovarian, endometrial and brain tumours. The mutation, NM_006231.2:c.1089C>A, p.Asn363Lys, also located in the proofreading exonuclease domain is directly involved in DNA binding. Theoretical prediction of the amino acid substitution suggests a profound effect of the substrate binding capability and a more severe impairment of the catalytic activity compared to the previously reported germline mutation. A possible genotype to phenotype correlation for deleterious mutations in POLE might exist that needs to be considered in the follow-up of mutation carriers. PMID:24788313
ROHLIN, ANNA; ZAGORAS, THEOFANIS; NILSSON, STAFFAN; LUNDSTAM, ULF; WAHLSTRÖM, JAN; HULTÉN, LEIF; MARTINSSON, TOMMY; KARLSSON, GÖRAN B.; NORDLING, MARGARETA
After three decades of intensive research, cytoreductive surgery remains the gold standard of treatment of malignant gliomas. Survivorship at both 1-year and 5-years has not drastically changed in the UK. Concomitant chemo- and radiotherapy has enhanced the efficiency of surgery, enabling more aggressive tumour resection whilst also preserving the surrounding healthy brain parenchyma. More accurate imaging techniques have also played a role in tumour identification, key to this has been pre- and intra-operative contrast enhancement and compounds that have a high affinity in binding to glioma cells. Intra-operative imaging has heralded the ability to give the operating surgeon continuous feedback to assess the completeness of resection. Research is shifting into investigating the complex cellular and molecular glial tumour-genesis, and has led to the development of efficacious chemotherapy agents and trial novel therapies. Oncolytic virotherapy has shown promise in clinical trials and gene therapy in-vitro studies. Surgery however remains the primary therapeutic option for the management of malignant gliomas removing the mass of proliferating malignant tumour cells and decompression of the space-occupying lesion.
Talibi, Sayed Samed; Talibi, Sayed Samie; Aweid, Bashaar; Aweid, Osama
By definition, tumours are heterogeneous. They are defined by marked differences in cells, microenvironmental factors (oxygenation levels, pH, VEGF, VPF and TGF-?) metabolism, vasculature, structure and function that in turn translate into heterogeneous drug delivery and therapeutic outcome. Ways to estimate quantitatively tumour heterogeneity can improve drug discovery, treatment planning and therapeutic responses. It is therefore of paramount importance to have reliable and reproducible biomarkers of cancerous lesions' heterogeneity. During the past decade, the number of studies using histogram approaches increased drastically with various magnetic resonance imaging (MRI) techniques (DCE-MRI, DWI, SWI etc.) although information on tumour heterogeneity remains poorly exploited. This fact can be attributed to a poor knowledge of the available metrics and of their specific meaning as well as to the lack of literature references to standardised histogram methods with which surrogate markers of heterogeneity can be compared. This review highlights the current knowledge and critical advances needed to investigate and quantify tumour heterogeneity. The key role of imaging techniques and in particular the key role of MRI for an accurate investigation of tumour heterogeneity is reviewed with a particular emphasis on histogram approaches and derived methods. PMID:25268373
The types of malignancy reported in carriers of constitutional ring chromosomes r(11), r(13), and r(22) are concordant with the chromosomal assignment of tumour suppressor loci associated with Wilms' tumour, retinoblastoma, and meningioma. It is suggested that the somatic instability of ring chromosomes may play a role in this association and that constitutional ring chromosomes may be a source for mapping of tumour suppressor loci with the potential for covering most or all of the human genome. The hypothesis predicts the presence of a locus on chromosome 10 associated with follicular carcinoma of the thyroid, in line with previous cytogenetic findings of rearrangements involving chromosome 10 in thyroid tumours, and a locus on chromosome 22 associated with testicular cancer. Development of neurofibromatoses (NF) that do not fulfil the clinical criteria of neurofibromatosis type 2 (NF2) in carriers with r(22) suggests either the presence of an additional NF locus on chromosome 22 or that ring chromosome mediated predisposition to somatic mutation of a specific tumour suppressor may be associated with atypical development of features usually associated with germline mutations. PMID:1336057
Tommerup, N; Lothe, R
Photofrin II (dihaematoporphyrin ether/ester, DHE) was labelled with indium-111 and its biodistribution in tumour bearing mice compared with that of 111In chloride. The uptake and clearance of 111In labelled DHE differed markedly from that of indium-111 chloride in that the former was not taken up by the tissues as much as the latter. Scintillation scanning with a gamma-camera showed marked uptake of both 111In agents at the site of the tumour, but a much lower tissue background (excluding the abdominal organs) for the mice given 111In DHE. Tumour:muscle ratios of dissected tissues were 2-3 times higher in 111In DHE treated animals as compared to the uptake of 111In chloride. There was a distinct difference in the pattern of distribution of the two 111In preparations in the tissues. The major accumulation of 111In chloride was in the kidneys, whereas the highest uptake of 111In DHE was in the liver, the organ in which unlabelled porphyrins accumulate. Extraction and testing of materials from tumours of 111In DHE treated animals indicated that most of the tumour extractable 111In had remained associated with the porphyrin in vivo up to 4 days after injection. Images Figure 1 PMID:2147858
Quastel, M. R.; Richter, A. M.; Levy, J. G.
Recently, we demonstrated that sigma-2 receptors may have the potential to be a biomarker of tumour cell proliferation (Mach et al (1997) Cancer Res57: 156–161). If sigma-2 receptors were a biomarker of tumour cell proliferation, they would be amenable to detection by non-invasive imaging procedures, thus eliminating many of the problems associated with the flow cytometric measures of tumour cell proliferation presently used in the clinic. To be a good biomarker of tumour cell proliferation, the expression of sigma-2 receptors must be essentially independent of many of the biological, physiological, and/or environmental properties that are found in solid tumours. In the investigation reported here, the mouse mammary adenocarcinoma lines, 66 (diploid) and 67 (aneuploid), 9L rat brain tumour cells, and MCF-7 human breast tumour cells were used to study the extent and kinetics of expression of sigma-2 receptors in proliferative (P) and quiescent (Q) tumour cells as a function of species, cell type, ploidy, pH, nutrient depletion, metabolic state, recruitment from the Q-cell compartment to the P-cell compartment, and treatment with tamoxifen. In these experiments, the expression of sigma-2 receptors solely reflected the proliferative status of the tumour cells. None of the biological, physiological, or environmental properties that were investigated had a measurable effect on the expression of sigma-2 receptors in these model systems. Consequently, these data suggest that the proliferative status of tumours and normal tissues can be non-invasively assessed using radiolabelled ligands that selectively bind sigma-2 receptors. © 1999 Cancer Research Campaign PMID:10576647
Al-Nabulsi, I; Mach, R H; Wang, L-M; Wallen, C A; Keng, P C; Sten, K; Childers, S R; Wheeler, K T
The presentation of synchronous primary tumours is rare and presents a difficult diagnostic and therapeutic challenge to primary care clinicians and hospital specialists. Increased life expectancy, improved radiological and biochemical investigation and more rigorous pre- and postoperative evaluation will lead to an increasing clinical trend for both metachronous and synchronous primary neoplasms. We report on a case of synchronous bladder and breast cancer in an elderly woman. We detail our investigation and management of the patient, review the literature and suggest the possible causative factors for the association of these synchronous tumours. We also highlight the extent of multiple primary cancers and discuss the diagnostic, treatment and preventative strategies for metachronous and synchronous primary tumours. PMID:24986985
Wallace, David; Arul, Dhilanthy; Chitale, Sudhanshu
Evaluation of isolated tumour cells in bone marrow (BM) and peripheral blood has become a major focus of translational cancer research. The presence of disseminated tumour cells in BM is a common phenomenon observed in 30–40% of primary breast cancer patients and independently predicts reduced clinical outcome. The detection of circulating tumour cells (CTCs) in blood might become a desired alternative to the invasive and painful BM biopsy. Recent clinical trials confirmed the feasibility of CTC detection as a robust and reproducible parameter for prognostication in both adjuvant and metastatic setting. The characterisation of CTCs might become an important biomarker for therapy monitoring and help to identify specific targets for novel therapeutic strategies. PMID:24066018
Krawczyk, Natalia; Banys, Malgorzata; Hartkopf, Andreas; Hagenbeck, Carsten; Melcher, Carola; Fehm, Tanja
Background The aim of this large collective and meticulous study of primary bone tumours and tumourous lesions of the hand was to enhance the knowledge about findings of traumatological radiographs and improve differential diagnosis. Methods This retrospective study reviewed data collected from 1976 until 2006 in our Bone Tumour Registry. The following data was documented: age, sex, radiological investigations, tumour location, histopathological features including type and dignity of the tumour, and diagnosis. Results The retrospective analysis yielded 631 patients with a mean age of 35.9?±?19.2 years. The majority of primary hand tumours were found in the phalanges (69.7%) followed by 24.7% in metacarpals and 5.6% in the carpals. Only 10.6% of all cases were malignant. The major lesion type was cartilage derived at 69.1%, followed by bone cysts 11.3% and osteogenic tumours 8.7%. The dominant tissue type found in phalanges and metacarpals was of cartilage origin. Osteogenic tumours were predominant in carpal bones. Enchondroma was the most commonly detected tumour in the hand (47.1%). Conclusions All primary skeletal tumours can be found in the hand and are most often of cartilage origin followed by bone cysts and osteogenic tumours. This study furthermore raises awareness about uncommon or rare tumours and helps clinicians to establish proper differential diagnosis, as the majority of detected tumours of the hand are asymptomatic and accidental findings on radiographs. PMID:24885007
Several lines of evidence indicate that tumour-infiltrating granulocytes (TIGs) promote tumour growth and progression. However, the prognostic significance of TIGs, the relationship between TIGs and Fas ligand (FasL) expressed on tumour cells remains unclear and warrants investigation. Using immunnostaining, we retrospectively investigated TIGs and FasL in 130 tissue specimens from gastric carcinoma. We analyzed the correlation among these markers, their association with clinicopathologic features and prognosis. The number of TIGs was significantly associated with FasL-expression (P=0.002). Further, TIGs were significantly associated with depth of tumour invasion, lymph node metastasis and tumour stage. Calculating the prognostic relevance, in multivariate analysis, TIGs [relative risk (RR)=1.014; 95% CI=1.002-1.027; P=0.015] and tumour stage were statistically significant factors for survival. Our results suggest that TIGs are conveniently measured by the immunostaining method, and possibly serve as an independent factor of prognosis in patients with gastric carcinoma. This is based on the fact that TIGs were significantly associated with tumour stage and shorter survival time. PMID:19513501
Liu, Huanran; Ubukata, Hideyuki; Tabuchi, Takanobu; Takemura, Akira; Motohashi, Gyou; Nishimura, Motoi; Satani, Tetsuro; Hong, Jianwei; Katano, Motonobu; Nakada, Ichiro; Saniabadi, Abbi R; Tabuchi, Takafumi
An audit of the Leeds regional bone tumour registry found that primary bone tumours of the thoracic skeleton constituted 90 of the 2004 cases (4.5%). Thirty seven per cent occurred in the ribs, 32% in the scapulae, 11% in the thoracic vertebrae, 11% in the sternum, and 9% in the clavicles. Malignant tumours were more common than benign (54 v 36) and occurred in an older population (mean ages 47 and 31 years). The scapula was the most common site for malignant lesions and the ribs the most common site for benign tumours. Chondrosarcoma was the commonest tumour in older patients, fibrous dysplasia and plasmacytoma in the middle age group, and eosinophilic granuloma in children. Presenting symptoms were a poor guide to whether the lesion was malignant or not. This and the small proportion of correct preoperative diagnoses indicate the need for early biopsy. Bone tumour registries provide a valuable source of cumulative information about uncommon tumours and facilitate accurate diagnosis, teaching, and research. PMID:2256013
Waller, D A; Newman, R J
This activity provides students with an in-class practice of landscape interpretation using slides of beaches shown by the instructor. Students view a select number of slides and are asked to classify each beach shown using the Wright and Short Beach Classification: dissipative, reflexive, and intermediate by visually identifying landforms and processes of each beach type. The outcome of this activity is that students have practice identifying landforms and processes and applying their observations and interpretations of geomorphic features and processes for an applied purpose. Designed for a geomorphology course Has minimal/no quantitative component
Gastrointestinal stromal tumours (GIST) are rare mesenchymal neoplasms of the gastrointestinal tract. Their development typically depends on mutations in the Kit or PDGFRA gene. We have diagnosed and treated a duodenal bulb GIST in a 63-year-old woman. The confirmation of the diagnosis was made on the basis of a histological test after radical resection of the tumour. Making the right diagnosis is crucial for patients, since complex surgical and pharmacological approaches are effective even in the advanced stages of the disease. Nevertheless, radical surgical treatment is still the primary choice for patients with GIST.
Sobo?, Marcin; Szylberg, Tadeusz; Rudzi?ski, Janusz
In advanced mammary tumours, extensive resections, sometimes involving sections of the thoracic wall, are often necessary. Plastic surgery reconstruction procedures offer sufficient opportunities to cover even large thoracic wall defects. Pedicled flaps from the torso but also free flap-plasties enable, through secure defect closure, the removal of large, ulcerated, painful or bleeding tumours with moderate donor site morbidity. The impact of thoracic wall resection on the respiratory mechanism can be easily compensated for and patients? quality of life in the palliative stage of disease can often be improved. PMID:24976636
Daigeler, A.; Harati, K.; Goertz, O.; Hirsch, T.; Behr, B.; Lehnhardt, M.; Kolbenschlag, J.
The high-dimensional pattern classification methods, e.g., support vector machines (SVM), have been widely investigated for analysis of structural and functional brain images (such as magnetic resonance imaging (MRI)) to assist the diagnosis of Alzheimer's disease (AD) including its prodromal stage, i.e., mild cognitive impairment (MCI). Most existing classification methods extract features from neuroimaging data and then construct a single classifier to perform classification. However, due to noise and small sample size of neuroimaging data, it is challenging to train only a global classifier that can be robust enough to achieve good classification performance. In this paper, instead of building a single global classifier, we propose a local patch-based subspace ensemble method which builds multiple individual classifiers based on different subsets of local patches and then combines them for more accurate and robust classification. Specifically, to capture the local spatial consistency, each brain image is partitioned into a number of local patches and a subset of patches is randomly selected from the patch pool to build a weak classifier. Here, the sparse representation-based classifier (SRC) method, which has shown to be effective for classification of image data (e.g., face), is used to construct each weak classifier. Then, multiple weak classifiers are combined to make the final decision. We evaluate our method on 652 subjects (including 198 AD patients, 225 MCI and 229 normal controls) from Alzheimer's Disease Neuroimaging Initiative (ADNI) database using MR images. The experimental results show that our method achieves an accuracy of 90.8% and an area under the ROC curve (AUC) of 94.86% for AD classification and an accuracy of 87.85% and an AUC of 92.90% for MCI classification, respectively, demonstrating a very promising performance of our method compared with the state-of-the-art methods for AD/MCI classification using MR images. PMID:22270352
Liu, Manhua; Zhang, Daoqiang; Shen, Dinggang
Genes identified as being mutated in Wilms’ tumour include TP53, a classic tumour suppressor gene (TSG); CTNNB1 (encoding ?-catenin), a classic oncogene; WTX, which accumulating data indicate is a TSG; and WT1, which is inactivated in some Wilms’ tumours, similar to a TSG. However, WT1 does not always conform to the TSG label, and some data indicate that WT1 enhances cell survival and proliferation, like an oncogene. Is WT1 a chameleon, functioning as either a TSG or an oncogene, depending on cellular context? Are these labels even appropriate for describing and understanding the function of WT1? PMID:21248786
A novel image segmentation algorithm was developed to allow the automatic segmentation of both normal and abnormal anatomy from medical images. The new algorithm is a form of spatially varying statistical classification, in which an explicit anatomical template is used to moderate the segmentation obtained by statistical classification. The algorithm consists of an iterated sequence of spatially varying classification and nonlinear registration, which forms an adaptive, template moderated (ATM), spatially varying statistical classification (SVC). Classification methods and nonlinear registration methods are often complementary, both in the tasks where they succeed and in the tasks where they fail. By integrating these approaches the new algorithm avoids many of the disadvantages of each approach alone while exploiting the combination. The ATM SVC algorithm was applied to several segmentation problems, involving different image contrast mechanisms and different locations in the body. Segmentation and validation experiments were carried out for problems involving the quantification of normal anatomy (MRI of brains of neonates) and pathology of various types (MRI of patients with multiple sclerosis, MRI of patients with brain tumors, MRI of patients with damaged knee cartilage). In each case, the ATM SVC algorithm provided a better segmentation than statistical classification or elastic matching alone. PMID:10972320
Warfield, S K; Kaus, M; Jolesz, F A; Kikinis, R
Asthma, as chronic inflammatory disease, shows variations in clinical manifestations and the degree of airflow obstruction, so its severity may change over time in the same patient. The Global Initiative for Asthma (GINA) established a practical system of classification, considering clinical and functional aspects as frequency of diurnal and nocturnal respiratory symptoms and lung function, their combination allows for classifying asthma severity as intermittent and persistent ( mild, moderate and severe). Recently, it has been proposed to classify the asthma according to degree of control: controlled, partly controlled and uncontrolled. The parameters used in this system are: frequency of diurnal and nocturnal respiratory symptoms, activity limitation, use of rescue therapy, determining the forced expiratory volume in one second (FEV1) or peak expiratory flow (PEF) and the exacerbations. The patient's participation on the asthma classification has also been considered through the self application of asthma control questionnaire (ACT). Patients with high risk of death are classified in the group of difficult asthma control (ADC), requiring major and minor criteria to define it; the common denominator is the decontrol of the disease, high dose steroids and appropriate treatment previously established. Sort asthma with any of these systems, information about its impact on the patient's life and thus establish the recommended treatment schedule for each patient group. PMID:20873054
Salas Hernández, Jorge; Fernández Vega, Margarita; Almeida Arvizu, Victor Manuel
Automated procedures to classify objects are discussed. The classification problem is reviewed, and the relation of epistemology and classification is considered. The classification of stellar spectra and of resolved images of galaxies is addressed.
Kurtz, Michael J.
This viewgraph presentation reviews the classification of Remote Sensing data in relation to epidemiology. Classification is a way to reduce the dimensionality and precision to something a human can understand. Classification changes SCALAR data into NOMINAL data.
Rickman, Douglas L.
Many neuroimaging applications require an initial step of skull stripping to extract the cerebrum, cerebellum, and brain stem. We approach this problem by combining deformable surface models and a fuzzy tissue classification technique. Our assumption is that contrast exists between brain tissue (gray matter and white matter) and cerebrospinal fluid, which separates the brain from the extra-cranial tissue. We first analyze the intensity of the entire image to find an approximate centroid of the brain and initialize an ellipsoidal surface around it. We then perform a fuzzy tissue classification with bias field correction within the surface. Tissue classification and bias field are extrapolated to the entire image. The surface iteratively deforms under a force field computed from the tissue classification and the surface smoothness. Because of the bias field correction and tissue classification, the proposed algorithm depends less on particular imaging contrast and is robust to inhomogeneous intensity often observed in magnetic resonance images. We tested the algorithm on all T1 weighted images in the OASIS database, which includes skull stripping results using Brain Extraction Tool; the Dice scores have an average of 0.948 with a standard deviation of 0.017, indicating a high degree of agreement. The algorithm takes on average 2 minutes to run on a typical PC and produces a brain mask and membership functions for gray matter, white matter, and cerebrospinal fluid. We also tested the algorithm on T2 images to demonstrate its generality, where the same algorithm without parameter adjustment gives satisfactory results.
Tao, Xiaodong; Chang, Ming-Ching
The influence of the microenvironment on tumour progression is becoming clearer. In this Review we address the role of an essential signalling pathway, that of transforming growth factor-?, in the regulation of components of the tumour microenvironment and how this contributes to tumour progression. PMID:24132110
Pickup, Michael; Novitskiy, Sergey; Moses, Harold L.
The model proposed here links together two approaches to describe tumours: a continuous medium to describe the movement and the mechanical properties of the tissue, and a population dynamics approach to represent internal genetic inhomogeneity and instability of the tumour. In this way one can build models which cover several stages of tumour progression. In this paper we focus on
Sergey Astanin; Luigi Preziosi
There are no effective therapies for many tumours of the nervous system. This is, in part, a consequence of their location within relatively inaccessible tissues. It is also likely, however, that the unique characteristics of the cells that give rise to these tumours create a set of conditions that facilitate tumour development. Here, we consider recent advances in molecular genetics,
Yuan Zhu; Luis F. Parada
An ayurvedic oil preparation containing flowers of ixora coccinea and cortus sativum was subjected to an animal experimentation to find out how far it is efficient in preventing the development of Dalton's lymphoma as solid tumour. The oil was applied after injecting the cells and we found it could retard the development of tumour and arrest further development of already formed tumour. PMID:22557556
Panikar, K R; Bhanumathy, P; Raghunath, P N
An ayurvedic oil preparation containing flowers of ixora coccinea and cortus sativum was subjected to an animal experimentation to find out how far it is efficient in preventing the development of Dalton's lymphoma as solid tumour. The oil was applied after injecting the cells and we found it could retard the development of tumour and arrest further development of already formed tumour. PMID:22557556
Panikar, K. R.; Bhanumathy, P.; Raghunath, P. N.
Without epithelial–mesenchymal transitions, in which polarized epithelial cells are converted into motile cells, multicellular organisms would be incapable of getting past the blastula stage of embryonic development. However, this important developmental programme has a more sinister role in tumour progression. Epithelial–mesenchymal transition provides a new basis for understanding the progression of carcinoma towards dedifferentiated and more malignant states.
Jean Paul Thiery
For the past 100 years, tumour immunology has witnessed peaks and troughs of interest. A recent meeting1The 5th Annual Congress of the British Society for Immunology was held at Brighton, UK, on 2–5 December 1997.1 covered new technologies and recent developments in the field.
Anton B Alexandroff; Richard A Robins; Anna Murray; Keith James
It is well known that an insufficiency of dietary methyl-group donors can cause cancer, and that a deficiency in methylation is characteristic of cancer, but how carcinogenesis results from abnormal methyl-donor metabolism has long remained a matter of speculation. Recently, however, it has been found that some histone methyltransferases, which require methyl donors for activity, are tumour suppressors.
Myeloid cells are the most abundant nucleated haematopoietic cells in the human body and are a collection of distinct cell populations with many diverse functions. The three groups of terminally differentiated myeloid cells — macrophages, dendritic cells and granulocytes — are essential for the normal function of both the innate and adaptive immune systems. Mounting evidence indicates that the tumour
Dmitry I. Gabrilovich; Suzanne Ostrand-Rosenberg; Vincenzo Bronte
The genetic modification of T lymphocytes is an important approach to investigating normal T-cell biology and to increasing antitumour immunity. A number of genetic strategies aim to increase the recognition of tumour antigens, enhance antitumour activities and prevent T-cell malfunction. T cells can also be engineered to increase safety, as well as to express markers that can be tracked by
Isabelle Rivière; Renier Brentjens; Michel Sadelain
The long-acting analogues of somatostatin have an established place in the medical treatment of patients with neuroendocrine tumours. They act through binding with specific, high-affinity membrane receptors. Somatostatin analogue therapy is an effective and safe treatment for most growth hormone and thyrothropin-secreting pituitary adenomas. The potential therapeutic consequences of the presence of somatostatin receptors on clinically 'nonfunctioning' pituitary tumours are still uncertain. Somatostatin analogues are not useful in the treatment of patients with prolactinomas, or adrenocorticotropin (ACTH)-secreting adenomas. However, the somatostatin analogue octreotide suppressed pathological ACTH release in some patients with Nelson's syndrome and ACTH and cortisol secretion in several patients with Cushing's syndrome caused by ectopic ACTH secretion. Somatostatin analogues are effective in the sympatomatic treatment of most (metastatic) pancreatic islet cell tumours and most (metastatic) carcinoids. In some of these patients, they also induce tumour stabilisation or reduction. In some patients with (metastatic) medullary thyroid carcinomas, continuous treatment with very high doses of octreotide can be of temporary relief. The clinical effectiveness of somatostatin analogues in patients with small cell lung cancer is currently under investigation. Long-term therapy with somatostatin analogues of catecholamine-secreting (malignant) paragangliomas and phaeochromocytomas has not shown clinical benefits. PMID:8935599
de Herder, W. W.; van der Lely, A. J.; Lamberts, S. W.
Tumour-associated macrophages (TAMs) have already been associated in human breast cancer to a poor prognosis. As a part of a tumoural microenvironment, TAMs have an important contribution influencing neoplastic progression. Hitherto, in canine mammary tumours (CMT) the prognostic value of TAMs has not been reported. In this study, MAC387 immunohistochemical expression was evaluated in 59 CMTs (20 benign and 39 malignant). The TAM value was significantly higher in malignant than benign CMT (P?=?0.011). In malignant CMT, TAMs were associated with skin ulceration (P?=?0.022), histological type (P?=?0.044), nuclear grade (P?=?0.031) and tubular differentiation (P?=?0.042). The survival analysis revealed a significant association between tumours with higher levels of TAMs and the decrease in overall survival (P?=?0.030). TAMs have proven to have a prognostic value. These findings suggest the future possibility of using TAMs as a novel therapeutic target in CMT. PMID:22533625
Raposo, T; Gregório, H; Pires, I; Prada, J; Queiroga, F L
Radiation survival curves for Lewis lung tumours in the lungs ranging in size from 0-5 to 20 mm3 have been obtained, and a size-dependent variation in hypoxic fraction was found. Cell-survival studies following treatment of various sizes of s.c. tumours indicated that the effects of 60Co gamma-rays and the chemotherapeutic agents 1,3-bas(2-chloroethyl)-1-nitrosourea (BCNU) and cyclophosphamide are all size-dependent. Large pulmonary nodules which had regressed but had not been cured by cyclophosphamide regrew with a radiosensitivity that was characteristic of previously untreated tumours. The results give additional experimental support to the clinical interest in early adjuvant therapy of micrometastases, and sequential combined modality therapy for larger tumours. PMID:889677
Stanley, J. A.; Shipley, W. U.; Steel, G. G.
Angiogenesis, activation of metastasis and avoidance of immune destruction are important for cancer progression. These biological capabilities are, apart from cancer cells, mediated by different cell types, including endothelial, haematopoietic progenitor and myeloid-derived suppressor cells. We show here that all these cell types frequently express the Wilms' tumour suppressor Wt1, which transcriptionally controls expression of Pecam-1 (CD31) and c-kit (CD117). Inducible conditional knockout of Wt1 in endothelial, haematopoietic and myeloid-derived suppressor cells is sufficient to cause regression of tumour vascularization and an enhanced immune response, leading to decreased metastasis, regression of established tumours and enhanced survival. Thus, Wt1 is an important regulator of cancer growth via modulation of tumour vascularization, immune response and metastasis formation. PMID:25510679
Wagner, Kay-Dietrich; Cherfils-Vicini, Julien; Hosen, Naoki; Hohenstein, Peter; Gilson, Eric; Hastie, Nicholas D; Michiels, Jean-François; Wagner, Nicole
The objective of the present study was to investigate the interest of convection-enhanced delivery (CED) for the administration\\u000a of a nanocarrier-based radiosensitizing chemotherapy in the rat brain. Pursuing on newly developed lipid nanocapsules (LNC)\\u000a that can be internalised within brain tumour cells, we studied their intracerebral distribution when labelled with fluorescent\\u000a Nile red (NR). As paclitaxel (Px) represents an interesting
Sandrine Vinchon-Petit; Delphine Jarnet; Archibald Paillard; Jean-Pierre Benoit; Emmanuel Garcion; Philippe Menei
PTEN is a putative tumour suppressor gene located on chromosome band 10q23. Mutations in PTEN have been identified in numerous human malignancies, including cancers of the brain, endometrium, ovary, and prostate. In this study, we screened 80 Barrett's oesophagus-associated adenocarcinomas (BOAd) for loss of heterozygosity (LOH) at 10q23, using the microsatellite markers D10S541, D10S219, and D10S551. Tumours demonstrating LOH were then screened for the presence or absence of PTEN mutations. LOH at one or more loci was identified in 17/80 (21%) cases. In none of these cases did we detect mutations in PTEN. The presence of LOH did not correlate with patient age, tumour stage, degree of differentiation, presence of perineural or vascular invasion, or overall survival. We conclude that LOH at chromosome 10q23 is uncommon in BOAd, is not associated with mutations in the PTEN tumour suppressor gene, and does not correlate with the clinical or pathologic features of these tumours. It is possible that PTEN is inactivated through other mechanisms in BOAd. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11259087
Kulke, M H; Odze, R D; Thakore, K S; Thomas, G; Wang, H; Loda, M; Eng, C
229 patients with Grade 1–2 tumours (WHO), all category Ta or T1 (UICC) and surgically treated, were followed clinically and by flowcytofluorometric DNA-analysis (FCM). The tumours were characterised by their DNA profile. 175 cases were found to be diploid and fiftyfour cases showed aneuploidy. The mean follow-up time with continous FCM analysis was 2.6 years. During this period 19 patients
H. Gustafson; B. Tribukait; P. L. Esposti
Breast cancer is the leading cause of death among women, and morphine is used to relieve the pain of patients with cancer.\\u000a The data on the effects of morphine on tumour growth and angiogenesis are contradictory. We determined in mouse breast cancer\\u000a model whether analgesic doses of morphine would affect tumour angiogenesis, and then the correlation between microvessel density\\u000a (MVD),
Funda UstunGulay; Gülay Durmus-Altun; Semsi Altaner; Nermin Tuncbilek; Cem Uzal; Sakir Berkarda
The paper presents a discussion of human mental processes as they relate to learning disabilities. Pathognomonic symptoms associated with disturbances to brain areas or functional systems are discussed, as well as treatment procedures. This brain behavior relationship is offered as a basis for a classification system that is seen to more clearly…
Scaramella-Nowinski, Valerie L.
Background: The possibility of eradicating cancer by selective destruction of tumour blood vessels may represent an attractive therapeutic avenue, but most pharmaceutical agents investigated so far did not achieve complete cures and are not completely specific. Antibody conjugates now allow us to evaluate the impact of selective vascular shutdown on tumour viability and to study mechanisms of action. Methods: We synthesised a novel porphyrin-based photosensitiser suitable for conjugation to antibodies and assessed anticancer properties of its conjugate with L19, a clinical-stage human monoclonal antibody specific to the alternatively spliced EDB domain of fibronectin, a marker of tumour angiogenesis. Results: Here we show in two mouse model of cancer (F9 and A431) that L19 is capable of highly selective in vivo localisation around tumour blood vessels and that its conjugate with a photosensitiser allows selective disruption of tumour vasculature upon irradiation, leading to complete and long-lasting cancer eradication. Furthermore, depletion experiments revealed that natural killer cells are essential for the induction of long-lasting complete responses. Conclusions: These results reinforce the concept that vascular shutdown can induce a curative avalanche of tumour cell death. Immuno-photodynamic therapy may be particularly indicated for squamous cell carcinoma of the skin, which we show to be strongly positive for markers of angiogenesis. PMID:21386847
Palumbo, A; Hauler, F; Dziunycz, P; Schwager, K; Soltermann, A; Pretto, F; Alonso, C; Hofbauer, G F; Boyle, R W; Neri, D
"Soft tissue giant cell tumour of low malignant potential" is considered as the soft tissue counterpart of osteoclastoma of the bone. It is a primary soft tissue tumour which is classified under the category of fibrohistiocytic tumours of intermediate malignancy.Seventy percent of the tumours involve the extremities and only about seven percent of them arise in head and neck region. They are composed of nodules of histiocytes in a vascular stroma, with multinucleated osteoclast-like giant cells positive for vimentin, smooth muscle actin (SMA), CD68 and Tarterate Resistant Acid Phosphatase (TRAP). We are presenting a case of a 75-year-old man who had a nodule on the ala of the nose. Histopathology showed a histiocytic lesion. Benign fibrous histiocytoma, plexiform fibrohistiocytic tumour, solitary reticulohistiocytoma and histioid leprosy were ruled out by using special stains and immunostains. Expression of smooth muscle actin and CD68 confirmed the diagnosis of a soft tissue giant cell tumour with a low malignant potential. PMID:24551690
Bhat, Amoolya; V, Geethamani; C, Vijaya
such as multiple sclerosis, epilepsy, Parkinson's disease, brain tumours, stroke, and many others. Brain Power and their family. Defective cell `battery' plays central role in neurodegenerative disease A big part of what makes to major neurodegenerative diseases like Parkinson's, Alzheimer's, Huntington's and a variety of ataxias
p53 is a crucial tumour suppressor that responds to diverse stress signals by orchestrating specific cellular responses, including transient cell cycle arrest, cellular senescence and apoptosis, which are all processes associated with tumour suppression. However, recent studies have challenged the relative importance of these canonical cellular responses for p53-mediated tumour suppression and have highlighted roles for p53 in modulating other cellular processes, including metabolism, stem cell maintenance, invasion and metastasis, as well as communication within the tumour microenvironment. In this Opinion article, we discuss the roles of classical p53 functions, as well as emerging p53-regulated processes, in tumour suppression. PMID:24739573
Bieging, Kathryn T.; Mello, Stephano Spano; Attardi, Laura D.
Objective To evaluate the effect of comorbidity as an independent prognostic factor in lung cancer. Method Data on 2991 consecutive cases of lung cancer were collected prospectively from 19 Spanish hospitals between 1993 and 1997 by the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB?S). To evaluate the effect of comorbidity on survival, 1121 patients with non?small cell lung cancer (NSCLC) in pathological stage I who underwent complete resection were selected, excluding operative mortality. The presence of specific comorbidities at the time of thoracotomy was registered prospectively. Results Cox regression analysis showed that tumour size (0–2, 2–4, 4–7, >7?cm) (HR 1.45 95% CI 1.08 to 1.95), 1.86 (95% CI 1.38 to 2.51), 2.84 (95% CI 1.98 to 4.08)), the presence of a previous tumour (HR 1.45 (95% CI 1.17 to 1.79)) and age (HR 1.02 (95% CI 1.01 to 1.03)) had a significant prognostic association with survival. This study excluded the presence of visceral pleural involvement or other comorbidities as independent variables. Conclusion The presence of a previous tumour is an independent prognostic factor in pathological stage I NSCLC with complete resection, increasing the probability of death by 1.5 times at 5?years. It is independent of other comorbidities, TNM classification and age. PMID:16449263
López?Encuentra, Angel; de la Cámara, Agustín Gómez; Rami?Porta, Ramón; Duque?Medina, José Luis; de Nicolás, José Luis Martín; Sayas, Javier
Factors associated with the potential for recurrence of keratocystic odontogenic tumours (KCOT) still remain to be clearly determined and no consensus exists concerning the management of KCOT. The purpose of this study was to evaluate different clinical factors associated with KCOT and its treatment methods. A retrospective review was performed of 55 cases treated from 2001 to 2010. Of the 55 cases, 27% were associated with an impacted or semi-impacted tooth. The majority of the lesions (82%) were located in tooth-bearing areas, and the overall mandibular to maxilla ratio of tumour occurrence was 5:1. The treatment options included enucleation, marsupialisation, or peripheral ostectomy, with or without the use of Carnoy´s solution. Recurrence was found in 14 cases (25%). No significant association was seen between recurrence and age, symptomatic cases, location of the lesion, or unilocular or multilocular appearance. The recurrence rate was higher in the group with tooth involvement, more marked in cases with third molar involvement. Statistical analysis showed a significant relation between recurrence and the type of treatment, with higher rates in cases treated with enucleation associated with tooth extraction. In our series, those cases with a closer relation with dental tissues showed a higher risk of recurrence, suggesting the need for a distinct classification for peripheral variants of KCOT. Key words:Keratocystic odontogenic tumour, Odontogenic keratocyst, Odontogenic cysts, Keratocyst, Carnoy’s solution. PMID:25136427
González-Martín-Moro, Javier; Pérez-Fernández, Elia; Burgueño-García, Miguel
Earth, the ecosphere, is a unified functional ecosystem. Ecological land classification (ELC) and regionalization divides and categorizes this unity into similar and dissimilar pieces-sectoral ecosystems - at various scales, in the interests of admiration and understanding. The recognition of land/water ecosystems in a hierarchy of sizes provides a rational base for the many-scaled problems of protection and careful exploitation in the fields of agriculture, forestry, wildlife and recreation. In forested terrain the protection of biodiversity, old growth forests, watersheds and wildlife habitat depends on spatial-temporal planning of forestry operations to maintain a preferred mosaic structure of local ecosystems within each ecological region. Without ecological understanding and a good ELC, this is impossible. Conceiving the world as comprising nested land/water ecosystems that are the source of life, elevates the role of Earth-as-context, an antidote to destructive anthropocentrism. PMID:24197992
Rowe, J S
Staging of heart failure represents a major issue in clinical practice. In this setting, the MOGE(S) classification was designed to be similar to the TNM classification used in oncology. Nevertheless, MOGE(S) nosology differs greatly from the key elements of the TNM classification, as well as its simplicity and clinical applicability. In fact, MOGE(S) acronym stands for morphofunctional characteristics (M), organ involvement (O), genetic or familial inheritance pattern (G), etiological information (E), and functional status (S). Recently, a new TNM-like classification for heart failure was proposed. This classification, named HLM, refers to heart damage arising from an initial stage of impaired systolic or diastolic function, without structural injury, to an advanced stage of biventricular dysfunction (H), different stages of lung involvement (L), and malfunction of peripheral organs such as the kidney, liver, and brain (M). HLM classification was influenced by the key elements of TNM staging: simplicity, clinical usefulness, efficacy for planning a therapeutic strategy, and ability to determine patient prognosis. HLM classification seems to be easily applied in the real world and valuable for balancing economic resources with the clinical complexity of patients. PMID:24657683
Fedele, Francesco; Severino, Paolo; Calcagno, Simone; Mancone, Massimo
HLA abnormalities on tumour cells for immune escape have been widely described. In addition, cellular components of the tumour microenvironment, in particular myeloid derived suppressor cells (MDSC) and alternatively activated M2 tumour-associated macrophages (TAMs), are involved in tumour promotion, progression, angiogenesis and suppression of anti-tumour immunity. However, the role of HLA in these activities is poorly understood. This review details MHC class I characteristics and describes MHC class I receptors functions. This analysis established the basis for a reflection about the crosstalk among the tumour cells, the TAMs and the cells mediating an immune response. The tumour cells and TAMs exploit MHC class I molecules to modulate the surrounding immune cells. HLA A, B, C and G molecules down-regulate the macrophage myeloid activation through the interaction with the inhibitory LILRB receptors. HLA A, B, C are able to engage inhibitory KIR receptors negatively regulating the Natural Killer and cytotoxic T lymphocytes function while HLA-G induces the secretion of pro-angiogenic cytokines and chemokine thanks to an activator KIR receptor expressed by a minority of peripheral NK cells. The open conformer of classical MHC-I is able to interact with LILRA receptors described as being associated to the Th2-type cytokine response, triggering a condition for the M2 like TAM polarization. In addition, HLA-E antigens on the surface of the TAMs bind the inhibitory receptor CD94/NKG2A expressed by a subset of NK cells and activated cytotoxic T lymphocytes protecting from the cytolysis. Furthermore MHC class II expression by antigen presenting cells is finely regulated by factors provided with immunological capacities. Tumour-associated macrophages show an epigenetically controlled down-regulation of the MHC class II expression induced by the decoy receptor DcR3, a member of the TNFR, which further enhances the M2-like polarization. BAT3, a positive regulator of MHC class II expression in normal macrophages, seems to be secreted by TAMs, consequently lacking its intracellular function, it looks like acting as an immunosuppressive factor. In conclusion HLA could cover a considerable role in tumour-development orchestrated by tumour-associated macrophages. PMID:24093459
HLA abnormalities on tumour cells for immune escape have been widely described. In addition, cellular components of the tumour microenvironment, in particular myeloid derived suppressor cells (MDSC) and alternatively activated M2 tumour-associated macrophages (TAMs), are involved in tumour promotion, progression, angiogenesis and suppression of anti-tumour immunity. However, the role of HLA in these activities is poorly understood. This review details MHC class I characteristics and describes MHC class I receptors functions. This analysis established the basis for a reflection about the crosstalk among the tumour cells, the TAMs and the cells mediating an immune response.The tumour cells and TAMs exploit MHC class I molecules to modulate the surrounding immune cells. HLA A, B, C and G molecules down-regulate the macrophage myeloid activation through the interaction with the inhibitory LILRB receptors. HLA A, B, C are able to engage inhibitory KIR receptors negatively regulating the Natural Killer and cytotoxic T lymphocytes function while HLA-G induces the secretion of pro-angiogenic cytokines and chemokine thanks to an activator KIR receptor expressed by a minority of peripheral NK cells. The open conformer of classical MHC-I is able to interact with LILRA receptors described as being associated to the Th2-type cytokine response, triggering a condition for the M2 like TAM polarization. In addition, HLA-E antigens on the surface of the TAMs bind the inhibitory receptor CD94/NKG2A expressed by a subset of NK cells and activated cytotoxic T lymphocytes protecting from the cytolysis.Furthermore MHC class II expression by antigen presenting cells is finely regulated by factors provided with immunological capacities. Tumour-associated macrophages show an epigenetically controlled down-regulation of the MHC class II expression induced by the decoy receptor DcR3, a member of the TNFR, which further enhances the M2-like polarization. BAT3, a positive regulator of MHC class II expression in normal macrophages, seems to be secreted by TAMs, consequently lacking its intracellular function, it looks like acting as an immunosuppressive factor.In conclusion HLA could cover a considerable role in tumour-development orchestrated by tumour-associated macrophages. PMID:24093459
Marchesi, Maddalena; Andersson, Emilia; Villabona, Lisa; Seliger, Barbara; Lundqvist, Andreas; Kiessling, Rolf; Masucci, Giuseppe V
Background: Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER?) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER? breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. Results: DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLEHRAS xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLEHRAS cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. Conclusion: Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation. PMID:23403820
Pervin, S; Tran, L; Urman, R; Braga, M; Parveen, M; Li, S A; Chaudhuri, G; Singh, R
Tumour necrosis factor-? (TNF-?) is a pro-inflammatory cytokine, expressed in many brain pathologies and associated with neuronal loss. We show here that addition of TNF-? to neuronal-glial co-cultures increases microglial proliferation and phagocytosis, and results in neuronal loss that is prevented by eliminating microglia. Blocking microglial phagocytosis by inhibiting phagocytic vitronectin and P2Y6 receptors, or genetically removing opsonin MFG-E8, prevented TNF-? induced loss of live neurons. Thus TNF-? appears to induce neuronal loss via microglial activation and phagocytosis of neurons, causing neuronal death by phagoptosis. PMID:24911209
Neniskyte, Urte; Vilalta, Anna; Brown, Guy C
Tumour necrosis factor-? (TNF-?) is a pro-inflammatory cytokine, expressed in many brain pathologies and associated with neuronal loss. We show here that addition of TNF-? to neuronal–glial co-cultures increases microglial proliferation and phagocytosis, and results in neuronal loss that is prevented by eliminating microglia. Blocking microglial phagocytosis by inhibiting phagocytic vitronectin and P2Y6 receptors, or genetically removing opsonin MFG-E8, prevented TNF-? induced loss of live neurons. Thus TNF-? appears to induce neuronal loss via microglial activation and phagocytosis of neurons, causing neuronal death by phagoptosis. PMID:24911209
Neniskyte, Urte; Vilalta, Anna; Brown, Guy C.
Cranial radiation is routinely used to manage pituitary tumours, craniopharyngiomas, primary brain tumours, tumours of the head and neck and, in the past, for the prophylaxis of intracranial disease in patients with acute lymphoblastic leukaemia. If the hypothalamic-pituitary axis falls within the radiation fields, the patient is at risk of developing hypopituitarism. The effect of radiation is determined by the dose and the time that has elapsed since treatment. Classically, growth hormone (GH) is the most sensitive of the anterior pituitary hormones to irradiation, followed by gonadotrophins, adrenocorticotrophic hormone (ACTH) and thyroid-stimulating hormone (TSH). Low-dose irradiation in prepubertal children can initially cause early or precocious puberty and subsequently gonadotrophin deficiency. Higher doses may cause gonadotrophin deficiency and pubertal delay. The ACTH and TSH axes are relatively resistant to the effects of irradiation, but minor abnormalities may occur. Patients who receive cranial irradiation that affects the hypothalamic-pituitary axis remain at risk of developing multiple hormone deficiencies for many years and require long-term follow-up by an endocrinologist. PMID:15135792
Toogood, A A
A 29-year-old man presented to his local orthopaedic service with a mass in the medial aspect of his left thigh, present for 1?year. It had not changed in size, although he complained of increasing tightness in the region. He denied any systemic symptoms or history of local trauma. Extensive imaging performed at his local hospital was thought suggestive of a musculoskeletal tumour. The patient was referred to our tertiary centre musculoskeletal tumour clinic. Review of external imaging and further investigations revealed a fluid-filled intramuscular mass containing an echogenic focus consistent with foreign body. Ultrasound-guided aspiration yielded fluid which grew Staphylococcus aureus. Only when presented with this information did the patient vaguely recall sitting on a wooden kebab stick 30?months previously. At surgery, a thick-walled abscess with a central foreign body was identified and drained. At follow-up 1?month later, he was well with no recurrent problems. PMID:23345476
Maempel, Julian Frederick; Nicol, Graeme; Clement, Rhys Gareth Ellis; Porter, Daniel
Granular cell tumour (GCT) is a rare, usually benign neoplasm that can mimic carcinoma on breast imaging. GCT can originate anywhere in the body but is most frequently found in the head and neck region, particularly in the tongue. Of the reported cases, 6% have occurred in the breast, most commonly in the upper inner quadrant. We report a case of GCT of the breast presenting as a spiculated mass infiltrating the greater thoracic muscle on breast screening mammogram. PMID:23420726
Gavriilidis, Paschalis; Michalopoulou, Ilektra; Baliaka, Aggeliki; Nikolaidou, Anastasia
Reticuloendothelial (RE) phagocytic and circulating plasma opsonic activity was evaluated in rats transplanted with the Walker 256 carcinoma tumour in an attempt to evaluate the role of opsonic protein in governing the functional state of the macrophage system. Animals transplanted intramuscularly with 2 X 10(4) viable tumour cells manifested 2 peaks of RE stimulation at 6 and 14 days post-transplantation with a subsequent decline in the phagocytic activity over the 14-30 day period. Increased phagocytic activity as determined by colloid clearance was primarily a reflection of hepatic Küpffer cell hyperphagocytosis while the decline in phagocytic activity was related to a decrease in Küpffer cell function. The initial peak of RE stimulation was associated with an elevation in the blood opsonin level and no significant enlargement of the liver and spleen. In contrast, the second peak of RE stimulation at 14 days was associated with both an elevation in opsonin levels and an associated hepatic and splenic enlargement. The decline in phagocytic activity over the 14-30 day interval was associated with a progressive decline in the plasma opsonic activity, a return of the spleen to its normal size in relationship to the body weight, and a persistent hepatomegaly. These findings suggest that the alterations in macrophage function during tumour growth may be mediated in part by changes in the opsonic or phagocytosis promoting capacity of plasma. Since opsonic protein contributes to the discriminatory capacity of macrophages, it is suggested that changes in the blood opsonin level may condition the anti-tumour capacity of the macrophage system with respect to host defence aginst malignant disease. PMID:1212411
Saba, T. M.; Antikatzides, T. G.
Cyclin C was cloned as a growth-promoting G1 cyclin, and was also shown to regulate gene transcription. Here we report that in vivo cyclin C acts as a haploinsufficient tumour suppressor, by controlling Notch1 oncogene levels. Cyclin C activates an 'orphan' CDK19 kinase, as well as CDK8 and CDK3. These cyclin-C-CDK complexes phosphorylate the Notch1 intracellular domain (ICN1) and promote ICN1 degradation. Genetic ablation of cyclin C blocks ICN1 phosphorylation in vivo, thereby elevating ICN1 levels in cyclin-C-knockout mice. Cyclin C ablation or heterozygosity collaborates with other oncogenic lesions and accelerates development of T-cell acute lymphoblastic leukaemia (T-ALL). Furthermore, the cyclin C encoding gene CCNC is heterozygously deleted in a significant fraction of human T-ALLs, and these tumours express reduced cyclin C levels. We also describe point mutations in human T-ALL that render cyclin-C-CDK unable to phosphorylate ICN1. Hence, tumour cells may develop different strategies to evade inhibition by cyclin C. PMID:25344755
Li, Na; Fassl, Anne; Chick, Joel; Inuzuka, Hiroyuki; Li, Xiaoyu; Mansour, Marc R; Liu, Lijun; Wang, Haizhen; King, Bryan; Shaik, Shavali; Gutierrez, Alejandro; Ordureau, Alban; Otto, Tobias; Kreslavsky, Taras; Baitsch, Lukas; Bury, Leah; Meyer, Clifford A; Ke, Nan; Mulry, Kristin A; Kluk, Michael J; Roy, Moni; Kim, Sunkyu; Zhang, Xiaowu; Geng, Yan; Zagozdzon, Agnieszka; Jenkinson, Sarah; Gale, Rosemary E; Linch, David C; Zhao, Jean J; Mullighan, Charles G; Harper, J Wade; Aster, Jon C; Aifantis, Iannis; von Boehmer, Harald; Gygi, Steven P; Wei, Wenyi; Look, A Thomas; Sicinski, Piotr
Brain metastases from solid tumours are associated with poor prognosis despite aggressive treatment. Temozolomide can be used for the treatment of glioblastoma multiforme as well as melanoma. It has also been shown to have activity in patients with brain metastases from various malignancies, since it can cross the blood-brain barrier. To better understand the efficacy of temozolomide in the treatment of brain metastases, we carried out a review of 21 published clinical trials to determine whether temozolomide would benefit patients with brain metastases from solid tumours. Information regarding complete response, partial response, stable disease, objective response and objective response rate were collected to assess clinical outcomes. A modest therapeutic effect was observed when temozolomide was used as a single agent, however, the combination of temozolomide with whole-brain radiotherapy and/or other anticancer drugs exhibited encouraging activity. Thus, future high quality studies are warranted to confirm our findings. PMID:24527399
Zhu, Wei; Zhou, Li; Qian, Jia-Qi; Qiu, Tian-Zhu; Shu, Yong-Qian; Liu, Ping
The treatment of lung cancer with radiation therapy is hindered by respiratory motion. Real-time adjustments to compensate for this motion are hampered by mechanical system latencies and imaging-rate restrictions. To better understand tumour motion behaviour for adaptive image-guided radiation therapy of lung cancer, the volume of a tumour's motion space was investigated. Motion data were collected by tracking an implanted fiducial using fluoroscopy at 30 Hz during treatment sessions. A total of 637 treatment fractions from 31 tumours were used in this study. For each fraction, data points collected from three consecutive breathing cycles were used to identify instantaneous tumour location. A convex hull was created over these data points, defining the tumour motion envelope. The study sought a correlation between the tumour location in the lung and the convex hull's volume and shape. It was found that tumours located in the upper apex had smaller motion envelopes (<50 mm3), whereas tumours located near the chest wall or diaphragm had larger envelopes (>70 mm3). Tumours attached to fixed anatomical structures had small motion spaces. Three general shapes described the tumour motion envelopes: 50% of motion envelopes enclosed largely 1D oscillation, 38% enclosed an ellipsoid path, 6% enclosed an arced path and 6% were of hybrid shape. This location-space correlation suggests it may be useful in developing a predictive model, but more work needs to be done to verify it.
Pepin, Eric W.; Wu, Huanmei; Sandison, George A.; Langer, Mark; Shirato, Hiroki
Neuroendocrine tumours may be broadly divided into pancreatic endocrine tumours (PETs) and carcinoid neuroendocrine tumours (NETs). In both cases, patients may present with a clinical syndrome related to hormone secretion by the tumour. In these cases, cross-sectional imaging plays an important role in the localization of the primary tumour, the detection of metastases, and the assessment of response to treatment. Computed tomography (CT) is established as the primary modality, although following technological advances detection rates on magnetic resonance imaging (MRI) are now challenging those of CT. Endoscopic ultrasound has an important role in the preoperative assessment of the pancreas where a small functioning tumour or the possibility of multiple tumours is suspected. The sensitivity for the detection of small functioning tumours depends upon optimal technique, whichever modality is used. Non-functioning tumours frequently present late with mass effect, as there is no accompanying clinical syndrome. Carcinoid neuroendocrine tumours are most frequently localized on CT. MRI is usually used as a problem-solving tool. As technology evolves, detection rates may continue to improve, and the highest sensitivities may be achieved by a combination of different modalities. PMID:17382265
Rockall, Andrea G; Reznek, Rodney H
Abstract Desmoid tumours are uncommon non-malignant tumours that show a locally aggressive growth pattern and a high local recurrence rate after surgery. Approximately 10% of the desmoid tumours are associated with familial adenomatous polyposis (FAP). Variable natural history of the disease challenges treatment decision-making in the absence of prospective, randomised data. Association of this rare tumour to GIST is speculated and the tumorigenesis may share common steps. This study reviews given treatment and reports prognostic factors for local control and concurrent neoplasms in patients evaluated by a single soft tissue tumour group. Patients referred to the soft tissue tumour group at Helsinki University Central Hospital (HUCH) for a desmoid tumour (primary or recurred) during 1987-2007 and receiving surgical treatment with or without adjuvant treatment were included in this retrospective review. All locations and also patients with a FAP-associated tumour were included. Extra-abdominal location showed lower local control despite the fact that 27% of patients also received radiation therapy. One amputation was performed. Female sex and location in the rectus abdominis muscle predicted improved local control in multivariate analysis. In this review, the occurrence (14%) of concurrent neoplasms was higher than expected with unusual tumour types noted including two GISTs. In those patients in whom surgical treatment is chosen, adjuvant radiation therapy should also be considered in order to decrease morbidity from aggressive surgery aiming at R0 resection. Further studies are suggested to illuminate the biological association between the desmoid tumour and other neoplasms. PMID:25116575
Ihalainen, Hanna R; Koljonen, Virve; Böhling, Tom O; Tukiainen, Erkki J; Sampo, Mika M
The immune system influences the fate of developing cancers by not only functioning as a tumour promoter that facilitates cellular transformation, promotes tumour growth and sculpts tumour cell immunogenicity, but also as an extrinsic tumour suppressor that either destroys developing tumours or restrains their expansion. Yet, clinically apparent cancers still arise in immunocompetent individuals in part as a consequence of cancer-induced immunosuppression. In many individuals, immunosuppression is mediated by cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1), two immunomodulatory receptors expressed on T cells. Monoclonal-antibody-based therapies targeting CTLA-4 and/or PD-1 (checkpoint blockade) have yielded significant clinical benefits-including durable responses--to patients with different malignancies. However, little is known about the identity of the tumour antigens that function as the targets of T cells activated by checkpoint blockade immunotherapy and whether these antigens can be used to generate vaccines that are highly tumour-specific. Here we use genomics and bioinformatics approaches to identify tumour-specific mutant proteins as a major class of T-cell rejection antigens following anti-PD-1 and/or anti-CTLA-4 therapy of mice bearing progressively growing sarcomas, and we show that therapeutic synthetic long-peptide vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy. Although mutant tumour-antigen-specific T cells are present in progressively growing tumours, they are reactivated following treatment with anti-PD-1 and/or anti-CTLA-4 and display some overlapping but mostly treatment-specific transcriptional profiles, rendering them capable of mediating tumour rejection. These results reveal that tumour-specific mutant antigens are not only important targets of checkpoint blockade therapy, but they can also be used to develop personalized cancer-specific vaccines and to probe the mechanistic underpinnings of different checkpoint blockade treatments. PMID:25428507
Gubin, Matthew M; Zhang, Xiuli; Schuster, Heiko; Caron, Etienne; Ward, Jeffrey P; Noguchi, Takuro; Ivanova, Yulia; Hundal, Jasreet; Arthur, Cora D; Krebber, Willem-Jan; Mulder, Gwenn E; Toebes, Mireille; Vesely, Matthew D; Lam, Samuel S K; Korman, Alan J; Allison, James P; Freeman, Gordon J; Sharpe, Arlene H; Pearce, Erika L; Schumacher, Ton N; Aebersold, Ruedi; Rammensee, Hans-Georg; Melief, Cornelis J M; Mardis, Elaine R; Gillanders, William E; Artyomov, Maxim N; Schreiber, Robert D
Background Sigma2 (?2) receptors are highly expressed in cancer cell lines and in tumours. Two novel selective 18F-phthalimido ?2 ligands, 18F-SIG343 and 18F-SIG353, were prepared and characterised for their potential tumour imaging properties. Methods Preparation of 18F-SIG343 and 18F-SIG353 was achieved via nucleophilic substitution of their respective nitro precursors. In vitro studies including radioreceptor binding assays in the rat brain membrane and cell uptake studies in the A375 cell line were performed. In vivo studies were carried out in mice bearing A375 tumours including positron emission tomography (PET) imaging, biodistribution, blocking and metabolite studies. Results In vitro studies showed that SIG343 and SIG353 displayed excellent affinity and selectivity for ?2 receptors (Ki(?2)?=?8 and 3 nM, ?2:?1?=?200- and 110-fold, respectively). The ?2 selectivity of 18F-SIG343 was further confirmed by blocking studies in A375 cells, however, not noted for 18F-SIG353. Biodistribution studies showed that both radiotracers had similar characteristics including moderately high tumour uptake (4%ID/g to 5%ID/g); low bone uptake (3%ID/g to 4%ID/g); and high tumour-to-muscle uptake ratios (four- to sevenfold) up to 120 min. Although radiotracer uptake in organs known to express ? receptors was significantly blocked by pre-injection of competing ? ligands, the blocking effect was not observed in the tumour. PET imaging studies indicated major radioactive localisation in the chest cavity for both ligands, with approximately 1%ID/g uptake in the tumour at 120 min. Metabolite studies showed that the original radiotracers remained unchanged 65% to 80% in the tumour up to 120 min. Conclusions The lead ligands showed promising in vitro and in vivo characteristics. However, PET imaging indicated low tumour-to-background ratios. Furthermore, we were unable to demonstrate that uptake in the A375 tumour was ?2-specific. 18F-SIG343 and 18F-SIG343 do not display ideal properties for imaging the ?2 receptor in the A375 tumour model. However, since the radiotracers show promising in vitro and in vivo characteristics, longer scans using appropriate half-life isotopes and alternative tumour models will be carried out in future studies to fully validate the imaging characteristics of these radiotracers. PMID:24330526
A systematic account of neuron cell types is a basic prerequisite for determining the vertebrate nervous system global wiring diagram. With comprehensive lineage and phylogenetic information unavailable, a general ontology based on structure-function taxonomy is proposed and implemented in a knowledge management system, and a prototype analysis of select regions (including retina, cerebellum, and hypothalamus) presented. The supporting Brain Architecture Knowledge Management System (BAMS) Neuron ontology is online and its user interface allows queries about terms and their definitions, classification criteria based on the original literature and "Petilla Convention" guidelines, hierarchies, and relations-with annotations documenting each ontology entry. Combined with three BAMS modules for neural regions, connections between regions and neuron types, and molecules, the Neuron ontology provides a general framework for physical descriptions and computational modeling of neural systems. The knowledge management system interacts with other web resources, is accessible in both XML and RDF/OWL, is extendible to the whole body, and awaits large-scale data population requiring community participation for timely implementation. PMID:17582506
Bota, Mihail; Swanson, Larry W
Although molecular alterations are reported in different types of odontogenic tumours, their pathogenesis remains to be established. Loss of heterozygosity (LOH) studies allow the identification of minimal regions of deletions of known or putative tumour suppressor genes, the losses of which may promote neoplastic growth. The purpose of this study was to investigate LOH in a set of odontogenic mixed tumours. Tumour suppressor gene loci on 3p, 9p, 11p, 11q and 17p chromosomes were analysed in five samples of ameloblastic fibroma (AF), three samples of ameloblastic fibro-odontoma (AFO) and three samples of ameloblastic fibrosarcoma (AFS). The most frequently lost genetic loci were p53 (17p13, 62%) and CHRNB1 (17p13, 55%). LOH at the chromosome regions 3p24.3, 9p22 and 9p22-p21 was identified only in AFS. No sample showed LOH at the chromosomal loci 3p21.2 and 11q13.4. For the region 9p22-p13, LOH occurred in one sample of AFO. The fractional allelic loss (FAL) was calculated for each sample. The mean FAL of the benign lesions (i.e. AF and AFO) was 22%, whereas the mean FAL of the malignant lesions (i.e. AFS) was 74.6%. In conclusion, our results show a higher FAL in AFS compared to its benign counterparts and reveal a different pattern of LOH of tumour suppressor genes in AFS, which may regulate changes in tumour behaviour. PMID:22082131
Galvão, Clarice F; Gomes, Carolina C; Diniz, Marina G; Vargas, Pablo A; de Paula, Alfredo M B; Mosqueda-Taylor, Adalberto; Loyola, Adriano M; Gomez, Ricardo S
Background: Tumour-associated stroma has a critical role in tumour proliferation. Our aim was to determine a specific protein expression profile of stromal angiogenic cytokines and matrix metalloproteinases (MMPs) to identify potential biomarkers or new therapy targets. Methods: Frozen tissue of primary colorectal cancer (n=25), liver (n=25) and lung metastases (n=23) was laser-microdissected to obtain tumour epithelial cells and adjacent tumour-associated stroma. Protein expression of nine angiogenic cytokines and eight MMPs was analysed using a multiplex-based protein assay. Results: We found a differential expression of several MMPs and angiogenic cytokines in tumour cells compared with adjacent tumour stroma. Cluster analysis displayed a tumour-site-dependent stromal expression of MMPs and angiogenic cytokines. Univariate analysis identified stromal MMP-2 and MMP-3 in primary colorectal cancer, stromal MMP-1, -2, -3 and Angiopoietin-2 in lung metastases and stromal MMP-12 and VEGF in liver metastases as prognostic markers (P>0.05, respectively). Furthermore, stroma-derived Angiopoietin-2 proved to be an independent prognostic marker in colorectal lung metastases. Conclusion: Expression of MMPs and angiogenic cytokines in tumour cells and adjacent tumour stroma is dependent on the tumour site. Stroma-derived MMPs and angiogenic cytokines may be useful prognostic biomarkers. These data can be helpful to identify new agents for a targeted therapy in patients with colorectal cancer. PMID:24292449
Kahlert, C; Pecqueux, M; Halama, N; Dienemann, H; Muley, T; Pfannschmidt, J; Lasitschka, F; Klupp, F; Schmidt, T; Rahbari, N; Reissfelder, C; Kunz, C; Benner, A; Falk, C; Weitz, J; Koch, M
Lysyl oxidase-like 2 (LOXL2), a secreted enzyme that catalyzes the cross-linking of collagen, plays an essential role in developmental angiogenesis. We found that administration of the LOXL2-neutralizing antibody AB0023 inhibited bFGF-induced angiogenesis in Matrigel plug assays and suppressed recruitment of angiogenesis promoting bone marrow cells. Small hairpin RNA-mediated inhibition of LOXL2 expression or inhibition of LOXL2 using AB0023 reduced the migration and network-forming ability of endothelial cells, suggesting that the inhibition of angiogenesis results from a direct effect on endothelial cells. To examine the effects of AB0023 on tumour angiogenesis, AB0023 was administered to mice bearing tumours derived from SKOV-3 ovarian carcinoma or Lewis lung carcinoma (LLC) cells. AB0023 treatment significantly reduced the microvascular density in these tumours but did not inhibit tumour growth. However, treatment of mice bearing SKOV-3-derived tumours with AB0023 also promoted increased coverage of tumour vessels with pericytes and reduced tumour hypoxia, providing evidence that anti-LOXL2 therapy results in the normalization of tumour blood vessels. In agreement with these data, treatment of mice bearing LLC-derived tumours with AB0023 improved the perfusion of the tumour-associated vessels as determined by ultrasonography. Improved perfusion and normalization of tumour vessels after treatment with anti-angiogenic agents were previously found to improve the delivery of chemotherapeutic agents into tumours and to result in an enhancement of chemotherapeutic efficiency. Indeed, treatment with AB0023 significantly enhanced the anti-tumourigenic effects of taxol. Our results suggest that inhibition of LOXL2 may prove beneficial for the treatment of angiogenic tumours. PMID:23828904
Zaffryar-Eilot, Shelly; Marshall, Derek; Voloshin, Tali; Bar-Zion, Avinoam; Spangler, Rhyannon; Kessler, Ofra; Ghermazien, Haben; Brekhman, Vera; Suss-Toby, Edith; Adam, Dan; Shaked, Yuval; Smith, Victoria; Neufeld, Gera
Wilms tumour has been reported in association with over 50 different clinical conditions and several abnormal constitutional karyotypes. Conclusive evidence of an increased risk of Wilms tumour exists for only a minority of these conditions, including WT1 associated syndromes, familial Wilms tumour, and certain overgrowth conditions such as Beckwith?Wiedemann syndrome. In many reported conditions the rare co?occurrence of Wilms tumour is probably due to chance. However, for several conditions the available evidence cannot either confirm or exclude an increased risk, usually because of the rarity of the syndrome. In addition, emerging evidence suggests that an increased risk of Wilms tumour occurs only in a subset of individuals for some syndromes. The complex clinical and molecular heterogeneity of disorders associated with Wilms tumour, together with the apparent absence of functional links between most of the known predisposition genes, suggests that abrogation of a variety of pathways can promote Wilms tumorigenesis. PMID:16690728
Scott, R H; Stiller, C A; Walker, L; Rahman, N
The granular cell tumour is a very rare tumour which originates in the Schwann cells, and is generally benign. It is usually located in the head and neck, and its appearance in the breast is uncommon. Although it is rare tumour, granular cell tumours of the breast have a higher prevalence than previously recognised. This tumour usually imitates breast cancer due to its clinical and imaging data, with its diagnosis being by histopathology. The treatment is a wide local excision, and its prognosis is good with a low recurrence rate. We present two cases of granular tumours of the breast in post-menopausal women that simulated a breast carcinoma in the ultrasound and mammography. The first was detected in the breast cancer screening program, and the second during follow up of an invasive ductal carcinoma. PMID:22325669
Escudero Esteban, R; Gómez Benítez, S; del Estad Cabello, G; Yáñez Fernández, P
Analysis of the low frequency region of Raman spectra enables determination of water structure. It has been previously demonstrated by various techniques that water content and possibly also the water structure is altered in some malignant tumours. To further elucidate possible change in water structure in tumours we performed NIR FT Raman spectroscopy on biopsies from selected benign and malignant skin tumours (benign: seborrheic keratosis, pigmented nevi; malignant: malignant melanoma, basal cell carcinoma). We did not observe any differences in water content between malignant and benign skin tumours with an exception of seborrheic keratosis, in which the water content was decreased. Increase in the tetrahedral (free) water was found in malignant skin tumours and sun-damaged skin relative to normal young skin and benign skin tumours. This finding may add to the understanding of molecular alterations in cancer.
Gniadecka, M.; Nielsen, O. F.; Wulf, H. C.
Tumours recruit mesenchymal stem cells to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours. CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites. Our results provide the molecular basis for mesenchymal stem cell recruitment into tumours and how this process leads to tumour metastasis. PMID:23653207
Jung, Younghun; Kim, Jin Koo; Shiozawa, Yusuke; Wang, Jingcheng; Mishra, Anjali; Joseph, Jeena; Berry, Janice E; McGee, Samantha; Lee, Eunsohl; Sun, Hongli; Wang, Jianhua; Jin, Taocong; Zhang, Honglai; Dai, Jinlu; Krebsbach, Paul H; Keller, Evan T; Pienta, Kenneth J; Taichman, Russell S
Mouse tumour cells were treated with various chemical modifiers. The number of modifying groups per cell was determined with labelled reagents. The effects of the different modifying groups on the immunogenicity of the tumour cells was tested in syngeneic mice for tumour protection using a challenge dose of viable cells at 1000 or 10,000 time LD100. Best protection was obtained after immunization of animals with tumour cells modified with dimethylsulphate or acetic anhydride, or with glutardialdehyde-fixed cells treated with a carbodiimide and methylamine. Up to 40% of the animals remained tumour-free. The other animals exhibited a greatly increased mean survival time. The post-challenge sera showed no detectable amounts of antibodies against the tumour cells. PMID:192259
Staab, H. J.; Anderer, F. A.
The polymeric immunoglobulin receptor (pIgR) is a key component of the mucosal immune system that mediates epithelial transcytosis of immunoglobulins. High pIgR expression has been reported to correlate with a less aggressive tumour phenotype and an improved prognosis in several human cancer types. Here, we examined the expression and prognostic significance of pIgR in pancreatic and periampullary adenocarcinoma. The study cohort encompasses a consecutive series of 175 patients surgically treated with pancreaticoduodenectomy for pancreatic and periampullary adenocarcinoma in Malmö and Lund University Hospitals, Sweden, between 2001–2011. Tissue microarrays were constructed from primary tumours (n?=?175) and paired lymph node metastases (n?=?105). A multiplied score was calculated from the fraction and intensity of pIgR staining. Classification and regression tree analysis was used to select the prognostic cut-off. Unadjusted and adjusted hazard ratios (HR) for death and recurrence within 5 years were calculated. pIgR expression could be evaluated in 172/175 (98.3%) primary tumours and in 96/105 (91.4%) lymph node metastases. pIgR expression was significantly down-regulated in lymph node metastases as compared with primary tumours (p?=?0.018). Low pIgR expression was significantly associated with poor differentiation grade (p<0.001), perineural growth (p?=?0.027), lymphatic invasion (p?=?0.016), vascular invasion (p?=?0.033) and infiltration of the peripancreatic fat (p?=?0.039). In the entire cohort, low pIgR expression was significantly associated with an impaired 5-year survival (HR?=?2.99, 95% confidence interval (CI) 1.71–5.25) and early recurrence (HR?=?2.89, 95% CI 1.67–4.98). This association remained significant for survival after adjustment for conventional clinicopathological factors, tumour origin and adjuvant treatment (HR?=?1.98, 95% CI 1.10–3.57). These results demonstrate, for the first time, that high tumour-specific pIgR expression signifies a more favourable tumour phenotype and that low expression independently predicts a shorter survival in patients with pancreatic and periampullary cancer. The mechanistic basis for the putative tumour suppressing properties of pIgR in these cancers merits further study. PMID:25397670
Fristedt, Richard; Elebro, Jacob; Gaber, Alexander; Jonsson, Liv; Heby, Margareta; Yudina, Yulyana; Nodin, Björn; Uhlén, Mathias; Eberhard, Jakob; Jirström, Karin
Granular cell tumours are uncommon, generally benign neoplasms of uncertain origin that occasionally affect the tracheobronchial tree. Their incidence seems to be increasing, despite the fact that such tumours are rarely suspected on clinical grounds or bronchoscopic appearance. Here we describe three cases of endobronchial granular cell tumours, one of which regressed spontaneously after biopsy, and review previous accounts of their bronchoscopic and clinical features. Images PMID:3590055
Hernandez, O G; Haponik, E F; Summer, W R
Breast cancer is a morphologically and clinically heterogeneous disease; however, it is less clear how risk factors relate to tumour features. We evaluated risk factors by tumour characteristics (histopathologic type, grade, size, and nodal status) in a population-based case–control of 2386 breast cancers and 2502 controls in Poland. Use of a novel extension of the polytomous logistic regression permitted simultaneous modelling of multiple tumour characteristics. Late age at first full-term birth was associated with increased risk of large (>2?cm) tumours (odds ratios (95% confidence intervals) 1.19 (1.07–1.33) for a 5-year increase in age), but not smaller tumours (P for heterogeneity adjusting for other tumour features (Phet)=0.007). On the other hand, multiparity was associated with reduced risk for small tumours (0.76 (0.68–0.86) per additional birth; Phet=0.004). Consideration of all tumour characteristics simultaneously revealed that current or recent use of combined hormone replacement therapy was associated with risk of small (2.29 (1.66–3.15)) and grade 1 (3.36 (2.22–5.08)) tumours (Phet=0.05 for size and 0.0008 for grade 1 vs 3), rather than specific histopathologic types (Phet=0.63 for ductal vs lobular). Finally, elevated body mass index was associated with larger tumour size among both pre- and postmenopausal women (Phet=0.05 and 0.0001, respectively). None of these relationships were explained by hormone receptor status of the tumours. In conclusion, these data support distinctive risk factor relationships by tumour characteristics of prognostic relevance. These findings might be useful in developing targeted prevention efforts. PMID:16755295
García-Closas, M; Brinton, L A; Lissowska, J; Chatterjee, N; Peplonska, B; Anderson, W F; Szeszenia-D?browska, N; Bardin-Mikolajczak, A; Zatonski, W; Blair, A; Kalaylioglu, Z; Rymkiewicz, G; Mazepa-Sikora, D; Kordek, R; Lukaszek, S; Sherman, M E
Fas Ligand (FasL) expression by cancer cells may contribute to tumour immune escape via the Fas counterattack against tumour-infiltrating\\u000a lymphocytes (TILs). Whether this plays a role in colorectal carcinogenesis in Lynch syndrome was examined studying FasL expression,\\u000a tumour cell apoptosis and number of TILs in colorectal neoplasms from Lynch syndrome patients (50 adenomas, 20 carcinomas)\\u000a compared with sporadic cases (69
Jan J. Koornstra; Steven de Jong; Wietske Boersma-van Eck; Nynke Zwart; Harry Hollema; Elisabeth G. E. de Vries; Jan H. Kleibeuker
Between the information transfer rate and the classification accuracy of a brain computer interface (BCI) system a balance occurs. If we want higher correct classification rates the BCI system will consequently become slower. Otherwise, a faster (online) BCI system assumes a lower classification rate. If we analyze the human motor system (HMS) we can view the hierarchical organization (with different
Dan M. Dobrea; Monica C. Dobrea
Associations between different bacteria and various tumours have been reported in patients for decades. Studies involving characterisation of bacteria within tumour tissues have traditionally been in the context of tumourigenesis as a result of bacterial presence within healthy tissues, and in general, dogma holds that such bacteria are causative agents of malignancy (directly or indirectly). While evidence suggests that this may be the case for certain tumour types and bacterial species, it is plausible that in many cases, clinical observations of bacteria within tumours arise from spontaneous infection of established tumours. Indeed, growth of bacteria specifically within tumours following deliberate systemic administration has been demonstrated for numerous bacterial species at preclinical and clinical levels. We present the available data on links between bacteria and tumours, and propose that besides the few instances in which pathogens are playing a pathogenic role in cancer, in many instances, the prevalent relationship between solid tumours and bacteria is opportunistic rather than causative, and discuss opportunities for exploiting tumour-specific bacterial growth for cancer treatment. PMID:23537317
Glycosylation changes that occur in cancer often lead to the expression of tumour-associated carbohydrate antigens. In breast cancer, these antigens are usually associated with a poor prognosis and a reduced overall survival. Cellular models have shown the implication of these antigens in cell adhesion, migration, proliferation and tumour growth. The present review summarizes our current knowledge of glycosylation changes (structures, biosynthesis and occurrence) in breast cancer cell lines and primary tumours, and the consequences on disease progression and aggressiveness. The therapeutic strategies attempted to target tumour-associated carbohydrate antigens in breast cancer are also discussed. PMID:20550729
Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack1,2. Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is enhanced in immune-compromised mice, while conversely, the capacity for such tumours to grow after transplantation into wild-type mice is reduced2,3. However, many questions about the process of cancer immunoediting remain unanswered due, in part, to the known antigenic complexity and heterogeneity of carcinogen-induced tumours4. Here we have adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allowed us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbor identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice to mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens (TSAs) by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or MHCI presentation was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of TSA expression in immune surveillance, and potentially, immunotherapy. PMID:22318517
DuPage, Michel; Mazumdar, Claire; Schmidt, Leah M.; Cheung, Ann F.; Jacks, Tyler
Aims To describe the incidence and relative frequencies of primary malignant orbital tumours in the Netherlands from 1989 to 2006. Methods All registered primary malignant orbital tumours were extracted from the population-based database of the Netherlands Cancer Registry. Age-adjusted incidence of malignant orbital tumours per 10?000?000 persons per year and the estimated annual percentage change (EAPC) were computed. Results A total of 367 malignant orbital tumours were registered. The average age-adjusted incidence of malignant orbital tumours is 10.9. Lymphoma has a relative frequency of 67%, rhabdomyosarcoma 12%, adenocarcinoma 6%, and adenoid cystic carcinoma 5%. The incidence of primary malignant orbital tumours has been increasing in the Netherlands (EAPC +2.8%). Conclusion In the Netherlands, lymphoma is the most common primary malignant orbital tumour, followed by rhabdomyosarcoma, adenocarcinoma, and adenoid cystic carcinoma. The relative frequencies of the different histological tumour types are comparable to the frequencies in other parts of the world. The incidence of malignant primary orbital tumours shows a slight increase between 1989 and 2006. PMID:21336252
Koopman, J H; van der Heiden-van der Loo, M; van Dijk, M R; Bijlsma, W R
Concomitant immunity is a phenomenon in which a tumour-bearing host is resistant to the growth of an implanted secondary tumour. Metastases are considered to be secondary tumours that develop spontaneously during primary tumour growth, suggesting the involvement of concomitant immunity in controlling the rise of metastases. It has been demonstrated that B-1 cells, a subset of B-lymphocytes found predominantly in pleural and peritoneal cavities, not only increase the metastatic development of murine melanoma B16F10, but also are capable of differentiating into mononuclear phagocytes, modulating inflammatory responses in wound healing, in oral tolerance and in Paracoccidiose brasiliensis infections. Here, we studied B-1 cells' participation in concomitant immunity during Ehrlich tumour progression. Our results show that B-1 cells obtained from BALB/c mice previously injected with Ehrlich tumour in the footpad were able to protect BALB/c and BALB/Xid mice against Ehrlich tumour challenge. In addition, it was demonstrated that BALB/Xid show faster tumour growth and have lost concomitant immunity, and that this state can be partially restored by reconstituting these animals with B-1 cells. However, further researches are required to establish the mechanism involving B-1 cells in Ehrlich tumour growth. PMID:24556035
Azevedo, M C; Palos, M C; Osugui, L; Laurindo, M F; Masutani, D; Nonogaki, S; Bachi, A L L; Melo, F H M; Mariano, M
The diagnosis of cardiac tumours is often based on images without tissue diagnosis or tissue obtained at surgery. Percutaneous myocardial biopsy via a transvenous approach has been described in literatures but this technique is not feasible with left atrial tumours. We report a patient presenting with heart failure and left atrial tumour. The diagnosis of spindle cell neoplasm was established pre-operatively via successful transseptal fine needle aspiration of cells from a left atrial tumour. We believe this technique worth consideration to aid pre-surgery diagnosis. PMID:19656723
Wong, Chi Wing; Ruygrok, Peter; Sutton, Timothy; Ding, Patricia; van Vliet, Chris; Occleshaw, Christopher; Smith, Warren
Pituitary tumour apoplexy (PA) is a rare clinical syndrome that occurs as a result of acute haemorrhage and/or infarction within a frequently undiagnosed pituitary tumour. The sudden enlargement of the pituitary mass undergoing PA is responsible for a wide range of acute symptoms/signs (severe headache, visual loss, diplopia, hypopituitarism, impaired consciousness) which, together with the radiological evidence of a pituitary lesion, establish the diagnosis. The optimal care of PA requires involvement of a multidisciplinary team including endocrinologist, neurosurgeon, neuroophthalmologist and the management strategy depends on the clinical manifestations, as well as the presence of co-morbidities. Prompt surgical decompression is initially indicated in cases with severe or progressive impairment of the visual acuity or the visual fields or with altered mental state and leads to visual and neurological recovery in most of the patients. Patients with mild, stable clinical picture (including those with isolated ocular palsies) can be managed conservatively (support of fluid and electrolyte balance and stress doses of steroids in most cases) with favourable visual and neurological outcome. Frequent reassessment is mandatory because the clinical course can be unpredictable; if progression of symptoms occurs, later elective surgery is indicated and is beneficial, especially in terms of visual outcome. The endocrinological outcome is less favourable, irrespective of the treatment option, with many patients remaining on long-term replacement therapy. Despite the above guidelines, clear proof of optimal outcomes in the form of randomised controlled trials is lacking. Regrowth of the pituitary tumour years after a PA episode is possible and patients require long-term surveillance. PMID:25452466
Capatina, Cristina; Inder, Warrick J; Karavitaki, Niki; Wass, John A H
Tumour-associated macrophages (TAMs) are enriched in glioblastoma multiformes (GBMs) that contain glioma stem cells (GSCs) at the apex of their cellular hierarchy. The correlation between TAM density and glioma grade suggests a supportive role for TAMs in tumour progression. Here we interrogated the molecular link between GSCs and TAM recruitment in GBMs and demonstrated that GSCs secrete periostin (POSTN) to recruit TAMs. TAM density correlates with POSTN levels in human GBMs. Silencing POSTN in GSCs markedly reduced TAM density, inhibited tumour growth, and increased survival of mice bearing GSC-derived xenografts. We found that TAMs in GBMs are not brain-resident microglia, but mainly monocyte-derived macrophages from peripheral blood. Disrupting POSTN specifically attenuated the tumour-supportive M2 type of TAMs in xenografts. POSTN recruits TAMs through the integrin ?v?3 as blocking this signalling by an RGD peptide inhibited TAM recruitment. Our findings highlight the possibility of improving GBM treatment by targeting POSTN-mediated TAM recruitment. PMID:25580734
Zhou, Wenchao; Ke, Susan Q; Huang, Zhi; Flavahan, William; Fang, Xiaoguang; Paul, Jeremy; Wu, Ling; Sloan, Andrew E; McLendon, Roger E; Li, Xiaoxia; Rich, Jeremy N; Bao, Shideng
This review focuses on the problems related to defining hydrocephalus and on the development of a consensus on the classification of this common problem. Such a consensus is needed so that diverse research efforts and plans of treatment can be understood in the same context. The literature was searched to determine the definition of hydrocephalus and to identify previously proposed classification schemes. The historic perspective, purpose, and result of these classifications are reviewed and analyzed. The concept of the hydrodynamics of cerebrospinal fluid (CSF) as a hydraulic circuit is presented to serve as a template for a contemporary classification scheme. Finally, a definition and classification that include all clinical causes and forms of hydrocephalus are suggested. The currently accepted classification of hydrocephalus into "communicating" and "noncommunicating" varieties is almost 90 years old and has not been modified despite major advances in neuroimaging, neurosciences, and treatment outcomes. Despite a thorough search of the literature using computerized search engines and bibliographies from review articles and book chapters, I identified only 6 previous attempts to define and classify different forms of hydrocephalus. This review proposes the following definition for hydrocephalus: hydrocephalus is an active distension of the ventricular system of the brain related to inadequate passage of CSF from its point of production within the ventricular system to its point of absorption into the systemic circulation. Based on this definition (potential points of flow restriction) and on the view of the CSF system as a hydraulic circuit, a classification system is proposed. The acceptance of this proposed definition and classification schema would allow clinicians and basic scientists to communicate effectively, to share information and results, and to develop testable hypotheses. PMID:19410151
Rekate, Harold L
Giant cell tumour (osteoclastoma) of talar bone is a rare entity and is seen more commonly in the third decade of life. We report this disease entity in a 17-years-old girl. The patient presented with painful swelling of the left ankle with an osteolytic lesion in the talus on conventional radiographs. Intralesional curettage and autologous bone grafting was performed following which patient's pain and swelling disappeared. Complete range of movement at the ankle joint was regained with minimal restriction at the subtalar joint. There is no evidence of relapse at six months follow up. PMID:11013480
Bapat, M R; Narlawar, R S; Pimple, M K; Bhosale, P B
For some time, it has been known that there is a substantial genetic component to testicular germ cell tumour susceptibility, supported by several pieces of evidence, including the significantly increased familial risk and differential risk among races. However, despite extensive linkage searches on available families, no high penetrance genes have been identified. Recently genome-wide association studies have revealed three candidate loci, which confer up to a four-fold risk of developing TGCT. The genome-wide association studies for this cancer are noteworthy, because of the high effect sizes demonstrated at each loci and the biological plausibility of the genes at or near the associated SNPs, particularly KITLG. PMID:20303738
Rapley, Elizabeth A; Nathanson, Katherine L
Audio Segmentation and Classification Abdillahi Hussein Omar Kgs. Lyngby 2005 #12;Preface The work describes the work done on the development of an audio segmentation and classification system. Many existing works on audio classification deal with the problem of classifying known homogeneous audio segments
Cardiac magnetic resonance imaging (MRI) is the reference standard technique for assessment and characterization of a suspected cardiac tumour. It provides an unrestricted field of view, high temporal resolution and non-invasive tissue characterization based on multi-parametric assessment of the chemical micro-environment. Sarcomas account for around 95% of all primary malignant cardiac tumours with lymphoma, and primary pericardial mesothelioma making up most of the remainder of cases. By contrast cardiac metastases are much more common. In this article we review the MRI features of the spectrum of histologically malignant cardiac and pericardial tumours as well as some potential tumour mimics. PMID:25525582
Shahid, Muhammad; Ganeshan, Arul; Baijal, Shobhit; Simpson, Helen; Watkin, Richard W.
Meningiomas of the lateral ventricles of the brain are rare tumours with an approximate incidence of 0.5-4.5% among all intracranial meningiomas. Four cases of intraventricular meningioma arising from the trigone are presented. In 1-st case the calcified mass was visible on straight radiographs. In 2-nd and 3-rd cases CT and angiography was performed. In 4-th case MRI and MRA proved to be very useful. The tumours were removed by transcortical approach in the posterior parietal area. The available literature on intraventricular meningiomas has been discussed. PMID:9487654
Imieli?ski, B L; Kloc, W
Introduction: Ochratoxin-A (OTA) is one of the most abundant food-contaminating mycotoxins, known for its nephrotoxicity, neurotoxicity, gonadotoxicity, teratogenicity, immunosuppression and carcinogenesis. OTA has been linked to several genitourinary pathologies, including Balkan nephropathy and genitourinary malignancies. We examine OTA levels in serum samples and tumour specimens collected from patients with renal and testicular tumours. Methods: Frozen samples were obtained from the Ontario Tumour Bank. Serum specimens, along with renal and testicular tumour biopsies, were included in this study. Normal tissue from the negative surgical margins of each tumour served as a control. OTA levels in serum was measured using the enzyme-linked immunosorbent assay (ELISA), while OTA detection in tissue specimens was determined using immunohistochemistry (IHC). Results: We included specimens collected from 56 patients (36 men and 20 women). Histopathology of the 52 renal tumours included 31 (60%) conventional type renal cell carcinomas (RCC), 5 (10%) chromophobe RCC, 5 (10%) papillary RCC, 1 (2%) oncocytoma and 10 (19%) upper tract urothelial carcinoma (UC). The 4 testicular tumours included 1 seminomatous (25%) germ cell tumour and 3 (75%) non-seminomatous germ cell tumours. OTA was detected in the serum of renal tumour patients, with a range from 0.004 to 0.25 ng/mL (mean: 0.07 and median 0.06 ng/mL). There was no OTA signal detected by IHC staining in all tested renal and testicular tumours. Conclusions: The OTA levels detected in the serum of patients were highly variable and relatively low. No OTA was detected in the tissue samples. PMID:24578744
Fahmy, Nader; Woo, Mark; Alameldin, Mona; MacDonald, Kyle; Goneau, Lee W.; Cadieux, Peter; Pautler, Stephen E.
This week-long exploration of brain structure and function through hands-on experiments and web Treasure Hunts ends with an open inquiry on the brain designed by students. Exploration topics include brain parts and their functions, surface area, optic nerve activity, touch receptors, muscle spindle fibers, motor learning, neuroscientists, and the effects of drugs on the brain. This teaching resource was developed by a K-12 science teacher in the American Physiological SocietyÂ?s 2004 Frontiers in Physiology Program. For more information on this program, please visit www.frontiersinphys.org.
Ms. Rachel Gillis (Arsenal Technical High School)
The histological classification of testicular germ cell tumours (TGCTs) to seminoma or non-seminomatous germ cell tumours is at present the main criterion for the clinical outcome and selection of the treatment strategy. In view of the need to identify novel prognostic biomarkers for TGCTs, we investigated the expression of the matrix metalloproteinases MMP-2 and MMP-9 in testicular tumour tissues and cell lines of both seminoma and non-seminoma origin. Immunohistochemistry and zymography analysis of tumoural tissues showed significantly higher levels of MMP-2 and MMP-9 compared with normal testis with the active forms detected only in the tumour tissues. Three cell lines representative of the different tumour types, JKT-1 seminoma, NCCIT teratocarcinoma and NTERA2/D1 embryonal carcinoma were also evaluated for their expression of these MMPs using qPCR and zymography and for their invasive properties. The more invasive non-seminomatous teratocarcinoma and embryonal cells expressed considerably more MMP-2 and MMP-9 compared with seminoma cells exhibiting lower invasiveness. Furthermore, an inverse relation was observed between invasiveness and the expression of endogenous inhibitors TIMP-1 and TIMP-2. The MMP inhibitor Marimastat inhibited invasion in all cell lines, the highest inhibition was observed in the more invasive NTERA2/D1 and NCCIT cells, which presented the highest ratio of MMP-2 and MMP-9 vs. TIMP-1 and TIMP-2. These results highlight the importance of MMP-2 and MMP-9 in the invasiveness of testicular tumours and suggest that their levels, vs. those of TIMP-1 and TIMP-2, may represent potential biomarkers for testicular malignancy. PMID:22712465
Milia-Argeiti, E; Huet, E; Labropoulou, V T; Mourah, S; Fenichel, P; Karamanos, N K; Menashi, S; Theocharis, A D
The incidence of hepatocellular carcinoma (HCC) is worldwide sharply on the rise and patients with advanced disease carry a poor prognosis. HCC is the sixth most common cancer and the third leading cause of cancer associated deaths in the world. Intra-arterially administered (131)I-Lipiodol is selectively retained by hepatocellular carcinomas, and has been used as a vehicle for delivery of therapeutic agents to these tumours. In this review we focus on the therapeutic indications, usefulness and methods of treatment with 131-Iodine Lipiodol. The effectiveness of (131)I-Lipiodol treatment is proven both in the treatment of HCC with portal thrombosis and also as an adjuvant to surgery after the resection of HCCs. It is at least as effective as chemoembolization and is tolerated much better. Severe liver dysfunction represents theoretic contraindication for radioembolization as well as for TACE. In such cases (131)I-Lipiodol is an alternative therapy option especially in tumours smaller than 6cm. PMID:21664971
Ahmadzadehfar, Hojjat; Sabet, Amir; Wilhelm, Kai; Biersack, Hans Jürgen; Risse, Jörn
Tumours that are low in oxygen (hypoxic) tend to be more aggressive and respond less well to treatment. Knowing the spatial distribution of oxygen within a tumour could therefore play an important role in treatment planning, enabling treatment to be targeted in such a way that higher doses of radiation are given to the more radioresistant tissue. Mapping the spatial distribution of oxygen in vivo is difficult. Radioactive tracers that are sensitive to different levels of oxygen are under development and in the early stages of clinical use. The concentration of these tracer chemicals can be detected via positron emission tomography resulting in a time dependent concentration profile known as a tissue activity curve (TAC). Pharmaco-kinetic models have then been used to deduce oxygen concentration from TACs. Some such models have included the fact that the spatial distribution of oxygen is often highly inhomogeneous and some have not. We show that the oxygen distribution has little impact on the form of a TAC; it is only the mean oxygen concentration that matters. This has significant consequences both in terms of the computational power needed, and in the amount of information that can be deduced from TACs. PMID:22761687
Skeldon, Anne C.; Chaffey, Gary; Lloyd, David J. B.; Mohan, Vineet; Bradley, David A.; Nisbet, Andrew
Tumour Banks (TB) are called upon to play a central role in Oncological translational research. TB have been existing since Pathology Departments started storing blocks of tissue samples, but in keeping this role they must face some urgent challenges including: an updated definition of hospital TB, integration into clinical trials and projects of excellence, networking and a new framework for ethics and laws. Current TB definition includes not only tissue storage, but also a series of hospital protocols that allow molecular studies of tumour and normal samples. The real value of these protocols and samples appears with scientific projects of excellence and integrated in clinical trials. Most of these trials need for a large number of cases with homogeneously treated tissue samples in the context of multicentre and multinational projects. Thereby, networking appears the best solution for TB to expand. Networking implies standardised technical procedures, a strict quality control programme, homogeneous ethic requirements and an open mentality for sharing. In the international setting the major challenge for networking is the various laws and customs in the different countries. To bring these diverse legislation together is, perhaps, the most important challenge for TB Networking in the very close future. PMID:16216033
Morente, Manuel M; Alonso, Soledad